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Siraya K.
ฮอร์�โมนสำคั�ญฮอร์�โมนสำคั�ญอย่�งไร์ในวั�ย่ทองอย่�งไร์ในวั�ย่ทอง
Clinical Practice Guideline
Evidence-Based Medicine
Strength of Recommendation
Level of Evidence
ABCDI
IIIIII
Guideline & Recommendations
International Menopause Society (Climacteric)http://www.imsociety.org/index.php (2007)
North American Menopause Society (Menopause)http://www.menopause.org/ (2010)
Asia Pacific Menopause Federationhttp://www.apmf.net/ (2008)
American Association of Clinical Endocrinologists Medical Guideline for Clinical Practice for the Diagnosis and the Treatment of Menopause (2006)
The Endocine Society. The Journal of Clinical Endocrinology & Metabolism, July 2010, Vol 95, Suppl 1. No 07
HRT – BenefitsSymptomatic
VasomotorMoodVaginal AtrophyInsomnia
Preventative:OsteoporosisCoronary Heart DzAlzheimer’sGenitourinary HealthColon CancerAtrophic VaginitisGeneral Sense of Well
BeingSexual Functioning
HRT – RISKBreast CaDeep Vein Thrombosis
(DVT)Pulmonary Emboli (PE)Endometrial CaGallbladder Dz
-> Overall strategy
- lifestyle recommendations: diet, exercise,
smoking and alcohol
- Hormone therapy
-> HT must be individualized (symptoms and
need for prevention)
-> The risks and benefits of HT differ
- Age of menopause woman
- hormonal products and routes of
administration
PrinciplesPrinciples
Climacteric 2007;10:181–94
- Spontaneous or iatrogenic menopause before
the age of 45 and particularly before 40 are
at higher risk for cardiovascular disease and
osteoporosis
-> benefit from hormone replacement
(should be given at least until the normal
age of menopause
- Counseling should convey the benefits and
risks
PrinciplesPrinciples
Climacteric 2007;10:181–94
- Dosage should be titrated to the lowest
effective dose
- Progestogen should be added to systemic
estrogen for all women with a uterus to
prevent endometrial hyperplasia and cancer
PrinciplesPrinciples
Climacteric 2007;10:181–94
Guideline & Recommendation
Contraindication
Indication
Indication
OneOneOneOne TwoTwoTwoTwo ThreeThreeThreeThree
Moderate to severe symptoms of vulvar and vaginal atrophy
Moderate to severe symptoms of vulvar and vaginal atrophy
Prevention of postmenopaus
al osteoporosis
Prevention of postmenopaus
al osteoporosis
Moderate to severe vasomotor symptoms associated with menopause
Moderate to severe vasomotor symptoms associated with menopause
LOE 1, Grade A
HRT VS placeboHot flushes frequency/week
Study HRT Placebo Mean Difference Weight Mean difference
N Mean (SD) N Mean (SD) 95% CI 95% CI
Less with HRT Less with placebo
Cochrane Database of Systematic Reviews 2004, Issue 4. Art
Study HRT Placebo Mean Difference Weight Mean difference
N Mean (SD) N Mean (SD) 95% CI 95% CI
Less with HRT Less with placebo
HRT VS placebo Hot flush severity
Cochrane Database of Systematic Reviews 2004, Issue 4. Art
Indication
OneOneOneOne TwoTwoTwoTwo ThreeThreeThreeThree
Moderate to severe symptoms of vulvar and vaginal atrophy
Moderate to severe symptoms of vulvar and vaginal atrophy
Prevention of postmenopaus
al osteoporosis
Prevention of postmenopaus
al osteoporosis
Moderate to severe vasomotor symptoms associated with menopause
Moderate to severe vasomotor symptoms associated with menopause
LOE 1, Grade A
equally effective for
vaginal atrophy
Creams
Pessaries
Rings
Tablets
Suckling JA, Kennedy R, Lethaby A, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4.
Systematic Review for Vaginal AtrophyThe CEE cream is associated with significant
adverse effects when compared to E2 tablets
(OR 0.18, 95% CI 0.07 to 0.50)
Uterine bleeding
Breast pain
Perineal pain
Suckling JA, Kennedy R, Lethaby A, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4.
Systematic Review for Vaginal Atrophy
Significant endometrial overstimulation with the
CEE cream group when compared to the ring
(OR 0.29, 95% CI 0.11 to 0.78)
2% incidence of simple hyperplasia in the ring
group when compared to the CEE cream
4% incidence of hyperplasia in the CEE cream
group when compared to the tablet (E2).
Suckling JA, Kennedy R, Lethaby A, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4.
