Menopause

Diagnosis Management of symptoms and conditions associated with menopause challenges both women and their physicians. The variety of symptoms and their fluctuating nature, the effects of menopause on other conditions, and uncertainty about the safety and effectiveness of available treatments contribute to the confusion. The demand for nonhormonal treatments for menopause symptoms has increased since the publication of the Women's Health Initiative (WHI) findings (1, 2). The importance of considering patient preferences and values in addition to their symptoms and health risks further complicates care of menopausal women. What is menopause? Menopause is the cessation of the menstrual cycle and the end of a woman's reproductive years. It is defined retrospectively, 12 months after the final menstrual period. Progressive oocyte depletion, either through atresia or ovulation, leads to the normal process of menopause. The final menstrual period occurs at a median age of 51.3 years, but irregular menses mark the menopause transition, which typically begins 4 years before the final menstrual period (3). Smokers typically have an earlier onset of menopause (median, 50.2 years) than nonsmokers. Surgery, chemotherapy, or radiation can induce premature menopause. Overall, the menopause transition manifests as a series of symptom complexes that follow a somewhat predictable pattern over a highly variable time course. The Stages of Reproductive Aging Workshop (STRAW) describes menopause as a series of distinct stages (Table 1) (4). Early perimenopause results from anovulatory menstrual cycles and is characterized by irregularity in menstrual cycle length and duration. The late perimenopause is marked by progressive menstrual irregularity. It ends 1 year after the final menstrual period. Early postmenopause is the interval within 4 years of the final menstrual period, and late postmenopause is 5 or more years after the final menstrual period. Table 1. Stages of Menopause What symptoms characterize menopause? The timing, prevalence, severity, range, and duration of menopausal symptoms vary markedly across individuals and cultures (5, 6). Common Symptoms in Women During the Menopausal Transition Symptoms definitely associated with menopausal hormonal changes Hot flashes Night sweats Vaginal dryness Symptoms not definitively related to hormonal changes Depression, anxiety, and irritability Cognitive disturbances Back pain, stiff or painful joint, mylagia Fatigue Urinary incontinence Vertigo Headache Palpitations Sexual dysfunction Vasomotor symptoms are the most common symptoms reported during menopause (7). A hot flash or flush is the sudden sensation of intense warmth that usually begins in the face or chest and spreads throughout the body, often with coincident sweating and palpitations, and can last 2 to 30 minutes. Night sweats are hot flashes that occur at night and can interrupt sleep. Vasomotor symptoms typically peak around the final menstrual period and then decrease in prevalence and severity. They usually resolve without treatment, although approximately 10% of women have persistent bothersome vasomotor symptoms 7 to 10 years after the final menstrual period. Urogenital atrophy results in vaginal dryness and can lead to discomfort, itching, and painful intercourse (dyspareunia). Studies suggest that vaginal dryness affects from one third to nearly one half of menopausal women, with symptoms increasing with advancing age (9). Sleep disturbances are commonly reported by women during the menopausal transition (10) and may be related to night sweats and the severity of vasomotor symptoms (11). Other symptoms reported during menopause include mood disorders (depression, anxiety, and irritability), cognitive disturbances (forgetfulness and difficulty thinking), somatic complaints (back pain, stiff or painful joints, tiredness, myalgia), urinary incontinence, vertigo, headache, palpitations, and sexual dysfunction that is not related to dyspareunia (9). However, these symptoms are considered atypical because they have not been conclusively related to menopausal hormonal changes. When should clinicians consider laboratory studies to confirm menopause? Obtaining a history of menstrual changes and typical menopausal symptoms is usually sufficient to diagnose menopause, and laboratory studies are rarely necessary. However, clinicians should consider laboratory studies to confirm menopause if the diagnosis is unclear in patients not currently receiving exogenous hormones (including oral contraception), if atypical symptoms are present, or if premature ovarian failure is suspected (that is, in women with symptom onset before age 40 years). Measurement of follicle-stimulating hormone (FSH) levels can confirm menopause and help to differentiate it from other conditions (4). An elevated FSH level (>30 mlU/mL) is objective evidence that a patient's symptoms are related to meno-pause. Levels of FSH gradually increase throughout