Postpartum Changes in Mood and Smoking-Related Symptomatology: An Ecological Momentary Assessment Investigation.

Introduction: Postpartum smoking relapse is a highly prevalent public health problem. Mood and breast feeding are significantly associated with smoking relapse, although less is known about the temporality of these relationships. Therefore, this study utilized ecological momentary assessments (EMA) to prospectively examine changes in mood and smoking-related symptomatology in relationship to three events-childbirth, termination of breast feeding, and smoking relapse. We expected all three events to significantly alter mood and smoking-related symptomatology. Methods: We enrolled a sample of pregnant women who had recently quit smoking and intended to remain quit during the postpartum. Participants were randomized to active/placebo progesterone to prevent postpartum relapse. Participants also completed daily EMA to collect data mood and smoking-related symptomatology as well as our three events of interest. Results: Participants (n = 46) were, on average, 26.5 ± 0.8 years old and, prior to pregnancy, smoked 10.1 ± 0.7 cigarettes/day. We noted a number of significant within- and between-subject relationships. For example, participants reported a 24% decline in negative affect after childbirth (p = .0016). Among those who relapsed to smoking (n = 23), participants randomized to placebo had a significant increase in cigarette craving after relapse (ß = 1.06, 95% confidence interval [CI] = 0.62 to 1.49, p value = .0003), whereas participants randomized to active progesterone did not (ß = 0.63, 95% CI = -0.35 to 1.62, p value = .1824). Conclusions: These observations suggest that mood and smoking-related symptomatology are influenced by childbirth, breast feeding, smoking relapse, and use of exogenous progesterone. Future research should explore how these observations may inform novel postpartum smoking relapse-prevention interventions. Implications: Postpartum smoking relapse has been a persistent public health problem for more than 40 years. Although a number of significant predictors of postpartum smoking relapse have been identified (eg, depression and breast feeding), much of these analyses have relied on cross-sectional and/or self-reported retrospective data. Therefore, for the first time, we utilized ecological momentary assessment to explore the effect of childbirth, termination of breast feeding, and smoking relapse on mood and smoking-related symptomatology (eg, craving). Numerous significant relationships were observed, including a 96% increase in craving after smoking relapse. These novel observations can inform new and effective postpartum smoking relapse-prevention programs.

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

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; 200mg 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.

The University of Minnesota's Clinical Research Support Center Feasibility Review: An objective protocol assessment carving a pathway to study success.

To successfully and efficiently initiate clinical research studies, it is critical to develop a strong, feasible, and well-written study protocol early in the start-up phase. The University of Minnesota's Clinical Research Support Center designed and implemented a structured Feasibility Review process in 2018 that addresses common start-up challenges such as poor study design, inappropriate outcomes, and limited resources. This process has been shown to turn an unfeasible study into a well-designed protocol that is IRB-approved with few protocol-related stipulations and well prepared for execution. It has also educated study teams on how to write better quality and more robust protocols for subsequent studies. Once a draft protocol is available, the entire process takes just six working days and is free of charge to investigators, study teams, and departments. From 2018-2021, one hundred sixteen Feasibility Reviews (n=116) have been completed across eight schools or colleges. Mean satisfaction scores for study team members who responded were high (N=126, M=4.71 ± 0.5) on a 5-point Likert-type scale. Most respondents (96%) indicated that they planned to modify their protocol based on reviewer feedback. Open ended/qualitative feedback was highly positive with most responses centered around the helpfulness of feasibility review, the high level of expertise, and fast turnaround time. The Feasibility Review is a valuable and multifunctional program providing timely expert guidance to study teams to efficiently and successfully launch and execute clinical research studies. It can be easily replicated, adapted, and implemented at other institutions to increase the quality and efficacy of academic research.

Response to nicotine following overnight smoking abstinence during short-term progesterone treatment in women.

