EFFECT OF SSRIS ON GONADAL STERIODS

SSRIS 对性腺类固醇的影响

• 批准号: 7604225
• 负责人: MARGARET ALTEMUS
• 金额: $ 1.15万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604225
• 关键词: Adrenal Glands; Adverse effects; Antidepressive Agents; Bupropion; Characteristics; Chronic; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Female; Fluoxetine; Functional disorder; Funding; Future; Gonadal Steroid Hormones; Grant; Hormones; Hypothalamic structure; Institution; Lead; Menstrual cycle; Ovarian; Pathway interactions; Pituitary Gland; Play; Production; Research; Research Personnel; Resources; Role; Selective Serotonin Reuptake Inhibitor; Severities; Sex Functioning; Source; United States National Institutes of Health; Woman; base; clinical efficacy; healthy volunteer; volunteer

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 血清素再摄取抑制剂（SRI）抗抑郁药抑制性腺类固醇激素的产生。初步证据表明，SRI治疗可降低17-OH孕烯醇酮和17-OH黄体酮的循环水平，这些物质是性腺类固醇合成途径中的中间前体。为了证实该试验数据并开始确定该效应是否是特定的SRI特征，将在健康志愿者女性中比较用SRI氟西汀长期治疗对性腺类固醇前体激素17-羟烯醇酮的效应与非SRI安非他酮的效应。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，并研究抗抑郁药治疗期间循环17-羟基烯醇酮水平的变化是否与性功能变化相关。很少有研究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发挥作用，或者性副作用的严重程度是否在月经周期中变化。将使用健康女性志愿者，以避免精神疾病对性功能以及下丘脑-垂体-肾上腺和卵巢轴活性的混杂影响。该研究旨在扩大对SRI作用机制的理解。如果氟西汀而不是安非他酮治疗与循环中17-羟基烯醇酮水平的降低相关，则将在未来的研究中检查这种效应对SRI治疗PMDD和OCD的不同临床疗效的潜在重要性。这也可能导致PMDD和OCD的神经基础治疗的发展。