Menopause and Aging Sylvia Ziegenbein MD M 3

Menopause and Aging Sylvia Ziegenbein, MD M 3 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

Case #1 /35 yo G 1 P 0101 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 G 2 P 2002 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

Classification System /STRAW /Help System communication

Menopause Terminology: STRAW* Staging System Final Menstrual Period 0 Stages: -2 -1 +1 Menopausal Transition Duration of Stage: Menstrual Cycles: Postmenopause Early Late† Perimenopause Variable 2 skipped cycle length cycles and an (>7 days interval of different amenorrhea from normal) ( 60 days) *STRAW = Stages of Reproductive Aging Workshop. †Stages most likely to be characterized by vasomotor symptoms. Soules MR, et al. Menopause. 2001; 8: 402 -7. Early† a 1 yr Amen. × 12 mos. Terminology: +2 b 4 yrs Late Until demise None

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

WHI: HRT vs Placebo /Large /16, 608 /Two prospective RCT, 2002, JAMA postmenopausal women (50 -79 y. o. ) /Ave age at enrollment = 63 yrs arms: /Estrogen + Progestin /Placebo, n=8102 /Outcomes (Prempro 0. 625/2. 5), n=8506 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 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

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 /Placebo, n=5429 0. 625 mg), n=5310 /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 /Nonfatal vs 4/10, 000 (1. 13) = 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+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 /Hormones herbals /Efficacy vs non-hormones vs

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?

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

Body Composition and Homeostasis /Decrease muscle mass /Increase body fat /Changes volume of distribution /Impaired baroreceptor /Impaired thermoregulation /Orthostatic hypotension

Cardiovascular /Decrease LV compliance /Increased /More LVH /Stiffer reliance on atria 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, FEV 1 /Decreased ventilatory response and chemoreceptor function /Increased hypoxia and hypercapnia

Renal /Decreased mass, # of glomeruli /Increased glomerulosclerosis /GFR slowly decreases /Cr. Cl 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/d. L/decade /Increased insulin resistance /Decreased GH, IGF-1 /Give elderly men GH, increases lean body mass