the menopause transition, but they can vary greatly during the perimenopausal stages. Lutenizing hormone levels change later than FSH levels but also increase gradually over time. Clinicians may wish to obtain additional laboratory tests to exclude nonmenopause-related causes of menstrual dysfunction in patients lacking typical menopausal symptoms (Table 2). Table 2. Laboratory Tests to Aid in the Differentiation of Menopause From Other Conditions What other conditions should clinicians consider in patients with vasomotor symptoms, menstrual irregularity, or abnormal vaginal bleeding before attributing the symptoms to menopause? Although vasomotor symptoms are highly suggestive of menopause, they are not exclusive to menopause. Hot flashes and night sweats can also occur with stress, panic attacks, alcohol, a variety of drugs (such as tamoxifen, raloxifene, danazol, the gonadotropin-releasing hormone agonists leuprolide, nafarelin, goserelin, and aromatase inhibitors), thyroid disease, infections, the carcinoid syndrome, pheochromocytoma, systemic mastocytosis, leukemia, and other malignant conditions (12). However, vasomotor symptoms without other worrisome symptoms in a healthy woman of menopause age in the context of progressive menstrual irregularity or amenorrhea do not typically require further evaluation. Other conditions that can cause menstrual irregularity or abnormal vaginal bleeding include thyroid disease; pregnancy; vaginal, cervical, or endometrial pathology; hormonal contraceptive use; hyperprolactinemia; virilizing tumors; and elevated serum androgens. The prevalence of abnormal thyroid-stimulating hormone (TSH) levels is high among middle-aged women (9.6% in 1 study) (13), and elevated TSH level is associated with menstrual irregularity. However, TSH measurement is not indicated in women with typical menopausal symptoms and no evidence of thyroid disease. Clinical Bottom Line: Diagnosis Menopause is defined retrospectively, 12 months after the final menstrual period. The menopause transition manifests as a series of symptom complexes that follow a somewhat predictable pattern over a variable time course. Hot flashes, night sweats, and vaginal dryness are consistently associated with menopausal hormonal changes, but other symptoms that women commonly report during the menopause transition are not. Laboratory studies are rarely necessary to diagnose menopause, but measurement of follicle-stimulating hormone levels can confirm menopause and help to differentiate it from other conditions. A follicle-stimulating hormone level greater than 30 mlU/mL is objective evidence of menopause. Treatment What lifestyle modifications should clinicians recommend for women who are having vasomotor symptoms? Lifestyle modifications are an appropriate first step to consider before initiating, or in conjunction with, pharmacologic therapies for vasomotor symptoms. Clinicians should counsel women that hot flashes are part of the normal process of estrogen withdrawal. Women can take several steps to decrease the number and severity of symptoms, such as quitting or decreasing cigarette smoking and alcohol consumption. Smoking is consistently associated with worsening of vasomotor symptoms (14, 15). Although alcohol use is not consistently associated with vasomotor symptoms, because it is a vasodilator limiting alcohol consumption is prudent. Data on exercise and menopausal symptoms are lacking, and available evidence has not shown a consistent reduction in vasomotor symptoms with exercise. However, exercise favorably affects mood, perceived stress, body image (16), and body weight. Some studies show an association between obesity and vasomotor symptoms (6, 15, 19), but others do not (20, 21). A 2007 systematic review of randomized, controlled trials comparing any type of exercise intervention with other treatments or no treatment in the management of menopausal vasomotor symptoms identified only 1 very small trial that compared exercise with hormone therapy. Both interventions were effective in reducing vasomotor symptoms, but women who received hormone therapy experienced significantly fewer hot flashes than women in the exercise group at follow-up (17). Researchers measured physical activity and menopausal symptoms in 401 women during an 8-year period. This study found no association between level of physical activity and vasomotor symptoms. However, high levels of physical activity were related to lower levels of stress. In addition, levels of anxiety, stress, and depression were lowest among physically active postmenopausal women compared with inactive women in the same phase of menopause (18). Practical measures that some women find helpful include dressing in layers; keeping a fan nearby for day or night symptoms; maintaining cool ambient temperatures; avoiding hot drinks, caffeine, and hot or spicy foods; and keeping an ice pack under a bed pillow. What nondrug treatments should clinicians recommend for wome