Campus & Community

Hormone mix raises breast cancer risk

4 min read

Risk may exceed benefits

In a 24-year study, Rulla Tamimi and her colleagues found that women who take a combination of estrogen and testosterone to relieve the symptoms of menopause dramatically increase their risk of getting breast cancer. (Staff photo Kris Snibbe/Harvard News Office)

Women who try to ease the symptoms of menopause by taking a testosterone-estrogen mix raise their risk for breast cancer, according to a Harvard Medical School study.

“As women age, their natural levels of testosterone decrease, along with those of estrogen,” according to Rulla Tamimi, lead researcher of the study. “Evidence suggests that a testosterone drop is associated with a poorer quality of life, including decreased sex drive and bad moods, experienced by women at this time of life.”

Estrogen plus testosterone treatment may reduce these unwanted effects, increase general well-being and even lessen bone thinning. That’s probably why its use has been increasing and can expect to continue increasing. Although only one federally approved pill now is available, researchers expect new formulations of the combination to be approved soon.

Because the effects on breast cancer risk of taking estrogen plus testosterone were not clear, Tamimi and her colleagues at Harvard Medical School and Brigham and Women’s Hospital in Boston decided to look into risks of using the mix. Giving the treatment to a large number of women then checking their health regularly was impractical because breast cancer takes years to develop. Instead, they mined data from a study of 121,700 female nurses. Called, appropriately, the Nurses’ Health Study, it collected data on use of post-menopausal hormones and other medical information of women between the ages of 30 and 55 years in 1976.

“To our knowledge, this is the first study to specifically address the risk of breast cancer for postmenopausal women in the United States who use oral estrogen plus testosterone therapy,” Tamimi says. “The results show that this combination therapy poses a significantly greater risk of breast cancer compared with that of estrogen-only therapy.”

Risk may double

During 24 years of follow-up, from 1976 to 2000, 4,610 postmenopausal nurses in the study developed breast cancer. Those using the estrogen and testosterone in had a significantly higher risk of getting breast cancer than those who never used hormone therapy or used estrogen only. When the Harvard investigators considered only women who went through menopause naturally, those who took the combination exposed themselves to more than double (2.5 times) the risk of breast cancer than women who used no hormones. The risk of combining estrogen and progestin, they conclude, is 58 percent greater than avoiding hormone treatment. Progestin-type drugs are often used with estrogen to reduce risk of cancer of the uterus.

The study group who underwent natural menopause and took the estrogen plus testosterone involved only 17 nurses. However, in the 10 years from 1988 to 1998, the number of women in the study who used the combination therapy jumped dramatically from 33 to 550, or almost 17 times. “This reflects a worrisome trend that makes our results especially important,” Tamimi notes.

Many people associate testosterone with males only, but the adrenal glands of females also produce the hormone. Too much of it causes development of male features like excess body hair, deepening of the voice, and absence of menstruation. Normal amounts, however, don’t cause these effects.

The researchers, who include Susan Hankinson, Wendy Chen, Bernard Rosner, and Graham Colditz, published their findings in the July 24 issue of the Archives of Internal Medicine. Given the substantial evidence from other studies implicating the risk of using estrogen plus progestin, and the results of this study, “women and their physicians should reconsider use, and specifically, long-term use of these therapies,” they advise. “Although [such] therapies may provide improvement with respect to sexual functioning, general well-being, and bone health, the increased risk of breast cancer may outweigh those benefits.”