It has been suggested in prior literature that the effects of cocaine are partially modulated by the gonadal hormones, estradiol and progesterone, which may account for sex differences in the use and abuse of cocaine (Evans et al. 2002 & Jackson et al. 2006). Because previous studies have shown that women who use cocaine tend to use less of this drug during periods of high endogenous progesterone levels, as in pregnancy or during the luteal phase of the menstrual cycle, a recent study explored whether progesterone replacement could be effective in reducing cocaine use in postpartum women with a cocaine use disorder.  In this recent double-blinded study performed by researchers at Yale School of Medicine, women were eligible for the study if they met DSM IV criteria for cocaine abuse or dependence in the 6 months prior to conception or during pregnancy and were within 12 weeks of delivery.

Participants (N=50) were randomly assigned to receive either exogenous micronised progesterone (100 mg twice per day) or placebo. The dosage of progesterone was selected in order to generate levels similar to those found during pregnancy or the luteal phase of the menstrual cycle. Women were evaluated for cocaine use, cocaine cravings, and depressive symptoms over 12 weeks. Cocaine use data was collected through self-report and weekly urine samples. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess depressive symptoms over the course of the study.

Women in the progesterone group reported significantly less cocaine use during the 12-week trial than women in the placebo group. Progesterone therapy showed the most promise in women who were not using cocaine at time of intake. Of the 41 participants who were not using cocaine at the start of the study, the women receiving placebo relapsed more quickly than those in the progesterone group. Women who were not using cocaine during pregnancy may be more sensitive to elevated levels of progesterone that occur during pregnancy than women who continued cocaine use during pregnancy. Thus this subset of women that were abstinent at baseline may benefit more from the exogenous progesterone treatment than women who were not abstinent.

There was no difference between the two groups on cocaine craving scores on the Cocaine Craving Questionnaire-Brief. EPDS scores decreased throughout the study with no significant differences between the two groups. Improvements in subjective mood ratings may be the result of concurrent psychotherapy or simply a trial effect.

While this study suggests that progesterone may be a promising treatment option for certain women with cocaine use disorder, future studies are necessary to determine the optimum dose of progesterone needed to reduce cocaine use in the postpartum period and to elucidate the mechanism of action by which progesterone may decrease cocaine use.


Alexandra Sosinsky, BS

Yonkers KA, Farray A, Nich C, Carroll KM, Hine C, Merry BC, Shaw H, Shaw J, Sofuoglu M. Progesterone Reduces Cocaine Use in Postpartum Women with a Cocaine Use Disorder: A Randomized, Double-Blind Study. Lancet Psychiatry. 2014 Sept 25.

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