Estrogen

At menopause, ovarian follicles no longer respond to stimulation by gonadotropins; consequently, estrogen levels decrease despite an increase in gonadotropin levels.

Estrogen is the most effective treatment for menopausal symptoms. However, estrogen therapy is now recommended only for short-term amelioration of moderate to severe menopausal symptoms (eg, hot flushes); alternative treatments should be offered for symptoms or effects that require long-term management. This change in recommendation reflects recent findings about long-term use of estrogen therapy. Long-term therapy is sometimes used, depending on a patient's preferences and risk of developing certain disorders and on severity of menopausal symptoms.

Estrogen increases risk of endometrial cancer; thus, if estrogen is used, women who have a uterus are given estrogen plus progesterone (combination therapy) to reduce this risk. Combination therapy reduces risk of postmenopausal bone loss, consequent spine and hip fractures, and colorectal cancer. However, long-term use to prevent such disorders is no longer recommended because combination therapy increases yearly incidence of breast cancer, ischemic stroke, deep vein thrombosis, pulmonary embolism, dementia, and coronary artery disease. Risk of coronary artery disease almost doubles during the first year of estrogen therapy and is particularly high for women with high pretreatment levels of low density lipoprotein cholesterol; aspirin and statins do not prevent the increase in risk. In women taking estrogen therapy, breast cancers that develop are larger and more likely to be metastatic, and false-positive mammograms are more common.

If estrogen is used, the lowest effective dose should be used for the shortest possible time, and women should be monitored for the above disorders and advised to modify risk factors for these disorders through lifestyle changes (eg, control of hypertension, smoking cessation, weight loss, exercise). Need for continued estrogen therapy should be reevaluated at least once a year.

Estrogen alone decreases incidence of hip fractures and does not affect the incidence of coronary artery disease; however, it increases the incidence of ischemic stroke and possibly of venous thromboembolism. Effects on risk of breast cancer, dementia, and colorectal cancer are less clear.

For treatment of hot flushes in menopausal women, commonly used estrogens (eg, oral conjugated equine estrogens, oral and transdermal 17-estradiol) appear to have consistent, comparable effects and may have similar adverse effects. Transdermal estrogen therapy is indicated for patients with certain medical conditions that preclude oral estrogens, including hypertriglyceridemia, no response to oral estrogens, oral estrogen-induced hypertension, and high-risk cholelithiasis. Using topical forms of estrogen avoids first-phase metabolism and minimizes fluctuations in blood estrogen levels. For treating vaginal dryness or atrophy, topical estrogens (eg, creams, vaginal tablets or rings) are as effective as oral estrogens. Systemic adverse effects of estrogens depend only on the amount of estrogen absorbed; long-term risks of oral and topical estrogen therapy are similar. Patches may cause local skin rash or itching. The most recent data from the Women's Health Initiative (WHI) study are available at the WHI participant web site.

Usually, other treatments can provide the same benefits as estrogen. For prevention of bone loss, options include raloxifene, Ca, vitamin D, and exercise. Options for treatment of osteoporosis include bisphosphonates and, for women who cannot tolerate bisphosphonates, raloxifene or calcitonin.

This topic was last updated March 2006.