I MENOPAUSE ^302 ^489 ^571 ^647

Menopause is the permanent cessation of menstruation that occurs 1 year after the last menstrual period and marks the end of a women’s reproduc­tive ability. In North America, the median age of menopause is 51 years.

Most women go through a period of irregular menstrual activity before menopause. Common symptoms of menopause include vasomotor symp­toms (hot flushes) and vaginal dryness. Atrophic changes of the external genitalia commonly occur with time. Certain medical conditions occur more often in this age group. These conditions include cancer, osteopo­rosis, coronary artery disease, cerebrovascular disease, diabetes mellitus, pulmonary disorders, Alzheimer disease, and adult macular degeneration. Many of these conditions are associated with aging and low estrogen levels after menopause.

The North American Menopause Society (NAMS) notes that women who experience premature menopause (at age 40 years or earlier) or pri­mary ovarian insufficiency are medically a distinctly different group from women who reach menopause at the median age. According to NAMS, the data regarding HT in women who experience menopause at the median age should not be extrapolated to women who initiate HT at the time of premature menopause. Given the potential harmful effects of estrogen deficiency on bone mass and the severity of vasomotor symptoms in young women, NAMS recommends the use of HT or oral contraceptives—if not contraindicated—until the median age of natural menopause, with peri­odic reassessment.

Counseling

Counseling should be provided as described in the “Well-Woman Annual Health Assessment” section and in the sections on specific health topics earlier in Part 3.

Patients in the perimenopausal period should be given information about the normal events of aging, including specific information regard­ing the reduction of ovarian hormonal function and the manifestations of these ovarian changes. In addition, women should be apprised that positive modifications in lifestyle, such as improvements in dietary and exercise habits, may benefit their overall health during menopause. Smoking cessation, lipid monitoring, blood pressure monitoring, weight management, and annual health care maintenance should be emphasized. Recommendations for cancer screening, such as cervical cancer testing and mammography, should be reviewed (see also the “Well-Woman Annual Health Assessment” section and the “Cancer Screening and Prevention” section earlier in Part 3). Discussions regarding elder abuse and intimate partner and domestic violence should be considered (see also the “Abuse” section later in Part 3).

Menopausal women should be counseled about the benefits of exercise, proper nutrition, and avoidance of certain lifestyle factors (cigarettes and alcohol) in preventing or slowing development of osteoporosis. They also should be informed about special dietary needs, including the importance of calcium intake. The 2011 Institute of Medicine recommended dietary allowance for calcium is 1,000 mg per day for individuals aged 19-50 years and 1,200 mg per day for those aged 51 years and older. The vitamin D recommended dietary allowance now ranges from 600 international units per day for most of life to 800 international units per day after age 70 years. Routine screening for vitamin D levels is not recommended. However, screening is recommended for individuals at high risk of vita­min D deficiency, such as those with certain medical conditions that may affect vitamin D absorption and those taking medications that affect vitamin D levels. Women who are at risk of fractures should be informed of the importance of accident prevention and safety issues (see also the “Osteoporosis” section earlier in Part 3).

Hormone Therapy

At least three treatment regimens are used for the administration of meno­pausal HT:

1. Cyclic. Estrogen is given for 25 days or more, with the addition of a cyclic progestin.

2. Combined. Estrogen and a low dose of progestin are given daily or through the levonorgestrel intrauterine system (levonorgestrel intra­uterine device).

3. Estrogen only. Estrogen is given for 25 days per month or more.

Endometrial sampling is not necessary before instituting therapy in asymptomatic patients. In women who have an intact uterus, the use of an estrogen-progestin regimen is recommended to reduce the risk of endo­metrial hyperplasia and endometrial cancer. Consideration also may be given to the use of the levonorgestrel intrauterine system as an alternative delivery method for the progestin component of combined HT.

Benefits and Risks Associated With Hormone Therapy

The benefits and risks of menopausal HT—either combined HT or estrogen therapy—should be discussed in detail with each patient before the initia­tion of therapy and when renewing her annual prescription so that she can make the best decision for her own health. After a thorough discussion regarding the risks and benefits of menopausal HT, the patient should undergo a medical evaluation before the initiation of treatment.

Benefits

Estrogens alone or estrogens plus progestins are highly effective for the alle­viation of hot flushes and night sweats. For patients with severe symptoms that affect quality of life, estrogens are the most effective treatment. Estrogen is effective for the treatment of patients with vaginal dryness and atrophic changes that impede sexual function. Topical and systemic estrogens appear to be equally effective in relieving vaginal atrophy and associated dyspareu- nia. Because some women aged 65 years and older may continue to need systemic HT for the management of vasomotor symptoms, the American College of Obstetricians and Gynecologists recommends against routine discontinuation of systemic estrogen at age 65 years.

