Menopause

Key Points

• The average age of menopause is 52.

• Vasomotor symptoms are the most common menopausal sign.

• The Women's Health Initiative showed that hormone replacement therapy did not prevent cardiovascular disease in postmenopausal women and in fact increased the risk of breast cancer.

Menopause is defined as the cessation of menstruation. It is a retrospective diagnosis that comes after a woman has not menstruated for 12 months. The menopausal transition occurs over several years as the number of ovarian follicles slowly decreases. This period in a woman's life can include menstrual cycles of variable lengths and durations, called the perimenopause. Because of the waxing number of follicles, the ovaries require higher levels of estrogen to stimulate a luteinizing hormone (LH) surge and subsequent ovulation. Consequently, serum levels of estrogen can vary substantially from one cycle to the next. The first physiologic change noted is a decrease in inhibin B levels (Burger et al., 1999). Subsequently, follicle-stimulating hormone (FSH) level will increase in response to lower estrogen levels. An FSH level greater than 40 U/L on two separate occasions at least 1 month apart is diagnostic of menopause. The main pathologic cause of abnormal vaginal bleeding during this period is anovulation in those cycles when estrogen did not reach target levels.

The average age of menopause in the United States is 52 years old. The majority of women will go through menopause between ages 40 and 58. Menopause before age 40 is defined as premature ovarian failure and may be related to other autoimmune disease. Factors associated with age at menopause include smoking and family history (Nelson, 2008).

Vasomotor symptoms, including hot flashes and night sweats, are the most common symptoms of menopause. Some women may begin to experience these symptoms years before their final menstrual period, during those months where their estrogen levels are lower. Many women will experience symptoms for several years. Up to 10% of women will continue to experience vasomotor symptoms into their 70s (Politi et al., 2008). Symptoms are worse in women who experience premature ovarian failure, have a premenopausal oophorectomy, are overweight or obese, or are depressed (Hendrix, 2005). Treatment of vasomotor symptoms begins with lifestyle changes and also can include pharmacologic treatment with hormonal or nonhormonal medications. Women may be able to manage their vasomotor symptoms by wearing natural-fiber clothing in layers, avoiding spicy foods, avoiding hot environments (e.g., saunas, hot tubs), avoiding alcohol, exercising, and maintaining a healthy weight.

Pharmacologic treatment of vasomotor symptoms includes hormone therapy (HT) at the lowest effective doses orally or transdermally (Bachmann et al., 2007). HT should include both estrogen and progestin in women who have a uterus and estrogen alone in women who have had a hysterectomy. HT should be used in women at the lowest possible doses to treat symptoms for as short a time as possible (NAMS, 2004). In women for whom HT is contraindicated or who are worried about the risks, several nonhormonal options have been studied. Antidepressant medications such as fluoxetine, paroxetine, and venlafaxine have been shown to be better than placebo. Gabapentin, 900 mg daily, is also better than placebo in treating hot flashes (Grady, 2006).

Many women use complementary therapies to treat vasomotor symptoms. Various herbal preparations (e.g., black cohosh) have been used to treat vasomotor symptoms with varying success. Many women also obtain relief from soy products or other isoflavones. None of these treatments has consistently been more effective than placebo in randomized trials (Nelson et al., 2006). Stress management and meditation show promise in controlling these troublesome symptoms (Tremblay et al., 2008).

Atrophic vaginitis, or thinning of the vaginal epithelium caused by a lack of estrogen stimulation after menopause, is common, affecting 10% to 40% of all postmenopausal women. Women complain of vaginal dryness, irritation, and pain with intercourse. Unlike vasomotor symptoms, atrophic vaginitis does not develop immediately after menopause but causes symptoms months to years after the withdrawal of estrogen. Left untreated, atrophic vaginitis is progressive and is unlikely to improve spontaneously. Treatment of atrophic vaginitis begins with use of appropriate water based lubricants to make intercourse more comfortable. The mainstay of treatment is vaginal estrogen (Castelo-Branco et al., 2005). Several preparations of vaginal estrogen are available in the United States. Estrogen cream, tablets, and a slow-release silicone ring are all well tolerated and are equally effective in reducing symptoms of atrophic vaginitis. Because the vaginal estrogen has limited systemic absorption, a concomitant dosing with progestin is not necessary (Suckling et al., 2006).

Other common menopausal changes include memory difficulty (mostly with word finding), mood lability, and decreased libido (from decreased testosterone levels after menopause).

Before the Women's Health Initiative (WHI), HT was the most common treatment for menopausal symptoms. HT was also used for prevention of heart disease and osteoporosis. WHI was a large (>16,000 participants) population-based study of women between 50 and 79 years studying the effectiveness of estrogen plus progestin on congestive heart disease (CHD) prevention. The trial was stopped early because of excess cardiovascular and breast cancer events. There was an excess of 7 CHD events, 8 strokes, 8 breast cancers, and 14 venous thromboembolic events per 10,000 women. The estrogen-only arm of the study was stopped 2 years later due to excess strokes (12 per 10,000 women). There was no statistically significant increase in breast cancer incidence in the estrogen-only group (Anderson et al., 2004). The HT group in both arms of the study had fewer hip fractures. The estrogenplus-progestin group also had fewer cases of colon cancer (Roussouw et al., 2002).

KEY TREATMENT

Hormone therapy can be used for treatment of menopausal symptoms but should be used at the lowest possible dose for the shortest time possible (NAMS, 2004) (SOR: C). Atrophic vaginitis is treated most effectively by vaginal estrogen cream or tablets, usually three times a week initially and titrated down based on symptoms (Castelo-Branco et al., 2005) (SOR: A). Antidepressant medications (fluoxetine, paroxetine, venlafaxine) are better than placebo in treating hot flashes (Grady, 2006) (SOR: A). Gabapentin (900 mg daily) is also better than placebo in treating hot flashes (Grady, 2006) (SOR: A).

Stress management and meditation show promise in controlling troublesome menopausal symptoms (Tremblay et al., 2008) (SOR: B).

References

Web Resources

The complete reference list is available online at www.expertconsult.com.

www.ahrq.gov/CLINIC/uspstfix.htm

U.S. Preventive Services Task Force screening recommendations, includes the Electronic Preventive Services Selector (enter a patient's age and gender and receive a list of evidence-based recommendations) and the option to sign up for e-mail updates on preventive services. www.cdc.gov/vaccines/recs/ACIP/default.htm

Centers for Disease Control and Prevention and Advisory Committee on Immunization Practices immunization guidelines, including tables for adults, adolescents, and pregnant women; e-mail updates also available.

www.asccp.org/consensus/cytological.shtml www.asccp.org/pdfs/consensus/algorithms_cyto_07.pdf

American Society for Colposcopy and Cervical Pathology guidelines for management of abnormal Pap tests; provides detailed algorithms describing how to manage each specific Pap smear abnormality. www.cdc.gov/std/treatment

The 2006 sexually transmitted infection (STI) treatment guidelines provide detailed recommendations for treatment of all sexually transmitted diseases (STDs) as well as other types of vaginitis.

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