Tobacco Withdrawal in Women and Menstrual Cycle Phase

Transcription

1 Journal of Consulting and Clinical Psychology Copyright 2 by the American Psychological Association, Inc. 2, Vol. 68, No. 1, X//$5. DOI: 1.137//22-6X Tobacco Withdrawal in Women and Menstrual Cycle Phase Kenneth A. Perkins, Michele Levine, and Marsha Marcus University of Pittsburgh School of Medicine Saul Shiffman University of Pittsburgh Delia D'Amico, Amy Miller, Andrea Keins, Jacquelyn Ashcom, and Michelle Broge University of Pittsburgh School of Medicine Because negative mood is a characteristic of both tobacco withdrawal and menstrual discomfort, withdrawal may vary by menstrual cycle phase. Tobacco withdrawal, mood, and menstrual discomfort were assessed in premenopausal women who quit smoking during either the follicular (Days 1-14 postmenstrnal onset; n = 41) or luteal (Day 15 or longer postmenstrual onset; n = 37) phase of the menstrual cycle and maintained biochemically verified smoking abstinence during the postquit week. Women quitting during the hiteal phase reported significantly greater increases in tobacco withdrawal and self-reported depressive symptoms than women quitting during the follicular phase. These results indicate that selecting a quit-smoking day early in the follicular phase may attenuate withdrawal and negative affect in premenopausal female smokers. In women, negative mood, including anxiety, depression, irritability, and impaired concentration, is often increased during the luteal, or premenstrual, phase of the menstrual cycle (e.g., Allen, McBride, & Pirie, 1991; DeBon, Klesges, & Klesges, 1995; Gallant, Hamilton, Popiel, Morokoff, & Chakraborty, 1991). Because these symptoms are also characteristic of tobacco withdrawal (Hughes, Higgins, & Hatsukami 199) and can be relieved by smoking, women may smoke more intensely during this cycle phase in order to ameliorate negative mood and related adverse symptoms (DeBon et al., 1995; Pomerleau, Garcia, Pomerleau, & Cameron, 1992; Steinberg & Cherek, 1989). Similarly, women who quit smoking during the luteal phase may experience heightened "withdrawal" from the combination of cycle-related symptoms and actual tobacco withdrawal. Therefore, relapse to smoking may be more likely to occur during the luteal phase in an effort to relieve these negative states. Consistent with the notion that tobacco withdrawal in women may vary depending on the menstrual cycle phase during initial. quitting, O'Hara, Portser, and Anderson (1989) found greater withdrawal during the first 3 days of cessation among women who quit during the luteal phase compared with those who quit during the follicular phase. Withdrawal was also correlated with menstrual symptoms. However, the reliability of this finding is uncertain. First, in addition to a small sample size (N = 22), more than one third of these women continued to smoke but were nevertheless included in analyses. Continued smoking would obviously dampen reported tobacco withdrawal, complicating comparisons between groups. Second, withdrawal was assessed only once before quitting, on the actual quit day. This single assessment on a day in which participants were likely anticipating effects of cessation may not provide a valid measure of prequit baseline withdrawal. The present study examined tobacco withdrawal and mood measures in 78 premenopausal women who maintained smoking abstinence during the 1st week after quitting. Withdrawal symptoms were assessed repeatedly for 2 weeks prior to quitting. Approximately half of the women in this study quit during the follicular phase (Days 1-14 postmenses), and half quit during the luteal phase (Day 15 or longer postmenses). Menstrual discomfort was also assessed to determine its relationship to withdrawal symptoms after quitting smoking. Method Kenneth A. Perkins, Michele Levine, Marsha Marcus, Delia D'Amico, Amy Miller, Andrea Keins, Jacquelyn Ashcom, and Michelle Broge, Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine; Saul Shiffman, Department of Psychology, University of Pittsburgh. Preparation of this article was supported by Grant DA4174 from the National Institute on Drug Abuse. We thank Mark Sanders for his able assistance. Correspondence concerning this article should be addressed to Kenneth