title: Effects of Steroid Hormones on Sex Differences in Cerebral Perfusion.
abstract: Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women). Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel-based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women.
authors.affiliation: Center for MR-Research, University Children's Hospital Zurich, Zürich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zürich, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ghisleni
authors.affiliation: Center for MR-Research, University Children's Hospital Zurich, Zürich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zürich, Switzerland.
authors.forename: Steffen
authors.initials: S
authors.lastname: Bollmann
authors.affiliation: Endocrinology, Department of Medicine, University of Fribourg, Fribourg, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Biason-Lauber
authors.affiliation: Center for MR-Research, University Children's Hospital Zurich, Zürich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland.
authors.forename: Simon-Shlomo
authors.initials: SS
authors.lastname: Poil
authors.affiliation: Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zürich, Switzerland; Department of Child and Adolescent Psychiatry, University of Zurich, Zürich, Switzerland; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/ Heidelberg University, Mannheim, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brandeis
authors.affiliation: Center for MR-Research, University Children's Hospital Zurich, Zürich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zürich, Switzerland.
authors.forename: Ernst
authors.initials: E
authors.lastname: Martin
authors.affiliation: Center for MR-Research, University Children's Hospital Zurich, Zürich, Switzerland; Klinik für Neuroradiologie, University Hospital Zurich, Zürich, Switzerland.
authors.forename: Lars
authors.initials: L
authors.lastname: Michels
authors.affiliation: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Hersberger
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, England.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Center for MR-Research, University Children's Hospital Zurich, Zürich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zürich, Switzerland; Department of Psychology, University of Zurich, Zürich, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Klaver
authors.affiliation: Center for MR-Research, University Children's Hospital Zurich, Zürich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland.
authors.forename: Ruth L
authors.initials: RL
authors.lastname: O'Gorman
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply*; D003687:Dehydroepiandrosterone / Q000097:blood; D003710:Demography; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D012739:Gonadal Steroid Hormones; D003687:Dehydroepiandrosterone