PATHOGENESIS OF FUNCTIONAL HYPOTHALAMIC AMENORRHEA

这项赠款的总体目标是增加我们对以下方面的了解： 功能性下丘脑闭经（FHA）的病因和测试 几种新的治疗方案来治疗这种生殖障碍。 排卵障碍是女性不孕的最常见原因， 是导致不排卵的最常见原因 FHA的近因 下丘脑促性腺激素释放激素（GnRH）不足 分泌物 然而，一系列神经内分泌分泌 存在可归因于改变的下丘脑功能的紊乱。 我们 目前对女性和猴子的研究表明， 态度、心理压力和相关行为，如 热量限制和运动的起源特点 下丘脑-垂体-肾上腺（HPA）、HP-甲状腺（HPT）和 HP-卵巢（HPO）分泌改变。 因此，我们将FHA概念化为 由协同作用引起的下丘脑内稳态改变的状态 心理挑战和Meta妥协之间的区别 基础上 根据这些发现，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， 逆转下丘脑紊乱恢复排卵 的一个目的 这项拨款是为了验证这个假设。 然而，因为不是所有的女性 随着FHA将对CBT做出回应，我们将继续寻求识别 在女性和猴子中， 心因性和代谢性应激源之间的协同作用， 确定有前途的药物干预措施。 完善我们 作为FHA发病机制的模型，猴研究对于 确定因果关系和药理学选择，而人类 研究是测试心理社会和 药物治疗 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的结合， 在精神病学，行为医学， 运动生理学、神经生物学和生殖内分泌学。 今年的新发现表明， 心率更容易发展为应激诱导生殖 与基础心率较低的猴子相比， 我们目前正在 研究这是否也适用于女性。 资助NIMH MH 出版物卡梅隆JL，桥梁MW，格雷厄姆RE，长凳L， 放大图片作者：贝尔加SL，马修斯K.基础心率预测 心理压力导致的生殖功能障碍。 在 内分泌学会计划和摘要第80届年会（在 New Orleans，LA，June 24-27，1998），p138（摘要#P1-76）。

The overall goal of this grant is to increase our understanding of the etiology of Functional Hypothalamic Amenorrhea (FHA) and to 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 meta boli c 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 grant 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. New findings this year indicate that monkeys with elevated basal heartrate are more prone to develop stress-induced reproductive dysfunction than monkeys with lower basal heartrate. We are currently examining whether this also holds true for women. FUNDING NIMH MH 50748-05 PUBLICATIONS Cameron JL, Bridges MW, Graham RE, Bench L, Berga SL, Matthews K. Basal heartrate predicts development of reproductive dysfunction in response to psychological stress. In The Endocrine Society Program and Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 138 (abstract #P1-76).