EFFECT OF SSRIS ON GONADAL STERIODS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 5-羟色胺再摄取抑制剂(SRI)抗抑郁药抑制性腺类固醇激素的产生。初步证据表明，SRI治疗降低了性腺类固醇合成途径中的中间前体17-羟孕烯醇酮和17-羟孕酮的循环水平。为了证实这一先导数据，并开始确定这种效应是否是特定的SRI特征，将在健康志愿者女性中比较SRI(氟西汀)长期治疗对性腺类固醇前体激素17-羟孕烯醇酮的影响与非SRI(安非他酮)的影响。我们将比较氟西汀和安非他酮对同一组健康女性性功能的影响，并调查循环中17-羟孕烯醇酮水平的变化是否与抗抑郁药物治疗期间性功能的变化有关。性腺类固醇激素活性的变化是否在SRI治疗期间的性副作用的病理生理学中起作用，或者性副作用的严重程度是否在月经周期中变化的研究很少。健康的女性志愿者将被用来避免精神疾病对性功能和下丘脑-垂体-肾上腺和卵巢轴活动的混淆影响。本研究旨在扩大对SRI作用机制的理解。如果氟西汀而不是安非他酮的治疗与17-羟孕烯醇酮循环水平的降低有关，那么这种效应对SRIs治疗PMDD和OCD的不同临床疗效的潜在重要性将在未来的研究中得到检验。这也可能导致以激素为基础的治疗PMDD和OCD的发展。

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.