Preventive Health Care
The menopausal transition offers women and their health care providers the opportunity to review and focus on preventive health care measures, including basic health habits, such as regular exercise, good nutrition with calcium and vitamin D supplementation, and avoidance of smoking [see Table 2].
WHI demonstrated that HT is effective for the prevention of osteoporotic fractures and colorectal cancer in postmenopausal women, but the risks outweigh the benefits88 [see Table 1]. The prevalence of certain medical conditions (e.g., dementia, coronary artery disease, breast cancer, colon cancer, and diabetes mellitus) increase with age, rising more steeply after loss of ovarian function. Recommended management for these conditions is almost always nonhormonal. HT is not indicated for primary prevention of disease, unless a woman at high risk for osteoporosis chooses HT over other options after consideration of the risks and benefits.60 Two chronic disease processes associated with hypoestrogenism and aging greatly impact women’s health in the postmenopausal years, namely cardiovascular disease and osteoporosis. Cardiovascular disease is the leading cause of death in women in the United States, and osteoporosis is a major cause of morbidity. The management of these diseases is discussed more fully elsewhere [see 16:IX Cardiovascular Disease in Women and 3:VI Diseases of Calcium Metabolism and Metabolic Bone Disease].
Table 2 Preventive and Screening Measures for Common Conditions in Postmenopausal Women
|
Condition |
Prevention |
Early Detection |
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Dementia |
Participation in cognitive leisure activities |
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Regular exercise |
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Treatment of hypertension |
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Statins and possibly other lipid-lowering agents |
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Long-term NSAID use* |
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Avoidance of HT initiation in postmenopause+ |
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CAD |
Smoking cessation |
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Regular exercise |
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Diet high in nuts, whole-grains, and total fiber (especially water-soluble fiber), folate, and marine n-3 fatty acids |
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Diet low in saturated fat, trans fatty acids, and glycemic load |
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Daily, low-dose alcohol |
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Prevention and treatment of hypertension, diabetes mellitus, and hyper-cholesterolemia |
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Consideration of low-dose daily aspirin if risk of CAD events is > 0.7%/yr |
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Avoidance of HT initiation in postmenopause |
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Statins, aspirin, and beta blockers for secondary prevention (underutilized) |
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Breast cancer |
Minimal exposure to HT (estrogen and/or progestin) |
Screening mammography every 1-2 yr, with or without clinical breast exam regardless of age until clinically significant comorbid conditions |
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Regular exercise |
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Avoidance of increase in weight and waist circumference |
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Weight loss if overweight/obese |
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Reduction of alcohol intake to 0-20 g/day |
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Raloxifene* if at average risk, or tamoxifen if risk > 1.67%/yr |
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Osteoporosis |
Adequate calcium and vitamin D intake |
Screening DEXA at age 65 (earlier if risk factors) |
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Weight-bearing exercise |
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Thiazide* diuretics |
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Antiresorptive treatment before first osteoporotic fracture |
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Antiresorptive treatment after osteoporotic fracture |
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HT+ if intolerant of or unresponsive to first-line agents |
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Colon cancer |
High-fiber diet for primary, but not secondary, prevention of polyps |
Periodic screeningt by fecal occult blood testing or sigmoidoscopy |
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Aspirin* if personal history of adenoma or colon cancer |
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Removal of adenomatous polyps |
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HT* effective but not advised for this indication+ |
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Diabetes mellitus |
Regular exercise |
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Weight loss if overweight/obese |
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Metformin, acarbose, and possibly thiazolidinediones for those at high risk |
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HT+ effective but not advised for this indication |
*Off-label indication.
^Increased risk of adverse outcomes has been demonstrated for HT initiation in the postmenopausal years. HT is not advised for the primary prevention of disease, because associated risks outweigh benefits for most women; in limited cases, HT may be used for prevention of osteoporosis, after consideration of all other options. HT should be used only for severe and debilitating symptoms, in the lowest dose and most directed therapy possible, and for the shortest time necessary to accomplish symptom control.
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The United States Preventive Services Task Force (USPSTF) recommends screening for colon cancer starting at age 50 using either annual fecal occult blood testing, sig-moidoscopy (periodicity unspecified), or both.
HT—hormone therapy
CAD—coronary artery disease
DEXA—dual x-ray absorptiometry
NSAID—nonsteroidal anti-inflammatory drug
*Premature Ovarian Failure
Premature ovarian failure (POF) is defined as menopause that occurs before 40 years of age that is not iatrogenically induced. The prevalence of POF is approximately 1%.120 The Study of Women Across the Nation (SWAN) investigated risk factors associated with POF121 and found that ethnicity influences risk: POF occurs in 1.1% of white women and 1.4% of African-American and Hispanic women, but it occurs in only 0.5% of Chinese-American women and 0.1% of Japanese-American women. Higher body mass index is associated with increased likelihood of POF, especially in African-American women. Disability and current smoking are associated with greater risk in white women.
