Menopause and Aging Sylvia Ziegenbein, MD M3 Student Lecture 2007 Sylvia Ziegenbein, MD M3 Student Lecture 2007

Objectives / 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 #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 #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 #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.

Case #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.”

Case #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.

Case #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.

Menopause / Definition / Average Age / Related Sxs / Definition / Average Age / Related Sxs

Classification 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: Stages: Terminology: Duration of Stage: Menstrual Cycles: Menopausal Transition Postmenopause Early Early † Late † Late Perimenopause Variable Variable cycle length (>7 days different from normal)  2 skipped cycles and an interval of amenorrhea (  60 days) 4 yrs Until demise None 0 Final Menstrual Period 1 yr Amen. × 12 mos. ab

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

WHI: 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 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 2004: JAMA / 10,739 postmenopausal women / s/p hysterectomy (50-79 y.o.) / Ave. enrollment = 63.6 y.o. / Two arms: / Estrogen (Premarin 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. enrollment = 63.6 y.o. / Two arms: / Estrogen (Premarin 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

Outcomes / 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 Event Hazard Ratio, 95% confidence interval HERS E+PWHI E+PWHI E alone CHD Events0.99 ( )1.29 ( )0.91 ( ) Stroke1.23 ( )1.41 ( )1.39 ( ) Pulm. Embolism2.79 ( )2.13 ( )1.34 ( ) Breast Cancer1.30 ( )1.26 ( )0.77 ( ) Colon Cancer0.69 ( )0.63 ( )1.08 ( ) Hip Fracture1.10 ( )0.66 ( )0.61 ( ) Death1.08 ( )0.98 ( )1.04 ( ) Global Index-1.15 ( )1.01 ( )

Menopausal Complaints: Treatments / Hormones vs non-hormones vs herbals / Efficacy / Hormones vs non-hormones vs herbals / Efficacy

Hormones 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

Demographics / 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 / 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

Cardiovascular / 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

Pulmonary / 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

Renal / 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

Endocrine / 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

Immunologic / 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 Issues Other assessments to be made.

Cognitive Function / Normal decline / Dementia / Alzheimer’s / Vascular / Others / Depression / Medications / EtOH / MMSE / Normal decline / Dementia / Alzheimer’s / Vascular / Others / Depression / Medications / EtOH / MMSE

Sensory / Visual / Auditory / Balance / Visual / Auditory / Balance

Incontinence / Types / Risk factors / Assess / Tests / Treatment / Types / Risk factors / Assess / Tests / Treatment

Types of Incontinence / Urge / Stress / Functional / Overflow / Mixed / Urge / Stress / Functional / Overflow / Mixed

Fall 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

Polypharmacy / Medication List / Drug-drug interactions / Altered pharmacokinetics, pharmacodynamics / Herbals / OTC / Medication List / Drug-drug interactions / Altered pharmacokinetics, pharmacodynamics / Herbals / OTC

Osteoporosis / Screening / Risk Factors / Treatments / Screening / Risk Factors / Treatments

Others / Abuse / Sexuality / Vaccinations / Financial / Support System / Driving / Abuse / Sexuality / Vaccinations / Financial / Support System / Driving

Screening / Thyroid / Cancer / Sxs / Pap / Mammogram / Colonoscopy / Lipids / Thyroid / Cancer / Sxs / Pap / Mammogram / Colonoscopy / Lipids

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!