PATHOGENESIS OF FUNCTIONAL HYPOTHALAMIC AMENORRHEA

这一建议，“功能性下丘脑闭经的发病机制，”是在 对PA-91 - 100“妇女心理健康的特殊问题， 生命周期“排卵功能障碍是不孕症最常见的原因 在女性中，功能性下丘脑性闭经（FHA）是最常见的 排卵障碍的原因FHA是月经停止， 先前排除了器质性病因的女性 因此理论上是可逆的 的星座 下丘脑改变引起的神经内分泌紊乱 功能，包括LH脉动性降低。的 FHA的近因是GnRH分泌不足。这个目标 我们的建议是调查下丘脑改变的起源， 功能，特别是GnRH脉冲发生器的中断， 可以制定有针对性的干预措施。总体假设 这一系列的研究表明，FHA遵循慢性和/或过度 应激反应，因此应激系统的两个主要组成部分，CRH 神经元网络和蓝斑-去甲肾上腺素/自主神经系统， 将在人类和猴子身上进行测试。 以下具体假设 将被测试：（l）FHA女性有不同的认知和 可能导致激活的心理特征 （2）FHA女性对行为反应更敏感， （3）调节下丘脑的中枢神经系统 功能（通过CSF水平评估）在FHA女性中发生改变;（4） 社会应激诱导FHA和一系列神经内分泌 猴子中的紊乱与FHA女性中观察到的紊乱相似;（5） 药理学阻断中枢神经系统激活 猴子的社会压力防止FHA;（6）猴子对 在FHA的发展方面反复出现的社会压力。与 为了完善我们的FHA发病机制模型， 研究对于确定因果关系和药理学试剂是至关重要的， 虽然人类研究是设计有针对性的心理社会 和/或药物干预。我们预计， 该提案将直接导致PA-91- 100的目标，即开发一种 “不孕症的社会心理干预”"

This proposal, "Pathogenesis of Functional Hypothalamic Amenorrhea," is in response to PA-9l-lOO, "Special Issues in Women's Mental Health Over the Life Cycle." Ovulatory dysfunction is the most common cause of infertility in women and functional hypothalamic amenorrhea (FHA) is the most common cause of ovulatory dysfunction. FHA is the cessation of menses in a previously eumenorrheic woman in whom organic causes have been excluded and therefore it is theoretically reversible. A constellation of neuroendocrine secretory disturbances attributable to altered hypothalamic function, including reduced LH pulsatility, have been documented. The proximate cause of FHA is insufficient GnRH secretion. The goal of this proposal is to investigate the genesis of the altered hypothalamic function, particularly the disruption of the GnRH pulse generator, so that targeted interventions can be devised. The overall hypothesis underlying this series of studies is that FHA follows a chronic and/or excessive stress response, so the two main components of the stress system, the CRH neuronal network and the locus ceruleus-norepinephrine/autonomic system, will be examined in humans and monkeys. The following specific hypotheses will be tested: (l) women with FHA have distinct cognitive and psychological characteristics that are likely to predispose to activation of the stress systems; (2) women with FHA are more reactive to behavioral challenge; (3) central neuronal systems that regulate hypothalamic function (as assessed by CSF levels) are altered in women with FHA; (4) social stress induces FHA and a constellation of neuroendocrine disturbances in monkeys similar to those seen in women with FHA; (5) pharmacological blockade of the central neuronal systems activated by social stress in monkeys prevents FHA; (6) monkeys become sensitized to repetitive social stress with regard to the development of FHA. With regard to refining our model of the pathogenesis of FHA, the monkey studies are critical to identifying causality and pharmacologic agents, while the human studies are integral to devising targeted psychosocial and/or pharmacologic interventions. We expect that the results of this proposal will lead directly to the PA-91-lOO objective of developing a "psychosocial intervention for infertility."