Preclinical and clinical literature suggest that sex hormones impact tobacco use behaviors in women. The goal of this double-blind crossover laboratory study was to examine the effect of oral exogenous progesterone (200 mg twice per day) versus placebo on nicotine response using measures of motor speed and cognitive function in women following overnight smoking abstinence. We hypothesized that increased progesterone would blunt the nicotine response whereby producing less change in motor speed and cognition in response to nicotine exposure. Female smokers, age 18-35, were randomized to participate in two 9-day crossover testing weeks. Participants completed a lab session following overnight abstinence where they were administered nicotine nasal spray and asked to complete measures of immediate memory (IMT), delayed memory (DMT), word recall (WR), and finger tapping speed (FT). After the first 9-day testing week, participants resumed smoking and returned the following month to complete the identical lab session in the crossover condition. Forty-seven women were included in this analysis (n = 47). We found no differences in the magnitude of response for IMT, DMT, and WR between conditions. For FT, women had a blunted response to nicotine during the placebo condition. When examining the association between hormone levels and relative performance, we found increases in DMT, WR, and FT but decreases in IMT during the progesterone condition. We observed differences between progesterone versus placebo in relative change in some measures of nicotine response following overnight abstinence. Future studies are needed to further characterize this response. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

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

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.

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

BACKGROUND AND AIMS: In some clinical studies men and women have been found to differ in their ability to quit smoking, perhaps as a result of progesterone. The primary aim of this study was to provide a preliminary test of whether progesterone (PRO), compared with placebo (PBO), was more effective for smoking cessation in men and women. DESIGN: Pilot double-blind, placebo-controlled randomized clinical trial. SETTING: Minneapolis/St Paul metro area, Minnesota, USA. PARTICIPANTS: A total of 216 participants were randomized, including 113 men (18-60 years; PRO = 56, PBO = 57) and 103 women (18-50 years, pre-menopausal with self-reported regular menstrual cycles; PRO = 51, PBO = 52). INTERVENTION: Participants were randomized (1 : 1 within sex group) to either PRO (200 mg twice daily) or PBO. Participants were assigned a quit date approximately 7 days after starting medication (luteal phase for women) and were followed for 12 weeks to assess relapse. MEASUREMENTS: The primary outcome was self-reported 7-day point prevalence abstinence (PPA) at week 4. Secondary outcomes included 7-day PPA at weeks 8 and 12, prolonged abstinence, continuous abstinence, urine cotinine < 50 ng/ml, expired carbon monoxide ≤ 5 parts per million (p.p.m.) and days to relapse. FINDINGS: There was a significant difference in 7-day PPA at week 4 among women [PRO: 18 (35.3%) versus PBO: 9 (17.3%), odds ratio (OR) = 2.61, 95% confidence interval (CI) = 1.04, 6.54, P = 0.041], but not among men [PRO: 13 (23.2%) versus PBO: 12 (21.1%), 1.13 (0.47, 2.76), P = 0.782]. There was some evidence that PRO delayed relapse in women (days to relapse; PRO: 20.5 ± 29.6 versus PBO: 14.3 ± 26.8, P = 0.03) but not in men (PRO: 13.4 ± 25.9 versus PBO: 13.3 ± 23.8, P = 0.69). CONCLUSIONS: Oral micronized progesterone may aid smoking cessation in women.

Menstrual Cycle in Women Who Co-use Marijuana and Tobacco.

OBJECTIVE: Marijuana is the most commonly used illicit drug in the United States and co-use with tobacco is increasing. Preliminary studies have indicated that marijuana may suppress luteinizing hormone (LH) or shorten the luteal phase. Although the literature is mixed, these sex hormones may play a role in smoking cessation outcomes. This secondary subgroup analysis aims to explore the menstrual cycle of females who co-use marijuana and tobacco compared with females who only use tobacco in a sample of tobacco treatment-seeking individuals. METHODS: Female participants, aged 18 to 50 years, who self-reported regular menstrual cycles and co-use of marijuana and tobacco were matched 1:3 by age to participants who only use tobacco. Length of the follicular and luteal phases was determined using First Response Urine LH tests. Wilcoxon 2-sample t tests were used to determine differences in phase lengths between groups. RESULTS: Thirteen women who co-use marijuana and tobacco, and 39 women who only use tobacco were included in this analysis. Overall, participants were 37.3 ±â€Š8.0 (SD) years of age, mostly Caucasian (67%), and smoked 12.6 ±â€Š5.2 (SD) cigarettes per day. The luteal phase length among participants who co-use marijuana and tobacco (11.4 days ±â€Š2.2 [SD]) was significantly shorter than among participants who only use tobacco (16.8 days ±â€Š11.3 [SD]; P = 0.002). No differences were found in follicular phase length or menstrual cycle length. CONCLUSIONS: These data suggest that females who co-use marijuana and tobacco may have a shortened luteal phase in comparison with females who only use tobacco. Further studies are needed to better understand how marijuana use may impact the menstrual cycle and affect smoking outcomes.