Urinary Disorders
Urinary incontinence
Systemic estrogen + progestin worsen
incontinence
RR 1.32, 95% CI 1.17 -1.48
Local estrogens use improve incontinence
RR 0.74, 95%CI 0.64-0.86
Cody JD et al. Cochrane Database of Systematic Reviews 2009, Issue 4.
Urinary tract infection
- Oral estrogens did not reduce UTI
- Vaginal estrogens versus placebo reduced the
number of women with UTIs
Perrotta C et al. Cochrane Database of Systematic Reviews 2008, Issue 2. Art
Urinary Disorders
Indication
OneOneOneOne TwoTwoTwoTwo ThreeThreeThreeThree
Moderate to severe symptoms of vulvar and vaginal atrophy
Moderate to severe symptoms of vulvar and vaginal atrophy
Prevention of postmenopaus
al osteoporosis
Prevention of postmenopaus
al osteoporosis
Moderate to severe vasomotor symptoms associated with menopause
Moderate to severe vasomotor symptoms associated with menopause
LOE 1, Grade A
Farquhar C, et al . Long term hormone therapy for perimenopausal
and postmenopausal women. Cochrane Database of Systematic Reviews 2009, Issue 2
Established reduction in bone mass,
regardless of menopause symptoms
when alternate therapies are not appropriate
or cause side effects
when the benefits of extended use are
expected to exceed the risks.
2010 The North American Menopause Society
When to use HRT for osteoporotic prevention?
Additional indication
Mood disorders (depression)Sexual dysfunctionCognitive disruption
CommentNeed to exclude other causes
AACE & IMS
IMS, NAM & APMFSleep disturbances associated with vasomotor symptom
HRT can be effective in relieving dyspareunia.LubricationBlood flowSensation in vaginal tissueHRT is not the sole treatment for diminished sexual function.
Sexual function
NAMS 2010
Guideline & Recommendation
Contraindication
Indication
Contraindication
1) Current, past, or suspected breast cancer
2) Known or suspected estrogen-sensitive malignant conditions
3) Undiagnosed genital bleeding
4) Untreated EH5) Known
hypersensitivity to the active substances of HT
1) Current, past, or suspected breast cancer
2) Known or suspected estrogen-sensitive malignant conditions
3) Undiagnosed genital bleeding
4) Untreated EH5) Known
hypersensitivity to the active substances of HT
6) Active liver disease
7) Previous idiopathic or current venous thromboembolism
7) Active or recent arterial thromboembolic disease
8) Untreated hypertension
9) Porphyria cutanea tarda
6) Active liver disease
7) Previous idiopathic or current venous thromboembolism
7) Active or recent arterial thromboembolic disease
8) Untreated hypertension
9) Porphyria cutanea tarda
2010 The North American Menopause Society
Mammogram & Breast Cancer Screening
Systematic Review & Meta-analysis
Reduction of Death from Mammogram
Ann Intern Med. 2002;137:347-360.
Breast Cancer Mortality & Screening Mammogram
Cancer Epidemiol Biomarkers Prev 2006;15(1):45–51
Screened Women Unscreened Women
Mortality Mortality
Mortality Mortality
Estrogen + Progestin , RR per 5 years of useRandomized Controlled trials
Observational trials
Tips
Endometrial & breast cancer remain
contraindications
Ovarian cancer, cervical cancer, are not
contraindication
HT is not a contraindication.
Women at different levels of CV risk with either
optimal BP or with HTProgestogens with antimineralocorticoid activity preferred
Routes Estrogen treatmentRoutes Estrogen treatment
TOPICAL VAGINAL
ORAL TRANSDERMAL INJECTABLE
Estrogen
Progestogen
Cyclic sequential regimen
Continued estrogen everyday
Estradiol gel 1 mg/dayEstradiol oral 1 mg/day
Progestogen in last 14 days of cycle
MPA 5 mg/dayDydrogesterone 10 mg/day
- Schering, Germany.
- Pills N=21 calendaristic packing.
Composition:
- Estradiol Valerate 2 mg (11 white Pills)
- Estradiol Valerate 2 mg and
Norgestrel 0.5 mg (10 light-brown Pills)
Cycloprogynova
Continuous combined regimen
E+P everyday
Estrogen
Estradiol gel 1 mg/day
Estradiol oral 1 mg/day
Progestogen
MPA 1.5 or 2.5 mg/day
Dydrogesterone 5 mg/day
Levonorgestrel IUD
Femoston conti.
- Solvay Pharmaceuticals
- Containing
5 mg dydrogesterone
1 mg estradiol
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