Effects of hormone replacement therapy on cerebral serotonin-1A receptor binding in postmenopausal women examined with [carbonyl-¹¹C]WAY-100635.
Preclinical research points to a strong modulatory influence of gonadal hormones on the serotonin system. However, human data corroborating this association remains scarce. The aim of this study was to examine the effects of hormone replacement therapy on 5-HT₁A receptor binding in postmenopausal women using positron emission tomography (PET) and the radioligand [carbonyl-(11)C]WAY-100635. In this randomized, double-blind, longitudinal study, 30 postmenopausal women underwent treatment with either a combination of oral 17β-estradiol valerate and micronized progesterone (group 1, n=10), oral 17β-estradiol valerate (group 2, n=10), or placebo (group 3, n=10). Two PET measurements were performed, one the day before treatment start and the second after at least eight weeks of treatment. Plasma levels of estradiol (E₂), progesterone (P₄), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were collected prior to PET measurements. As expected, hormone replacement therapy led to a significant increase in E₂ and P4 plasma levels in group 1 and to a significant increase in E₂ levels in group 2. The 5-HT₁A receptor binding did not change significantly after estrogen, combined estrogen/progesterone treatment or placebo in any of the investigated brain regions. There were no significant correlations between changes in E₂ or P4 values and changes in 5-HT₁A receptor binding. Although we were not able to confirm effects of gonadal hormone treatment on 5-HT₁A receptor binding, our data do not preclude associations between sex steroid levels and serotonin, the neurotransmitter implicated most strongly in the pathogenesis of affective and anxiety disorders. ClinicalTrials.gov Identifier: NCT00755963.
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria(1).
Georg S
GS
Kranz
Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Austria.
Christina
C
Rami-Mark
Department of Obstetrics and Gynecology, Medical University of Vienna, Austria.
Ulrike
U
Kaufmann
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria(1).
Pia
P
Baldinger
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria(1).
Andreas
A
Hahn
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria(1).
Anna
A
Höflich
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria(1).
Markus
M
Savli
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria(1).
Patrycja
P
Stein
Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Austria.
Wolfgang
W
Wadsak
Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Austria.
Markus
M
Mitterhauser
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria(1).
Dietmar
D
Winkler
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria(1). Electronic address: rupert.lanzenberger@meduniwien.ac.at.
Rupert
R
Lanzenberger
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria(1).
Siegfried
S
Kasper
D000368:Aged; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D010879:Piperazines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D017698:Postmenopause / Q000097:blood / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D011485:Protein Binding; D011725:Pyridines / Q000493:pharmacokinetics*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D012738:Sex Hormone-Binding Globulin; D044282:Receptor, Serotonin, 5-HT1A; D011374:Progesterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D005640:Follicle Stimulating Hormone
Estradiol; Hormone replacement therapy; Positron emission tomography; Postmenopausal; Progesterone; Serotonin-1A receptor