Etiology
There is good evidence to suggest that the timing of the age of menopause is genetically programmed15,16 and that genes play a significant role in the etiology of premature ovarian failure.120 Rare genetic and chromosomal causes of premature ovarian failure include familial predisposition, FSH receptor mutations, galactosemia, 17a-hydroxylase deficiency, alterations in gonad-otropin structure or function, and structural alterations of the Xchromosome (e.g., Turner syndrome mosaicism). A common genetic cause of POF is the fragile X premutation. Up to 3% to 5% of women with POF are carriers of the fragile X premutation, the most common cause of mental retardation in males.122 Approximately 16% of women who are fragile X premutation het-erozygotes have POF.123
Premature menopause may be immune-mediated in 30% to 50% of women with POF.123 Family history is often positive for autoimmune conditions,124 and other autoimmune diseases may be present in the patient herself,124 including autoimmune thy-roiditis, type 1 diabetes mellitus, autoimmune hemolytic anemia, Addison disease, hypoparathyroidism, idiopathic throm-bocytopenic purpura, Crohn disease, myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus, vitiligo, and polyendocrine failure.
Diagnosis
Clinical Manifestations
The presentation of premature ovarian failure is identical to that observed in natural menopause, with the exception that POF occurs before 40 years of age. It is more common, however, for women with POF to experience waxing and waning of symptoms over longer periods than it is for women who have natural menopause, and some women will ovulate several years after a diagnosis of POF is made.
Physical Examination
A targeted examination for women with oligomenorrhea or secondary amenorrhea is described elsewhere [see Natural Menopause, Physical Examination, above]. Less common etiologies of POF, such as Turner Syndrome (i.e., short stature, webbed neck, shield chest, small fourth metacarpal, and minimal breast development with normal hair distribution), can be detected with a specifically targeted physical examination. Findings of other autoimmune conditions often associated with POF [see Etiology, above] may be present in some women, including signs of thyroid disease (i.e., enlarged, asymmetrical, or nodular thyroid gland; dry skin; lateral eyebrow thinning; delayed relaxation phase on deep tendon reflexes; and myxedema), adrenal dysfunction (i.e., hyperpigmentation and orthostatic hypotension), and systemic lupus erythematosus (i.e., synovitis or malar rash). Galactorrhea suggests an elevated prolactin (PRL) pro-lactinoma [see Differential Diagnosis, below].
Laboratory Tests
Ovarian failure is most accurately confirmed by measurement of serum FSH. In women with incipient ovarian failure, FSH levels are often between 15 and 25 IU/L and can fluctuate. Complete ovarian failure is associated with repeated serum FSH levels greater than 25 IU/L. Therefore, FSH levels persistently greater than 25 IU/L (drawn on at least two separate occasions) can be useful in making the diagnosis of POF. Testing of urine or serum fi-hCG, TSH, and prolactin concentrations should not be deferred if indicated in the evaluation of oligomenorrhea or secondary amenorrhea [see Natural Menopause, Laboratory Tests, above]. If a diagnosis of POF is made, consideration of genetic testing for a premutation allele of fragile X may be advisable, providing that this information would benefit family members and that the patient agrees to testing. If a woman younger than 30 years is diagnosed with POF, a karyotype test should be considered to rule out Turner syndrome mosaicism. When POF may be caused by autoimmunity, the complete blood count (CBC), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), antinuclear antibody (ANA), glucose, calcium, and phosphorus levels can point to associated autoimmune conditions that may not otherwise be clinically apparent.
Differential diagnosis
Hypergonadotropic amenorrhea can be caused by thyroid dysfunction, hyperprolactinemia, heroin addiction, and the use of some antidepressant and antipsychotic medications.
Management
All women with POF should be treated with exogenous estrogen, either in the form of a low-dose estrogen-progestin combination contraceptive or a postmenopausal HT formulation to manage symptoms and decrease the risk of osteoporosis and os-teopenia. Bone mineral density should be obtained at baseline and followed at intervals of 3 to 5 years. It is recommended that women continue estrogen replacement until at least age 50 (approximately the time of natural menopause). Progestin therapy is recommended for women who have a uterus. Women who are at risk for unintended pregnancy should receive exogenous estrogen and progestin in the form of a contraceptive. For those desiring pregnancy, artificial reproductive technology is available. In vitro fertilization utilizing donor eggs and hormonal manipulation to mature the endometrium result in successful pregnancy in women with POF as often as in women with infertility from other causes.125
Treatment with oral contraceptives in the general population is associated with an increased risk of thromboembolic disease, cardiovascular disease in smokers, and stroke in women with migraine headaches or hypertension.126 The risks of using oral contraceptives and postmenopausal HT in women with POF has not been specifically studied.
Complications and prognosis
The chance of spontaneous pregnancy in POF is estimated to be less than 10%.127 Women with POF may be at higher risk for younger onset of cardiovascular disease.128 It is estimated that women with POF who do not take estrogen have a lower background risk of breast cancer and thromboembolism than the general population.129 New onset of autoimmune disorders is not uncommon after the diagnosis of POF has been made.
Early-age mortality may occur in women with POF because of autoimmune phenomena, cardiovascular disease, and osteoporosis. A few epidemiologic studies suggest that an earlier age at menopause is associated with substantially increased mortal-ity128,129; thus, careful screening for and management of chronic disease processes associated with hypoestrogenism [see Table 2] may be important for sustaining long-term health and quality of life. In addition, careful management of any coexisting autoimmune disorder and reduction, when possible, of potential risks posed by medications used to treat such disorders (e.g., cortico-steroids) may be crucial for the long-term health of affected women.
