The role of ovarian steroids in affective disorders

The role of reproductive steroids in the pathophysiology or treatment of traditional affective disorders remains unestablished. However, there is strong evidence documenting roles of ovarian steroids in reproductive endocrine-related mood disorders including Premenstrual Dysphoric Disorder (PMDD). Studies in PMDD have consistently demonstrated the absence of a deficiency or excess of circulating ovarian steroid hormones. Thus, if ovarian steroids play a role in PMDD, the pathophysiologic paradigm is that normal levels of ovarian steroids induce an abnormal behavioral state in those women with PMDD but not those without PMDD. Recent studies have demonstrated that it is the change in ovarian steroid levels rather than stable levels that trigger the altered affective state in PMDD. Neuroimaging studies have identified potential neural targets of ovarian steroids in women with PMDD within several large-scale brain networks, including the prefrontal cortex and regions involved in affect regulation. Finally, preliminary findings suggest that an intrinsic cellular difference confers a differential response to ovarian steroids in women with PMDD compared with those who do not experience this condition.