Testosterone Supplementation May Increase Serotonin Levels in the Brain

Studies conducted over the years have often shown that testosterone supplements bolster the mood of some users, particularly those who start off in low spirits.

But researchers could not explain exactly why the hormone increases happiness — until now.

A team from MedUni Vienna believes it has demonstrated that testosterone increases the number of proteins that transport serotonin into the brain. “We used the cross-sex steroid hormone treatment of transsexuals seeking sex reassignment as a model to investigate acute and chronic effects of testosterone and estradiol on serotonin reuptake transporter (SERT) binding in female-to-male and male-to-female transsexuals,” the study authors wrote in Biological Psychiatry.

“Androgen treatment in female-to-male transsexuals increased SERT binding in amygdala, caudate, putamen, and median raphe nucleus,” wrote the authors.

The study team performed positron emission topography on 33 transsexuals immediately before they began receiving hormone therapy and then repeated the procedure on a subset of the initial group after 4 weeks and then again after 4 months. The brain scans allowed them to quantify nondisplaceable binding potential from SERT in 12 regions of interest and then correlate changes in that binding potential with changes in hormone plasma levels.

When the researchers looked at female-to-male transsexuals, they noticed that SERT binding increased along with plasma testosterone, a finding that suggests testosterone increases SERT expression on the cell surface. When they looked at the male-to-female transsexuals, on the other hand, they found thatantiandrogen and estrogen treatment led to decreases in SERT binding in insula, anterior, and mid-cingulate cortex.

Increases in estradiol levels, however, correlated negatively with decreases in regional SERT binding, indicating that the hormone protects somewhat against SERT loss.

The study team believes this apparent link between testosterone and serotonin — when considered in combination with the long-established link between serotonin and happiness — explains not only why testosterone supplements can boost mood but also why depression affects women more than men and older men more than younger men.

The study may also suggest strategies for boosting the efficacy of the most common form of antidepressant, the selective serotonin reuptake inhibitor.

“The study has shown that testosterone increases the potential binding sites for commonly prescribed antidepressants such as SSRIs in the brain and therefore provides major insights into how sex hormones affect the human brain and gender differences in psychiatric illnesses,” said Siegfried Kasper, who heads the Psychiatry and Psychotherapy Department at Head at the MedUni Vienna.

Kasper is not the first person to hypothesize that testosterone supplements might increase the effects of SSRIs. Anecdotal evidence suggests that some doctors have long been pairing antidepressants and hormones in hypogonadal men. Indeed, previous research on testosterone supplements and user moods practically guaranteed that some doctors would try it as an antidepressant.

A study published a decade ago in the Journal of Clinical Psychiatry, examined the connection between low testosterone and future depression in more than 700 veterans and found that the former condition at baseline predicted a greater tendency toward developing the latter. Studies of currently depressed men, moreover, have repeatedly found them to have lower testosterone levels than happy men who were otherwise comparable.

Research has also found that hypogonadal men who use supplements to boost testosterone suffer less depression than men who avoid treatment. Some studies have even evaluated testosterone supplements as a direct treatment and, though individual studies have reached varying conclusions, a 2009 meta-study published in the Journal of Psychiatric Practice suggests that results, on the whole, have been favorable.