A. Perkins, Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, Pennsylvania Electronic mail may be sent to msx.upmc.edu. Participants Participants for this study were women in a larger smoking cessation trial that did not involve any medication. The larger trial compared three different group-based behavioral counseling approaches to addressing women's concern about weight gain after quitting smoking. All of the participants received standard cognitive-behavioral smoking cessation counseling modeled on the FreshStart program (Shiffman & Cline, 199), in addition to one of three weight-gain-related adjuncts: cognitivebehavioral treatment to reduce concerns, behavioral weight control to prevent weight gain, and social support (no discussion of weight issue; see Perkins, Levine, Marcus, & Shiffman, 1997, for a description of these treatments). Women eligible for the larger trial were required to be 18 to

2 BRIEF REPORTS 177 years of age, smoke at least 1 cigarettes per day, be free of any illicit drugs, report significant interest in quitting smoking, and endorse considerable concern about weight gain after quitting. (Both interest in quitting smoking and weight-gain concern were defined by responding at least 5 on 1-mm Visual Analog Scales of interest or concern ranging from [not at all] to 1 [extremely]). Informed consent was obtained from all of the participants after the nature and consequences of their participation were explained. Of the 219 women who participated in the trial, 129 were premenopausai and reported menstrual cycles. Of those 129, 26 women were excluded for dropping out before the end of follow-up (n = 11), for providing inadequate information by which to determine cycle phase (i.e., no specific date for most recent menstruation prior to quitting; n = 14), or for not quitting smoking as instructed (n = 1). This left 13 premenopausal women with complete data who attempted toquit smoking. The menstrual cycle during which participants quit smoking was determined by treatment program schedule. Participants were required to select 1 of only a few days on or near the weekend before their fifth treatment session as their quit smoking day. Of the 13 women in this study, the quit smoking day for 54 fell between 1 and 14 days postmenstrual bleeding onset, which was identified as their follicular phase, and the quit day for the other 49 fell 15 days or longer postmenstrual onset, which was identified as their luteal phase (Jensvold, 1996). (This definition of menstrual phase was also used by O'Hara et al., 1989.) There were no differences between the follicular and hiteal groups in age, demographic information, Fagerstrom score (Heatherton, Kozlowski, Frecker, & Fagerstrom, 1991), or smoking history, as shown in Table 1. Subjective Measures Tobacco withdrawal and desire to smoke. Tobacco withdrawal was assessed with self-reported symptoms based on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) criteria and adapted from Hughes, Gust, Skoog, Keenan, and Fenwick (1991): irritable, anxious, difficulty concentrating, restless, impatient, hungry, and depressed. Each was rated by the participants on a scale ranging from (not at all) to 1 (extremely). Total withdrawal was the mean of these scales. Desire to smoke was assessed using a similar - to 1-point scale. Other mood measures. Participants also completed the Beck Depression Inventory (BDI; Beck, Ward, Mendelsohn, Mock, & Erbaugh, 1961) and the Profile of Mood States (POMS; McNair, Loor, & Droppleman, 1971) at each session to provide a more complete measure of negative affect. The POMS contains scales tapping vigor, depression, anxiety, fatigue, and arousal. Table 1 Mean Demographic and Smoking History Characteristics and Standard Errors in Premenopausal Women Attempting to Quit Smoking During the Follicular Versus Luteal Phase Follicular group Luteal group (n = 54) (n = 49) Menstrual discomfort and cycle phase. At every other session, participants completed the short version of the Premenstrual Assessment Form (PAF; Allen et al. 199i), which assesses 1 symptoms related to menstrual discomfort on 6-point scales (1 = not present or no change, 6 = extreme change). Typical items are "outbursts of 'irritability' or bad temper," "feel bloated," and "have