Systematic review and meta-analyses on associations of endogenous testosterone concentration with health outcomes in community-dwelling men

Objectives The overall study aim is to clarify the relation of endogenous sex hormones with major health outcomes in men. This paper reports a systematic review focusing on published estimates for testosterone associations. Setting Community-dwelling men. Participants 20 180 adult men participated in the final set of studies identified and selected from a systematic review. Eligible studies included prospective cohort studies with plasma or serum testosterone concentrations measured for adult men using mass spectrometry with at least 5 years of follow-up data and one of the specified outcome measures recorded. Only published or grey literature items written in English were considered. Primary and secondary outcome measures Planned prospective outcome measures: cardiovascular disease (CVD) events, CVD deaths, all-cause mortality, cancer deaths, cancer diagnoses, cognitive decline, dementia. Meta-analyses were of the most frequently reported outcomes in selected studies: CVD deaths and all-cause mortality. Succinct characterisations of testosterone associations with other outcomes are also presented. Results Screening of 1994 deduplicated items identified 9 suitable studies, with an additional 2 identified by colleagues (11 in total). Summary estimates of mean testosterone concentration and age at recruitment for 20 180 adult men were 15.4 +/- 0.7 nmol/L and 64.9 +/- 3.3 year. Despite considerable variation in mean testosterone, a metaregression estimated no significant dependence on mean age at recruitment among studies (slope=-0.03, 95% CI -0.11 to 0.06). Meta-analyses demonstrated negligible heterogeneity and no significant effect of a 5 nmol/L increase in testosterone on the risk of all-cause mortality (HR=0.96, 95% CI 0.89 to 1.03) or death from CVD (HR=0.95, 95% CI 0.83 to 1.08). Conclusions Analyses of published estimates did not demonstrate associations of endogenous testosterone with CVD deaths or with all-cause mortality. Suggested further research includes the planned individual participant data meta-analyses for selected studies, enabling the investigation of non-linear summary effects. PROSPERO registration number PROSPERO: CRD42019139668.

Automated summary

The overall aim of the study is to clarify the relationship between endogenous sex hormones and major health outcomes in men, focusing on published estimates for testosterone associations. The systematic review did not show any significant associations between endogenous testosterone and CVD deaths or all-cause mortality.