A Placebo-Controlled Trial of a Depot Gonadotropin-Releasing Hormone Analogue (Leuprolide) in the Treatment of Uterine Leiomyomata
A Placebo-Controlled Trial of a Depot Gonadotropin-Releasing Hormone Analogue (Leuprolide) in the Treatment of Uterine Leiomyomata
复制标题
长效促性腺激素释放激素类似物（亮丙瑞林）治疗子宫平滑肌瘤的安慰剂对照试验
作者：
W. Schlaff;E. Zerhouni;J. Huth;James Chen;M. Damewood;J. Rock
多项研究表明，使用促性腺激素释放激素 (GnRH) 类似物治疗可以减少患有平滑肌瘤的女性的子宫体积。然而，迄今为止，还没有任何研究使用对照人群进行比较，也没有任何研究描述体积减少的生理机制。我们对 11 名有症状的子宫肌瘤患者进行了一项双盲、安慰剂对照研究，每月给予 GnRH 类似物（亮丙瑞林）长效制剂，持续 24 周。最初接受安慰剂治疗的患者随后接受活性药物治疗 24 周。使用磁共振成像来具体识别子宫总体积、肌瘤总体积和非肌瘤总体积。与安慰剂患者相比，治疗患者的子宫总体积和非肌瘤体积显着减少（P < .02）。肌瘤总体积也减少了，但仅达到 P=0.06 的水平。所有 11 名患者的治疗前与治疗后值均显示所有三个体积均显着减少 (P < .02)。大多数症状明显改善。治疗后 24 周，所有体积均恢复至基线水平，但症状改善通常持续存在。非肌瘤体积按比例减少的程度比肌瘤体积更大（42.7% vs 30.4%），因此我们可以解释治疗停止时看到的重新扩大。副作用的耐受性良好，并且没有研究中途退出。我们的结论是，GnRH 类似物引起的暂时性雌激素低下可导致子宫体积显着但暂时的减少，并且非肌瘤体积是造成子宫体积减少和重新增大的主要原因。该治疗具有良好的耐受性，即使子宫体积恢复至治疗前的大小，症状获益也可能持续存在。
Several studies have shown that treatment with a gonadotropin- releasing hormone (GnRH) analogue can reduce uterine volume in women with leiomyomata. However, no study to date has used a controlled population for comparison, nor has any study delineated the physiologic mechanism of volume reduction. We performed a double-blind, placebo-controlled study of a depot form of a GnRH analogue (leuprolide) given monthly for 24 weeks in 11 patients with symptomatic uterine leiomyomata. Patients initially treated with placebo were subsequently treated with active drug for 24 weeks. Magnetic resonance imaging was used to identify specifically the total uterine volume, total myoma volume, and total non-myoma volume. Treated patients had a significant reduction in total uterine and non-myoma volumes as compared with placebo patients (P < .02). Total myoma volume was also reduced, but only to a P=.06 level. Pre- versus post-therapy values for all 11 patients showed significant reduction in all three volumes (P < .02). Most symptoms were markedly improved. By 24 weeks post-therapy, all volumes had returned to baseline levels, although symptomatic improvement commonly persisted. The non-myoma volume was proportionally reduced to a greater extent than the myoma volume (42.7 versus 30.4%), and we therefore could explain the reenlargement seen when treatment was discontinued. Side effects were well tolerated and there were no study dropouts. We conclude that temporary hypoestrogenism induced by GnRH analogues can produce significant though temporary reduction in uterine volumes, and that the non-myoma volume is responsible for much of the reduction and reenlargement. The treatment is well tolerated, and symptomatic benefits may well persist even with return of uterine volumes to pre-treatment size.