1. Menopause and Aging Sylvia Ziegenbein, MD M3 Student Lecture 2016 Sylvia Ziegenbein, MD M3 Student Lecture 2016

2. 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

3. 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

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

5. 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

6. 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.

7. 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.”

8. 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.

9. 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.

10. Menopause / Definition / Average Age / Related Sxs / Definition / Average Age / Related Sxs

12. Classification System / STRAW System / Help communication / STRAW System / Help communication

13. 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.

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

15. 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

16. 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 / 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

17. 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

18. 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)

19. Clinical Event Hazard Ratio, 95% confidence interval HERS E+PWHI E+PWHI E alone CHD Events0.99 (0.80-1.22)1.29 (1.02-1.63)0.91 (0.75-1.12) Stroke1.23 (0.89-1.70)1.41 (1.07-1.85)1.39 (1.10-1.77) Pulm. Embolism2.79 (0.89-8.75)2.13 (1.39-3.25)1.34 (0.87-2.06) Breast Cancer1.30 (0.77-2.19)1.26 (1.00-1.59)0.77 (0.59-1.01) Colon Cancer0.69 (0.32-1.49)0.63 (0.43-0.92)1.08 (0.75-1.55) Hip Fracture1.10 (0.49-2.50)0.66 (0.45-0.98)0.61 (0.41-0.91) Death1.08 (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)

20. Menopausal Complaints: Treatments / Hormones / vs / Non-hormones / vs / Herbals / Efficacy? / Hormones / vs / Non-hormones / vs / Herbals / Efficacy?

21. Treatments / First / Staying cool, avoid triggers / Exercise, healthy lifestyle / Vitamin E / First / Staying cool, avoid triggers / Exercise, healthy lifestyle / Vitamin E

22. 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?

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

24. Hormones Estrogen and progesterone  Pills, patches Estrogen only  s/p hysterectomy  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 Estrogen and progesterone  Pills, patches Estrogen only  s/p hysterectomy  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

25. Non-Hormonal Medications / SSRI- paroxetine (Paxil) / 60-65% effective / SNRIs- venlafaxine (Effexor) / 60-70% effective / Gabapentin-(Neurontin)-anti seizure / 60-70% effective / Sedating / Clonidine- anti hypertensive / 45-50% effective / SSRI- paroxetine (Paxil) / 60-65% effective / SNRIs- venlafaxine (Effexor) / 60-70% effective / Gabapentin-(Neurontin)-anti seizure / 60-70% effective / Sedating / Clonidine- anti hypertensive / 45-50% effective

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

27. Other Treatment Methods / Acupuncture / Reflexology / Magnetic devices / Acupuncture / Reflexology / Magnetic devices

28. Specific Geriatric Issues Other assessments to be made.

29. 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

30. Osteoporosis / Screening / Start at 65, earlier if risk factors / Risk Factors / Treatments / bisphosphonates / Screening / Start at 65, earlier if risk factors / Risk Factors / Treatments / bisphosphonates

31. Screening / Thyroid / Cancer / Sxs / 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 45yoa for healthy women / Thyroid / Cancer / Sxs / 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 45yoa for healthy women

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

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

34. 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

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

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

37. Normal Physiologic Changes of Aging

38. 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

39. 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

40. 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

41. 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

42. 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

43. 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

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

45. Sensory / Visual / Auditory / Balance / Visual / Auditory / Balance

46. 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!