Androgen Treatment of Depressive Symptoms in Older Men: A Systematic Review of Feasibility and Effectiveness

Objective: To determine the feasibility and effectiveness of androgen treatment of depressive symptoms in older men. Method: We searched MEDLINE, PsycINFO, Eric, HealthStar, and the Cochrane Database of Systematic Reviews for potentially relevant articles. The bibliographies of relevant articles were searched for additional references and experts were consulted. Seventeen reports (8 open and 12 randomized trials; 3 articles reported studies of 2 designs) met the following inclusion criteria: original investigation; published in English or French, use of acknowledged criteria or scale for depression, and open or randomized trial of androgen treatment. Four criteria assessed study validity: randomization, double blinding, comparability of treatment and control groups at baseline, and description of dropouts. We abstracted, tabulated, and compared information from each article. Results: Most studies had methodological limitations. With regard to feasibility, there were few reported withdrawals due to adverse events. With regard to effectiveness, 6 of 8 open trials had positive results, and 5 of 12 randomized trials had positive results, although 1 was equivocal. However, testosterone was combined with antidepressant medication in 3 of these positive randomized trials. Only 2 open trials enrolled subjects whose mean age was 60 years or over. One had positive results, and the other had negative results. Conclusion: Androgen therapy may be feasible in the short term, but there is little evidence that it is an effective treatment for depressive symptoms in older men. (Can J Psychiatry 2006;51:295-299) Information on funding and support and author affiliations appears at the end of the article. Clinical Implication * Little evidence supports the use of androgen therapy for depressive symptoms in older men. Limitations * The literature search was restricted to articles published in English or French. * There was heterogeneity in study designs, populations, androgens used, dosages, duration of therapy, and outcome measures. Key Words: androgen therapy, depression, aged For 3 reasons, depressive disorders in the elderly are becoming one of the most frequent clinical situations challenging health care professionals. First, people aged 65 years and over represent the fastest-growing population in Canada. Their numbers rose by almost 60% between 1981 and 1998, reaching a total of 3.7 million (for Health Canada 2003 statistics, see www.hc-sc.gc.ca/seniors-aines). second, the prevalence rate of major depression in the elderly ranges from 1% to 4% in the community (1); the rate rises to 10% to 30% in elderly medical inpatients (2). Third, major depression in many elderly individuals is a chronic disorder characterized by recovery and recurrence. A recent study confirmed that elderly subjects suffer from more rapid recurrence than younger patients, with a median time to recurrence of 90 weeks in the group aged 65 to 79 years (3). Moreover, older patients seem to suffer much more frequently from minor or subthreshold depression than from major depression. Among those aged 55 years and over in a community sample, the prevalence rate was 12.9% (1). Among older men, subthreshold depression is associated with as much disability as MDD and with an increased risk of death, compared with control subjects not suffering from depression (4,5). Beekman and others followed a group of 277 elderly subjects with depression for 6 years (average age at the beginning of the study, 71.8 years) (1). The most frequent diagnosis was subthreshold depression (75%, compared with 8% having MDD); 66% of these patients had a chronic-intermittent or chronic course of disease over the 6 years. The prevalence rate of low levels of total testosterone in men aged over 60 years is reported to be approximately 20% (6,7). Low levels of testosterone are associated with depressive symptoms that include lack of energy, an irritable or sad mood, and decreased enjoyment of life, as determined by the St-Louis Testosterone Deficiency Questionnaire (8). …