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.
To determine if hypogonadal men have an increased incidence of depressive
illness compared with eugonadal men.
Historical cohort study using computerized medical records, followed
by a manual medical record review.
Veterans Affairs Puget Sound Health Care System.
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
Main Outcome Measures
Incidence of, and time to, a depression diagnosis.
The 2-year incidence of diagnosed depressive illness was 21.7% in hypogonadal
men vs 7.1% in others (χ21 = 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 χ21 = 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).
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.