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: < or = 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.

Low testosterone is associated with decreased function and increased mortality risk: a preliminary study of men in a geriatric rehabilitation unit.

OBJECTIVES: To evaluate whether low testosterone levels are associated with greater depression or poorer function in a geriatric rehabilitation unit. DESIGN: Retrospective review. SETTING: Geriatric rehabilitation unit. MEASUREMENTS: Low testosterone levels were defined as total testosterone of 3.0 ng/mL or less or free testosterone of 9.0 pg/mL or less. Age, ethnicity, weight, depression, ambulation, length of rehabilitation, and 6-month rehospitalization and mortality rates were obtained. Overall illness severity was determined using the Cumulative Illness Rating Scale for Geriatrics. RESULTS: Low testosterone levels were present in 29 of 44 (65.9%) men. There were no significant differences between men with low and normal testosterone levels in ethnicity, age, weight, depression, and overall illness severity. Lower testosterone levels were correlated with decreased ability to ambulate and transfer (Spearman P>.34; P<.05). There were no significant differences between men with low and normal testosterone in length of stay on the rehabilitation unit (mean+/-standard deviation= 19.6+/-11.6 vs 17.7+/-17.5 days, P=.68) or rehospitalization rates (41.4% vs 26.7%; P=.34). Men with low testosterone had a trend toward increased 6-month mortality (31.0% vs 6.7%; chi(2)=3.3, P=.07) and shorter survival time (log rank=3.2; df 1, P=.07). After entering testosterone and variables with potential prognostic significance for mortality in a stepwise manner in a Cox regression analysis, there was a significant mortality risk associated with low testosterone (hazard ratio=27.9, 95% confidence interval=2.0-384.0; P=.01). CONCLUSION: Low testosterone levels were correlated with decreased physical function and increased risk for 6-month mortality. Prospective studies with larger sample sizes and better standardized testosterone measures are needed to confirm these findings.

Increased incidence of diagnosed depressive illness in hypogonadal older men.

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 < or =200 ng/dL [< or =6.94 nmol/L]; or free testosterone level < or =0.9 ng/dL [< or =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 (chi2(1)=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 chi2(1)=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.