1. ¹Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
2. ²Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA
3. ³Yale Child Study Center, Yale University School of Medicine, New Haven, CT, USA
4. ⁴Departments of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA

Correspondence: Dr Z Amin, Department of Psychiatry, Yale University School of Medicine, 100 York Street, Suite 2H, New Haven, CT 06511, USA, Tel: +1 203 764 9945, Fax: +1 203 764 9990, E-mail: zenab.amin@yale.edu

Received 27 December 2005; Revised 30 March 2006; Accepted 3 May 2006; Published online 7 June 2006.

Abstract

Despite an abundance of data in animals, there is little research in humans regarding how estrogen and serotonin (5-HT) may interact to influence cognition. Through the use of estrogen treatment (ET) and tryptophan depletion (TRP-D) in a within-subject design involving healthy menopausal women, we have manipulated both estrogen and 5-HT in order to evaluate their individual and joint effects. Although neither manipulation influenced visuospatial learning, a significant interaction suggested that estrogen exerted a protective effect on verbal memory, such that TRP-D impaired performance to a greater extent before the administration of ET. In consonance with this finding, ET was associated with a small, but positive mood effect on the day following active TRP-D. In addition, ET significantly improved letter-cued verbal fluency with and without TRP-D. Finally, time since last menstrual period was significantly associated with verbal memory scores, such that longer length of hypogonadism resulted in decreased verbal memory performance. These data support the interaction of estrogen and 5-HT in nonreproductive behavior in humans as well as highlight the role of ovarian steroids in cognition.