Progesterone and Postpartum Smoking Relapse: A Pilot Double-Blind Placebo-Controlled Randomized Trial

Abstract

Introduction: Pregnancy is a strong motivator to quit smoking, yet postpartum relapse rates are high. Growing evidence suggests a role of sex hormones in drug abuse behavior and given the precipitous drop in sex hormones at delivery, they may play a role in postpartum relapse. This pilot study evaluates the feasibility and potential role of exogenous progesterone in postpartum smoking relapse. Methods: This 12-week double-blind placebo-controlled randomized pilot trial randomized 46 abstinent postpartum women to active progesterone (PRO; 200 mg twice a day) versus placebo (PBO) for 4 weeks. Participants were followed for relapse for 12 weeks. Main study outcomes include abstinence (point prevalence), feasibility (compliance per number of clinic visits attended, pill counts and Electronic Data Capture [EDC] completed) and self-reported acceptability. Safety was also measured by depressive symptom scores, adverse events, and breastfeeding. Results: Overall retention rate was 87% at week 12. At week 4, abstinence rates were 75% in the PRO group and 68.2% in the PBO group (p = .75). Medication adherence was 68% and clinic visit attendance was 80%, with no differences by randomization. Depressive symptom scores, adverse events, and breastfeeding did not vary by randomization. Conclusions: Although the study was not powered to evaluate abstinence rates, we did observe a higher prevalence of abstinence at week 4 in the PRO group. Further, exogenous progesterone was well tolerated and did not adversely affect depressive symptoms or breastfeeding. Thus, the results of this pilot study indicate further investigation into progesterone as a postpartum relapse prevention strategy is warranted. Implications: This innovative pilot trial determined the feasibility of delivering exogenous progesterone as a potential prevention of postpartum smoking relapse. We observed high retention and moderate adherence rates, as well as high acceptability among participants. Further, though not statistically significant, more women in the treatment group remained abstinent from smoking during follow-up. This project adds to the growing body of literature on the role of sex hormones in smoking relapse and also provides support for a fully powered clinical trial.

Exogenous progesterone for smoking cessation in men and women: a pilot double‐blind, placebo‐controlled randomized clinical trial

“…Results of this study support our and others’ prior findings that women who attempt to quit smoking in the luteal phase of the menstrual cycle (high progesterone) may have better smoking cessation outcomes . Results of this study also complement previous findings that exogenous progesterone may be helpful in preventing postpartum smoking relapse . However, the lack of an association between endogenous progesterone levels and study outcomes suggests that the progesterone itself may not be the direct cause of improved cessation outcomes in women.…”

“…Typically, 50–60% of micronized progesterone is absorbed after oral administration; it reaches its peak plasma levels in 2–3 hours and has an elimination half‐life of 3–4 hours . As found in our previous study with postpartum women, a dose of 200 mg of micronized progesterone results in serum progesterone levels comparable to those found in the mid‐luteal phase of the menstrual cycle (3–25 ng/ml) . For men, a dose of 200 mg of micronized progesterone results in similar serum progesterone levels .…”

“…Among clinical trials examining the effects of longerterm administration of progesterone versus placebo (8-12 weeks), research is limited and has focused on the prevention of postpartum smoking relapse. In a recent 12-week double-blind, placebo-controlled randomized pilot trial (n = 46), we observed that at 4 weeks postpartum, 7day point prevalence abstinence (PPA) rates were higher in the progesterone-treated group versus the placebo group (75.0 versus 68.2%; P = 0.75) [37]. A similar study by Forray and colleagues (2017; n = 41) found that postpartum women taking progesterone were 1.8 times more likely to be abstinent during week 8 of treatment [38].…”

A systematic review of behaviour change techniques within interventions to prevent return to smoking postpartum

“…Handsearching identified a further 69 relevant trials (after removal of duplicates). In total, articles from 117 studies were retrieved for full text assessment with the final inclusion of 32 primary RCTs (106 articles : Supplementary Table 1 ) which satisfied all inclusion criteria ( Allen, Allen, Lunos, & Tosun, 2016 ; Brandon, Simmons, Meade, et al, 2012 ; Cummins, Tedeschi, Anderson, & Zhu, 2016 ; Edwards & Sims-Jones, 1997 ; El-Mohandes, El-Khorazaty, Kiely, & Gantz, 2011 ; Ershoff, Quinn, & Mullen, 1995 ; Forray, Gilstad-Hayden, Sofuoglu, & Yonkers, 2016 ; Forray & Waters, 2015 ; Hajek, West, Lee, et al, 2001 ; Hannover, Thyrian, Roske, et al, 2009 ; Jimenez-Muro, Nerin, Samper, et al, 2013 ; Johnson, Ratner, Bottorff, Hall, & Dahinten, 2000 ; Kendrick, Zahniser, Miller, et al, 1995 ; Kientz & Kupperschmidt, 2005 ; Levine, Cheng, Marcus, Kalarchian, & Emery, 2016 ; Lillington, Royce, Novak, Ruvalcaba, & Chlebowski, 1995 ; McBride et al, 1999 ; McBride, Baucom, Peterson, et al, 2004 ; Morasco, Dornelas, Fischer, Oncken, & Lando, 2006 ; Mullen, DiClemente, & Bartholomew, 2001 ; Pbert, Ockene, Zapka, et al, 2004 ; Petersen, Handel, Kotch, Podedworny, & Rosen, 1992 ; Polanska, Hanke, Sobala, & Lowe, 2004 ; Pollak, Fish, Lyna, et al, 2016 ; Reitzel, Vidrine, Businelle, et al, 2010 ; Ruger, Weinstein, Hammond, Kearney, & Emmons, 2008 ; Secker-Walker, Solomon, Flynn, et al, 1995 ; Strecher et al, 2000 ; Secker-Walker, Solomon, Flynn, Skelly, & Mead, 1998 ; Suplee, 2005 ; Thornton, 1997 ; Winickoff et al, 2010 ).…”

Progesterone for smoking relapse prevention following delivery: A pilot, randomized, double-blind study

“…In a 12-week trial conducted by our group, we found that postpartum women with a cocaine use disorder who were randomly assigned to progesterone reported significantly less cocaine use and had a slower rate of relapse among those who were abstinent at baseline compared to women randomized to placebo (Yonkers et al, 2014). A recent pilot trial of progesterone in postpartum smokers showed more women remained abstinent after 4 weeks of progesterone treatment compared to women receiving placebo, although this difference did not reach statistical significance (Allen et al, 2016). In both studies, as in the current one, progesterone was well tolerated.…”