title: High-Dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People.
abstract: 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 [(11)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, 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.
authors.affiliation: Department of Psychiatry and Psychotherapy.
authors.forename: Georg S
authors.initials: GS
authors.lastname: Kranz
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kaufmann
authors.affiliation: Department of Psychiatry and Psychotherapy.
authors.forename: Markus
authors.initials: M
authors.lastname: Savli
authors.affiliation: Department of Psychiatry and Psychotherapy.
authors.forename: Pia
authors.initials: P
authors.lastname: Baldinger
authors.affiliation: Department of Psychiatry and Psychotherapy.
authors.forename: Gregor
authors.initials: G
authors.lastname: Gryglewski
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine.
authors.forename: Daniela
authors.initials: D
authors.lastname: Haeusler
authors.affiliation: Department of Psychiatry and Psychotherapy.
authors.forename: Marie
authors.initials: M
authors.lastname: Spies
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine.
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.affiliation: Department of Psychiatry and Psychotherapy.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.affiliation: Department of Psychiatry and Psychotherapy. Electronic address: rupert.lanzenberger@meduniwien.ac.at.
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
mesh_terms: D000328:Adult; D000728:Androgens / Q000008:administration & dosage*; D016022:Case-Control Studies; D004958:Estradiol / Q000008:administration & dosage*; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011699:Putamen / Q000187:drug effects; D011903:Raphe Nuclei / Q000187:drug effects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects*; D013739:Testosterone / Q000008:administration & dosage*; D063106:Transgender Persons / Q000145:classification*; D055815:Young Adult
chemical_list: D000728:Androgens; D004967:Estrogens; D050486:Serotonin Plasma Membrane Transport Proteins; D013739:Testosterone; D004958:Estradiol
keywords: Estradiol; Hormone treatment; Positron emission tomography; Serotonin transporter; Testosterone; Transsexual