COCAINE AND REPRODUCTIVE DYSFUNCTION

可卡因是育龄妇女普遍滥用的药物。 有 新出现的临床证据表明，女性长期使用可卡因与 生殖功能障碍，包括性欲下降，不规则 月经周期和闭经。尽管可卡因的泛滥 滥用和证据表明它与生殖功能障碍有关， 没有评估长期使用可卡因的影响的对照研究 对女性下丘脑-垂体-卵巢轴和月经周期的影响， 非人灵长类对老鼠的研究表明， 发情周期，降低排卵率，改变下丘脑 调节促性腺激素释放激素释放的神经递质。 将这些发现外推到女性或非人灵长类动物身上， 因为生殖功能的调节不同， 啮齿类动物和灵长类动物之间的差异。因此，本提案将评估 卵泡期每日服用可卡因对生殖系统的影响 在正常循环的恒河猴中发挥作用。拟议的研究将： (1)描述每日卵泡相的剂量反应效应 可卡因给药对月经周期、促性腺激素和卵巢 类固醇水平、排卵率和黄体功能，（2） 描述每日卵泡期可卡因给药的影响 对促性腺激素脉动性的影响，（3）确定是否每日卵泡期 可卡因给药直接损害垂体促性腺激素分泌， 以及（4）确定是否每日卵泡期可卡因施用 直接影响卵巢类固醇分泌和排卵。完成 这些目标，猴子将被放置在一个移动的背心和系绳组件， 允许在没有麻醉或压力的情况下给药和采血 这是已知的损害循环激素水平和卵巢/月经 周期性这些研究将确定可卡因的破坏性影响， 卵巢/月经周期和排卵，并确定剂量 可卡因来破坏循环。这些研究也将决定 可卡因的作用部位在下丘脑-垂体-卵巢轴内， 未来的研究可能会更好地确定可卡因的机制， 在轴中的每个站点内的动作。这些信息将是有价值的， 可卡因所致生殖功能障碍的临床处理 虐待

Cocaine is a commonly abused drug among reproductive age women. there is emerging clinical evidence that chronic cocaine use in women is associated with reproductive dysfunction, including decreased libido, irregular menstrual cycles and amenorrhea. Despite the growing epidemic of cocaine abuse and evidence associating it with reproductive dysfunction, there are no control studies that have assessed the effects of chronic cocaine use on hypothalamic-pituitary-ovarian axis and menstrual cyclicity in women or subhuman primates. Studies in rats have demonstrated cocaine disrupts estrous cyclicity, decreases ovulation rates and alters hypothalamic neurotransmitters that regulate gonadotropin-releasing hormone release. Extrapolation these findings to women or subhuman primates may not be appropriate because the regulation of reproductive function differs between rodents and primates. Accordingly, this proposal will assess the effects of daily follicular phase cocaine administration on reproductive function in normally cycling rhesus monkeys. The studies proposed will: (1) characterize the dose-response effects of daily follicular-phase cocaine administration on menstrual cyclicity, gonadotropin and ovarian steroid levels, ovulation rates, and corpus luteum function, (2) characterize the effects of daily follicular-phase cocaine administration on gonadotropin pulsatility, (3) determine whether daily follicular-phase cocaine administration directly impairs pituitary gonadotropin secretion, and (4) determine whether daily follicular-phase cocaine administration directly affects ovarian steroid secretion and ovulation. To accomplish these aims, monkeys will be placed in a mobile vest and tether assembly to allow drug administration and blood sampling without anesthesia or stress which are known to impair circulating hormone levels and ovarian/menstrual cyclicity. These studies will define cocaine's disruptive effects on ovarian/menstrual cyclicity and ovulation, and determine the dose of cocaine required to disrupt cyclicity. These studies will also determine cocaine's site of action within the hypothalamic-pituitary-ovarian axis, from which future studies may better determine cocaine's mechanism of action within each site in the axis. This information will be of value in the clinical management of reproductive dysfunction related to cocaine abuse.