Clinical review: Endogenous testosterone and mortality in men: a systematic review and meta-analysis

Abstract

Context: Low testosterone levels have been associated with outcomes that reduce survival in men.

Objective: Our objective was to perform a systematic review and meta-analysis of published studies to evaluate the association between endogenous testosterone and mortality.

Data sources: Data sources included MEDLINE (1966 to December 2010), EMBASE (1988 to December 2010), and reference lists.

Study selection: Eligible studies were published English-language observational studies of men that reported the association between endogenous testosterone and all-cause or cardiovascular disease (CVD) mortality. A two-stage process was used for study selection. 1) Working independently and in duplicate, reviewers screened a subset (10%) of abstracts. Results indicated 96% agreement, and thereafter, abstract screening was conducted in singlicate. 2) All full-text publications were reviewed independently and in duplicate for eligibility.

Data extraction: Reviewers working independently and in duplicate determined methodological quality of studies and extracted descriptive, quality, and outcome data.

Data synthesis: Of 820 studies identified, 21 were included in the systematic review, and 12 were eligible for meta-analysis [n = 11 studies of all-cause mortality (16,184 subjects); n = 7 studies of CVD mortality (11,831 subjects)]. Subject mean age and testosterone level were 61 yr and 487 ng/dl, respectively, and mean follow-up time was 9.7 yr. Between-study heterogeneity was observed among studies of all-cause (P < .001) and CVD mortality (P = 0.06), limiting the ability to provide valid summary estimates. Heterogeneity in all-cause mortality (higher relative risks) was observed in studies that included older subjects (P = 0.020), reported lower testosterone levels (P = 0.018), followed subjects for a shorter time period (P = 0.010), and sampled blood throughout the day (P = 0.030).

Conclusion: Low endogenous testosterone levels are associated with increased risk of all-cause and CVD death in community-based studies of men, but considerable between-study heterogeneity, which was related to study and subject characteristics, suggests that effects are driven by differences between cohorts (e.g. in underlying health status).

Fig. 1.

Results of the systematic search.

Fig. 2.

Association between total testosterone and all-cause (A) and cardiovascular (B) mortality. Each square shows the study-specific RR estimate comparing the bottom tertile with the top tertile of the testosterone distribution (the size of the square reflects the study-specific statistical weight, computed as the inverse of the variance), and the horizontal line shows the 95% CI on the RR. The diamond shows the pooled RR and 95% CI based on random-effects modeling of all studies.