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Original Investigation
July 24, 2006

Combined Estrogen and Testosterone Use and Risk of Breast Cancer in Postmenopausal Women

Author Affiliations

Author Affiliations: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School (Drs Tamimi, Hankinson, Chen, Rosner, and Colditz), Department of Epidemiology, Harvard School of Public Health (Drs Tamimi, Hankinson, and Colditz), Department of Medical Oncology, Dana-Farber Cancer Institute (Dr Chen), and Harvard Center for Cancer Prevention (Dr Colditz), Boston, Mass.

Arch Intern Med. 2006;166(14):1483-1489. doi:10.1001/archinte.166.14.1483

Background  The role of androgens in breast cancer etiology has been unclear. Epidemiologic studies suggest that endogenous testosterone levels are positively associated with breast cancer risk in postmenopausal women. Given the increasing trend in the use of hormone therapies containing androgens, we evaluated the relation between the use of estrogen and testosterone therapies and breast cancer.

Methods  We conducted a prospective cohort study in the Nurses' Health Study from 1978 to 2002 to assess the risk of breast cancer associated with different types of postmenopausal hormone (PMH) formulations containing testosterone. During 24 years of follow-up (1 359 323 person-years), 4610 incident cases of invasive breast cancer were identified among postmenopausal women. Information on menopausal status, PMH use, and breast cancer diagnosis was updated every 2 years through questionnaires.

Results  Among women with a natural menopause, the risk of breast cancer was nearly 2.5-fold greater among current users of estrogen plus testosterone therapies (multivariate relative risk, 2.48; 95% confidence interval, 1.53-4.04) than among never users of PMHs. This analysis showed that risk of breast cancer associated with current use of estrogen and testosterone therapy was significantly greater compared with estrogen-only therapy (P for heterogeneity, .007) and marginally greater than estrogen and progesterone therapy (P for heterogeneity, .11). Women receiving PMHs with testosterone had a 17.2% (95% confidence interval, 6.7%-28.7%) increased risk of breast cancer per year of use.

Conclusion  Consistent with the elevation in risk for endogenous testosterone levels, women using estrogen and testosterone therapies have a significantly increased risk of invasive breast cancer.