EFFECT OF SSRIS ON GONADAL STERIODS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Serotonin reuptake inhibitor (SRI) antidepressants suppress production of gonadal steroid hormones. Preliminary evidence indicates that SRI treatment reduces circulating levels of 17-OHpregnenolone and 17-OHprogesterone which are intermediary precursors in the gonadal steroid synthesis pathway. To confirm this pilot data and begin determining whether this effect is a specific SRI characteristic, the effect of chronic treatment with SRI, fluoxetine, on the gonadal steroid precursor hormone 17-OHpregnenolone will be compared to the effect of non-SRI, bupropion, in healthy volunteer women. We will compare effects of fluoxetine and bupropion on sexual functioning in the same group of healthy women, and investigate whether changes in circulating 17-OHpregnenolone levels are related to changes in sexual function during antidepressant treatment. There is little study of whether changes in gonadal steroid hormone activity play a role in the pathophysiology of sexual side effects during SRI treatment, or whether severity of sexual side effects varies across the menstrual cycle. Healthy female volunteers will be used to avoid confounding effects of psychiatric illness on sexual function and on activity of hypothalamic-pituitary-adrenal and -ovarian axes. The study is intended to expand understanding of the mechanism of SRI action. If fluoxetine, but not bupropion treatment, is associated with a reduction in circulating levels of 17-OHpregnenolone, the potential importance of this effect to the distinct clinical efficacy of SRIs for PMDD and OCD will be examined in future studies. This also may lead to development of hormonally based treatments for PMDD and OCD.