Estrogen Plus Testosterone Therapy May Increase Risk of Breast Cancer

Women who take a combination of estrogen and testosterone to treat the symptoms of menopause may have an increased risk of breast cancer, according to an article in the July 24 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

As women age, their natural levels of the hormone testosterone tend to decrease, according to background information in the article. 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 in testosterone. Clinical trials have shown that taking testosterone in combination with estrogen may reduce these symptoms and also promote bone health. Only one estrogen plus testosterone therapy is currently available to U.S. women, but the number and prevalence of such treatments are expected to increase in coming years, the authors write.

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 years beginning in 1976. The women completed an initial questionnaire and follow-up surveys every two years that included questions about menopausal status, medical conditions and the use of postmenopausal hormone therapy. For those who reported a diagnosis of breast cancer, medical records were reviewed for verification.

During 24 years of follow-up, 4,610 cases of breast cancer occurred among postmenopausal women. Overall, only 33 women included in this analysis reported current use of estrogen and testosterone in 1988. Women who were currently taking estrogen plus testosterone (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 current estrogen use (15 percent) and current use of estrogen plus progestin (58 percent). When the researchers considered only women who had gone through menopause naturally rather those whose menopause began when they had a hysterectomy, those who took estrogen plus testosterone (17 women) had 2.5 times the risk of breast cancer than those who had never used hormones.

Enzymes in the breast tissue may convert testosterone to estradiol, an estrogen-like hormone that may contribute to the development of breast cancer, the authors write. Previous studies have indicated that women who use estrogen plus testosterone therapy have higher levels of estradiol and testosterone circulating in their bodies than women who take estrogen alone. Higher levels of testosterone alone have also been linked to increased breast cancer risk in postmenopausal women.

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."