« prise en charge de la ménopause » 7.9.18 amub · •animal data : estrogen enhancement of...
TRANSCRIPT
In the center of the city in the center of life with passion for care
Serge Rozenberg CHU St Pierre ULB-VUB Belgium
serge_rozenbergstpierre-brube
laquo Prise en charge de la meacutenopause raquo
7918 AMUB
La lute pour les droits de la femme nrsquoest pas
termineacutee
Manifestation ce dimanche
La carvanne des femmes
Conflict of interest amp Disclosure
Conflict of interest None
Disclosure SR
Research funding IRIS- King Baudouin
Fondation Vesale research Foundation Amgen
MSD
Speakers bureau ampor Advisory Boards
Abbot Pfizer Will Gedeon Richter MSD
Amgen Serylis Pharma
Concours
bull Ne pas oublier de reacutepondre hellipSinon on ne peut pas gagner
Goals
Risk Benefit of MHT
Indications - Contraindications
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 3 months ago
Patient case developed for educational purposes only
1 Sherman S Am J Med 2005118(128) 3S-7S
Defining the Menopausal
Transition1
FSH Follical Stimulating Hormone
Menopause stages most likely to be associated with vasomotor symptoms
Patterns of Estradiol Progesterone
Luteinizing and Follicle-stimulating
Hormones1
1 Santoro N Am J Med 2005 118 (12B) 8Sndash13S
Patterns of estradiol progesterone luteinizing hormone and follicle-stimulating hormone levels in a sample of 8 midreproductive-aged (MRA) and 14 older reproductive-aged (ORA) women Error bars indicate mean plusmn 10 standard error
Pooled Estimates of Proportion of
Vasomotor Symptoms During
Perimenopause1
1 Politi MC et al J Gen Intern Med 23(9)1507ndash13
Pooled estimates of proportion of vasomotor symptoms by year tofrom final menstrual period Six studies provided data for the main meta-analysis One was longitudinal and the others were cross-sectional
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 13 months ago
Patient case developed for educational purposes only
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
La lute pour les droits de la femme nrsquoest pas
termineacutee
Manifestation ce dimanche
La carvanne des femmes
Conflict of interest amp Disclosure
Conflict of interest None
Disclosure SR
Research funding IRIS- King Baudouin
Fondation Vesale research Foundation Amgen
MSD
Speakers bureau ampor Advisory Boards
Abbot Pfizer Will Gedeon Richter MSD
Amgen Serylis Pharma
Concours
bull Ne pas oublier de reacutepondre hellipSinon on ne peut pas gagner
Goals
Risk Benefit of MHT
Indications - Contraindications
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 3 months ago
Patient case developed for educational purposes only
1 Sherman S Am J Med 2005118(128) 3S-7S
Defining the Menopausal
Transition1
FSH Follical Stimulating Hormone
Menopause stages most likely to be associated with vasomotor symptoms
Patterns of Estradiol Progesterone
Luteinizing and Follicle-stimulating
Hormones1
1 Santoro N Am J Med 2005 118 (12B) 8Sndash13S
Patterns of estradiol progesterone luteinizing hormone and follicle-stimulating hormone levels in a sample of 8 midreproductive-aged (MRA) and 14 older reproductive-aged (ORA) women Error bars indicate mean plusmn 10 standard error
Pooled Estimates of Proportion of
Vasomotor Symptoms During
Perimenopause1
1 Politi MC et al J Gen Intern Med 23(9)1507ndash13
Pooled estimates of proportion of vasomotor symptoms by year tofrom final menstrual period Six studies provided data for the main meta-analysis One was longitudinal and the others were cross-sectional
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 13 months ago
Patient case developed for educational purposes only
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Conflict of interest amp Disclosure
Conflict of interest None
Disclosure SR
Research funding IRIS- King Baudouin
Fondation Vesale research Foundation Amgen
MSD
Speakers bureau ampor Advisory Boards
Abbot Pfizer Will Gedeon Richter MSD
Amgen Serylis Pharma
Concours
bull Ne pas oublier de reacutepondre hellipSinon on ne peut pas gagner
Goals
Risk Benefit of MHT
Indications - Contraindications
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 3 months ago
Patient case developed for educational purposes only
1 Sherman S Am J Med 2005118(128) 3S-7S
Defining the Menopausal
Transition1
FSH Follical Stimulating Hormone
Menopause stages most likely to be associated with vasomotor symptoms
Patterns of Estradiol Progesterone
Luteinizing and Follicle-stimulating
Hormones1
1 Santoro N Am J Med 2005 118 (12B) 8Sndash13S
Patterns of estradiol progesterone luteinizing hormone and follicle-stimulating hormone levels in a sample of 8 midreproductive-aged (MRA) and 14 older reproductive-aged (ORA) women Error bars indicate mean plusmn 10 standard error
Pooled Estimates of Proportion of
Vasomotor Symptoms During
Perimenopause1
1 Politi MC et al J Gen Intern Med 23(9)1507ndash13
Pooled estimates of proportion of vasomotor symptoms by year tofrom final menstrual period Six studies provided data for the main meta-analysis One was longitudinal and the others were cross-sectional
