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Menopause MS II

Learn about the physiology of menopause and the natural experiences women go through during this stage. Explore the challenges of symptom treatment and the proportion of a woman's lifespan spent in menopause. Discover factors that affect the age at menopause and the potential of predicting it. Understand the clinical issues of menopause, including changes in uterine bleeding, vasomotor symptoms, sleep disturbances, cognition, psychological symptoms, urinary health, sexual function, and hair changes.

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Menopause MS II

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  1. MenopauseMS II Joanna Wilson, D.O. Internal Medicine, HerCare at Amarillo Diagnostic Clinic Community Associate Professor of Internal Medicine Texas Tech, Amarillo

  2. Objectives: To recognize the physiology of the menopause To review the natural experiences of menopause To appreciate the challenges of symptom treatment Proportion of average female lifespan spent in menopause years: 1/3 to 1/2

  3. STRAW¥ Staging System Final Menstrual Period (FMP) 0 * Stages most likely to be characterized by vasomotor symptoms ¥ STages of Reproductive Aging Workshop Adapted from Soules et al., Fertility and Sterility, VOL. 76, NO. 5, November 2001, p. 875

  4. Unaffected by: Race Socioeconomic status Number of pregnancies Oral contraceptive use Education Physical characteristics Age of menarche Age of last pregnancy Affected by: Smoking Family pattern Chemotherapy Nulliparity Hysterectomy* Excessive alcohol intake* *=possible assn Determinants of Age at Menopause (Average Age =51 years)

  5. Can We Predict Menopause? No • Antimullerian hormone • Synthesized in the granulosa cells of preantral and small antral follicles • Inhibits the transition from primordial into primary follicles preventing excessive follicular recruitment by FSH • Correlates strongly to antral follicle count = “functional ovarian reserve” • Peak level at age 30 • Undetectable about 5 years prior to final menstrual period • Potential predictor of menopause • Less useful for younger (<41 years) and older (>57 years)

  6. FSH >30 Suggests Cessation of Ovulation

  7. Hypothalamic-Pituitary Circulation:Prior to Menopause Hypothalamus Hypothalamic-PituitaryCirculation GnRH Anterior Pituitary Gland LH FSH Estrogen Progesterone

  8. Hypothalamic-Pituitary Circulation:Peri-Menopause (anovulatory cycle) Hypothalamus Hypothalamic-PituitaryCirculation GnRH Anterior Pituitary Gland LH FSH Estrogen X Progesterone

  9. Perimenopause: Intermittent Ovulation and Irregular Cycles Estradiol (pg/mL) Progesterone (ng/mL) 300 200 100 0 20 10 0 Cycle 1 Anovulation Irregular Bleeding Cycle 2 Anovulation Irregular Bleeding Cycle 3 Ovulation Short Follicular Phase

  10. Clinical Issues of Menopause: Change in Uterine Bleeding • Most common symptom of menopause • Irregular bleeding occurs from 10 years prior to final menstrual period (FMP) • Decreased frequency of ovulation (anovulatory cycles) • Pregnancy is possible until ALL ovulation ceases • Uterine bleeding after menopause is always cause for concern if the patient is not taking hormones

  11. Estrogen Receptors Are In Almost Every Cell!

  12. Clinical Issues of Menopause: Vasomotor Symptoms • Second most common symptom of menopause • Primary reason women seek medical treatment • 1-5 minutes with increased skin temp. 1-7˚C • More frequent and severe after premenopausal oophorectomy

  13. Prevalence of Vasomotor Symptoms • > 75% of women report hot flashes within the 2-year period surrounding their menopause • 25% remain symptomatic for > 5 years • 5% of women have hot flashes or night sweats forever Prevalence of Hot Flashes Menopause Years Before Years After 3 2 1 1 2 3 Kronenberg F. Ann N Y Acad Sci. 1990;592:52-86.

  14. Clinical Issues of Menopause: Sleep Disturbances • Trouble getting and staying asleep • Triggers may be joint pain, flashes, stress • Usually cause fatigue, poor focus, and irritability • Often associated with underlying sleep disorder • Melatonin, Trazodone, non-BZD’s, BZD’s, sleep hygiene, meditation • Progesterone may help

  15. Clinical Issues of Menopause: Cognition (“Menopause Fog”) • Forgetfulness, “cloudy” thinking • Due to variations in estrogen • Exacerbated by multi-tasking, depression, anxiety • Treatment includes daily physical exercise and adequate sleep • Refer for neurocognitive testing for dementia or ADHD if severe • Alzheimer’s Dementia is more common in older women

  16. Clinical Issues of Menopause: Psychological Symptoms • Menopause does not cause depression • Depression is more likely to resurface if present prior to menopause • Anxiety is frequent • Stressors: children leaving, ill parents, job changes, financial, marriage, physical changes • Counseling, cognitive behavioral therapy, antidepressants, BZD’s, exercise, estrogen

  17. Clinical Issues of Menopause: Urinary Health • Ureteral thickening recurrent cystitis, frequency • pH rises alters vaginal flora balance • Loss of pelvic organ support cystocele, rectocele • Loss of pelvic floor tone incontinence, muscle spasms • Overactive Bladder (wet or dry)

  18. Clinical Issues of Menopause: Sexual Function • Majority of women state their sexual relationships did not change during menopause • Most common complaints: low libido, vaginal dryness • Barrier methods of prevention should be encouraged for sexually active women with a new partner

