Prospective longitudinal study of testosterone and incident depression in older men: The health in men study

Crown Copyright © 2015 Background: Depression in older men has been associated with low circulating testosterone concentrationbut data from prospective studies are limited.Methods: We conducted a prospective longitudinal study in a community representative cohort of 3179older men free of clinically significant depressive symptoms at baseline. The main objective of this studywas to determine if low serum testosterone, dihydrotestosterone and estradiol concentrations are asso-ciated with the development of depressive symptoms. Incident depression was assessed with the PatientHealth Questionnaire and via an electronic health record database (The West Australian Data LinkageSystem). The main exposures of interest were serum testosterone, dihydrotestosterone and estradiolmeasured by liquid chromatography–mass spectrometry and calculated free testosterone in baselineblood samples (collected between 2001 and 2004).Results: One hundred and thirty five men (4.2%) developed depression over a median follow up time of 9.4years (range 8.4–10.9). Men with incident depression were older (median age 77.7 vs 76.1 years, z = −3.82,p = 0 < 0.001) and were more likely to have cardiovascular disease (43.0% vs 32.6%, 2= 6.32, p = 0.012)and diabetes (22.2% vs 13.2%, 2= 8.95, p = 0.003). Low serum total testosterone (<6.4 nmol/L) was associ-ated with incident depression (HR 2.07, 95%CI 1.17–3.68) and this remained significant after adjustmentfor relevant potential confounding factors (HR 1.86, 95%CI 1.05–3.31). Low serum dihydrotestosterone,estradiol and calculated free testosterone were not associated with risk of depression.Conclusions: Low serum total testosterone, but not calculated free testosterone, was associated withincident depression in this sample of older men.Crown Copyright © 2015