Hormonal treatments taken as part of the sex-reassignment process have obvious and well-known effects on the physical, secondary sexual characteristics of the human body.But a new study that examined the effect of these hormone treatments beyond appearance found that they also alter brain chemistry.

Led by senior authors Dr. Siegfried Kasper and Dr. Rupert Lanzenberger, researchers at the Medical University of Vienna explored the relationship between hormonal sex-change treatments and a brain protein called SERT, which transports the neurotransmitter serotonin into nerve cells. The team found that administration of the male hormone testosterone in female-to-male transsexuals increased brain levels of SERT, while male-to-female transsexuals who received a testosterone blocker and estrogen showed decreased levels of SERT in the brain.

SERT plays a significant role in treating mood and anxiety disorders. Many common antidepressants (including Prozac) block its activity by inhibiting serotonin reuptake. Also, some studies have suggested that having a higher level of SERT could increase resistance to stress, and lower the risk of stress and mood disorders.

Currently, women are twice as likely to be diagnosed with depression as men, so the changes in SERT levels associated with the blocking of testosterone are consistent with increased risk of mood and anxiety disorders in females compared to males.

“These results may explain why testosterone improves symptoms in some forms of depression,” Lanzenberger said in a statement. “Our study also increases our knowledge in the role of sex hormones in sex differences of mood disorders.”

These findings suggest that when a person transitions from female to male, their brain chemistry changes in a way that is associated with a reduced risk for mood and anxiety disorders, while the reverse happens when males switch to females.

“This study is the first to show changes in brain chemistry associated with the hormonal treatments administered in the sex change process,” said Dr. John Krystal, editor of Biological Psychiatry, where the study was published. “It provides new insight into the ways that the hormonal differences between men and women influence mood and risk for mood disorders.”

Source: Kranz G, Lanzanberger R, Kasper S, et al. High-dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People. Biological Psychiatry. 2015.