  19. Clinical Issues of Menopause:Hair Changes • Female pattern hair loss (FPHL): thinning on the crown • Hypoestrogenemic and relative hyperandrogenic state • Estrogen prolongs anagen phase • Testosterone shortens anagen phase with progressive miniaturization of susceptible hair follicles • Off-label treatment may include antiandrogens (spironolactone) or topical minoxidil, biotin, finasteride

  20. Clinical Issues of Menopause:Dental Health • Hormone receptors exist in the basal and spinous layers of the epithelium and connective tissue • Fluctuations of sex hormones around menopause have been implicated in inflammatory changes in gingiva • Atrophy of bony tooth sockets leading to gum retraction, periodontal pocket development, bacterial invasion, and periodontitis • Rate of systemic bone loss is a predictor of tooth loss • For each 1%/year decrease in BMD, the risk for tooth loss more than quadruples

  21. Clinical Issues of Menopause:Bone Loss

  22. Clinical Issues of Menopause: Bone Loss • First 5 years after menopause is time of more accelerated bone loss • DXA indicated for patients with risk factors, and for those whom treatment would be initiated • http://www.shef.ac.uk/FRAX/tool • NOF Clinician’s Guidelines

  23. Clinical Issues of Menopause: Body Composition Change • Average weight gain = 5 lbs. • Increased central fat distribution • Weight gain assd with • Metabolic Syndrome • Hot flashes • Sleep deprivation • Sedentary lifestyle • Decrease in muscle mass • Resistance training most beneficial

  24. Hypertension: Gender and Age Effects

  25. LDL Cholesterol Levels After Menopause Menopause Jensen J, et al. Influence of menopause on serum lipids and lipoproteins. Maturitas 1990; 12:321-31

  26. HDL Cholesterol Levels After Menopause Menopause Jensen J, et al. Influence of menopause on serum lipids and lipoproteins. Maturitas 1990; 12:321-31

  27. Endothelial Cell Layers in Healthy Postmenopausal and Premenopausal Women • Postmenopausal cells show evidence of endothelial cell death, denudation, and RBC, platelet, and protein attachment, as well as fractured basal membranes, and loss of intercellular junctions • Premenopausal cells show tight connections, a continuous layer of endothelial cells, and thick plasma membranes

  28. Compounded “Bioidentical” Hormones • Dosing schedule mimics premenopausal state in postmenopausal women • Plant derived hormones modified to be identical to human molecules • Not regulated for purity of modification process • Saliva levels do not accurately measure tissue levels • Progestogen skin cream has not been proven effective to prevent endometrial cancer

  29. Hormone Therapy (HT) • Estrogen (E) treats: • Hot flashes • Night sweats • Mood • Vaginal dryness • Cognitive slowing • Progesterone (P) treats: • Endometrial proliferation from estrogen stimulation

  30. Cyclic Advantages Predictable withdrawal bleeding every month Disadvantages 2-pill dosing may discourage compliance Withdrawal bleeding persists indefinitely Continuous Combined Advantages Most women will achieve amenorrhea in time Convenient 1-pill dosing enhances compliance and ensures appropriate progestin treatment Lower risk of endometrial hyperplasia compared with cyclic regimen Disadvantages Unpredictable spotting Daily progesterone exposure and side effects HT Regimen Choices: Cyclic: daily E with cycles of P vs. Continuous Combined

  31. The Women’s Health Initiative in Women With Uteri

  32. The Women’s Health Initiative in Women Without Uteri

  33. Estrogen and Progestin Risks • Venous thromboembolism (DVT, PE) risk is increased with both E and P use • Risk appears reduced in transdermal estrogen vs oral • Risk appears reduced in first and second generation progestins vs newer • Arterial clot risk is higher in smokers, and women with HTN, DM, and high cholesterol • Risks of both types increase with age

  34. “The Timing Hypothesis”(Early exposure to HT might be good!) • Sex steroid hormones alter the biology of vessel wall cells and the inflammatory cells that accumulate differently according to the stage of the disease • It is likely that early physiological sex hormone replacement can improve or reverse early endothelial dysfunction • HT given in advanced atherosclerotic lesions likely predisposes the lesion to inflammatory and hemostatic abnormalities

  35. Assess Your Patient’s Risk Before Starting HT

  36. Next Studies to Evaluate Type and Exposure Age • Elite: Early Versus Late Intervention Trial With Estradiol • Oral E2 vs. placebo • Measuring Carotid intimal medial thickness • KEEPS: Kronos Early Estrogen Prevention Study • CEE vs transdermal E2 with micronized progesterone • Measuring carotid IMT

  37. Non-Estrogen Symptom Therapies • Selective Serotonin Reuptake Inhibitors • Serotonin Norepinephrine Reuptake Inhibitors • Gabapentin • Clonidine • OTC Vaginal moisturizers and lubes • Vitamin E, coconut oil, olive oil • Phytoestrogens (soy, black cohosh, flax)

  38. Variable Stimulation of the Estrogen Receptor Results in Tissue Specific Responses

  39. Creating the Perfect Estrogen Replacement

  40. Newest Menopause Therapies • Duavee (CEE + bazedoxifene) • FDA-approved for vasomotor symptoms and prevention of postmenopausal osteoporosis • Osphena (Ospemiphene) • FDA-approved for painful intercourse due to vulvovaginal atrophy

  41. Menopause Summary • The sex hormone deficiency of menopause affects nearly every cell of the body • Vascular disease, osteoporosis, genitourinary, dental, and skin changes increase in prevalence after menopause • Estrogen and non-estrogen treatments are available for symptom management • Hormone therapy given near the age of menopause has many benefits, but the safety data is inconclusive

  42. Thank You!Questions? Arrange for a 4th-year rotation in Women’s Health in my clinic!

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