Examining characteristics associated with quitting smoking during pregnancy and relapse postpartum.

INTRODUCTION: Smoking during pregnancy is a significant public health concern that can cause adverse health outcomes for both the mother and fetus. Studies have shown only 40% of women quit smoking during pregnancy, with more than half relapsing within 6months, and up to 90% relapsing within one year. This study investigates differences in demographics and smoking-related symptomatology between pregnant smokers and pregnant quitters, as well as factors associated with postpartum relapse. METHODS: Data on pregnant smokers and pregnant quitters were obtained from two separate parent studies. Data on smoking demographics and smoking-related symptomatology were collected at screening visits. RESULTS: Compared to pregnant smokers, pregnant quitters had more favorable smoking characteristics (e.g., smoked fewer cigarettes per day, reported higher motivation for abstinence and less dependency). They also had more favorable relationship characteristics (e.g., were more likely to be married, less likely to have a significant other who smokes) and had less reproductive liability (e.g., fewer pregnancies, fewer children). In terms of symptomatology, pregnant quitters reported more positive affect, negative affect, physical symptoms and withdrawal but less craving. Predictors of postpartum relapse included increased maternal age, having a significant other who smokes and an increased likelihood of returning to smoking after pregnancy (self-reported prior to delivery). CONCLUSIONS: Several demographics and smoking-related symptomatology were significantly different between pregnant quitters and pregnant smokers. In addition, multiple factors predicting postpartum relapse were identified. This information can inform personalized interventions for high risk pregnant smokers and pregnant quitters at risk for postpartum relapse.

Association of exercise with smoking-related symptomatology, smoking behavior and impulsivity in men and women.

INTRODUCTION: Despite extensive efforts to develop effective smoking cessation interventions, 70-85% of American cigarette smokers who quit relapse within one year. Exercise has shown promise as an intervention; however, many results have been equivocal. This study explored how exercise is associated with smoking-related symptomatology, smoking behavior and impulsivity in male and female smokers. METHODS: Participants were recruited throughout the United States using the on-line crowdsourcing platform, Amazon's Mechanical Turk. They completed a survey with self-report measures assessing exercise, smoking-related symptomatology, smoking behavior and impulsivity. Differences between men and women were tested using t- and chi-square tests. Regression analyses tested for associations between exercise and smoking-related symptomatology, smoking behavior and impulsivity. RESULTS: Participants (N = 604) were, on average, 32 (SD = 6.2) years old, mostly Caucasian, with at least some college education and approximately half were women. Women exercised slightly less than men and had more negative affect, craving, physical symptoms and withdrawal. Women smoked more cigarettes per day, had greater nicotine dependency and more years of smoking. Positive affect was positively associated with exercise for both men and women; however, this association was significantly stronger in women. Negative affect and withdrawal were inversely associated with exercise for women only. Impulsivity was inversely associated with exercise for both men and women. CONCLUSION: Exercise was significantly associated with several smoking-related symptomatology, smoking behavior and impulsivity variables for both men and women, suggesting that exercise may be a useful intervention for smoking cessation. Future prospective research should determine how exercise directly impacts smoking cessation.

The effect of combination oral contraceptives on smoking-related symptomatology during short-term smoking abstinence.

