Exploring associations between testosterone and cardiovascular disease in females: A systematic review

There are increasingly recognised yet modestly understood sex-based differences in cardiovascular physiology, implicating endogenous sex hormones in cardiovascular disease aetiology. However, the role of androgens in female cardiovascular disease risk remains unclear. Therefore, this systematic review examined associations between endogenous testosterone concentrations and cardiovascular disease in females. MEDLINE complete, Embase and CINAHL complete were searched from 2000 to September 2025. Articles that investigated the association between endogenous plasma testosterone and cardiovascular disease in female adults were included. Quality assessment was performed using the QUALSYST tool. Of the 445 articles that underwent full-text screening, 28 met the inclusion criteria (n = 598,440), most (75%) of which had a low risk of bias. Findings for incident cardiovascular disease outcomes were inconsistent or absent. Substantial and systematic methodological heterogeneity across the evidence base precluded meta-analyses; only 10 of the 28 studies (35.7%) quantified testosterone using gold-standard liquid chromatography-mass spectrometry, only seven (25%) excluded exogenous hormone (menopause hormone therapy or oral contraceptive) users, and disease definitions, exposure metrics (total, free, bioavailable, free androgen index) and statistical models varied widely. This review highlights substantial methodological heterogeneity throughout the evidence base. We provide four addressable areas which require resolution before definitive conclusions regarding the association between testosterone and cardiovascular disease in females can be made.