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In the name of God

In the name of God. Menopause. Ferdous Mehrabian M.D . Professor of Department of Obstetrics and Gynecology Isfahan University of Medical Sciences. What is Menopause?. 12 months of amenorrhea (no menses) Average age 51

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In the name of God

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  1. In the name of God

  2. Menopause FerdousMehrabian M.D. Professor of Department of Obstetrics and Gynecology Isfahan University of Medical Sciences

  3. What is Menopause? • 12 months of amenorrhea (no menses) • Average age 51 • Derived from the Greek words “men” (month) and “pausis” (cessation) • Primary ovarian function stops • Marks the permanent end of fertility

  4. Menopause • Premature menopause • Surgical menopause • Natural menopause

  5. Target organs of oestrogen • Bone • Urogenital • Vasomotor • Heart • Eyes • Teeth • Breast • Colon

  6. Life expectancy and age of menopause

  7. Midlife Event Viewed Negatively • Negative experiences coincide • Onset of major illness or disability in self or loved ones • Retirement/financial insecurity • Care needed for aging parents • Empty nest syndrome • Physicians • Majority of healthy/happy patients do not seek help • Conflicting and lack of data • Time consuming

  8. Perimenopause • Transition • Change from normal ovulatory cycles to complete cessation of menses • Marked by menstrual irregularity • May begin years prior to menopause • Onset of menopausal symptoms

  9. The Reproductive Cycle

  10. Perimenopausal Bleeding • Anovulatory cycles can lead to hyperplasia • Prolonged, heavy or frequent bleeding should raise red flag • Options for controlling bleeding (and protecting endometrium against hyperplasia) • Low dose birth control pills • Cyclic progesterone • Mirena intrauterine device • Ablation may also be used to control bleeding (need EMB first)

  11. Changes in Hormone Patterns • Inhibin levels fall • Produced by granulosa cells • Decrease may be from declining number of follicles or reduced quality/capacity of aging follicles Speroff • Serum FSH levels rise • Slight increase in estradiol levels

  12. Changes in Hormone Patterns • Cycle variability increases • Hormone levels fluctuate • FSH and estradiol may return to premenopausal ranges • After menopause, ovary no longer secretes estradiol – continues to produce androgens (under continued stimulation of LH) • Elevated levels of FSH and LH = evidence of ovarian failure Speroff

  13. Low Dose Birth Control Pills vs Hormone Replacement Therapy • Postmenopausal hormone (HRT) regimens do not suppress ovulation • Oral contraceptive that contains 20 micrograms estrogen provides effective contraception • Even lowest dose OCP provides 4x estrogen dose in standard (HRT)

  14. Menopausal Symptoms • Hot flashes • Sleep disturbances • Vaginal dryness • Mood changes • Difficulty concentrating • Memory impairment • Bladder irritability/urgency • Changes in balance • Decreased interest in sex, possibly decreased response to sexual stimulation

  15. Vasomotor Symptoms • Most often begin in perimenopause • Sudden onset reddening of the skin (head/neck/chest), feeling of intense body heat, profuse perspiration Speroff • Intervals vary (minutes to hours) • More frequent and severe at night • Generally stop spontaneously w/in few years, may persist for many years • 12-15 % of women in 60’s • 9% of women after age 70 Casper

  16. Other Causes to Consider • Thyroid disorders • Pheochromocytoma • Leukemia • Cancer • Infection

  17. Estrogen Benefits • Oral estrogen lowers: • LDL • Lipoprotein(a) • Glucose • Insulin • Homocysteine levels • Oxidation of LDL • Increases • HDL

  18. Estrogen Benefits • One HT study of women taking 0.625 or 1.25 mg of conjugated equine estrogens with 5 mg medroxyprogesterone daily showed that total and low density lipoprotein cholesterol were reduced to nearly the same extent as that of women treated with 10 mg simvastatin daily. • HDL was increased to a greater extent than did simvastatin in this study.Harman

