Effect of exogenous progesterone administration on cigarette smoking-related symptomology in oral contraceptive users who smoke

•Smoking-related symptomatology (SRS; e.g., craving) varies by menstrual phase.•Progesterone is thought to influence SRS levels, this has not yet been tested.•Using a cross-over design, we administered progesterone and measured SRS.•Progesterone administration had no significant effects on SRS. Cigarette smoking-related symptomatology (e.g., craving; SRS) is linked to relapse after a quit attempt. SRS varies by menstrual phase, possibly due to variations in sex hormones (e.g., progesterone), though much of the research to-date has relied on observations from the menstrual cycle acting as a proxy for hormone levels. The goal of this study was to examine the effect of exogenous progesterone on SRS during ad libitum smoking and following overnight abstinence. Oral contraceptive users who smoked completed two 9-day crossover testing periods (7 days of ad libitum smoking and 2 days following overnight abstinence) while taking double-blind active/placebo exogenous progesterone. Participants completed questionnaires to measure SRS. The effect of exogenous progesterone and endogenous hormones (progesterone, estradiol, and progesterone-to-estradiol [P/E2] ratio) on SRS was assessed with paired t-tests and linear mixed effect models. Participants (n = 53) were, on average, 24 years old and smoked 11 cigarettes per day. During ad libitum smoking, a doubling of the P/E2 ratio was associated with 0.09 points lower anticipated relief from negative affect (95% confidence interval [CI]: 0.03–0.15 points lower; p = 0.008) and 0.11 points lower psychological reward (95% CI: 0.03–0.18 points lower; p = 0.006). After correction for multiple testing, these associations were not statistically significant: anticipated relief from negative effect (p = 0.10) and psychological reward (p = 0.09). No other significant associations were observed. Although substantial previous literature indicates that progesterone influences SRS, exogenous progesterone administration did not alter SRS here. Additional research is needed to elucidate alternative mechanisms involved in menstrual phase effects on SRS.