Vol 4 n° 2 - Cerebral aspects of reproductive endocrinology
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ver a century ago, numerous case reports des- cribed the onset of mood and behavioral disorders in temporal association with altered reproductive function, as well as the dramatic remission of mood and behav- ioral  symptoms  following  the  resumption  of  normal menstruation. Indeed, treatment strategies frequently included efforts to either normalize menstruation or remove the reproductive organs of women with mental illness.Although interest in reproductive endocrine ther- apies for mood disorders has persisted throughout the past century, the specific role, if any, that reproductive endocrine interventions should play in the treatment of mood disorders is still unclear. In  this  article, we  will  describe  the  recent  history  of reproductive endocrine therapies for mood disorders, review the biology of gonadal steroids that may be rele- vant to mood regulation, discuss the current role for reproductive endocrine therapies in both reproductive endocrine–related mood disorders and classical mood disorders, and review theories about the mechanisms of action of gonadal steroids in the treatment of these con- ditions. Finally, we will discuss the potential future role of  these  and  related  compounds  in  the  treatment  of mood disorders. Background The 19th century medical literature contained several presumptions about the pathophysiology of mood dis- orders in women largely based on anecdotal observa- tions of reproductive endocrine dysfunction (eg, amen- orrhea) in psychiatrically ill women.1-5 These inferences, in turn, were translated into therapeutics. Thus, numer- ous reports also documented the beneficial effects on mood and behavior associated with medical or surgical manipulations of a woman’s reproductive function.6-9 In addition to their interest in the role of reproductive func- tion in psychiatry, medical researchers in the late 19th 2 1 1 C l i n i c a l   r e s e a r c h Reproductive hormonal treatments for mood disorders in women Peter J. Schmidt, MD; David R. Rubinow, MD Keywords: women; depression; estrogen; progesterone; DHEA; antidepressants

Author affiliations: Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, Md, USA

Address for correspondence: Peter J. Schmidt, MD, National Institute of Mental Health, Building 10, Room 3N238, 10 Center Dr MSC 1276, Bethesda MD 20892-1276, USA (e-mail: schmidtp@intra.nimh.nih.gov)

 There  has  been  a  century-long  view  in  medicine  that reproductive function in both men and women is inti- mately involved with mood regulation. The 19th centu- ry  witnessed  a  proliferation  of  medical  reports  docu- menting beneficial effects on mood and behavior after medical or surgical manipulations of women’s reproduc- tive function. More recently, the results of several studies suggest that gonadal steroids do regulate mood in some women. Thus, there is considerable interest in the poten- tial role of reproductive therapies in the management of depressive illness, including both classical and reproduc- tive endocrine–related mood disorders. Future studies need to determine the predictors of response to hor- monal therapies compared with traditional antidepres- sant agents, and to characterize the long-term safety and benefits of these therapies. Dialogues Clin Neurosci. 2002;4:211-223. O