Tamimi RM et al. (2006) Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women. Arch Intern Med 166: 1483–1489

Despite epidemiological studies suggesting a link between endogenous testosterone levels and increased risk of breast cancer in postmenopausal women, the use of hormone therapies containing androgens in such women is increasing.

Tamimi et al. conducted a prospective cohort study to examine the relationship between the use of testosterone-containing postmenopausal hormone (PMH) formulations and invasive breast cancer. They identified 4,610 cases of invasive breast cancer over 24 years of follow-up (1,359,323 person-years). Overall, the risk of breast cancer was 77% greater among current users of estrogen plus testosterone therapies, and 58% greater among current users of estrogen plus progesterone therapies, than among those who had never used PMHs; in comparison, estrogen-only therapy was associated with only a 15% increased risk.

Risk estimates for PMH users were greatest in women with a natural menopause. In this group, the risk of breast cancer amongst current users of estrogen plus testosterone was almost 2.5 times that of women who had never used PMHs; current use of estrogen and testosterone was associated with a significantly increased risk of breast cancer compared with estrogen-only therapy (P = 0.007), and a marginally greater risk than estrogen and progesterone therapy (P = 0.11). Among these women, those using PMHs with testosterone had a 17.2% (95% CI 6.7–28.7%) increased risk of breast cancer per year of use.

Estrogen and testosterone therapies are, therefore, associated with a significantly increased risk of invasive breast cancer. The authors suggest that the use of such therapies in postmenopausal women, especially in the long term, should be reconsidered.