Hypogonadism, Testosterone Replacement Therapy and Risk of Depression in Middle Aged and Older Men in the US

Hypogonadism is posited as a risk factor for depression. Limited evidence from randomized controlled trials (RCTs) suggests that testosterone replacement therapy (TRT) may improve depressive symptoms in hypogonadal men. However, evidence from real world, population-based studies is lacking. Moreover, TRT prescription increased by over three-fold for middle aged and older men in the past decade; however little is known about TRT prescribing patterns in men with depression. To the best of our knowledge, this is the first large-scale, real-world, nationally representative study of middle aged and older men to examine: a) TRT prescribing patterns, by depression status b) the association between untreated hypogonadism and incident depression and c) the risk of depression in hypogonadal men exposed to TRT. This dissertation used data from Clinformatics Data Mart-one of the nation’s largest commercial health insurance programs. The association between hypogonadism and depression was tested using a case-control study design. The effects of TRT on risk of depression were assessed using nested case control and retrospective cohort study designs. In order to examine TRT prescribing patterns, annual incident TRT use was calculated for each year from 2002-2016 and stratified by age and hypogonadal status. Separate conditional logistic regression models tested whether a) hypogonadism is associated with increased odds of incident depression and b) exposure to TRT in hypogonadal men is associated with reduced odds of incident depression. Cox proportional hazards regression analyses assessed whether exposure to TRT in hypogonadal men is associated with reduced risk of depression. For each given calendar year from 2002-2016, TRT prescription rates were higher among depressed men, compared to their counterparts; the overall increase was similar for the two groups. After adjusting for relevant covariates, we did not find a consistent association between hypogonadism and depression. No association was observed between TRT and depression. This dissertation will add significantly to current knowledge of TRT prescription patterns in depressed men. Contrary to our hypothesis, we did not find an association between TRT and depression. Our results will improve current knowledge regarding the link between hypogonadism, TRT and depression, and inform future research in light of methodological challenges discussed herein.