Although an estimated 25% of premenopausal smokers report using oral contraceptives (OC), little is known about how OC use may influence smoking cessation. The purpose of this study was to examine the difference in smoking-related symptomatology during acute smoking abstinence between women on a standardized combination OC (Tri-Sprintec(™)) compared to women not on OCs (no-OC). Participants were women aged 18-40 who smoked ≥5 cigarettes/day and reported regular menstrual cycles. Using a controlled cross-over design, participants completed two six-day testing weeks: Low Progesterone Week (LPW; Follicular (F) phase in no-OC or 1st week of pills in OC) and High Progesterone Week (HPW; Luteal (L) phase in no-OC or 3rd week of pills in OC). Each testing week included daily assessment of symptomatology and biochemical confirmation of smoking status. During smoking abstinence, the OC group (n=14) reported significantly lower levels of positive affect (21.56±7.12 vs. 24.57±6.46; ß=3.63, p=0.0323) than the no-OC group (n=28). Further significant interactions between group and testing week were observed as follows: Smoking satisfaction was higher during LPW in the OC group (LPW: 4.29±1.30 vs. HPW: 4.10±1.37) but higher during HPW in the no-OC group (LPW: 3.91±1.30 vs. HPW: 4.23±1.30; ß=-0.5499, p<0.0001). Similar interactions were noted in negative affect and psychological reward of smoking. These results suggest that women on OCs may have different patterns of smoking-related symptomatology during short-term smoking abstinence as compared to women not on OCs. Additional work is needed to examine how this may affect smoking cessation efforts.

Associations between adrenocortical activity and nicotine response in female smokers by menstrual phase.

Previous research suggests that menstrual phase may influence smoking-related symptomatology. The present study analyzes the relationship between menstrual phase and salivary cortisol with subjective responses to nicotine among female smokers during ad libitum smoking. We hypothesize higher cortisol levels would be associated with increased positive and decreased negative subjective responses to nicotine. We also expected that these associations would vary by menstrual phase. Females aged 18-40 who smoke at least five cigarettes/day, reported regular menstrual cycles and did not use exogenous hormones or psychotropic medications were enrolled into a controlled cross-over trial. Participants completed identical data collection procedures during follicular (F) and luteal (L) phases; including self-collected salivary cortisol samples and completion of a nicotine response lab session involving administration of nicotine nasal spray and monitoring of subjective response to nicotine via the Subjective State Scale and Visual Analog Scale. Participants (n = 116) were 29.1 ± 6.9 years old and smoked an average of 12.3 ± 5.5 cigarettes daily. During F phase, higher morning cortisol was associated with decreased negative affect (r = -0.21, p = 0.03), withdrawal (r = -0.30, p < 0.01) and increased relaxation (r = 0.24, p = 0.02) after administration of nicotine nasal spray. Conversely, during L phase, higher morning cortisol was associated with a decrease in head rush (r = -0.26, p = 0.01) and urge to smoke (r = -0.21, p = 0.04) after administration of nicotine nasal spray. Similar associations between greater diurnal cortisol variation and response to nicotine were seen. These observations indicate that cortisol may have a phase-specific association with some subjective responses to nicotine in female smokers. Additional research should explore how these relationships may influence smoking cessation efforts.

Smoking- and menstrual-related symptomatology during short-term smoking abstinence by menstrual phase and depressive symptoms.

Menstrual phase and depressive symptoms are known to minimize quit attempts in women. Therefore, the influence of these factors on smoking- and menstrual-related symptomatology during acute smoking cessation was investigated in a controlled cross-over lab-study. Participants (n=147) completed two six-day testing weeks during their menstrual cycle with testing order randomly assigned (follicular vs. luteal). The testing week consisted of two days of ad libitum smoking followed by four days of biochemically verified smoking abstinence. Daily symptomatology measures were collected. Out of the 11 total symptoms investigated, six were significantly associated with menstrual phase and nine were significantly associated with level of depressive symptoms. Two significant interactions were noted indicating that there may be a stronger association between depressive symptoms with negative affect and premenstrual pain during the follicular phase compared to the luteal phase. Overall, these observations suggest that during acute smoking abstinence in premenopausal smokers, there is an association between depressive symptoms and symptomatology whereas menstrual phase appears to have less of an effect. Further study is needed to determine the effect of these observations on smoking cessation outcomes, as well as to define the mechanism of menstrual phase and depressive symptoms on smoking-related symptomatology.