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Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreasing ovarian function. Manifestations may include hot flushes, atrophic vaginitis, and osteoporosis. Diagnosis is clinical: absence of menses for 1 yr. Manifestations may be treated (eg, with hormone therapy or SSRIs).
Physiologic menopause is established when menses have been absent for 1 yr. In the US, average age of physiologic menopause is 51. Perimenopause refers to the years before (duration varies greatly) and the 1 yr after the last menses. Perimenopause is usually characterized initially by an increase in frequency of menses, followed by a decrease (oligomenorrhea), but any pattern is possible; conception is possible during perimenopause. Climacteric refers to a longer phase in which women lose reproductive capacity; it begins before perimenopause.
As ovaries age, their response to the pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) decreases, initially causing a shorter follicular phase (with shorter and more irregular menstrual cycles), fewer ovulations, and thus decreased progesterone production (see Fig. 5: Female Reproductive Endocrinology: The idealized cyclic changes in pituitary gonadotropins, estradiol (E2), progesterone (P), and uterine endometrium during the normal menstrual cycle. ). Eventually, follicles do not respond, producing little estradiol. Some estrogens (mainly estrone) still circulate; they are produced by peripheral tissues (eg, fat, skin) from androgens (eg, androstenedione, testosterone). However, the total estrogen level is much lower. Around menopause, androstenedione levels decrease by half, but the decrease in testosterone levels, which begins gradually in young adulthood, does not accelerate during menopause because the stroma of the postmenopausal ovary and adrenal gland continue to secrete substantial amounts. Decreased levels of ovarian inhibin and estrogen, which inhibit pituitary release of LH and FSH, result in a substantial increase in circulating LH and FSH levels.
Premature menopause (premature ovarian failure—see Menstrual Abnormalities: Premature Ovarian Insufficiency or Failure) is cessation of menses due to noniatrogenic ovarian failure before age 40. Contributory factors may include smoking, living at high altitude, and undernutrition. Iatrogenic (artificial) menopause results from medical interventions (eg, oophorectomy, chemotherapy, pelvic irradiation, any intervention that impairs ovarian blood supply).
Symptoms and Signs
Perimenopausal changes in menstruation usually begin during a woman's 40s. Menstrual flow and cycle length can vary. Menses become irregular, then are skipped.
Large daily fluctuations in estrogen levels usually begin at least 1 yr before menopause and are thought to cause perimenopausal symptoms. Symptoms can last from 6 mo to over 10 yr and range from nonexistent to severe.
Vasomotor:
Hot flushes (flashes) and sweating due to vasomotor instability affect 75 to 85% of women and usually begin before menses stop. Hot flushes continue for > 1 yr in most women and for > 5 yr in 50%. Women feel warm or hot and may perspire, sometimes profusely; core temperature increases. The skin, especially of the head and neck, may become red and warm. The episodic flush, which may last from 30 sec to 5 min, may be followed by chills. Flushes may manifest during the night as night sweats. The mechanism of hot flushes is unknown, but they may be triggered by cigarette smoking, hot beverages, foods containing nitrites or sulfites, spicy food, alcohol, and possibly caffeine.
Neuropsychiatric:
Neuropsychiatric changes (eg, poor concentration, memory loss, depression, anxiety) may accompany menopause but are not directly related to decreased estrogen. Recurrent night sweats, which can disrupt sleep, can contribute to insomnia, fatigue, irritability, and poor concentration.
Genital:
Decreased estrogen leads to vaginal and vulvar dryness and thinning, which may result in inflammation of the vaginal mucosa (atrophic vaginitis). Atrophy may cause irritation, dyspareunia, and dysuria and may increase vaginal pH. The labia minora, clitoris, uterus, and ovaries decrease in size.
Other:
Although menopause is normal, health problems can occur, and for some, quality of life may decrease. Risk of osteoporosis increases because estrogen is decreased, increasing bone resorption by osteoclasts (see Osteoporosis). The most rapid loss occurs during the first 2 yr after estrogen begins to decrease.
Diagnosis
Diagnosis is clinical. Menopause is likely if menses have gradually decreased in frequency and have been absent for 6 mo. Women with amenorrhea are examined to exclude pregnancy if they are < 50 and are always examined to exclude ovarian tumors (for evaluation of amenorrhea, see Menstrual Abnormalities: Evaluation). Abnormal pelvic masses are evaluated (see Symptoms of Gynecologic Disorders: Evaluation). If women in their 50s have a history of irregular menses followed by cessation of menses, with or without symptoms of estrogen deficiency, and no other abnormal findings, no diagnostic testing is necessary.
FSH levels may be measured, but this test is rarely necessary. Consistently elevated levels predict menopause, sometimes many months to a year in advance.
Postmenopausal women who have risk factors for osteoporosis and all women > 65 should be screened for osteoporosis (see Osteoporosis: Diagnosis).
Treatment
Discussing the physiologic causes of menopause and possible symptoms and signs with patients helps them manage the changes that occur. Treatment is symptomatic.
