Low testosterone levels in men associated with mortality risk

Low endogenous serum testosterone concentration in men was associated with increased risk for all-cause mortality, and very low testosterone levels were associated with increased risk of cardiovascular death, according to a systematic review and meta-analysis.

Researchers included 11 studies with more than 24,000 participants to analyze associations of sex hormones with mortality and cardiovascular disease (CVD) risk in aging men. All were prospective cohort studies of community-dwelling men with total testosterone concentrations measured using mass spectrometry and at least five years of follow-up. Nine studies provided individual patient data, and two provided aggregate data. The findings were published by Annals of Internal Medicine on May 14.

Men with baseline testosterone concentrations below 7.4 nmol/L, luteinizing hormone concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L had higher CVD mortality. Lower sex hormone-binding globulin concentration was associated with lower all-cause mortality (median for quintile [Q] 1 vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81; 95% CI, 0.65 to 1.00). Men with lower baseline dihydrotestosterone concentrations had higher all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [95% CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29; 95% CI, 1.03 to 1.61). These risks were also increased with dihydrotestosterone concentrations above 2.45 nmol/L. Men with dihydrotestosterone concentrations below 0.59 nmol/L had increased risk for incident CVD events.

According to the authors, the study clarified previous inconsistent findings on the influence of sex hormones on health outcomes in aging men. An accompanying editorial said that this meta-analysis had rigorous methodology. "Overall, these epidemiologic data support the hypothesis that hypogonadism is associated with higher cardiovascular and/or all-cause mortality," the editorial stated. "The data also support the free testosterone hypothesis that states that unbound testosterone is the active form of the hormone—a hypothesis that is somewhat controversial."

The study raised questions about estradiol and dihydrotestosterone that should be further studied, the editorial continued. "Although these epidemiologic data do not prove a causal relationship, they remind us that sex steroid hormones have complex actions and interactions in human health."