Once routinely prescribed to decrease the risk of osteoporosis and relieve menopausal symptoms, estrogen plus progesterone hormone therapy is now known to significantly increase the risk of breast cancer and other adverse health outcomes. But it is less clear how another form of hormone therapy—estrogen plus testosterone—affects breast cancer risk. Many women continue to take estrogen plus testosterone to improve their mood, libido, and bone health. Studies have suggested that higher levels of circulating testosterone are associated with increased breast cancer risk in postmenopausal women, but animal and lab studies have suggested that testosterone may work to inhibit breast cancer growth.

A new study in the July 24, 2006 Archives of Internal Medicine found that postmenopausal women who take estrogen plus testosterone are at significantly higher risk of developing breast cancer than women who take estrogen only or who have never used hormone therapy.

About the Study

This study was part of the larger Nurses’ Health Study, which followed a group of 121,700 female registered nurses who were ages 30-55 when the study began in 1976. The researchers used questionnaires every two years to collect information about the women’s life and health events. In this case, researchers focused on survey results for the participants’ menopausal status, medical conditions, and use of postmenopausal hormone therapy.

Postmenopausal women were categorized according to their hormone therapy use as: never users, current users of estrogen alone, current users of estrogen plus progesterone, or current users of estrogen plus testosterone. The researchers followed the women for 24 years and tracked how hormone therapy use affected breast cancer risk.

During the study, 4,610 cases of invasive breast cancer were diagnosed. The postmenopausal women using estrogen plus testosterone had a 77% increased risk of developing breast cancer, compared to those who had never used hormone therapy. Among women who had natural as opposed to surgical (eg, hysterectomy -induced) menopause, those who were taking estrogen plus testosterone had a 2.5-fold increased risk of developing breast cancer, compared to those who had never used hormone therapy.

In all postmenopausal women, breast cancer risk was significantly higher for those taking estrogen plus testosterone than those taking estrogen alone. In women with natural menopause, the risk associated with estrogen plus testosterone was marginally higher than that associated with estrogen plus progesterone.

This study is limited because many estrogen plus testosterone users previously used other types of hormone therapy, which may have affected breast cancer risk.

How Does This Affect You?

These findings suggest that estrogen plus testosterone may increase breast cancer risk in postmenopausal women. This is especially important, since the use of this hormone combination increased significantly over a ten-year period: in this study, only 33 women reported estrogen plus testosterone use in 1988, which increased more than eight-fold by 1998, to 550.

Though this study cannot say why testosterone use is associated with breast cancer, the researchers propose that circulating testosterone may be converted to a form of estrogen that promotes the growth of breast cancer cells. Alternatively, extra testosterone may activate testosterone (ie, androgen) receptors that contribute to the cause of breast cancer.

If you are using estrogen plus testosterone, talk with your doctor. Short-term use may be perfectly safe, but there is a chance that the risks associated with the long-term use of this combination outweigh the benefits in your situation.