menopause and aging sylvia ziegenbein, md m3 student lecture 2007 sylvia ziegenbein, md m3 student...

Menopause and AgingMenopause and Aging

Sylvia Ziegenbein, MDM3 Student Lecture

2007

Sylvia Ziegenbein, MDM3 Student Lecture

2007

ObjectivesObjectives

Define menopause Describe associated changes and

symptoms Treatment options for bothersome

symptoms Review physiologic changes of aging,

specific age related problems and screening in elderly

Define menopause Describe associated changes and

symptoms Treatment options for bothersome

symptoms Review physiologic changes of aging,

specific age related problems and screening in elderly

Case #1Case #1

35 yo G1 P0101 female presents with c/o hot flashes and amenorrhea for 12 months. She doesn’t know why this is happening, her sxs are worsening. She wants your help.

DDx Tests

35 yo G1 P0101 female presents with c/o hot flashes and amenorrhea for 12 months. She doesn’t know why this is happening, her sxs are worsening. She wants your help.

DDx Tests

Case #2Case #2 45 yo G2 P2002 female presents with

c/o hot flashes and irregular menses (q 3-5 mos) for the past 9 months. She doesn’t know why this is happening, she wants your help. By the way, she wants your help to stop smoking also.

DDx Tests

45 yo G2 P2002 female presents with c/o hot flashes and irregular menses (q 3-5 mos) for the past 9 months. She doesn’t know why this is happening, she wants your help. By the way, she wants your help to stop smoking also.

DDx Tests

Case #3Case #3 65 yo WF presents to start HRT. She

heard it would help protect her heart, make her feel younger and help her memory. She went through menopause 10 years ago and has not had any problems except an occasional hot flash. She is 5’4”, 108 lbs. By the way, she had a wrist fx 2 yrs ago takes her Viactiv faithfully.

65 yo WF presents to start HRT. She heard it would help protect her heart, make her feel younger and help her memory. She went through menopause 10 years ago and has not had any problems except an occasional hot flash. She is 5’4”, 108 lbs. By the way, she had a wrist fx 2 yrs ago takes her Viactiv faithfully.

Case #4Case #4 49 yo WF presence b/c she can’t stand

her hot flashes anymore. She can’t sleep very well b/c she wakes up 3 times a night drenched with sweat. She is an executive at First National Bank. She has a history of breast cancer 2 years ago. “Please Dr. Ziegenbein, I need some hormones or something.”

49 yo WF presence b/c she can’t stand her hot flashes anymore. She can’t sleep very well b/c she wakes up 3 times a night drenched with sweat. She is an executive at First National Bank. She has a history of breast cancer 2 years ago. “Please Dr. Ziegenbein, I need some hormones or something.”

Case #5Case #5

55 yo BF returns to discuss stopping her HRT. She has been taking it for 5 years now with good relief of her vasomotor sxs.

55 yo BF returns to discuss stopping her HRT. She has been taking it for 5 years now with good relief of her vasomotor sxs.

Case #6Case #6

53 yo WF began continuous HRT 4 wks ago. She is now having some vaginal spotting after being amenorrheic for 14 months. She is concerned.

53 yo WF began continuous HRT 4 wks ago. She is now having some vaginal spotting after being amenorrheic for 14 months. She is concerned.

MenopauseMenopause

Definition Average Age Related Sxs

Definition Average Age Related Sxs

Classification SystemClassification System

STRAW System Help communication

STRAW System Help communication

Menopause Terminology: STRAW* Staging System

*STRAW = Stages of Reproductive Aging Workshop.†Stages most likely to be characterized by vasomotor symptoms.Soules MR, et al. Menopause. 2001;8:402-7.

Stages:Stages: -2-2 -1-1 +1+1 +2+2

Terminology:

Duration of Stage:

Menstrual Cycles:

Menopausal TransitionMenopausal Transition PostmenopausePostmenopause

EarlyEarly EarlyEarly††LateLate†† LateLate

PerimenopausePerimenopause

VariableVariable

Variable Variable cycle length cycle length

(>7 days(>7 daysdifferent different

from normal)from normal)

2 skipped2 skippedcycles and ancycles and an

interval of interval of amenorrheaamenorrhea((60 days)60 days)

4 yrs4 yrsUntilUntil

demisedemise

NoneNone

00Final Menstrual PeriodFinal Menstrual Period

1 yr1 yr

Am

en. ×

12

mos

.A

men

. × 1

2 m

os.

aa bb

Vasomotor symptoms:Why don’t we treat every women with hormones?

Vasomotor symptoms:Why don’t we treat every women with hormones?

WHI: HRT vs PlaceboWHI: HRT vs Placebo Large prospective RCT, 2002, JAMA 16,608 postmenopausal women (50-79 y.o.)

Ave age at enrollment = 63 yrs Two arms:

Estrogen + Progestin (Prempro 0.625/2.5), n=8506 Placebo, n=8102

Outcomes measured: Primary : Coronary heart disease (CHD) and invasive

breast cancer Secondary : stroke, pulmonary embolism, DVT,

endometrial CA, colorectal CA, hip and vertebral fractures and death from other causes

Large prospective RCT, 2002, JAMA 16,608 postmenopausal women (50-79 y.o.)

