Rittmaster R S
Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
J Clin Endocrinol Metab. 1988 Oct;67(4):651-5. doi: 10.1210/jcem-67-4-651.
To determine the dose of the GnRH agonist leuprolide necessary to maximally suppress ovarian testosterone secretion, 10 moderately to severely hirsute women (5 with idiopathic hirsutism and 5 with polycystic ovarian syndrome) were given gradually increasing leuprolide doses, starting with either 5 or 10 micrograms/kg.day. Serum testosterone and estradiol, basal LH, and the LH response to GnRH were measured before and at the end of each treatment period, until maximal suppression of estradiol and testosterone occurred. Leuprolide was then continued for a total of 6 months to assess its clinical efficacy. Hirsutism scores and hair growth rates were determined before and after therapy. Serum estradiol and the LH response to GnRH were maximally or near-maximally suppressed in all women by the lowest doses of leuprolide used. Basal serum LH was not maximally suppressed in all women until a dose of 15 micrograms/kg.day was reached, and maximal testosterone suppression required 15 micrograms/kg.day or more in 7 of the 10 women. The addition of 0.5 mg dexamethasone daily for 4 weeks at the end of the study in 5 of the women reduced serum testosterone to undetectable levels. Symptomatic improvement in hirsutism occurred in 9 women, hirsutism scores decreased by at least 3 points in 5 women, and hair growth rates decreased in 8 women. These data indicate that low doses of leuprolide were sufficient to maximally suppress serum estradiol and the LH response to exogenous GnRH. Higher leuprolide doses were needed to maximally suppress serum testosterone and the basal LH levels. Leuprolide (20 micrograms/kg.day) effectively reduced hair growth in the majority of these women.
为确定能最大程度抑制卵巢睾酮分泌所需的促性腺激素释放激素（GnRH）激动剂亮丙瑞林的剂量，对10名中度至重度多毛女性（5名特发性多毛症患者和5名多囊卵巢综合征患者）给予逐渐增加剂量的亮丙瑞林，起始剂量为5或10微克/千克·天。在每个治疗期开始前及结束时测量血清睾酮、雌二醇、基础促黄体生成素（LH）以及LH对GnRH的反应，直至雌二醇和睾酮受到最大程度抑制。然后持续使用亮丙瑞林共6个月以评估其临床疗效。在治疗前后测定多毛症评分和头发生长速率。使用的最低剂量亮丙瑞林可使所有女性的血清雌二醇和LH对GnRH的反应受到最大程度或接近最大程度的抑制。直到达到15微克/千克·天的剂量，所有女性的基础血清LH才受到最大程度抑制，10名女性中有7名最大程度抑制睾酮需要15微克/千克·天或更高剂量。在研究结束时，5名女性每天加用0.5毫克地塞米松，持续4周，可使血清睾酮降至检测不到的水平。9名女性的多毛症症状有所改善，5名女性的多毛症评分至少降低了3分，8名女性的头发生长速率下降。这些数据表明，低剂量亮丙瑞林足以最大程度抑制血清雌二醇和LH对外源性GnRH的反应。需要更高剂量的亮丙瑞林才能最大程度抑制血清睾酮和基础LH水平。亮丙瑞林（20微克/千克·天）可有效减少这些女性中的大多数人的毛发生长。
