MENOPAUSE AND AGING Sylvia Ziegenbein MD M 3

MENOPAUSE AND AGING Sylvia Ziegenbein, MD M 3 Student Lecture 2019

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

Premature Ovarian Failure ■ <40 ■ Idiopathic – – 300 x increased risk of adrenal insufficiency Anti adrenal and Anti 21 -hydroxylase antibodies ■ Surgical, radiation, chemotherapy ■ Chromosomal- 45 XO, Fragile X ■ Infectious-mumps, cmv ■ Autoimmune ■ Galactosemia ■ Increased risk of osteoporosis

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 presents 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 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.

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

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 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

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)

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 ■ Non hormonal meds ■ Herbals? ?

Treatments ■ First – Staying cool, avoid triggers – Exercise, healthy lifestyle – Vitamin E

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?

OB/GYN Mantra from WHI ■ Lowest dosage for the least amount of time.

Hormones Estrogen and progesterone Pills, patches Estrogen only s/p hysterectomy –no unopposed systemic estrogen Oral-Pills Usually about 1/4 th dose of OCPs Topically or transdermal-gels, patches IM depot Vaginally-creams, rings and tabs Low dose vaginal estrogen can be used in a woman with a uterus No guidelines for monitoring, at this time Progestins only, are also effective

Non-Hormonal Medications ■ SSRI- paroxetine (Paxil or Sarafem, FDA approved) – 60 -65% effective ■ SNRIs- venlafaxine (Effexor) – 60 -70% effective ■ Gabapentin-(Neurontin)-anti seizure – 60 -70% effective – Sedating ■ Clonidine- anti hypertensive – 45 -50% effective

Herbals: ■ Not FDA regulated ■ Efficacy equal to placebo Black cohosh Red clover Soy Flaxseed Dong quai Wild Yam Ginseng Evening primrose oil

Other Treatment Methods ■ Acupuncture ■ Reflexology ■ Magnetic devices

SPECIFIC GERIATRIC ISSUES Other assessments to be made.

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

Osteoporosis ■ Screening – Start at 65, earlier if risk factors ■ Risk Factors ■ Treatments – bisphonates

Screening ■ Thyroid – ACOG says check if they have symptoms ■ Cancer – – Pap Mammogram ■ ■ ■ – ACS - yearly from 45 -54, then every other year ACOG - every 1 -2 yrs 40 -50, then every year USPSTF – every other year starting at 50 Colonoscopy ■ Lipids-risk based, usually 45 yoa then q 5 years for healthy women

Incontinence ■ Types ■ Risk factors ■ Assess ■ Tests ■ Treatment

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

Fall Risks ■ Intrinsic – Person oriented issues… – Mobility – “Get up and go” test ■ Extrinsic – Environment

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

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

NORMAL PHYSIOLOGIC CHANGES OF AGING

Body Composition and Homeostasis ■ 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

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