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.