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Molly M. Shores, MD; Kevin L. Sloan, MD; Alvin M. Matsumoto, MD; Victoria M. Moceri, PhD; Bradford Felker, MD; Daniel R. Kivlahan, PhD

Arch Gen Psychiatry. 2004;61:162-167.

Context  Age-associated hypogonadism (testosterone deficit) occurs in 30% of men after the age of 55; it is associated with decreased muscle mass, bone mineral density, and libido, and with anorexia, fatigue, and irritability. Although some of these symptoms overlap with those of depression, the association between the 2 disorders is unclear.

Objective  To determine if hypogonadal men have an increased incidence of depressive illness compared with eugonadal men.

Design  Historical cohort study using computerized medical records, followed by a manual medical record review.

Setting  Veterans Affairs Puget Sound Health Care System.

Participants  Two hundred seventy-eight men 45 years and older, without prior diagnosed depressive illness and with consistently normal or low testosterone levels (total testosterone level 200 ng/dL [6.94 nmol/L]; or free testosterone level 0.9 ng/dL [0.03 nmol/L]) at baseline and during a 2-year follow-up period.

Main Outcome Measures  Incidence of, and time to, a depression diagnosis.

Results  The 2-year incidence of diagnosed depressive illness was 21.7% in hypogonadal men vs 7.1% in others (²₁ = 6.0, P = .01). A Kaplan-Meier survival analysis showed a significant difference between hypogonadal and eugonadal men in time to diagnosed depression (log-rank test ²₁ = 6.9, P = .008). We used Cox proportional hazards regression models to examine the association of hypogonadism and time to depression diagnosis, adjusting for age, race, number of clinic visits, alcohol use disorders, prostate cancer, and overall medical comorbidity. The unadjusted hazard ratio for depression with hypogonadism was 3.5 (95% confidence interval, 1.3-9.4) (P = .01). Controlling for all covariates, hypogonadism remained significantly associated with depression (adjusted hazard ratio, 4.2; 95% confidence interval, 1.5-12.0) (P = .008).

Conclusions  Hypogonadal men showed an increased incidence of depressive illness and a shorter time to diagnosis of depression. Further prospective studies are needed to confirm these preliminary findings and to clarify the role of testosterone in the treatment of depressive illness in older men.

From the Veterans Affairs Puget Sound Health Care System, Seattle, Wash (Drs Shores, Sloan, Matsumoto, Moceri, Felker, and Kivlahan); and the Departments of Psychiatry and Behavioral Sciences (Drs Shores, Sloan, Felker, and Kivlahan), Medicine (Dr Matsumoto), and Epidemiology (Dr Moceri), University of Washington, Seattle. Since the submission of this manuscript for publication, Dr Shores has received testosterone gel, placebo gel, and laboratory expenses from Solvay, Inc, for a new study related to the one described herein; Dr Matsumoto is a consultant for Solvay, Inc; and Drs Shores and Matsumoto have received honoraria to attend a conference sponsored by Solvay, Inc. Solvay, Inc, was not involved in any way with the research reported herein.

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