Ave age at enrollment = 63 yrs Two arms:

Estrogen + Progestin (Prempro 0.625/2.5), n=8506 Placebo, n=8102

Outcomes measured: Primary : Coronary heart disease (CHD) and invasive

breast cancer Secondary : stroke, pulmonary embolism, DVT,

endometrial CA, colorectal CA, hip and vertebral fractures and death from other causes

HRT Arm: Stopped Early @ 5.2 yrsHRT Arm: Stopped Early @ 5.2 yrs Invasive Breast Cancer = 38 vs 30/10,000

person yrs (HR 1.26) CHD = 37 vs 30/10,000 (HR 1.29) Stroke = 29 vs 21/10,000 (HR 1.41) Venous Thromboembolic disease = 34 vs

16/10,000 (HR 2.11)

Colorectal cancer = 10 vs 16/10,000 (HR 0.63) Hip fracture = 10 vs 15/10,000 (HR 0.66) Vertebral fracture = 9 vs 15/10,000 (HR 0.66) No change in endometrial and lung cancer

Invasive Breast Cancer = 38 vs 30/10,000 person yrs (HR 1.26)

CHD = 37 vs 30/10,000 (HR 1.29) Stroke = 29 vs 21/10,000 (HR 1.41) Venous Thromboembolic disease = 34 vs

16/10,000 (HR 2.11)

Colorectal cancer = 10 vs 16/10,000 (HR 0.63) Hip fracture = 10 vs 15/10,000 (HR 0.66) Vertebral fracture = 9 vs 15/10,000 (HR 0.66) No change in endometrial and lung cancer

WHI: Estrogen Only vs Placebo

WHI: Estrogen Only vs Placebo

WHI 2004: JAMA 10,739 postmenopausal women

s/p hysterectomy (50-79 y.o.) Ave. age @ enrollment = 63.6 y.o.

Two arms: Estrogen (Premarin 0.625 mg), n=5310 Placebo, n=5429

Outcomes: Primary: CHD and invasive breast cancer Secondary: stroke, pulmonary embolism, DVT,

colorectal cancer, hip/vertebral fractures and death from other causes

WHI 2004: JAMA 10,739 postmenopausal women

s/p hysterectomy (50-79 y.o.) Ave. age @ enrollment = 63.6 y.o.

Two arms: Estrogen (Premarin 0.625 mg), n=5310 Placebo, n=5429

Outcomes: Primary: CHD and invasive breast cancer Secondary: stroke, pulmonary embolism, DVT,

colorectal cancer, hip/vertebral fractures and death from other causes

OutcomesOutcomes Ave. follow up 6.8 years (Hazard Ratio)

Invasive breast Cancer = 26 vs 33/10,000 person yrs (0.77)

CHD = 49 vs 54/10,000 (0.91) Venous Thromboembolic disease = 28 vs

21/10,000 (1.33) Stroke = 44 vs 32/10,000 (1.39)

Fatal = 4 vs 4/10,000 (1.13) Nonfatal = 32 vs 23/10,000 (1.39)

Colorectal cancer = 17 vs 16/10,000 (1.08) Hip fracture = 11 vs 17/10,000 (0.61) Vertebral fracture = 11 vs 17/10,000 (0.62)

Ave. follow up 6.8 years (Hazard Ratio) Invasive breast Cancer = 26 vs 33/10,000

person yrs (0.77) CHD = 49 vs 54/10,000 (0.91) Venous Thromboembolic disease = 28 vs

21/10,000 (1.33) Stroke = 44 vs 32/10,000 (1.39)

Fatal = 4 vs 4/10,000 (1.13) Nonfatal = 32 vs 23/10,000 (1.39)

Colorectal cancer = 17 vs 16/10,000 (1.08) Hip fracture = 11 vs 17/10,000 (0.61) Vertebral fracture = 11 vs 17/10,000 (0.62)

Clinical EventHazard Ratio, 95% confidence interval

HERS E+P WHI E+P WHI E alone

CHD Events 0.99 (0.80-1.22)

1.29 (1.02-1.63) 0.91 (0.75-1.12)

Stroke 1.23 (0.89-1.70)

1.41 (1.07-1.85) 1.39 (1.10-1.77)

Pulm. Embolism

2.79 (0.89-8.75)

2.13 (1.39-3.25) 1.34 (0.87-2.06)

Breast Cancer 1.30 (0.77-2.19)

1.26 (1.00-1.59) 0.77 (0.59-1.01)

Colon Cancer 0.69 (0.32-1.49)

0.63 (0.43-0.92) 1.08 (0.75-1.55)

Hip Fracture 1.10 (0.49-2.50)

0.66 (0.45-0.98) 0.61 (0.41-0.91)

Death 1.08 (0.84-1.38)

0.98 (0.82-1.18) 1.04 (0.88-1.22)

Global Index - 1.15 (1.03-1.28) 1.01 (0.89-1.70)

Menopausal Complaints: Treatments

Menopausal Complaints: Treatments

Hormones vs non-hormones vs herbals Efficacy

Hormones vs non-hormones vs herbals Efficacy

Hormones ContraindicatedHormones Contraindicated Breast CA Endometrial CA Undiagnosed vaginal bleeding CHD Venous thrombosis Stroke Pregnancy What is not here, that is a CI on OCP’s?