Hormone therapy (either estrogen therapy or combined therapy) has a beneficial effect on bone health and is approved for the prevention of osteoporosis in women at an increased risk of osteoporosis and fracture (see also the “Osteoporosis” section earlier in Part 3). The benefit of HT for bone health is dose related, and today’s lower doses may not be as effective for fracture prevention as the higher doses used in the past. If use of HT for bone health is being considered, the clinician must work closely with the patient to determine what is in her best interest.

Risks

The following are some concerns patients may have regarding HT:

• Endometrial neoplasia. Unopposed systematic estrogen use increases the risk of endometrial cancer. Treatment with a combination of progestin and estrogen eliminates this increased risk.

• Ovarian neoplasia. There are conflicting data pertaining to the asso­ciation of HT and ovarian cancer. Current HT users who had been on the therapy for less than 5 years did not have an increased risk of ovarian cancer, whereas data did suggest a small increased risk of ovarian cancer with use for longer than 5 years.

• Breast neoplasia. Current data suggest that combined estrogen and progestin therapy can be used for 3-5 years before encountering an increased risk of breast cancer. Estrogen therapy can be used for a longer period of time, in the absence of other risk factors, because of the delayed risk of breast cancer seen with estrogen therapy.

• Cholelithiasis. Women should be cautioned about the increased risks of gallstones and biliary tract surgery with the use of meno­pausal HT.

• Thromboembolic disease. Combined HT or estrogen therapy for the management of menopausal symptoms and related disorders is associated with an increased risk of venous thromboembolism. In healthy women with a negative risk history, the probability of venous thromboembolism is generally low.

• Hypertension. Hormone therapy modestly lowers blood pressure; however, in a few women it may induce or exacerbate hypertension. Routine blood pressure monitoring is appropriate.

• Cardiovascular. Hormone therapy should not be initiated or con­tinued for primary or secondary prevention of coronary heart dis­ease. Evidence is insufficient to conclude that long-term estrogen therapy or combined HT use improves cardiovascular outcomes. In addition, in the Women’s Health Initiative trial, women taking combined estrogen and progestin therapy and those taking an estrogen-only regimen had an increased risk of stroke. Recent evi­dence suggests that women in early menopause who are in good cardiovascular health are at low risk of adverse cardiovascular out­comes and should be considered candidates for the use of estrogen therapy or conjugated equine estrogen plus a progestin for relief of menopausal symptoms.

Contraindications to Hormone Therapy

Contraindications to estrogen therapy include the following:

• Undiagnosed abnormal genital bleeding

• Known or suspected estrogen-dependent neoplasia except in appro­priately selected patients

• Active deep vein thrombosis, pulmonary embolism, or a history of these conditions

• Active or recent arterial thromboembolic disease (stroke, myocardial infarction)

• Liver dysfunction or liver disease

• Known or suspected pregnancy

• Hypersensitivity to estrogen therapy preparations

The safety of estrogen therapy or combined HT for the treatment of vaso­motor symptoms in breast cancer survivors is unknown.

A history of endometrial cancer generally also is considered to be a con­traindication to HT. This opinion is based on the fact that adenocarcinoma is considered an estrogen-dependent neoplasm. Although this contraindi­cation is widely accepted, there is a lack of scientific evidence to support the theory that estrogen therapy is potentially dangerous for endometrial cancer patients who have had a hysterectomy.

Compounded Bioidentical Hormone Therapy

Compounded bioidentical menopausal HT consists of plant-derived hor­mones that are prepared by a pharmacist and can be custom made for a patient according to a physician’s specifications. Evidence is lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal HT. Most compounded products have not undergone rigorous clinical testing for safety or efficacy. These prepara­tions have variable purity and potency and lack efficacy and safety data. Although it is required that manufactured drugs be consistent from batch to batch, there are no similar quality control measures for compounded drugs to ensure that the bioavailability of active ingredients is consistent, such that underdosage and overdosage are possible. Therefore, although interest in and requests for compounded pharmaceutical products appear to be increasing, physicians and patients should exercise caution in pre­scribing and using them. Conventional HT is preferred over compounded HT given the available data. Advocates and compounders of bioidentical hormones also recommend the use of hormone level testing as a means of offering individualized therapy. Despite claims to the contrary, evidence is inadequate to support increased efficacy or safety for individualized HT regimens based on salivary, serum, or urinary testing.

Nonhormonal Therapy

Management of menopausal symptoms often can be accomplished through nonhormonal options. Treatments for vasomotor symptoms include phar­macologic agents, complementary and alternative therapies, and lifestyle and behavioral alterations. Safety and efficacy data on herbal treatments are unclear, and more data are needed on the efficacy of lifestyle changes and alternative therapies. Nonhormonal treatment options for vaginal symptoms include vaginal lubricants and moisturizers. For patients in whom nonhormonal treatments fail, the use of low-dose estrogen methods (vaginal, topical, ring, and tablets) may be considered. Hormone therapy generally is contraindicated in women with a history of hormone-sensitive cancer, and consideration of its use should be made in consultation with an expert in cancer treatment such as an oncologist.

