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August 2014

Estradiol Modulation of Monoamine Metabolism: One Possible Mechanism Underlying Sex Differences in Risk for Depression and Dementia

Author Affiliations
  • 1Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 2Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 3School of Veterinary Medicine, University of Pennsylvania, Philadelphia
JAMA Psychiatry. 2014;71(8):869-870. doi:10.1001/jamapsychiatry.2014.729

Sex differences in the timing of onset, prevalence, and clinical course of neuropsychiatric and substance use disorders provide clues to the underlying pathophysiology of these disorders. Disorders that occur more frequently in males tend to be neurodevelopmental in nature and include attention-deficit/hyperactivity disorder, autism, Tourette syndrome, oppositional defiant disorder, and, arguably, schizophrenia, suggesting potential prenatal origins and possibly involving the sexually dimorphic organizational effects of androgens for this sex-specific vulnerability. In contrast, it is not until puberty that the sex bias for affective disorders in females is revealed, coinciding with the timing of activational effects of gonadal steroids. From puberty until postmenopause, females are approximately twice as likely as males to have affective and anxiety disorders such as major depressive disorder (MDD), dysthymia, generalized anxiety disorder, panic disorder, and posttraumatic stress disorder. Risk for dementia, particularly Alzheimer disease, is also greater for aging women, although females are relatively protected from early-onset Parkinson disease.1

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