Short CommunicationSubjective response to nicotine by menstrual phase
Introduction
Women relapse to smoking at different rates and for different reasons compared to men (CDC, 2012, Nakajima and al’Absi, 2012, Perkins, 2001). Although research indicates women smoke more for non-nicotine reinforcers such as sensory effects and weight control (Perkins, 2001), women smokers are more sensitive to the effects of nicotine than men. Many studies using various forms of nicotine (nasal spray, oral, transdermal patch, and intravenous) have demonstrated that women have a greater subjective and physiological response to nicotine (Evans et al., 2006, Myers et al., 2008, Netter et al., 1994, Sofuoglu and Mooney, 2009). DeVito and colleagues, however, noted that men displayed a greater subjective response to intravenous nicotine, whereas women displayed a greater physiological response (DeVito, Herman, Waters, Valentine, & Sofuoglu, 2014). Thus, sex hormones might play a role in response to nicotine.
Recent research has examined the role of menstrual phase (as a proxy for sex hormones) in smoking behavior and cessation (for additional information see the following review articles: Carpenter et al., 2006, Lynch and Sofuoglu, 2010). Overall, the follicular phase (low progesterone/estradiol [PE) ratio) seems favorable for smoking cessation when nicotine replacement therapy (NRT) is used (Carpenter et al., 2008, Franklin et al., 2008). However, in the absence of NRT, the luteal phase (high PE ratio) may lead to more favorable outcomes (Allen et al., 2008, Mazure et al., 2011). The specific mechanisms involved are unknown, but may be related to the biological response to nicotine at varying levels of sex hormones (Franklin & Allen, 2009). Understanding the effect of menstrual phase and sex hormones on response to nicotine will allow for the development of smoking cessation interventions tailored to the specific needs of premenopausal women.
Although individual differences in the subjective nicotine response have not been well studied, they are likely associated with the reinforcing effects of smoking (Stolerman & Jarvis, 1995). While it remains unknown as to whether subjective response may serve as an indicator of risk for smoking relapse (Pillitteri et al., 1997, Pomerleau, 1995), limited new research has begun exploring the effect of menstrual phase on nicotine response. Subjective nicotine response was greater during the follicular phase compared to the luteal phase in female smokers after overnight abstinence (DeVito et al., 2014). However, this relationship has not been examined in women who were abstinent for greater than 12 hours. The aim of this project was to determine if menstrual phase influenced the subjective response to nicotine during acute smoking abstinence. We hypothesized that the subjective response to nicotine would be greater in follicular compared to luteal phase.
Section snippets
Study sample
A sample of women were recruited for a study designed to explore the differences in smoking-related symptomatology by menstrual phase and depressive symptoms (Allen et al., 2014). Inclusion criteria included women between the ages of 18 and 40, smoking at least five cigarettes per day for at least the past year, regular menstrual cycles for at least the past six months, and stable physical and mental health. Exclusion criteria were recent (< 3 months) pregnancy or breastfeeding, current
Study sample
A total of 208 women were enrolled into the study. Of those, 61 participants were excluded from the analyses due to participant discontinuing study participation (n = 51), inability to achieve smoking abstinence (n = 11) or having hormone levels that were not consistent with menstrual phase of testing (n = 6). Therefore, the final sample size for this analysis was 140, including 72 who were randomized to the F-L order and 68 randomized to L-F order. Overall, women were 29.7 (S.D. ± 6.6) years old and
Discussion
The aim of this controlled, cross-over trial was to examine the differences in subjective response to nicotine by menstrual phase during acute smoking abstinence. We found that after the first dose of nicotine nasal spray, the luteal phase was associated with a greater increase in stimulated (as indicator of acute spray response) and a greater decrease in urge to smoke (an indicator of abstinence relief). However, the majority of the associations explored were null, providing little evidence
Role of funding sources
This project was funded by National Institute on Drug Abuse (NIDA) Grant R01-DA08075 and supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. ). A. Allen was supported by the University of Minnesota’s Masonic Cancer Center and the Building Interdisciplinary Research Careers in Women’s Health Grant (# K12HD055887; A. Allen) from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD), the Office of Research on Women’s
Contributors
Alicia Allen completed the literature review, participated in protocol development and wrote the first draft of the manuscript. Scott Lunos conducted the statistical analysis. Stephen Heishman provided expertise on the measurement and interpretation of nicotine response measurements. Mustafa al’Absi and Dorothy Hatsukami were co-investigators on the project. Sharon Allen was the principle investigator on the project. All authors participated in interpretation of data, as well as writing,
Conflict of interest
All authors declare that they have no conflict of interest.
Acknowledgements
The authors would like to thank our research staff – Lindsay Jarvis, Kathryn Resner, Sara Paradise, Nicole Tosun, Jennifer Vanvliet, Jennifer Widenmier, and Danielle Young – for their dedication to subject recruitment and retention, as well as data collection, entry and management. Additional thanks go to Elizabeth Greene for her editorial assistance.
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