PROS AND CONS OF ESTROGEN REPLACEMENT IN POSTMENOPAUSAL WOMEN: WHAT THE CURRENT EVIDENCE MEANS





Jan Shifren, M.D.*

Harvard Medical School Massachusetts General Hospital, Boston, MA 02114



Menopause, the permanent cessation of menstruation, occurs at a mean age of 51 years. Despite a great increase in female life expectancy, the age at menopause has remained remarkably constant. A woman in the United States today will live approximately 30 years, or greater than a third of her life, beyond menopause. The menopausal ovary ceases to produce significant amounts of estrogen therefore symptoms and diseases associated with estrogen deficiency are of increasing importance in women's health.

Options for caring for menopausal women have increased greatly since estrogen replacement therapy (ERT) was first introduced in the 1960's. With respect to hormone use, there are many choices of hormone type, dose, and method of administration. Not only have new forms of estrogens and progestins been introduced, but novel ways of combining the two hormones are available. Androgen replacement therapy for older women currently is being studied as well. In addition to hormones, selective estrogen receptor modulators are available, as are bisphosphonates. Women also are requesting more information on alternative and complementary therapies. The many options now available make caring for the postmenopausal woman more rewarding, but also a greater challenge.

Estrogen replacement therapy may play a role in several important health concerns of postmenopausal women including vasomotor symptoms and genitourinary atrophy, osteoporosis, cardiovascular disease, Alzheimer's disease, breast cancer, colon cancer, and sexual dysfunction. Randomized controlled trials demonstrate that ERT effectively treats hot flashes and night sweats as well as vaginal dryness and dyspareunia associated with genital atrophy. Strong evidence also supports a role for ERT in the prevention and treatment of osteoporosis, with changes in bone mineral density often used as an intermediate marker for reduced fracture risk. Observational data demonstrate a significant reduction in cardiovascular disease and overall mortality in ERT users, but these findings may be confounded by healthy user and compliance bias. Favorable changes in lipids and lipoproteins, as well as effects on vascular reactivity provide potential biological mechanisms for heart disease risk reduction in ERT users. With respect to the secondary prevention of heart disease in postmenopausal women with established disease, randomized controlled trials of combination estrogen/progestin hormone replacement therapy (HRT) or ERT alone have not shown a benefit for therapy. Whether there is a role for HRT or ERT in the primary prevention of heart disease currently is being studied as part of the Women's Health Initiative.

Although several small observational and controlled studies suggest that ERT may reduce the risk and slow the progression of Alzheimer's disease, a large randomized controlled trial of ERT in women with established disease did not demonstrate any benefit. Whether there is a role for HRT in the primary prevention of Alzheimer's disease currently is being studied as part of the Women's Health Initiative Memory study.

The risks of ERT include an increased risk of endometrial cancer in women with a uterus who do not use concurrent progestin, an increase in venous thromboembolic events, gallbladder disease, and a probable small increased risk of breast cancer in long term ERT/HRT users.







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