Yonkers Kimberly Ann, Forray Ariadna, Nich Charla, Carroll Kathleen M, Hine Cristine, Merry Brian C, Shaw Howard, Shaw Julia, Sofuoglu Mehmet
Departments of Psychiatry, Obstetrics and Gynecology and School of Epidemiology and Public Health, Yale University School of Medicine,40 Temple Street, Suite 6B, New Haven, Connecticut, USA 06510.
Department of Psychiatry, Yale University School of Medicine,40 Temple Street, Suite 6B, New Haven, Connecticut, USA 06510.
Lancet Psychiatry. 2014 Oct 1;1(5):360-367. doi: 10.1016/S2215-0366(14)70333-5.
Progesterone modulates multiple brain functions implicated in the pathogenesis ofdrug addiction. During high endogenous progesterone states, women reduce use of cocaine. We sought to test whether progesterone replacement reduces cocaine use in postpartum women with a cocaine use disorder (CUD).
A 12-week, double-blind, parallel, randomized, placebo-controlled pilot trial with a 3-month post trial follow-up. 25 women within 12 weeks of deliverywere randomized to placeboand 25 to100 mgs of oral micronized progesterone, administered twice daily. Participants were recruited from obstetrical clinics. Randomization and allocation were performed by the study biostatistician. Attrition was 18% and the analysis included all50participants. Outcomes were self-reported days of cocaine use and positive urine toxicology assays for cocaine metabolites.
Participants randomized to placebo compared to progesterone had increased likelihood of cocaine use per week (RR=1·19; 95% confidence interval (CI)=1·05 to 1·36; p<0·01). At the three-month post trial visit the difference between groups was not significant (Likelihood RatioΧ =5·16; P=·08). There were no group differences in rates of submission of a positive urine test. A post hoc analysis showed a higher rate of relapse for participants randomized to placebo (HR=4·71; 95% CI= 1·09 to 20·5). We did not observe groups differences in the rate of adverse events.
These preliminary findings support the promise of progesterone treatment in postpartum women with a CUD and could constitute a therapeutic break through.
US National Institute on Drug Abuse; Veterans Administration.
孕酮可调节与药物成瘾发病机制相关的多种脑功能。在高内源性孕酮状态下，女性会减少可卡因的使用。我们试图测试孕酮替代疗法是否能减少患有可卡因使用障碍（CUD）的产后女性的可卡因使用量。
一项为期12周的双盲、平行、随机、安慰剂对照试验，并进行3个月的试验后随访。25名在分娩12周内的女性被随机分为安慰剂组，25名被随机分为口服100毫克微粒化孕酮组，每日服用两次。参与者从产科诊所招募。随机分组和分配由研究生物统计学家进行。失访率为18%，分析纳入了所有50名参与者。结果指标为自我报告的可卡因使用天数和可卡因代谢物的尿毒理学阳性检测。
与孕酮组相比，随机分配到安慰剂组的参与者每周使用可卡因的可能性增加（风险比=1·19；95%置信区间（CI）=1·05至1·36；p<0·01）。在试验后三个月的随访中，两组之间的差异不显著（似然比Χ =5·16；P=·08）。尿检测阳性率在两组之间没有差异。事后分析显示，随机分配到安慰剂组的参与者复发率更高（风险比=4·71；95%置信区间= 1·09至20·5）。我们没有观察到两组在不良事件发生率上的差异。
这些初步研究结果支持了孕酮治疗患有CUD的产后女性的前景，并可能构成一项治疗突破。
美国国家药物滥用研究所；退伍军人管理局。
