A protocol for modifying progesterone to increase postpartum cigarette smoking abstinence and reduce secondhand smoke exposure in infants.

New interventions are necessary to increase postpartum abstinence from cigarette smoking. Sex hormones, specifically progesterone, have been found to be protective against drug-taking behaviors. Our pilot double-blind, randomized, controlled trial, although underpowered, suggested a trend toward a higher prevalence of smoking abstinence among postpartum participants receiving exogenous progesterone compared to those receiving placebo. This paper outlines the protocol used in our study to evaluate the efficacy of modifying progesterone to increase postpartum smoking abstinence and, subsequently, decrease secondhand smoke exposure in infants. In the intervention arm, participants will receive open-label exogenous oral progesterone (200 mg twice daily). Using a concurrent control group that does not receive progesterone treatment, we hypothesize that progesterone treatment will increase postpartum smoking abstinence as measured using a 7-day point prevalence at six months post-treatment allocation, as well as reduce smoking-related risk factors. Secondary objectives include examining the impact of this maternal smoking intervention on infant health. In addition to describing the protocol, we also discuss the protocol changes made due to the COVID-19 pandemic. Upon completion, this study will provide new information on how sex hormones may influence smoking cessation in postpartum populations, which can have broad public health implications. Clinical trials registration #: NCT04783857.