Breast CA Endometrial CA Undiagnosed vaginal bleeding CHD Venous thrombosis Stroke Pregnancy What is not here, that is a CI on OCP’s?

Normal Physiologic Changes of Aging

Normal Physiologic Changes of Aging

DemographicsDemographics

34 million elderly now 69 million in 2030

Gerontology Health in the aged

Absence of ds Maintain function and comfort Presence of satisfactory support systems

34 million elderly now 69 million in 2030

Gerontology Health in the aged

Absence of ds Maintain function and comfort Presence of satisfactory support systems

Body Composition and Homeostasis

Body Composition and Homeostasis

Decrease muscle mass Increase body fat Changes volume of distribution

Impaired baroreceptor Orthostatic hypotension

Impaired thermoregulation

Decrease muscle mass Increase body fat Changes volume of distribution

Impaired baroreceptor Orthostatic hypotension

Impaired thermoregulation

CardiovascularCardiovascular

Decrease LV compliance Increased reliance on atria

More LVH Stiffer arteries

Decreased beta-adrenergic responsiveness Decreased max. HR with exercise

Decrease LV compliance Increased reliance on atria

More LVH Stiffer arteries

Decreased beta-adrenergic responsiveness Decreased max. HR with exercise

PulmonaryPulmonary

Decreased elastic recoil, airways collapse earlier

Decreased forced vital capacity, functional residual capacity, residual volume, FEV1

Decreased ventilatory response and chemoreceptor function Increased hypoxia and hypercapnia

Decreased elastic recoil, airways collapse earlier

Decreased forced vital capacity, functional residual capacity, residual volume, FEV1

Decreased ventilatory response and chemoreceptor function Increased hypoxia and hypercapnia

RenalRenal Decreased mass, # of glomeruli Increased glomerulosclerosis GFR slowly decreases CrCl maintains

Decreased Na+ rentention, decreased responsiveness to AVP; less concentration of urine

Decreased thirst and drink response Increased dehydration

Decreased mass, # of glomeruli Increased glomerulosclerosis GFR slowly decreases CrCl maintains

Decreased Na+ rentention, decreased responsiveness to AVP; less concentration of urine

Decreased thirst and drink response Increased dehydration

EndocrineEndocrine

Decreased glucose tolerance Independent of obesity and inactivity FG decreases 1 mg/dL/decade

Increased insulin resistance Decreased GH, IGF-1

Give elderly men GH, increases lean body mass

Decreased glucose tolerance Independent of obesity and inactivity FG decreases 1 mg/dL/decade

Increased insulin resistance Decreased GH, IGF-1

Give elderly men GH, increases lean body mass

ImmunologicImmunologic

Decreased T-cell activity Decreased Ab response to foreign

antigen Increased autoantibodies

Decreased T-cell activity Decreased Ab response to foreign

antigen Increased autoantibodies

Specific Geriatric IssuesSpecific Geriatric Issues

Other assessments to be made.

Other assessments to be made.

Cognitive FunctionCognitive Function

Normal decline Dementia

Alzheimer’s Vascular Others

Depression Medications EtOH

MMSE

Normal decline Dementia

Alzheimer’s Vascular Others

Depression Medications EtOH

MMSE

SensorySensory

Visual Auditory Balance

Visual Auditory Balance

IncontinenceIncontinence

Types Risk factors Assess Tests Treatment

Types Risk factors Assess Tests Treatment

Types of IncontinenceTypes of Incontinence

Urge Stress Functional Overflow Mixed

Urge Stress Functional Overflow Mixed

Fall RisksFall Risks

Intrinsic Person oriented issues… Mobility “Get up and go” test

Extrinsic Environment

Intrinsic Person oriented issues… Mobility “Get up and go” test

Extrinsic Environment

PolypharmacyPolypharmacy

Medication List Drug-drug interactions Altered pharmacokinetics,

pharmacodynamics Herbals OTC

Medication List Drug-drug interactions Altered pharmacokinetics,

pharmacodynamics Herbals OTC

OsteoporosisOsteoporosis

Screening Risk Factors Treatments

Screening Risk Factors Treatments

OthersOthers

Abuse Sexuality Vaccinations Financial Support System Driving

Abuse Sexuality Vaccinations Financial Support System Driving

ScreeningScreening

Thyroid Cancer

Sxs Pap Mammogram Colonoscopy

Lipids

Thyroid Cancer

Sxs Pap Mammogram Colonoscopy

Lipids

Questions???Questions???

Thank you very much for your participation!!

Good luck on your shelf!

Thank you very much for your participation!!

Good luck on your shelf!