PATHOGENESIS OF FUNCTIONAL HYPOTHALAMIC AMENORRHEA

这笔赠款的总体目标是增加我们对 功能性下丘脑闭经(FHA)的病因及检测 针对这种生殖障碍的几种新的治疗方案。 无排卵是女性不孕症最常见的原因，FHA 是导致无排卵的最常见原因。FHA的直接原因 下丘脑促性腺激素释放激素(GnRH)不足 分泌物。然而，一群神经内分泌分泌 存在可归因于下丘脑功能改变的障碍。我们的 目前对女性和猴子的研究表明功能障碍 态度、心理社会压力和相关行为，如 卡路里限制和运动在性格形成中的作用 下丘脑-垂体-肾上腺(HPA)、HP-甲状腺(HPT)和 幽门螺杆菌卵巢(HPO)分泌改变。因此，我们将FHA概念化为 协同作用引起的下丘脑动态平衡的改变 在心理挑战和新陈代谢妥协之间。在基础上建设 这些发现，我们假设认知行为疗法(CBT) 旨在改善态度和纠正有问题的行为将 逆转下丘脑紊乱，恢复排卵。一个目标是 这个项目就是为了验证这一假设。然而，因为并不是所有的 患有FHA的女性将对CBT做出回应，我们正在继续我们的追求 在女性和猴子身上辨别神经生物学机制 心理应激源和代谢应激源之间的协同作用 目的是确定有前景的药物干预措施。 为了完善我们关于FHA发病机制的模型，猴子的研究包括 对于确定因果关系和药理学选择至关重要，而 人体研究是测试心理和社会功能的有效性不可或缺的一部分 药物疗法。建立了一个跨学科的团队 研究人员正在进行这些临床和基础研究相结合的工作， 在精神病学、行为医学等领域拥有专业知识， 运动生理学、神经生物学和生殖内分泌学。

The overall goal of this grant is to increase our understanding of the etiology of Functional Hypothalamic Amenorrhea (FHA) and test several novel treatment regimens for this reproductive disorder. Anovulation is the most common cause of infertility in women and FHA is the most common cause of anovulation. The proximate cause of FHA is insufficient hypothalamic gonadotropin-releasing hormone (GnRH) secretion. However, a constellation of neuroendocrine secretory disturbances attributable to altered hypothalamic function exist. Our current investigation in women and in monkeys implicates dysfunctional attitudes, psychosocial stress, and associated behaviors such as calorie restriction and exercise in the genesis of characteristic hypothalamic-pituitary-adrenal (HPA), HP-thyroidal (HPT), and HP-ovarian (HPO) secretory alterations. Thus, we conceptualize FHA as a state of altered hypothalamic homeostasis caused by synergism between psychogenic challenge and metabolic compromise. Building on these findings, we hypothesize that cognitive behavior therapy (CBT) aimed at improving attitudes and correcting problematic behaviors will reverse hypothalamic derangements and restore ovulation. One aim of this project is to test this hypothesis. However, because not all women with FHA will respond to CBT, we are continuing our quest to discern in women and in monkeys the neurobiological mechanisms underlying the synergism between psychogenic and metabolic stressors with the goal of identifying promising pharmacologic interventions. To refine our model of the pathogenesis of FHA, monkey studies are critical to identifying causality and pharmacologic options, while the human studies are integral to testing the efficacy of psychosocial and pharmacologic therapies. An interdisciplinary team of established investigators is working on these combined clinical and basic studies, with expertise in the areas of psychiatry, behavioral medicine, exercise physiology, neurobiology, and reproductive endocrinology.