  19. Estrogen Risks • Estrogen also increases: • Triglycerides • Coagulation factors • C-reactive protein (inflammatory risk factor for CHD) • Certain progestogens offset some of estrogen’s benefitsManson

  20. Hormone Therapy - WHI • Estrogen only arm • 0.625 mg conjugated estrogens • Randomized 10,739 women (s/p hyst) • Feb 2004, NIH canceled study • Increased risk of stroke similar to combined arm • No increase or decrease in CHD • Trend towards increased risk of probable dementia and/or mild cognitive impairment • Reduction in hip fractures • No increase in breast cancer

  21. Reanalysis of Data from WHI • Secondary analysis of data stratified based on age and time from menopause • No increased risk seen in women between 50-59 or in those within 10 years of menopause (underpowered to reach statistical significance) • Stroke increased regardless of age and years since menopause • Hazard ratios for breast cancer and total cancer higher in women who initiated hormone therapy soon after menopause (both regimens)

  22. Is Transdermal Better?

  23. Transdermal Estrogen • Oral estrogen has greater effect on liver – first pass effect • Absorbed through intestine, then passes through liver • Increases liver production of • Sex steroid binding globulins • Triglycerides • HDL • Clotting factors • Liver is not normally exposed to such high levels of estrogen, except during pregnancy

  24. What Now? • For women with moderate to severe vasomotor symptoms, depending on individual risk, and patient’s willingness to accept risk, use the lowest dose of estrogen (with progesterone, if uterus intact) effective for the shortest amount of time possible.

  25. How Long? • Risk of Breast Cancer: • For estrogen/progesterone therapy, time is limited by the increased risk of breast cancer that is seen with more than 3-5 years of use • For estrogen only, no sign of an increased risk of breast cancer was seen during an average of 7 years of treatment • Risk of Heart Disease/Stroke: • Most healthy women below age 60 will not have an increased risk of heart disease with hormone therapy • In women below age 60, risks of stroke and blood clots are less than 1/1000 women per year.

  26. Cessation of Hormone Therapy • Abrupt withdrawal increases return of moderate to severe symptoms • Tapering dose of hormones lowers risk of recurrent symptoms • Weaning off • Decrease to lowest dose first • Decrease by one pill per week, or • Skip 1 day, then 2 days, etc • Slower tapering may benefit women with recurrence

  27. Protecting the Endometrium • Daily progesterone • 10-14 days Q month • Long-cycle • Q3-6 months • Insufficient evidence regarding endometrial safety NAMS • Progesterone is a large molecule, does not absorb well through skin

  28. How do you choose?!?!

  29. Alterations of Estrogen Metabolism • Anticonvulsants increase hepatic clearance of estrogen • Estrogen may increase T4 requirements • Acute alcohol ingestion increases serum estradiol • End stage renal disease – higher serum estradiol levels Martin

  30. Alternative Therapies • Lifestyle modifications • Keeping core temperature cool • Regular exercise, weight loss • Relaxation therapy/stress management/reflexology • Isoflavone supplements: • Soy, red clover, black cohosh • Acupuncture • Black cohosh • may have estrogenic effect on breast – do not use in breast cancer pt

  31. Alternatives: SSRIs • Venlafaxine (effexor) • Selectively inhibits both serotonin and NE reuptake • No benefit seen above 75 mg • SE = dry mouth, nausea, insomnia, sexual dysfunction • Paroxetine (paxil) • Avoid in women receiving tamoxifen – reduces formation of active metabolites

  32. Alternatives: Gabapentin • Gabapentin reduces frequency of hot flashes • Large study 420 women with breast cancer – 3 groups, randomly assigned, 8 wks • Placebo – decrease 15% (hot flash score) • 300 mg/d – decrease 31% • 900 mg/d – decrease 46% Rapkin • Other studies have shown similar results