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 13 months ago
Patient case developed for educational purposes only
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Concours
bull Ne pas oublier de reacutepondre hellipSinon on ne peut pas gagner
Goals
Risk Benefit of MHT
Indications - Contraindications
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 3 months ago
Patient case developed for educational purposes only
1 Sherman S Am J Med 2005118(128) 3S-7S
Defining the Menopausal
Transition1
FSH Follical Stimulating Hormone
Menopause stages most likely to be associated with vasomotor symptoms
Patterns of Estradiol Progesterone
Luteinizing and Follicle-stimulating
Hormones1
1 Santoro N Am J Med 2005 118 (12B) 8Sndash13S
Patterns of estradiol progesterone luteinizing hormone and follicle-stimulating hormone levels in a sample of 8 midreproductive-aged (MRA) and 14 older reproductive-aged (ORA) women Error bars indicate mean plusmn 10 standard error
Pooled Estimates of Proportion of
Vasomotor Symptoms During
Perimenopause1
1 Politi MC et al J Gen Intern Med 23(9)1507ndash13
Pooled estimates of proportion of vasomotor symptoms by year tofrom final menstrual period Six studies provided data for the main meta-analysis One was longitudinal and the others were cross-sectional
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 13 months ago
Patient case developed for educational purposes only
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Goals
Risk Benefit of MHT
Indications - Contraindications
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 3 months ago
Patient case developed for educational purposes only
1 Sherman S Am J Med 2005118(128) 3S-7S
Defining the Menopausal
Transition1
FSH Follical Stimulating Hormone
Menopause stages most likely to be associated with vasomotor symptoms
Patterns of Estradiol Progesterone
Luteinizing and Follicle-stimulating
Hormones1
1 Santoro N Am J Med 2005 118 (12B) 8Sndash13S
Patterns of estradiol progesterone luteinizing hormone and follicle-stimulating hormone levels in a sample of 8 midreproductive-aged (MRA) and 14 older reproductive-aged (ORA) women Error bars indicate mean plusmn 10 standard error
Pooled Estimates of Proportion of
Vasomotor Symptoms During
Perimenopause1
1 Politi MC et al J Gen Intern Med 23(9)1507ndash13
Pooled estimates of proportion of vasomotor symptoms by year tofrom final menstrual period Six studies provided data for the main meta-analysis One was longitudinal and the others were cross-sectional
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 13 months ago
Patient case developed for educational purposes only
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 3 months ago
Patient case developed for educational purposes only
1 Sherman S Am J Med 2005118(128) 3S-7S
Defining the Menopausal
Transition1
FSH Follical Stimulating Hormone
Menopause stages most likely to be associated with vasomotor symptoms
Patterns of Estradiol Progesterone
Luteinizing and Follicle-stimulating
Hormones1
1 Santoro N Am J Med 2005 118 (12B) 8Sndash13S
Patterns of estradiol progesterone luteinizing hormone and follicle-stimulating hormone levels in a sample of 8 midreproductive-aged (MRA) and 14 older reproductive-aged (ORA) women Error bars indicate mean plusmn 10 standard error
Pooled Estimates of Proportion of
Vasomotor Symptoms During
Perimenopause1
1 Politi MC et al J Gen Intern Med 23(9)1507ndash13
Pooled estimates of proportion of vasomotor symptoms by year tofrom final menstrual period Six studies provided data for the main meta-analysis One was longitudinal and the others were cross-sectional
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 13 months ago
Patient case developed for educational purposes only
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
1 Sherman S Am J Med 2005118(128) 3S-7S
Defining the Menopausal
Transition1
FSH Follical Stimulating Hormone
Menopause stages most likely to be associated with vasomotor symptoms
Patterns of Estradiol Progesterone
Luteinizing and Follicle-stimulating
Hormones1
1 Santoro N Am J Med 2005 118 (12B) 8Sndash13S
Patterns of estradiol progesterone luteinizing hormone and follicle-stimulating hormone levels in a sample of 8 midreproductive-aged (MRA) and 14 older reproductive-aged (ORA) women Error bars indicate mean plusmn 10 standard error
Pooled Estimates of Proportion of
Vasomotor Symptoms During
Perimenopause1
1 Politi MC et al J Gen Intern Med 23(9)1507ndash13
Pooled estimates of proportion of vasomotor symptoms by year tofrom final menstrual period Six studies provided data for the main meta-analysis One was longitudinal and the others were cross-sectional
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 13 months ago
Patient case developed for educational purposes only
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Patterns of Estradiol Progesterone
Luteinizing and Follicle-stimulating
Hormones1
1 Santoro N Am J Med 2005 118 (12B) 8Sndash13S