relatively steady abdominal heaviness, discomfort, or pain." The 1 items are added up to provide a total menstrual discomfort score (range = -6). The PAF was used to determine whether changes in the withdrawal and mood measures after quitting smoking may be related to severity of menstrual discomfort. Each participant also recorded the date of onset of her most recent menstrual period. The number of days between menstrual onset and the quit day was determined from this record. As noted, the quit day was identified as occurring during the follicular or luteal phase of the cycle if the number of days was 14 or fewer or 15 or more, respectively. Procedure During the 3-week period of assessment for this study, participants attended six 9-min counseling sessions, two per week. Four sessions were held over the 2 weeks prior to their quit day. The remaining two sessions occurred within 1 week after their quit day. Sessions were held in groups of about 8 to 12 women each. The first four sessions focused on preparations for quitting smoking (e.g., stimulus control and increasing motivation), and the last two focused on cognitive and behavioral strategies for coping with urges to smoke (Shiffman & Cline 199). All the participants were instructed to quit before the fifth session, at the beginning of the 3rd week. Participants were considered abstinent if they had an expired-air carbon monoxide reading of 8 ppm or less at each session since their quit day and did not report that they had resumed smoking (Ossip-Klein et al., 1986). Withdrawal measure, BDI, and POMS scores were obtained at every session (i.e., four times before the quit day and twice after quitting), and PAF (the menstrual discomfort measure) scores were obtained at every other session (i.e., twice before the quit day and once after quitting). Data Analysis Mood measures (withdrawal, the BDI, and the POMS) were averaged across the four prequit sessions and the two postquit sessions to obtain reliable values of symptoms before and after quitting. Only those women who were abstinent after their quit day were included in analyses because continued smoking would confound report of withdrawal symptoms. Initially, we conducted an analysis of variance to determine any significant main effects or interactions involving the three counseling approaches directed at weight-gain concerns on the mood and withdrawal measures (withdrawal, the BDI, and the POMS). Because there were no significant differences in these variables across the three treatment groups, we collapsed participants across counseling approach for analyses. We used t tests to analyze the differences between follicular and luteal quit groups in change in these measures from prequit baseline to postquit. These measures were also related by Pearson correlation to change in menstrual discomfort score. Results Characteristic Age (years) Marital status (% married or living with partner) Education (% college graduate) Fagerstrom score (-1) Cigarettes/day Years smoking No. of prior serious quit attempts M SE M SE Twenty-five women (13 follicular, 12 luteal) relapsed during the week after their quit day and were excluded from analyses of symptoms. Thus, abstinent women in the follicular and luteal groups numbered 41 and 37, respectively. There was no difference between the follicular and luteal groups in tobacco withdrawal during the 2-week prequit baseline. As shown in Figure 1, women quitting during the luteal phase had a significantly greater increase in tobacco withdrawal during their quit week than women quitting during the follicular phase,

3 178 BRIEF REPORTS A B E Baseline Week 1 Baseline Week 1 C D 1 3 S" 8 ~ 25 2 E ~ 2 e~ ~ 15 e. b. Baseline Week 1 Baseline Week 1 Figure 1. Mean (+_SE) scores for (A) total withdrawal, (B) desire to smoke, (C) Beck Depression Inventory (BDI), and (D) total menstrual discomfort during prequit baseline and postquit Week 1 in abstinent premenopausal women whose quit day fell within the follicular (n = 41; empty circle) versus luteal (n = 37; filled circle) menstrual cycle phase. For all of the measures, there were no group differences at baseline. *p <.5. **p <.1. lo t(76) = 2.8, p <.5. Increases across all withdrawal symptoms were greater for women in the luteal versus follicular