High-dose testosterone treatment increases serotonin transporter binding in transgender people

Georg Kranz, W. Wadsak, U. Kaufmann, M. Savli, P. Baldinger, G. Gryglewski, D. Haeusler, M. Spies, M. Mitterhauser, S. Kasper, R. Lanzenberger

Research output: Journal article publicationJournal articleAcademic researchpeer-review

50 Citations (Scopus)


© 2015 Society of Biological Psychiatry.Background Women are two times more likely to be diagnosed with depression than men. Sex hormones modulating serotonergic transmission are proposed to partly underlie these epidemiologic findings. Here, 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. Methods Thirty-three transsexuals underwent [<sup>11</sup>C]DASB positron emission tomography before start of treatment, a subset of which underwent a second scan 4 weeks and a third scan 4 months after treatment start. SERT nondisplaceable binding potential was quantified in 12 regions of interest. Treatment effects were analyzed using linear mixed models. Changes of hormone plasma levels were correlated with changes in regional SERT nondisplaceable binding potential. Results One and 4 months of androgen treatment in female-to-male transsexuals increased SERT binding in amygdala, caudate, putamen, and median raphe nucleus. SERT binding increases correlated with treatment-induced increases in testosterone levels, suggesting that testosterone increases SERT expression on the cell surface. Conversely, 4 months of antiandrogen and estrogen treatment in male-to-female transsexuals led to decreases in SERT binding in insula, anterior, and mid-cingulate cortex. Increases in estradiol levels correlated negatively with decreases in regional SERT binding<inf>,</inf> indicating a protective effect of estradiol against SERT loss. Conclusions Given the central role of the SERT in the treatment of depression and anxiety disorders, these findings may lead to new treatment modalities and expand our understanding of the mechanism of action of antidepressant treatment properties.
Original languageEnglish
Pages (from-to)525-533
Number of pages9
JournalBiological Psychiatry
Issue number8
Publication statusPublished - 1 Jan 2015
Externally publishedYes


  • Estradiol
  • Hormone treatment
  • Positron emission tomography
  • Serotonin transporter
  • Testosterone
  • Transsexual

ASJC Scopus subject areas

  • Biological Psychiatry


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