Patterns of estradiol progesterone luteinizing hormone and follicle-stimulating hormone levels in a sample of 8 midreproductive-aged (MRA) and 14 older reproductive-aged (ORA) women Error bars indicate mean plusmn 10 standard error
Pooled Estimates of Proportion of
Vasomotor Symptoms During
Perimenopause1
1 Politi MC et al J Gen Intern Med 23(9)1507ndash13
Pooled estimates of proportion of vasomotor symptoms by year tofrom final menstrual period Six studies provided data for the main meta-analysis One was longitudinal and the others were cross-sectional
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 13 months ago
Patient case developed for educational purposes only
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Pooled Estimates of Proportion of
Vasomotor Symptoms During
Perimenopause1
1 Politi MC et al J Gen Intern Med 23(9)1507ndash13
Pooled estimates of proportion of vasomotor symptoms by year tofrom final menstrual period Six studies provided data for the main meta-analysis One was longitudinal and the others were cross-sectional
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 13 months ago
Patient case developed for educational purposes only
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Mrs V Her Complaint
bull 52 years old
bull Has suffered from severe hot flushes(7 timesday) and night sweats (4 times night)for 6 months
bull She complains also about breast tenderness
bull Her last menstruation occurred 13 months ago
Patient case developed for educational purposes only
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Womens experience of the menopause problem symptoms
Hot flushes
Night sweats
Sleep problems
Dry v agina
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Womens experience of the menopause problem symptoms
Painful joints
Headaches
Concentration problems
Depression
0
10
20
30
40
50
60
70
Experienced symptoms
Experienced as problems
Adapted from Porter et al 1996
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Indication of therapy
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Flushes
bull Over half (503) of postmenopausal women experienced either mild (246) moderate (176) or severe (81) VMS
bull DiBonaventura et al Int J WomensHealth 2013 May 245261-9
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
The Impact of Menopausal Symptoms on
Quality of Life Productivity and Economic
Outcomes
Whiteley et al JOURNAL OF WOMENrsquoS HEALTH Volume 22 Number 11 2013
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
HRT reduces symptom frequencye and severity as
compared with placebo OR= 013 95 CI 008-022
MacLennan et al Climacteric 2001 Mar4(1)58-74Cochrane review
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Antoine Ameye Paesmans Rozenberg Maturitas 2016
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
In favour of MHT
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
bull Timing of treatment
bull Choice of treatment
bull Low dose
bull Regimen with the least innocuousness
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Dose Response to Estrogen Therapy
Notelovitz et al Obstet Gynecol 200095726
Number of moderate-severe hot flushes
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Placebo
025 mg E2
05 mg E2
1 mg E2
2 mg E2
Significantly different from
placebo (Plt005)
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
-40
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Efficacy of 1mg E2 + 05mg NETA
on BMD
Adapted from McClung et al 1998
L1-L4 Femoral Neck Femoral Trochanter
0
2
4
6
-2
-4
BMD change af ter 26 months
placebo E2 025mg E2 05mg E2 1mg
E2 1mgNETA 025mg E2 1mgNETA 05mg E2 2mgNETA 1mg
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Endogenous hormones and risk of Hip amp
vertebral fractures among older women
Cummings et al NEJM1998
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
No Increase in Fractures After Stopping Hormone Therapy
Results From the Womens Health Initiative
bull Examine fractures after discontinuation of HT
bull 2 RCT (CEE+ MPA) CEE alone) WHI participants (N = 15187) who continued active HT or placebo through the intervention period and who did not take HT in the post-intervention period
bull Hip fractures were infrequent (sim25 1000 person-years) this finding was similar between trials and in former HT and placebo groups
bull CEE + MPA trial No difference in total fractures HR= 097 95 CI 087 -109 P = 063)
bull CEE-alone trial higher total fractures in former placebo users (3691000 person-years vs former active group 3111000 person-years) residual benefit of CEE (HR 085 95 CI 073 to 098 P = 003)
bull Watts et al J Clin Endocrinol Metab 2017 Jan 1102(1)302-308
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Routinely Asking Patients Dyspareunia is
Recommended
bull About 70 with vaginal dryness and dyspareunia
Reduction of quality of life
bull Recurrent Urinary tract Infection
Nappi RE et al Maturitas 2010 67233-8
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
HRT andor Vaginal Estrogen1
bull Systemic estrogen therapy (+ local ) vaginal tablets or creams