group. Change in desire to smoke after quitting was not significantly different between groups (see Figure 1). There were no differences between groups in baseline scores on the BDI and the POMS. Similar to results for tobacco withdrawal, women quitting during the luteal phase reported a significantly greater increase in their BDI scores after qui~ng smoking compared with women quitting during the follicular phase, t(76) = 2.14, p <.4 (see Figure 1). However, there were no differences between groups on any of the POMS scale scores after quitting. Because oral contraceptives can alter menstrual cycling, we repeated the analyses of differences in withdrawal and mood between follicular and luteal groups after excluding women taking oral contraceptives (9 follicular, 6 luteal). Results were unchanged: for the withdrawal measure, t(61) = 2.59, p =.1; for the BDI, t(61) = 2.25, p <.3. The follicular and luteal groups were defined by the menstrual cycle phase on the quit date, so it is not surprising that menstrual discomfort differed between the groups at postquit (see Figure 1). Significant positive correlations were found between change in menstrual discomfort after quitting smoking and change in (a) tobacco withdrawal, r(77) =.46, p <.1; (b) desire to smoke, r(77) =.31, p <.1; and (c) BDI scores, r(77) =.43, p <.1. Discussion Tobacco withdrawal was significantly greater among women who quit smoking during the luteal phase of the menstrual cycle compared with women who quit smoking during the follicular

4 BRIEF REPORTS 179 phase. This result is consistent with findings by O'Hara et al. (1989), who observed very little increase in withdrawal among women quitting during the follicular phase. Other recent research has shown no effect of cycle phase on withdrawal symptoms in female smokers who do not attempt to quit (Marks, Pomerleau, & Pomedeau, 1999), suggesting that the greater withdrawal during the luteal phase in this study was specific to the quit attempt and not reflective of a general worsening of mood due to cycle phase. One implication of these results is that premenopausal women preparing to quit smoking should select a quit day early in the follicular phase of their menstrual cycle to attenuate withdrawal symptoms and negative affect. However, it is not clear that strategies aimed specifically at attenuating withdrawal will significantly reduce the likelihood of smoking relapse (Hughes et al. 199), as perhaps evidenced here by the lack of differences between groups in smoking relapse or desire to smoke during the 1-week follow-up. Nevertheless, this simple strategy for timing the quit day may decrease adverse mood effects of cessation, if not actual relapse, with essentially no cost. Results from this study are not completely clear regarding whether tobacco withdrawal in particular or more broadly defined negative affect was influenced by cycle phase when quitting smoking. Women quitting during the luteal phase experienced greater increase in depressive symptomatology (as measured by the BDI), as well as withdrawal, compared with women quitting during the follicular phase. Because several tobacco withdrawal symptoms reflect negative affect, it may be that the luteal cycle phase exacerbated negative affect from quitting smoking and did not specifically increase withdrawal per se. However, the greater increase in withdrawal experienced by those quitting during the luteal phase was observed across all individual withdrawal symptoms and not just those related to negative affect. On the other hand, it is possible that women quitting during the luteal phase simply endorsed all the adverse response options because of expectations of poorer affect after quitting and not because of actually greater symptomatology. This possibility seems unlikely because there were no differences between the luteal and follicular groups on any of the POMS scale scores, suggesting that women quitting during the luteal phase did not respond to all of the measures with a negative response set (i.e., there was some response specificity in the influence of menstrual cycle on mood after quitting smoking). Our finding of an effect of menstrual cycle on withdrawal during smoking cessation is perhaps consistent with observations that estrus