A recent article in the Archives of General Psychiatry reports that older men with depression have lower total and free testosterone levels in their blood, but a randomized controlled trial is necessary to determine whether or not the association is causal.

Researcher Osvaldo P. Almeida, M.D., Ph.D., F.R.A.N.Z.C.P. (University of Western Australia, Perth) and colleagues first note that between 2 and 5 percent of the population suffer from depression. Up to age 65, women are more likely to be depressed than men. The sex differences are negligible after this age, and previous research has argued that sex hormones may be responsible.

In their cross-sectional study, the researchers analyzed 3,987 men between 71 and 89 years of age. To gather information about demographics and health history, the study participants completed a questionnaire between 2001 and 2004. The researchers assessed participants for depression and cognitive (thinking, learning and memory) difficulties, and they procured information about physical health conditions from a short survey and an Australian health database. Blood samples provided the study authors with information on two types of testosterone levels: total and free. Total testosterone is chemically bound to proteins, whereas free testosterone is bioavailable and unbound.

About 5% (203) participants were diagnosed as depressed, and they had significantly lower total and free testosterone levels compared to men who did not meet the criteria for depression. Variables were then added to the model to control for possibly confounding characteristics such as education level, body mass index, and cognitive scores. Dr. Almeida and colleagues found that compared to men in the highest quintile (20%) of free testosterone concentrations, men in the lowest quintile had three times the odds of having depression.

The authors speculate that changes in the levels of neurotransmitters or brain hormones may be how low testosterone levels actually affect the risk of depression.

“A randomized controlled trial is required to determine whether reducing prolonged exposure to low free testosterone is associated with a reduction in the prevalence of depression in elderly men,” the authors conclude. “If so, older men with depression may benefit from systematic screening of free testosterone concentration, and testosterone supplementation may contribute to the successful treatment of hypogonadal [with low hormone levels] older men with depression.”

Low Free Testosterone Concentration as a Potentially Treatable Cause of Depressive Symptoms in Older Men
Osvaldo P. Almeida, MD, PhD, FRANZCP; Bu B. Yeap, MBBS, PhD; Graeme J. Hankey, MBBS, MD; Konrad Jamrozik, MBBS, DPhil; Leon Flicker, MBBS, FRACP, PhD
Archives of General Psychiatry
(2008). 64(3):283-289
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Written by: Peter M Crosta