Low testosterone levels predict incident depressive illness in older men: Effects of age and medical morbidity

Objective: Prior studies found that chronic low testosterone levels are associated with an increased risk of depression. We investigated whether low testosterone levels in older men predict depressive illness over 2 years, while controlling for age and medical morbidity. Method: Participants were 748 men, aged 50 years or older, without prior ICD-9-diagnosed depressive illness, with a testosterone level obtained between 1995 and 1997. Measures were age, mean total testosterone levels (low: less than or equal to 2.5 ng/mL), medical morbidity, and incidence and time to depressive illness. Results: Men with low testosterone levels had a greater 2-year incidence of depressive illness (18.5% vs. 10.4%, df = 1. p = .006) and a shorter time to onset of depressive illness (log-rank chi(2) = 8.1. df = 1, p = .004). The unadjusted hazard ratio (HR) for depressive illness in men with low testosterone levels was 1.9 (95% confidence interval [CI] = 1.2 to 3.0, p = .005). After adjustment for age and medical morbidity, men with low testosterone levels continued to have a shorter time to depressive illness (adjusted HR = 2.1; 95% CI = 1.3 to 3.2, p = .002). Due to a significant interaction between age and medical morbidity, we conducted stratified Cox regression analyses and found that low testosterone levels and high medical morbidity or an age of 50 to 65 years were associated with increased depressive illness (p = .002). Conclusion: Low testosterone levels are associated with an earlier onset and greater incidence of depressive illness. Men with low testosterone levels who had high medical morbidity or were aged 50 to 65 years had an increased risk for depressive illness. Further prospective studies are needed to examine the role of testosterone in depressive illness in older men.