cycle phase and sex hormones influence drug reinforcement in animals (Almeida et al., 1998; Roberts, Bennett, & Vickers, 1989). These results suggest that sex hormones may affect some responses to drugs or to abrupt cessation of drug use, although one recent study found no effect of cycle phase on acute responses to nasal nicotine in female smokers (Marks et al., 1999). Progesterone, for example, is a noncompetitive inhibitor of nicotinic receptor function in vitro (Valera, Ballivet, & Bertrand, 1992), and progesterone, estradiol, and other steroids inhibit functioning of muscle and ganglionic nicotinic receptors (Ke & Lukas, 1996). Such influences could help explain sex differences in nicotine reinforcement (Perkins, 1996), in nicotine discrimination (Perkins, 1999), and in patterns of other drug use (Lex, 1991) in humans. This study was not without limitations, and further study of the influence of menstrual cycle phase on withdrawal and abstinence from smoking is warranted. As in the O'Hara et al. (1989) study, our participants were not strictly assigned randomly to quit during the follicular versus luteal phase. By the same token, the timing of the quit day (within 1 or 2 days) in this study was not self-selected but determined by the fixed schedule of treatment sessions. Nevertheless, random assignment may provide a stronger test of the influence of menstrual cycle. Phase of the menstrual cycle was defined in this study by self-reported days since onset of menstruation. More sophisticated assessment of multiple cycle phases by analysis of progesterone, estradlol, and other hormones may reveal more complex effects of cycle phase on withdrawal. These effects of cycle phase should also be examined in a broader sample of premenopausal women attempting to quit and not just in those who express concern about weight gain after quitting, as in this trial. Regarding future research directions, cycle differences in women's withdrawal should be compared with withdrawal in men. O'Hara et al. (1989) observed withdrawal in a small group of men that was similar in magnitude to the women quitting during the follicular phase but less than that in women quitting during the luteal phase. In addition, the influence of cycle phase on drug withdrawal symptoms of women abstaining from other drugs of abuse should be examined in order to determine the possible generalizability of these findings to other substance abuse treatment in women (e.g., McKay, Rutherford, Cacciola, Kabasakalian~ McKay, & Alterman, 1996). If quitting smoking during the follicular phase is associated with superior abstinence, menstrual cycle phase should be routinely assessed and considered in treatment programs, perhaps including other substance abuse interventions. It would be important to determine whether nicotine replacement or other medications differentially relieve withdrawal during the follicular versus luteal" phase. One study found less withdrawal relief from 2-mg nicotine gum in women versus men (Hatsukami, Skoog, Allen, & Bliss, 1995), but menstrual cycle was not examined and its effect on response to nicotine replacement is therefore unknown. If hormonal variations across the cycle are found to be directly related to withdrawal, negative affect, and abstinence, medications that attenuate these hormonal effects on mood may be a reasonable direction for improving smoking cessation treatment for women. Women are in particular need of more effective interventions for smoking cessation because they tend to have greater difficulty in quitting (Ockene, 1993; Perkins 1996) and may suffer greater health risks from smoking (e.g., Prescott, Hippe, Schnohr, Hein, & Vestbo, 1998) compared with men. References Allen, S. S., McBride, C. M., & Pirie, P. L. (1991). The shortened Premenstrual Assessment Form. Journal of Reproductive Medicine, 36, Almeida, O. F. X., Shoaib, M., Deicke, J., Fischer, D., Darwish, M. H., & Patchev, V. K. (1998). Gender differences in ethanol preference and ingestion in rats: The role of the gonadal steroid environment. Journal of Clinical Investigation, 11, American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author. Beck, A. T., Ward, C. H., Mendelsohn, M., Mock, J., & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4, DeBon, M., Klesges, R. C., & Klesges, L. M. (1995). Symptomatology

