Mathias J R, Clench M H, Roberts P H, Reeves-Darby V G
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0764.
Dig Dis Sci. 1994 Jun;39(6):1163-70. doi: 10.1007/BF02093779.
We initially investigated the effects of a gonadotropin-releasing hormone analog, leuprolide acetate, in 28 patients with moderate to severe functional bowel disease in a phase-II, randomized, double-blind, and placebo-controlled study using Lupron Depot 3.75 mg (which delivers a continuous low dose of drug for one month) or placebo given intramuscularly. After completing that 12-week study period during which their symptoms had improved significantly (P < 0.01-0.5), the 28 patients were allowed to continue receiving leuprolide acetate; they were monitored for an additional 40 weeks. Of those 28, 25 (89%) finished the 52-week treatment. Drug administration was changed from the monthly low-dose form of leuprolide acetate to a daily subcutaneous dose that was gradually increased from 0.5 mg daily to an effective therapeutic dose (1.0-1.5 mg). All subjects received estrogen replacement during this period. Continued use of leuprolide acetate at maximum therapeutic dosage and over longer periods of time produced even more striking and significant changes in the disabling and debilitating symptoms of functional bowel disease. Nausea, abdominal pain, early satiety, anorexia, and abdominal distension decreased markedly (P < 0.0001) and vomiting was also reduced (P < 0.01) more than in the short-term, low-dosage, double-blind study. Combined total symptom scores and overall assessment also changed significantly in the long-term phase (both P < 0.0001).
在一项II期随机双盲安慰剂对照研究中，我们最初使用3.75毫克的醋酸亮丙瑞林缓释微球（Lupron Depot，每月持续释放低剂量药物）或安慰剂进行肌肉注射，研究促性腺激素释放激素类似物醋酸亮丙瑞林对28例中重度功能性肠病患者的影响。在完成为期12周的研究期后，这些患者的症状有显著改善（P<0.01 - 0.5），这28例患者被允许继续接受醋酸亮丙瑞林治疗；对他们进行了另外40周的监测。在这28例患者中，25例（89%）完成了52周的治疗。给药方式从每月低剂量的醋酸亮丙瑞林改为每日皮下注射，剂量从每日0.5毫克逐渐增加至有效治疗剂量（1.0 - 1.5毫克）。在此期间，所有受试者均接受雌激素替代治疗。以最大治疗剂量持续使用醋酸亮丙瑞林更长时间，在功能性肠病的致残和衰弱症状方面产生了更显著的变化。恶心、腹痛、早饱、厌食和腹胀明显减轻（P<0.0001），呕吐也比短期低剂量双盲研究时减少（P<0.01）。长期阶段的综合总症状评分和总体评估也有显著变化（均为P<0.0001）。