Pharmacologic Agents

A variety of low-dose antidepressant medications or the anticonvulsant gabapentin can be used to manage vasomotor symptoms, although this use is generally off label. Selective serotonin reuptake inhibitors (eg, citalopram or fluoxetine) and serotonin-norepinephrine reuptake inhibitors (eg, ven­lafaxine) have been shown to be safe and effective in reducing the sever­ity of hot flushes in menopausal women and patients with breast cancer, although caution must be used when these agents are used in conjunction with tamoxifen; serotonin-norepinephrine reuptake inhibitors are gener­ally preferable to selective serotonin reuptake inhibitors in women using tamoxifen. A lower-dose form of paroxetine was recently approved by the U.S. Food and Drug Administration (FDA) as the first nonhormonal treat­ment for moderate-to-severe vasomotor symptoms associated with meno­pause. As with other antidepressants, the lower-dose paroxetine carries a black box warning regarding suicidality. Other options for management of vasomotor symptoms in women who cannot use estrogens or progestins or choose not to use these methods include gabapentin and clonidine, although these agents are not FDA-approved for this indication.

Complementary and Alternative Therapies

Several natural products have been used for the management of vasomotor symptoms. In the United States, none of these complementary therapies are regulated by the FDA and have not been tested for safety, efficacy, or purity because they are considered nutritional supplements. Data do not show that phytoestrogens (eg, soy products) and herbal supplements (eg, Chinese herbal medicine, black cohosh, ginseng, St. John’s wort, and ginkgo biloba) are efficacious for the treatment of vasomotor symptoms. There also are insufficient data to support the use of soy products or herbal remedies for the treatment of vaginal symptoms.

Acupuncture has shown no benefit over placebo for the management of vasomotor symptoms. Similarly, reflexology has not been shown to significantly reduce vasomotor symptoms compared with nonspecific foot massage. There are some preliminary data to suggest that local injection of anesthetic into the stellate ganglion may reduce vasomotor symptoms in women with contraindications to HT. However, additional studies are needed to assess the safety and effectiveness of this novel technique.

Lifestyle and Behavioral Alterations

Despite limited supporting data, common-sense lifestyle solutions such as layering of clothing, maintaining a lower ambient temperature, and consuming cool drinks are reasonable measures for the management of vasomotor symptoms. Women also may be advised to avoid consumption of alcohol and caffeine, which have been associated with increased severity and frequency of vasomotor symptoms. Although there is some evidence that aerobic exercise may improve quality of life and mood in women with vasomotor symptoms, there are insufficient data to recommend exercise for the treatment of vasomotor symptoms.

Vaginal Lubricants and Moisturizers

Nonestrogen water-based or silicone-based vaginal lubricants and moistur­izers may alleviate vaginal symptoms related to menopause. These products may be particularly helpful in women who do not wish to use hormonal therapies. Vaginal lubricants are intended to be used to relieve friction and dyspareunia related to vaginal dryness during intercourse and are applied to the vaginal introitus before intercourse. Vaginal moisturizers are intended to trap moisture and provide long-term relief of vaginal dryness. Although there are limited data regarding the effectiveness of these products, prospec­tive studies have demonstrated that vaginal moisturizers improve vaginal dryness, pH balance, and elasticity and reduce vaginal itching, irritation, and dyspareunia, and many women have found nonhormonal vaginal lubricants and moisturizers to be effective in managing vaginal dryness.

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Resources

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American College of Obstetricians and Gynecologists. Perimenopausal bleeding and bleeding after menopause. Patient Education Pamphlet AP162. Washington, DC: American College of Obstetricians and Gynecologists; 2010.

American College of Obstetricians and Gynecologists. The menopause years. Patient Education Pamphlet AP047. Washington, DC: American College of Obstetricians and Gynecologists; 2013.

Food and Drug Administration. Estrogen and estrogen with progestin therapies for postmenopausal women. Available at: http://www.fda.gov/Drugs/DrugSafety/ InformationbyDrugClass∕ucm135318.htm. Retrieved July 30, 2013.

Moyer VA. Menopausal hormone therapy for the primary prevention of chronic conditions: U.S. Preventive Services Task Force recommendation statement. U.S. Preventive Services Task Force. Ann Intern Med 2013;158:47-54. [PubMed] [Full Text]

North American Menopause Society. Menopause practice: a clinician’s guide. 4th ed. Mayfield Heights (OH): NAMS; 2010.