Reviews

Oestrogen: an overlooked mediator in the neuropsychopharmacology of treatment response?

Charlotte Keating^a1 c1, Alan Tilbrook^a2 and Jayashri Kulkarni^a3

^a1 Monash Alfred Psychiatry Research Centre (MAPrc), Monash University and The Alfred, Prahran, Victoria, Australia

^a2 Department of Physiology, School of Biomedical Sciences, Monash University, Wellington Road, Clayton, Australia

^a3 Monash Alfred Psychiatry Research Centre (MAPrc), Monash University and The Alfred, Melbourne, Australia

Abstract

Major depression (MD) and anorexia nervosa (AN) often present comorbidly and both share some affective symptoms, despite obvious phenotypic differences. In the illness phase, pathophysiological evidence indicates similar abnormalities in both clinical groups including dysfunction in the serotonin (5-HT) system (of which some abnormalities persist following recovery) and between 60% and 80% of patients in both groups present with significant hyperactivity of the hypothalamo–pituitary–adrenal (HPA) axis. First-line approach to treatment for MD involves modulation of the 5-HT system using selective serotonin reuptake inhibitors (SSRIs). For AN, treatment with SSRIs has been shown to be considerably less effective compared to MD. Both illnesses show marked dysregulation in the HPA axis. A consequence of SSRI treatment is a reduction and/or normalization of indices of the HPA axis [i.e. cortisol, adrenocorticotropic hormone (ACTH)], which is consistent with recovery levels in both clinical groups. Oestrogen (in high doses) has been shown to exert antidepressant effects and positively impact on MD symptoms as a treatment in its own right, or in combination with antidepressants, in women of menopausal age. It is proposed that a combination of SSRIs and oestrogen therapy may facilitate physiological normalization in MD in women of non-menopausal age and in AN. Preliminary evidence suggests oestrogen treatment alone is of some benefit to patients and it is proposed that a combination of SSRI and oestrogen will precipitate and potentially accelerate symptomatic remission. Should this approach be successful, it offers the capacity for improvement over traditional antidepressant use in women diagnosed with MD and a novel strategy for the treatment of AN, a serious clinical illness associated with the highest mortality of any psychiatric condition.

(Received May 19 2010)

(Reviewed June 30 2010)

(Revised July 17 2010)

(Accepted July 26 2010)

(Online publication September 22 2010)

Key Words:

• Anorexia nervosa;
• antidepressant;
• HPA axis;
• major depression,;
• estrogen

Correspondence:

^c1 Address for correspondence: Ms. C. Keating, Monash Alfred Psychiatry Research Centre (MAPrc), Monash University and The Alfred, PO Box 315, Prahran, Victoria, Australia, 3181. Tel.: +61 3 9076 6564 Fax: +61 3 99076 6588 Email: charlottekeating1@gmail.com