Endogenous sex steroid hormones, sex hormone binding globulin and risk of all-cause and cardiovascular mortality in patients with established cardiovascular diseases: a systematic review and meta-analysis of prospective studies.

BACKGROUND: Endogenous sex steroid hormones are involved in numerous regulatory mechanisms of the cardiovascular system and their imbalances are frequently observed in patients with established cardiovascular disease (CVD). However, their prognostic significance for mortality remains unclear. This study aims to systematically synthesize existing research and quantify the association between endogenous sex steroid hormones, sex hormone binding globulin (SHBG), and the risk of all-cause and cardiovascular mortality in individuals with established CVD. METHODS: Six bibliographic databases were systematically searched. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model, comparing the highest versus lowest levels of sex hormones/SHBG. The risk of bias was evaluated using the ROBINS-E tool (Risk Of Bias In Non-randomized Studies - of Exposures). RESULTS: Twelve studies with a total of 5,981 patients with established CVD were included. No significant association was found between endogenous total testosterone and risk of all-cause ((HR (95%CI): 0.78 (0.56 to 1.09), n= 5 studies) or CVD (HR (95%CI): 1.30 (0.28 to 6.01), n= 3) mortality in men. Most studies (seven out of twelve studies) were classified as having a high risk of bias, particularly due to confounding. CONCLUSIONS: We found no evidence for an association between endogenous sex hormones and mortality outcomes in patients with CVD. This study underscored the lack of sufficient evidence on this topic, especially concerning women. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD42022329605, identifier CRD42022329605.