bull Estradiol Estriol CEE
bull Improvement of urge incontinence but not of Stress Incontinence
bull Moisturisers
bull Lubricants
bull Sexual therapy
bull hellipHRT Hormonal Replacement Therapy
CEE Conjugated Equine Estrogen1 Castelo-Branco C et al Maturitas 2005 52S S46-52
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Not in favour
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Cumulative Annualized Incidence Rates for Clinical Outcomes in the WHI Estrogen-Alone Trial According to 10-Year Age Groups at Enrolment1
1 LaCroix A Z et al JAMA 20113051305-1314
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Hodis et al NEJM 2016
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Timing hypothesis amp window of opportunity
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Young healthy woman
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
In favour of MHT
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
10 year risk
gt40
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
VTE
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Postmenopausal Hormone Therapy and Risk of
Idiopathic Venous Thromboembolism Results From
the E3N Cohort Study
Canonico et al Arterioscler Thromb Vasc Biol 201030340-345
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Variations in Associated Breast Cancer Risk Between CE alone and
CEMPA
Cumulative hazards
adjusted for age and
raceethnicity for
invasive breast cancer
by randomization
assignment in the WHI
CE-alone and CEMPA
trials
Anderson GL et al Lancet
Oncol 2012
00
1 2 3 4 5 6 7 8 9 10 11 12 13
001
002
003
004
005
Cu
mu
lati
ve
ha
za
rd
Time since randomization (years)
CEMPA
Placebo (in CEMPA arm)
HR 125 (95 CI 107ndash146)
CE alone
Placebo (in CE-alone arm)
HR 077 (95 CI 062ndash095)
CEMPA
CE alone
Placebo (CE-alone)
Placebo (CEMPA)
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
From Risk of breast cancer after stopping menopausal hormone
therapy in the E3N cohort Fournier A et al 2014
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
httpwwwems-
trialsorgriskevaluator
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Perspective Menopause Management mdash
Getting Clinical Care Back on Track
JE Manson AM Kaunitz
N Engl J Med
March 3 2016
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
What if there is a
contraindication for MHT
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Copyright restrictions may applyNelson H D et al JAMA 20062952057-2071
Metaanalysis of Clonidine
4 weeks
8 weeks
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Forest plots of hot flash reduction in newer antidepressant studies
Loprinzi C L et al JCO 2009272831-2837
copy2009 by American Society of Clinical Oncology
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Metaanalysis of gabapentin
Loprinzi 2009
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Cognitive Function
bull estrogen neuroprotective
bull Animal data estrogen enhancement of synaptic plasticity and reduced production of β-amyloid the protein associated with Alzheimer disease development
bull Neuroimaging studies in humans suggest that estrogen enhances brain activity related to memory processing
bull no data exist showing direct cognitive benefits of HRT in young women with POI
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Premature and early
menopause
bull Premature (before 40 years) and early menopause (before 45 years) whether natural or induced is associated with increased morbidity amp mortality when women are untreated with MHT
bull Several recent meta-analyses reported in particular increased cardiovascular morbi-mortality (Grade 1C)
bull Muka T et al JAMA Cardiol 2016
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points
bull Postmenopausal hormone therapy (PMHT) is indicated for the relief of menopausal symptoms in patients aged with climacteric symptoms
bull Low doses of PMHT should be used when possible
bull PMHT can be prescribed to treat osteoporosis when non-oestrogen therapies are unsuitable or in women who suffer simultaneously from climacteric symptoms and osteoporosis
bull Postmenopausal hormone therapy risks and benefits Rozenberg S
Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19
Key points bull PMHT for Prevention of coronary heart disease
bull Oestrogen therapy might reduce the risk of atherosclerosis in young women early after menopause but risk of coronary heart disease might be worsened as a result of thrombosis in at-risk and elderly patients
bull PMHT may increase Breast cancer risk
bull Use of a estrogen only (hysterectomized women) sequential progestin and a non-androgenic progestin might be safer than use of continuous androgenic progestin
bull Short term entails less or no risk
bull long-term EPT containing progestagens other than progesterone or dydrogesterone may be associated with some residual risk even many years after treatment cessation
bull Postmenopausal hormone therapy risks and benefits Rozenberg S Vandromme J Antoine C Nat Rev Endocrinol 2013 Feb 19