A retrospective cohort study presented at the Menopause Society annual meeting used the TriNetX research network to compare 3,164 postmenopausal women who initiated testosterone therapy with a matched group of nonusers. Over five years, cardiovascular events occurred in 3.8% of the testosterone group versus 0.5% of controls, corresponding to a hazard ratio of 8.08. The association remained elevated at 10 years and in an unrestricted follow-up analysis, with hazard ratios of 11.50 and 5.92, respectively.
The authors, led by Xuezhi (Daniel) Jiang of Drexel University College of Medicine, stressed that the observational findings do not establish causation. A sensitivity analysis comparing women using testosterone plus menopausal hormone therapy with those using hormone therapy alone also showed higher cardiovascular risk, with a five-year hazard ratio of 6.73. However, the study lacked data on testosterone dose, formulation, route, delivery, or indication, and the mean follow-up was only 2.6 years with few overall events. Stephen Burgess, a biostatistics professor at the University of Cambridge, said the eight-fold difference is concerning but that the study cannot prove testosterone is the cause.
The findings arrive amid limited evidence on testosterone for menopausal symptoms and no FDA-approved testosterone products for women, though some clinicians prescribe low-dose male formulations off-label. Jiang noted that most prior trials were too small or short to evaluate major cardiovascular events, and he called for prospective studies to validate the results and examine individual outcomes such as coronary artery disease, cerebrovascular disease, and heart failure separately.