Safety and tolerability of progesterone treatment for women with cocaine use disorder: a pilot treatment trial

ABSTRACT

Background: Problematic cocaine use remains a significant public health issue, particularly among women. However, no concerted efforts have been made to target a pharmacological treatment option for women with cocaine use disorder (CUD) despite preclinical, human laboratory, and a limited number of clinical studies demonstrating that progesterone can attenuate the effects of cocaine to a greater extent in women than men.

Objectives: To evaluate the safety, tolerability, and preliminary efficacy of progesterone for treating women with CUD.

Methods: A 10-week double-blind randomized treatment trial was conducted. Prior to randomization, participants were required to achieve cocaine abstinence (1 week) before assignment to progesterone (up to 400 mg/day) or placebo. The primary efficacy outcomes were days to relapse and cocaine abstinence during the last 3 weeks of the trial. The frequency of side effects was also assessed.

Results: 227 women were assessed for eligibility. Twenty-five women entered treatment and 21 were randomized to progesterone (n = 11) or placebo (n = 10). The majority of women relapsed in less than 4 days with no differences between the two groups. Further, there were no significant differences between the progesterone and placebo groups in terms of cocaine abstinence during the last 3 weeks of the trial (27% and 10% respectively). The most commonly reported side effects were headache and fatigue, but no group differences were noted.

Conclusions: Progesterone was well tolerated and safe and supports further study is in a larger sample to determine if exogenous progesterone is an effective treatment option for women with CUD.

(ClinicalTrials.gov Identifier: NCT00632099)

KEYWORDS:

• Women
• cocaine
• progesterone
• clinical trial
• voucher incentives

Acknowledgements

We want to thank the staff of the Substance Treatment and Research Service (STARS) of the New York State Psychiatric Institute for their medical, clinical, and research support.

Author’s contributions

Author S.M.E. was the primary investigator and F.R.L. was the secondary investigator of the study at Columbia University; both authors were responsible for conceptualization, methodology, funding acquisition, and implementation. Authors A.O. and S.C.R. undertook statistical analysis and authors A.O., S.C.R., S.M.E., and F.R.L. were responsible for data interpretation. Author D.J.B. was responsible for administrative aspects of study implementation, data collection, and supervision of research staff while F.R.L. was responsible for supervision of clinical staff. Authors A.O. and S.M.E. wrote the first draft of the manuscript. All authors contributed to, edited, and have approved of the final manuscript and its submission to the journal.

Disclosure statement

F.R.L. receives grant support from the NIDA, SAMHSA and US World Meds and has been an unpaid member of a Scientific Advisory Board for Alkermes, Novartis and US WorldMeds. Authors A.O., S.M.E., S.C.R., and D.J.B reported no biomedical financial interests or potential conflicts of interest. The authors alone are responsible for the content and writing of this paper.

Additional information

Funding

Funding for this research was supported by NIDA grants DA022218 (S.M.E., F.R.L.) and DA022282 (S.C.R.). Progesterone and matching placebo were generously provided by the Women’s International Pharmacy.