5 18 BRIEF REPORTS across the menstrual cycle in smoking and nonsmoking women. Addictive Behaviors, 2, Gallant, S. J., Hamilton, J. A., Popiel, D. A., Morokoff, P. J., & Chakraborty, P. K. (1991). Daily moods and symptoms: Effects of awareness of study focus, gender, menstrual-cycle phase, and day of the week. Health Psychology, 1, Hatsukami, D., Skoog, K., Allen, S., & Bliss, R. (1995). Gender and the effects of different doses of nicotine gum on tobacco withdrawal symptoms. Experimental and Clinical Psychopharmacology, 3, Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., & Fagerstrom, K. -O. (1991). The Fagerstrom Test for Nicotine Dependence: A Revision of the Fagerstrom Tolerance Questionnaire. British Journal of Addiction, 86, Hughes, J. R., Gust, S. W., Skoog, K., Keenan, R. M., & Fenwick, J. W. (1991). Symptoms of tobacco withdrawal. Archives of General Psychiatry, 48, Hughes, J. R., Higgins, S. T., & Hatsukami, D. (199). Effects of abstinence from tobacco. In L. T. Kozlowski, H. M. Annis, H. D. Cappell, F. B. Glaser, M. S. Goodstadt, Y. Israel, H. Kalant, E. M. Sellers, & E. R. Vingilis (Eds.), Research advances in alcohol and drug problems (Vol. 1, pp ). New York: Plenum. Jensvold, M. F. (1996). Nonpregnant reproductive-age women: Part I. The menstrual cycle and psychopharmacology. In M. F. Jensvold, U. Halbreich, & J. Hamilton (Eds.), Psychopharmacology and women (pp ). Washington, DC: American Psychiatric Press. Ke, L., & Lukas, R. (1996). Effects of steroid exposure on ligand binding and functional activities of diverse nicotinic acetylcholine receptor subtypes. Journal of Neurochemistry, 67, Lex, B. (1991). Some gender differences in alcohol and polysubstance users. Health Psychology, 1, Marks, J. L., Pomerleau, C. S., & Pomerleau, O. F. (1999). Effects of menstrual phase on reactivity to nicotine. Addictive Behaviors, 24, McKay, J. R., Rutherford, M. J., Cacciola, J. S., Kabasakalian-McKay, R., & Alterman, A. I. (1996). Gender differences in the relapse experiences of cocaine patients. The Journal of Nervous and Mental Disease, 184, McNair, D. M., Loor, M., & Droppleman L. F. (1971). Profile of Mood States. San Diego, CA: Educational Testing Service. Ockene, J. K. (1993). Smoking among women across the lifespan: Prevalence, interventions, and implications for cessation research. Annals of Behavioral Medicine, 15, O'Hara, P., Portser, S. A., & Anderson, B. P. (1989). The influence of menstrual cycle changes on the tobacco withdrawal syndrome in women. Addictive Behaviors, 14, Ossip-Klein, D. J., Bigelow, G., Parker, S. R., Curry, S., Hall, S., & Kirkland, S. (1986). Classification and assessment of smoking behavior. Health Psychology, 5(Suppl.), Perkins, K. A. (1996). Sex differences in nicotine vs. non-nicotine reinforcement as determinants of tobacco smoking. Experimental and Clinical Psychopharmacology, 4, Perkins, K. A. (1999). Nicotine discrimination in men and women. Pharmacology, Biochemistry & Behavior, 64, Perkins, K. A., Levine, M., Marcus, M. D., & Shiffman, S. (1997). Addressing women's concerns about weight gain due to smoking cessation. Journal of Substance Abuse Treatment, 14, 1-1. Pomerleau, C. S., Garcia, A. W., Pomerleau, O. F., & Cameron, O. G. (1992). The effects of menstrual phase and nicotine abstinence on nicotine intake and on biochemical and subjective measures in women smokers: A preliminary report. Psychoneuroendocrinology, 17, Prescott, E., Hippe, M., Schnohr, P., Hein, H. O., & Vestbo, J. (1998). Smoking and risk of myocardial infarction in women and men: Longitudinal population study. British Medical Journal, 316, Roberts, D. C. S., Bennett, S. A. L., & Vickers, G. L. (1989). The estrous cycle affects cocaine self-administration on a progressive ratio schedule in rats. Psychopharmacology, 98, Shiffman, S., & Cline, T. R. (199). FreshStart plus. Washington, DC: American Cancer Society. Steinberg, J. L., & Cherek, D. R. (1989). Menstrual cycle and cigarette smoking behavior. Addictive Behaviors, 14, Valera, S., Ballivet, M., & Bertrand, D. (1992). Progesterone modulates a neuronal nicotinic acetylcholine receptor. Proceedings of the National Academy of Sciences, 89, Received October 5, 1998 Accepted May 26, 1999