Benifla J L, Dumont M, Levardon M, Foucher E, Cadiot G, Crenn-Hebert C, Heid M, Lelaidier C, Rosenbaum A, Bernuau J, Erlinger S, Frydman R, Madelenat P
Service de Gynécologie-Obstétrique, Hôpital Bichat, Paris.
Contracept Fertil Sex. 1997 Feb;25(2):165-9.
In France, prescription of micronized progesterone at high doses of 900 to 1200 mg/day is common practice in the case of preterm delivery, even though this is neither an indication nor a posology given for marketing authorisation. A few cases of gestational pruritus have been reported during such use, associated with cholestasic and/or cytolytic hepatic disorders. We report here the results of a controlled, double-blind study versus a placebo, aimed at assessing the effects on the liver of micronized progesterone administered orally at high doses (900-1200 mg/day), conducted in a population of 201 women presenting moderate menace of preterm delivery during the third trimester of pregnancy. 85 patients received micronized progesterone and 116 the placebo. The increase above normal levels of total biliary acids (TBA) and aminotransferases (ASAT, ALAT), was significantly more frequent in the micronized progesterone than in the placebo group. Among the 26 patients (14%) with a level of TBA superior to 10 mumoles/l during treatment, 18 belonged to the progesterone and 8 to the placebo group (p = 0.004); the 6 patients (3.4%) with increased ASAT were all under micronized progesterone (p < 0.001), as were the 10 patients (5.6%) with increased ALAT (p < 0.001). However, there is no statistically significant difference between the two groups regarding the occurrence of clinical manifestations (icterus, pruritus) which could be attributed to gravid cholestasis. We may conclude from this prospective study that, during the third trimester of pregnancy, micronized progesterone is associated with a significant risk of biological cholestasis. This would suggest that in patients genetically predisposed towards gravid cholestasis, micronized progesterone could be a factor favoursing this disease.
在法国，对于早产情况，高剂量（900至1200毫克/天）微粒化孕酮的处方是常见做法，尽管这既不是上市许可给出的适应证也不是剂量说明。在这种使用过程中，已有几例妊娠瘙痒症的报告，伴有胆汁淤积性和/或细胞溶解性肝脏疾病。我们在此报告一项针对安慰剂的对照双盲研究结果，该研究旨在评估高剂量（900 - 1200毫克/天）口服微粒化孕酮对肝脏的影响，研究对象为201名在妊娠晚期有中度早产风险的女性。85名患者接受微粒化孕酮治疗，116名接受安慰剂治疗。微粒化孕酮组总胆汁酸（TBA）和氨基转移酶（ASAT、ALAT）高于正常水平的增加情况显著比安慰剂组更频繁。在治疗期间TBA水平高于10微摩尔/升的26名患者（14%）中，18名属于孕酮组，8名属于安慰剂组（p = 0.004）；ASAT升高的6名患者（3.4%）均在微粒化孕酮治疗组（p < 0.001），ALAT升高的10名患者（5.6%）也均在微粒化孕酮治疗组（p < 0.001）。然而，在可归因于妊娠胆汁淤积的临床表现（黄疸、瘙痒）的发生方面，两组之间没有统计学上的显著差异。从这项前瞻性研究我们可以得出结论，在妊娠晚期，微粒化孕酮与生物学胆汁淤积的显著风险相关。这表明在遗传上易患妊娠胆汁淤积的患者中，微粒化孕酮可能是促成这种疾病的一个因素。
