title: Effects of estrogen and testosterone treatment on serotonin transporter binding in the brain of surgically postmenopausal women--a PET study.
abstract: Sex hormones and the serotonergic system interact in the regulation of mood, learning, memory and sexual behaviour. However, the mechanisms have not been fully explored. The serotonin transporter protein (5-HTT) regulates synaptic concentrations of serotonin and is a primary target for selective serotonin reuptake inhibitors. The aim of this study was to explore how estrogen treatment alone or in combination with testosterone affects 5-HTT binding potentials measured by positron emission tomography (PET) in specific brain regions of postmenopausal women. Ten healthy surgically postmenopausal women (years since oophorectomy 7.5 ± 4.0, mean ± SD) underwent PET examinations at baseline, after three months of estrogen treatment (transdermal estradiol 100 μg/24 hours) and after another three months of combined estrogen and testosterone (testosterone undecanoate 40 mg daily) treatment using the radioligand [(11)C] MADAM developed for examination of the serotonin transporter. The 5-HTT binding potentials decreased significantly in several cortical regions, as well as in limbic and striatal regions after both estrogen treatment alone and combined estrogen/testosterone treatment in comparison to baseline. The observed decrease in 5-HTT could either be due to direct effects on serotonin transporter expression or be the result of indirect adaptation to estrogen and /or testosterone effects on synaptic serotonin levels. Although the mechanism still needs further exploration, the study supports the view that gonadal hormones play a role in serotonin regulated mood disorders.
authors.affiliation: Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet and University Hospital, Stockholm, Sweden. Electronic address: nina.jovanovic@sll.se.
authors.forename: Hristina
authors.initials: H
authors.lastname: Jovanovic
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Kocoska-Maras
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Angelique Flöter
authors.initials: AF
authors.lastname: Rådestad
authors.affiliation: Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.affiliation: Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Borg
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Angelica Lindén
authors.initials: AL
authors.lastname: Hirschberg
authors.affiliation: Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Nordström
mesh_terms: D000328:Adult; D000368:Aged; D001596:Benzylamines / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D017698:Postmenopause / Q000187:drug effects / Q000378:metabolism*; D011184:Postoperative Period; D011485:Protein Binding / Q000187:drug effects; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013739:Testosterone / Q000008:administration & dosage*; D014018:Tissue Distribution
chemical_list: D001596:Benzylamines; D004967:Estrogens; C470437:N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013739:Testosterone
keywords: Depression; Estrogen treatment; PET; Postmenopausal; Serotonin; Testosterone treatment