For hot flushes, avoiding triggers and wearing clothing in layers that can be removed as needed may help. Soy protein has been used, but its efficacy has not been confirmed. Black cohosh, other medicinal herbs, vitamin E, and acupuncture do not appear helpful. Regular exercise, stress avoidance, and relaxation techniques may improve sleep and reduce irritability; relaxation techniques can also reduce vasomotor symptoms. Paced respiration, a type of slow, deep breathing, may also help relieve hot flushes.
Nonhormonal drug treatments for hot flushes include SSRIs (eg, fluoxetine, sustained-release paroxetine, sertraline), SNRIs (eg, venlafaxine), and clonidine 0.1 mg transdermally once/day. Dose requirements for SSRIs and SNRIs vary; starting doses can be lower than those used to treat depression and increased as needed. It is not clear whether gabapentin is helpful.
OTC vaginal lubricants and moisturizers help relieve vaginal dryness. Measures to prevent and treat osteoporosis are considered (see Osteoporosis: Treatment).
Hormone therapy:
For many women, risks of oral hormone therapy outweigh the benefits.
Hormone therapy may be used to relieve moderate to severe menopausal symptoms. For women who have had a hysterectomy, estrogen should be used alone. Forms may be oral, transdermal (a patch, lotions, or gels), or a tablet inserted vaginally. Women who have a uterus, if given estrogen in any form or type, are also given a progestin (as combination therapy) because unopposed estrogen increases risk of endometrial cancer (and possibly ovarian cancer if unopposed estrogen is taken > 10 yr). Oral hormone therapy also has other risks (see Table 1: Menopause: Effects of Oral Hormone Therapy on Yearly Incidence* of Selected Disorders in Postmenopausal Women ). For most women, these risks outweigh benefits. For other forms of hormone therapy, risks and other effects are not as well known. The risk of venous thromboembolism may be lower with transdermal estrogen.
Benefits of oral combination therapy include reduction in yearly incidence of osteoporosis and colorectal cancer, as well as relief of menopausal symptoms. For asymptomatic women, overall effects of therapy on quality of life are not very meaningful.
Risks of oral combination therapy are reflected in an increased yearly incidence of breast cancer, ischemic stroke, deep venous thromboembolism, pulmonary embolism, dementia, and coronary artery disease. Risk of coronary artery disease almost doubles during the first year of therapy and is particularly high for women with high pretreatment low-density lipoprotein levels; aspirin and statins do not prevent the increase in risk. Also, the breast cancers that develop are larger and more likely to be metastatic, and false-positive mammograms are more common. Urinary incontinence, particularly stress incontinence, develops more often, and existing incontinence tends to worsen.
Oral estrogen-only therapy does not affect incidence of coronary artery disease but increases incidence of ischemic stroke and deep venous thromboembolism. It decreases incidence of hip fractures. Effects on breast cancer, colorectal cancer, and pulmonary embolism are less clear. Estrogen-only therapy, like combination therapy, contributes to urinary incontinence. Dementia risk is probably increased with estrogen-only therapy.
Despite its beneficial effects on bone, hormone therapy (with or without a progestin) is not recommended for prevention and treatment of osteoporosis because other effective measures (eg, raloxifene, bisphosphonates), which usually have fewer risks, are available.
Oral estrogen therapy can be used to relieve hot flushes, night sweats (with consequent sleep disturbance), and vaginal dryness. For vaginal dryness or atrophy, topical forms of estrogen (eg, creams, vaginal tablets or rings) are as effective as oral forms. Vaginal tablets and rings that contain low doses (eg, 25 μg) deliver less estrogen to the systemic circulation; vaginal estrogen creams usually deliver as much as oral therapy.
Progestins (eg, megestrol acetate 10 to 20 mg po once/day, medroxyprogesterone acetate 10 mg po once/day or depot 150 mg IM once/mo) can be used alone to relieve hot flushes, but they do not relieve vaginal dryness. Progestins may have adverse effects (eg, abdominal bloating, breast tenderness, increased breast density, headache, increased low-density lipoprotein, decreased high-density lipoprotein); micronized progesterone appears to have fewer adverse effects but may increase the risk of venous thromboembolism. There are no long-term safety data about use of progestins.
When prescribing solely for the prevention of postmenopausal osteoporosis, clinicians should consider hormone therapy only for women at significant risk of osteoporosis and for whom nonestrogen drugs are considered inappropriate.
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Table 1
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| Effects of Oral Hormone Therapy on Yearly Incidence* of Selected Disorders in Postmenopausal Women |
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Disorder
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Without Treatment
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With Treatment
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Combined estrogen/progestin therapy
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Breast cancer
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30
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38
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Colorectal cancer
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16
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10
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Coronary artery disease†
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30
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37
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Dementia
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22
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45
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Ischemic stroke
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21
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29
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Osteoporosis
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15
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10
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Pulmonary embolism
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16
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34
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Estrogen-only therapy
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Hip fractures
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17
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11
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Ischemic stroke
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32
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44
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*Per 10,000 women.
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†Number of coronary events such as nonfatal acute coronary syndrome and death due to coronary artery disease.
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Last full review/revision July 2007 by Susan L. Hendrix, DO
Content last modified February 2012
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