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Updated: Jun 26, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Influence of estrogen plus testosterone supplementation on breast cancer
Roberta B Ness1, Jessica D Albano, Anne McTiernan
1Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. roberta.b.ness@uth.tmc.edu
Background:
Concern that the use of exogenous testosterone may increase breast cancer risk coexists with rising use of this medication in the United States. We sought to examine the relationship between the use of estrogen plus testosterone (E + T) therapy (esterified estradiol plus methyltestosterone) and the occurrence of breast cancer.
Methods:
A total of 31,842 postmenopausal participants in the Women's Health Initiative Observational Study were followed for a mean of 4.6 years. At the 3-year visit, E + T users were compared with non-hormone therapy users for time to incident invasive breast cancer. Cox proportional hazards estimates were adjusted for known predictors of breast cancer including prior hormone use and screening mammography.
Results:
Thirty five women using E + T at visit 3 developed invasive breast cancer. Use of E + T had a nonsignificant impact on invasive breast cancer risk (adjusted hazard ratio, 1.42; 95% confidence interval, 0.95-2.11). The most commonly used E + T preparation, Estratest, was associated with a significant elevation in invasive breast cancer (adjusted hazard ratio, 1.78; 95% confidence interval, 1.05-3.01). However, rates of breast cancer were lower in longer-term E + T users than in shorter-term E + T users.
Conclusion:
Although our results have less strength than an initial report linking E + T to breast cancer, we found a modest, albeit nonsignificant, elevation in breast cancer risk associated with E + T use.
