• Last spontaneous menstrual period 12 months prior. • Average age of onset is 51 years. • Symptoms can, but do not necessarily, include hot flashes, night sweats, palpitations, headache, insomnia, mood swings, anxiety, vaginal dryness, urinary incontinence, rheumatism, fatigue, hair thinning, skin dryness, acne, facial hair, low libido, bladder infections, vaginal infections, nausea, and mild cognitive changes (irregular bleeding with perimenopause). • Physical examination: vaginal thinning, hair thinning and facial hair, height, weight, abdominal fat, general physical. • Lab analysis: increase in follicle-stimulating hormone (FSH). • Lab analysis and imaging may assess risks for osteoporosis and cardiovascular disease. • Causes of menopause: thought to occur when no eggs are left in the ovaries. At birth a female has approximately 1 million eggs (ova) which drop to 300,000-400,000 at puberty. Only 400 actually mature during the reproductive years. The absence of active follicles reduces estrogen and progesterone, causing the pituitary to increase follicle-stimulating hormone (FSH) in large and continuous quantities. Luteinizing hormone (LH) and FSH cause ovaries and adrenals to secrete androgens, which can be converted to estrogens by fat cells of the hips and thighs. Converted androgens are the source of most circulating estrogen in postmenopausal women. Total estrogen is still far below reproductive levels. • Menopause as social construct: social and cultural factors contribute greatly to how women react to menopause. Modern society values allure of everlasting youth, culturally devaluing of older women. The cultural view of menopause is directly related to symptoms of menopause. If the cultural view is negative, symptoms are common; if menopause is viewed in a positive light, symptoms are less frequent. In a study of rural Mayan Indians, no women had hot flashes or any other symptoms, and no women showed evidence of osteoporosis despite hormonal patterns identical to postmenopausal women in the United States. Mayan women saw menopause as a positive event, provid-ing acceptance as a respected elder as well as relief from childbearing. • Options for managing menopause: diet, exercise, stress management, nutrition, botanicals, natural hormones, conventional hormones, additional pharmaceuticals. • Reasons to discontinue cHRT: uterine bleeding, mood changes, breast tenderness, bloating and weight gain, fear of breast cancer, misunderstanding or disbelief in need for long-term use, lack of patient education. • Benefits of continuing cHRT: symptomatic relief from hot flashes, night sweats, vaginal dryness, insomnia, mood swings, depression, incontinence, infections. ERT controls vasomotor symptoms and genitourinary symptoms. Vaginal estrogen is as efficacious as oral or transdermal estrogen for genitourinary symptoms and advantageous because of local delivery and effect. Sex steroids affect sleep, libido, cognitive function, motor coordination, and pain sensitivity. In perimenopause or early menopause, depression and mood disorders are more common than in reproductive years. HRT benefits many women. • Osteoporosis: inhibits age-related bone loss, reduces risk of vertebral and hip fracture, decreases bone resorption, prevents osteoporosis, and reduces fractures. But ERT is no longer approved by the Food and Drug Administration for treating osteoporosis in deference to drugs such as bisphosphonates (risedronate and alendronate). Continuous-combined estrogen-progestogen therapy reduced relative risk for hip, vertebral, other osteoporotic, and total fractures. Estrogen agents approved for prevention of osteoporosis are: • Colorectal cancer: ERT reduces risk of colorectal cancer and risk of dying from colon cancer. • Endometrial cancer: unopposed ERT is linked to increased risk of endometrial cancer by a factor of 8 to 10 over 10+ years. Risk decreases after discontinuing ERT but remains elevated after 10+ years. Proven dose/delivery progestogen (progestins or progesterone), opposing estrogen, minimizes risk and helps prevent endometrial hyperplasia and cancer. Oral micronized progesterone (OMP) and cyclic OMP (200 mg q.d. for 12 days per month) protect endometrium. OMP is equally appropriate to use as medroxyprogesterone acetate (MPA) to protect endometrium. Compounded OMP and Prometrium are indicated products. • Venous thromboembolism: deep vein thromboembolism is complication expected of HRT. For women at risk for thromboembolism or those who are older, absolute risks of HRT are higher. • Breast cancer: no data clearly and consistently demonstrate an increased risk of breast cancer associated with HRT. An analysis of 90% of postmenopausal women who had ever used HRT had a small but statistically significant increase in risk compared with those who never used HRT. Among current users or recent users, relative risk increased by factor of 1.02 to 1.04 for each year of use. After not using HRT for 5 years, no significant excess risk remains. Breast cancers diagnosed in HRT users tend to be less advanced and more localized. No studies found an increased risk of breast cancer with short-term use of HRT. If long-term use increases risk, it is a small increase. • Cognitive function: HRT may prevent or delay Alzheimer’s disease (AD). In women symptomatic from menopause, ERT improves verbal memory, vigilance, reasoning, and motor speed, but no consistent effects were seen on visual recall, working memory, complex attention, mental tracking, mental status, or verbal functions. ERT does not enhance asymptomatic women’s performance. HRT may decrease the risk of dementia. Efficacy of preparations or doses, progestin use, and duration of treatment have not been assessed because of insufficient data. Prior use of HRT reduces risk of AD, but duration of use specifically affects benefit. No apparent benefit is found with currently using HRT unless use exceeds 10 years. • Ovarian cancer: a weak possible positive association exists between HRT and ovarian cancer risk. Women currently using HRT may have higher death rates from ovarian cancer than those who had never used HRT. Given the low incidence of ovarian cancer, even if relative risk increases significantly, it may not affect absolute risk. Ovarian cancer mortality rate in postmenopausal women is extremely low, and 7+ years of oral contraceptive use during the reproductive age lowers the incidence of ovarian cancer. A twofold increased risk exists among long-term users of HRT and ERT. Users of ERT for >10 years have a much increased risk of ovarian cancer, with a relative risk of 1.8. Users of ERT for 20+ years have a relative risk of 3.2. Users of short-term combination HRT are not at increased risk.
Menopause
DIAGNOSTIC SUMMARY
GENERAL CONSIDERATIONS
Estrogen Replacement Therapy
Benefits and Risks of Conventional HRT (cHRT) and Natural HRT (nHRT)
Risks
Areas of uncertainty
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