[Effects of micronized natural progesterone on the liver during the third trimester of pregnancy]

Abstract

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.