Depressed Men Have Lower Testosterone Levels

Louise Gagnon

November 14, 2006

November 14, 2006 (Toronto) — Middle-aged men with depression have reduced levels of bioavailable testosterone as well as circulating total testosterone compared with their counterparts without depression, according to a study published in the October issue of Psychoneuroendocrinology.

Presented here as a poster at the annual meeting of the Canadian Psychiatric Association, the study aimed to elucidate the role of reproductive hormones in mood disorders and define the base hormonal state of depressed men and nondepressed men, explained Sidney Kennedy, MD, FRCPC, senior investigator of the study and a professor of psychiatry at the University of Toronto in Ontario, Canada.

"There has been an interest for many years in regards to the question of reproductive hormones in relationship to depression," said Dr. Kennedy, also the psychiatrist-in-chief at the University Health Network of Toronto. "There is a logic to this in that the loss of libido is thought to be associated with low testosterone, but there hasn't been much robust research done in the area."

The study recruited 94 men: 44 untreated depressed men, aged 45 to 60 years, who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)–defined criteria for a major depressive episode typical of major depressive disorder, and 50 matched control subjects who did not have depression.

The study did not include subjects who had a clinically unstable comorbid medical or psychiatric disorder. Subjects who had a history of drug or alcohol dependence in the last 6 months, as defined by the DSM-IV-TR, were excluded. In addition, subjects with uncorrected thyroid disease, those using other psychotropic medications, herbal preparations like St. John's wort, or electroconvulsive therapy within the previous 3 months, were all excluded. Subjects' body mass index ranged between 20 and 29 kg/m2, but being overweight was not a basis for exclusion.

Depressed subjects were untreated at the time of enrollment, but they underwent a washout period in the event they had received an antidepressant drug during the index period or for a previous episode of illness.

Investigators measured circulating total testosterone (TT) and bioavailable testosterone (BT), the more physiologically active component of testosterone. They found depressed men had decreased mean BT levels compared with nondepressed men: 3.51 nmol/L vs 4.69 nmol/L (P = .008). In addition, they had significantly lower TT levels than control subjects: 11.94 nmol/L vs 17.64 nmol/L (P < .001).

Investigators also found biochemical hypogonadism, defined as BT levels of 2.4 nmol/L or less or TT levels of 12.14 nmol/L or less, was more common in depressed subjects than in controls. A total of 34% of depressed men vs 6% of control patients had BT levels measuring 2.4 nmol/L or less (P < .001). A total of 61% of depressed men had TT levels measuring 12.14 nmol/L or less while 14% of controls had such TT levels, a difference that was also significant at P < .001.

"Low testosterone is associated with depression, even when you control for the effects of age," said Dr. Kennedy. "It supports a trend that was generally uninformed by research, that there may be some merit in adding a testosterone supplement in the treatment of depression, particularly if men report low libido."

Organon Canada, which manufactures an orally active testosterone preparation, funded the study.

Mark Berber, MD, FRCPC, a lecturer in the Department of Psychiatry at the University of Toronto and a consultant psychiatrist at Markham Stouffville Hospital in Markham, Ontario, Canada, said the results show a link between decreased hormonal levels and depression, but it is too premature to support hormonal therapy in the way of a testosterone supplement for depressed men.

"It is an association," said Dr. Berber. "This does not mean patients should be on testosterone. The next step in research would look at whether treating men with testosterone makes them less depressed. This study did not address that."

Dr. Berber added that the finding of reduced bioavailable testosterone does not establish if the decreased expression of testosterone caused depression or was a consequence of the depression, noting depression can cause changes in how hormones are processed in the body.

"The depression itself may be lowering the bioavailable testosterone, rather than the other way around," said Dr. Berber.

A future study would recruit depressed men with low bioavailable testosterone. Subjects would be treated with testosterone or placebo and followed for at least 2 months to evaluate if there is a difference in their depression from baseline, according to Dr. Berber. An open-label study would be insufficient, he stressed.

Dr. Berber cautioned that some physicians fear giving testosterone supplements, noting there is concern of potential risk to the prostate gland, especially in older men.

"Going by the adage to first do no harm, we would want to know that the testosterone [supplement] is more effective than placebo," he said.

Because many pharmacologic treatments for depression do not prove effective in clinical practice, researchers are examining novel approaches to therapy, added Dr. Berber.

Dr. Kennedy has received research funding from Organon Canada and has been a member of an advisory board for Organon Canada. Dr. Berber reports no relevant financial relationships.

CPA 2006 Annual Meeting: Poster 22. Presented November 10, 2006.
Psychoneuroendocrinol. 2006;31(9):1029-1035.

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