Women who take a combination of estrogen and testosterone to treat the symptoms of menopause may be putting themselves at greater risk for breast cancer.

As women age, their natural levels of testosterone tend to decrease. Some evidence suggests that many of the symptoms of menopause-including decreased sex drive, worse moods and poorer quality of life-are related to this decline. Clinical trials have shown that taking testosterone in combination with estrogen can reduce these symptoms and also prevent osteoporosis. Only one estrogen plus testosterone menopause drug is currently available to U.S. women but the number and popularity of such treatments are expected to increase in coming years.

Rulla M. Tamimi, Sc.D., Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues studied the long-term effects of estrogen plus testosterone therapy in 121,700 women who were part of the Nurses' Health Study. The study enrolled female nurses between the ages of 30 and 55 beginning in 1976.

During 24 years of follow-up, 4,610 cases of breast cancer occurred among postmenopausal women. Those who were taking estrogen plus testosterone in 1988 (29 women) had a 77 percent higher risk of developing breast cancer than those who had never used hormone therapy; this was higher than the increased risk associated with estrogen use (15 percent) and use of estrogen plus progestin (58 percent).

The number of women in the study who used estrogen plus testosterone therapy increased dramatically over time, from 33 in 1988 to 550 in 1998. This reflects a broader trend that makes the results especially important, the authors write. "Given the substantial evidence implicating combined estrogen plus progestin therapy in breast cancer and the results of the present study regarding estrogen plus testosterone therapy, women and their physicians should reconsider use and, more specifically, long-term use of these therapies," they conclude. "Although postmenopausal therapies may provide improvement with respect to sexual functioning, general well-being and bone health, the increased risk of breast cancer may outweigh these benefits."