  33. Effect of Estrogen on Vaginal Tissue • Maintains collagen content – effects thickness and elasticity • Maintains mucopolysaccharides and hyaluronic acid – keep epithelial surfaces moist • Maintains optimal blood flow • Keeps epithelium rich in glycogen • Glycogen = substrate for lactobacilli, which convert glucose to lactic acid (creating acidic pH) • Acidic environment protects against vaginal and urinary tract infections

  34. Without Estrogen • Vagina loses collagen, adipose tissue and ability to retain H20 • Labia and vulva lose fullness • Blood vessels narrow and secretions from sebaceous glands decrease • Vaginal opening may narrow • Vaginal length may shorten

  35. Without Estrogen Surface epithelium loses outer fibrous layer, decreases ratio of superficial to parabasal cells.

  36. Vaginal Atrophy • With loss of glycogen, pH increases (generally > 5) • Environment less hospitable for lactobacilli • More susceptible to pathogens from skin and rectum • Urogenital problems • Urgency • Dysuria • Abacterial urethritis • Recurrent UTIs • Urethral caruncles

  37. Most Common Complaints • Vaginal dryness • Pruritis (itching) • Discharge – yellow, malodorous • Dyspareunia (painful intercourse) • Vaginal bleeding or spotting • Unlike hot flushes, symptoms do not improve with time

  38. Vaginal Atrophy – Treatment • Estrogen replacement • Sytemic and local are effective • Low vaginal doses usually do not reach serum levels sufficient to create systemic side effects (endometrial stimulation) Bachman • Creams, rings, tablets similarly effective

  39. Vaginal Atrophy - Alternatives • Sexual activity • Improves blood supply • Preserves elasticity • Prevents introital narrowing • Lubricants • K-Y Jelly • Astroglide • K-Y Liquid beads (silicone based)

  40. Vaginal Atrophy - Alternatives • Replens • Long-acting moisturizer • Polcarbophil-based polymer, binds to vaginal epithelium, releases H20, produces moist film over vaginal tissue • May restore normal vagina pH, does not affect cytology • K-Y Silk-E • Feminease • Contains mineral oil, glycerin, yerba santa

  41. Physical Changes of Menopause • Weight gain • Decrease bone mineral density

  42. Osteoporosis • Oestrogen deficiency • Peak bone mass at 30-35 years old • Bone loss at a rate of 0.5-1% per year afterward • Bone loss at a rate of 2-3% per year for 10 years after menopause • Osteoporosis is associated with fracture ( femoral neck, vertebral body and distal radius)

  43. Risk factors of osteoporosis • Family history • Ethnicity • Early menopause • Hypoestrogenism (excessive exercise, anorexia, bulimia) • Hyperthyroidism, excessive thyroxine therapy • Cigarette smoking • Caffeine • High alcohol intake

  44. Prevention of osteoporosis • Change lifestyle risk factors • Exercise • Adequate calcium / vitamin D intake • Hormone Replacement Therapy • Alendronate • Raloxifene

  45. Prevention of Osteoporosis • 10 years after HRT has been stopped, bone density and fracture risk are similar in women who had used HRT and those have not • Long term treatment (>10-15 years) is required to prevent osteoporosis • Constant reassessment (general health, risk factors and life expectancy) is required.

  46. Other options for management of menopausal symptoms and prevention of osteoporosis

  47. Other options for prevention of osteoporosis

  48. Bisphosphates • Etidronate and Alendronate • Inhibitors of bone turnover and slow down or prevent bone loss • Both need to be taken on an empty stomach • Non-hormonal agents • Treatment of choice for older women and those with contra-indications to HRT

  49. Raloxifene • Selective oestrogen receptor modulators (SERMs) • Agonist and antagonist properties • Bone protective and reduce cholesterol • No effect on the endometrium • Evidence to suggest that it is protective against breast cancer • Does not help menopausal symptoms and may worsen them

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