Wildt L, Leyendecker G, Sir-Petermann T, Waibel-Treber S
Department of Obstetrics and Gynaecology, University of Erlangen, Germany.
Hum Reprod. 1993 Mar;8(3):350-8. doi: 10.1093/oxfordjournals.humrep.a138050.
Sixty-six women suffering from various grades of hypothalamic ovarian failure were treated with the opiate antagonist naltrexone at doses ranging from 25 to 150 mg per day. This treatment resulted in complete normalization of the menstrual cycle in 49 of 66 patients, as indicated by the pattern of circulating levels of gonadotrophins and ovarian steroids. Five patients failed to respond, three of whom were suffering from primary hypothalamic amenorrhoea. In patients who responded to the administration of naltrexone, there was a dramatic increase in the amplitude and frequency of gonadotrophin pulses, reflecting disinhibition of the hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator. Eighteen pregnancies were achieved in 16 women who were also treated for infertility, resulting in a cumulative pregnancy rate closely resembling that of a normal population. There were only minor side-effects that could be attributed to the drug. These data demonstrate that chronic administration of an opiate antagonist will normalize ovarian function in women suffering from different grades of hypothalamic ovarian failure. The data therefore support the view that suppression of the activity of the hypothalamic pulse generator, that directs GnRH release, is mediated by endogenous opioids. Also, that hypothalamic ovarian failure is the consequence of an inappropriate increase in opioid tone impinging on neurons that release GnRH in a pulsatile manner into the pituitary portal circulation.
66名患有不同程度下丘脑性卵巢功能衰竭的女性接受了阿片类拮抗剂纳曲酮治疗，剂量为每日25至150毫克。根据促性腺激素和卵巢甾体激素的循环水平模式显示，该治疗使66名患者中的49名月经周期完全恢复正常。5名患者无反应，其中3名患有原发性下丘脑闭经。在对纳曲酮给药有反应的患者中，促性腺激素脉冲的幅度和频率显著增加，这反映了下丘脑促性腺激素释放激素（GnRH）脉冲发生器的去抑制作用。16名接受不育治疗的女性中有18次妊娠，累积妊娠率与正常人群非常相似。仅出现了一些可归因于该药物的轻微副作用。这些数据表明，长期给予阿片类拮抗剂可使患有不同程度下丘脑性卵巢功能衰竭的女性卵巢功能恢复正常。因此，这些数据支持以下观点：指导GnRH释放的下丘脑脉冲发生器活动的抑制是由内源性阿片类物质介导的。此外，下丘脑性卵巢功能衰竭是由于作用于以脉冲方式向垂体门脉循环释放GnRH的神经元的阿片类物质张力不适当增加所致。
