Abstract Background Cardiovascular disease (CVD) in a leading cause of disease burden and mortality globally. Sex differences exist regarding CVD incidence, but the reasons for this are unclear. Further, women with polycystic ovary syndrome and chronically high levels of testosterone consistently present with worse cardiometabolic profiles than their normoandrogenic counterparts. But whether this is a direct consequence of higher levels of testosterone is unclear. Aim This systematic review aimed to examine current evidence regarding the associations between testosterone and CVD incidence in women. Method MEDLINE complete, Embase and CINAHL complete were systematically searched in September 2024. Articles that investigated the relationship between plasma testosterone concentrations and overt CVD in pre- or post-menopausal women were included. Results Forty-two studies were included in the final review. Outcome measures included the occurrence of a major adverse cardiac event, CVD mortality and morbidity, coronary artery disease/coronary heart disease, atherosclerotic disease, heart failure, myocardial infarction and stroke. Eight studies were case-control studies, 13 were observational cross-sectional studies, 19 were prospective cohort studies and two were retrospective cohort studies. Of the prospective cohort studies, the median follow-up length was 11.5 years (range 2.4-19.2 years). Thirty-nine articles included endogenous plasma testosterone concentrations as an exposure, one article assessed the safety of exogenous testosterone administration and two studies included genetically predicted testosterone concentrations from large-scale genome-wide associative studies (GWAS). Sixteen studies combined pre- and post-menopausal women, 24 examined post-menopausal women only, one study was conducted in peri-menopausal women, and one study did not specify the menopausal status or age of the participants. Conclusion Discrepancies existed between studies regarding the associations between testosterone and CVD outcomes. This may be due to the heterogeneity of cohorts, differences in endpoint definitions or testosterone analytic techniques. Further, no studies examined pre-menopausal cohorts alone. This highlights the need for well-controlled studies using gold standard testosterone analytic techniques. There is also an unmet requirement for knowledge regarding the effect of testosterone on CVD outcomes in pre-menopausal women.
Alexander et al. (Sat,) studied this question.