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LIFESTYLE & HEALTH

Smoking Cessation in the Female Patient

Vijaya Galic, MD; Martin Martino, MD

Common Clinical Scenario: A 22-year-old woman presented for her annual exam. She had been smoking 15 cigarettes per day and was interested in quitting. Since she was healthy and not planning a pregnancy, she was started on varenicline and quit smoking 1 week later. She was initially seen weekly for brief counseling support sessions and to monitor for behavioral changes. She was continued on varenicline for 6 months and remained abstinent 1 year later.

Approximately 22% of US women smoke, and nearly 174,000 die annually from smoking-related conditions.1,2 The top 4 causes of death in women are heart disease, cancer, stroke, and chronic lower respiratory diseases, accounting for mortality rates of 27.3%, 22%, 7.5%, and 5.2%, respectively.3 The risk for death from each is dramatically increased by smoking.4-6 In the Nurses’ Health Study, 64% of the deaths in current smokers were attributable to smoking, while in ex-smokers only 28% of deaths were attributed to smoking.7

Interventions for tobacco use greatly benefit patient health. The mortality risk from cardiovascular disease decreases by 36% following tobacco cessation, comparable to what can be achieved with statins, aspirin, ACE inhibitors, or β-blockers.4 An estimated 79,000 women will die of lung cancer annually, with 90% of these deaths attributable to tobacco smoke carcinogens. While quitting smoking reduces the risk for lung cancer by 90%, decreasing use by 60% translates into a 27% decrease in the risk for lung cancer.8 Finally, while women are more susceptible to and have a higher mortality risk from chronic obstructive pulmonary disease than do men, due to smaller lung capacity and differences in P450-mediated toxin metabolism, women recover more lung function after they stop smoking.5

Smoking has gender-specific effects. Female smokers go through menopause earlier than nonsmokers and are at increased risk for osteoporosis. Pregnant women who smoke are at increased risk for reproductive complications, including placental abruption, preterm labor, low infant birth weight, and infertility. Also, the risks for cervical dysplasia and cancer are markedly increased in women who smoke, and smokers are more likely to have persistent cervical histologic abnormalities.9,10

Since the introduction of tobacco control policies in 1955, smoking prevalence has steadily decreased. The decline was more pronounced in men.9 This reflects gender-specific factors relating to smoking initiation and maintenance, such as susceptibility to abuse or the unequal distribution of power in relationships. These factors are underresearched and are often not considered when tobacco control policies are developed, which may explain their reduced effectiveness in women.11 There are definite differences in characteristics between male and female smokers. Women begin smoking later, smoke fewer cigarettes, and are more likely to have a history of depression or alcoholism than are male smokers. However, a recent study has shown no difference in abstinence rates.12

The Role of the Clinician

Screening for smoking is easily accomplished as part of the initial patient intake. Since 70% of smokers see a clinician at least annually, each visit is an opportunity to provide brief counseling on cessation.6 Advice from a health care professional, even if minimal, has been shown consistently to result in a reduction in smoking.13 Anecdotally, in our office, counseling at the time of a visit for cervical dysplasia has resulted in several patients quitting smoking. Nonpharmacologic interventions shown to be effective are individual, group, and telephone counseling.6 Pharmacologic cessation aids are shown in the Table. These may be used individually or in combination, with or without nonpharmacologic interventions. All women who smoke more than 10 cigarettes per day should be offered medication, except where contraindicated.6 Many pregnant women will quit spontaneously; however, both behavioral therapy and nicotine gum have been shown to be effective.14 Nonpharmacologic methods should be used whenever possible in pregnant women. While many cessation aids demonstrate high rates of abstinence during ongoing therapy, patients often relapse after the interventions are discontinued.15

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Pharmacotherapy

Nicotine Replacement

Nicotine, via the dopaminergic reward system, creates physical and psychologic dependence. Nicotine replacement therapy (NRT) ameliorates withdrawal symptoms resulting from abrupt cessation. When used at recommended doses, NRT generally delivers less nicotine over a 24-hour period than smoking 10 cigarettes. The available formulations are gum, patch, lozenge, nasal spray, and inhaler. A recent meta-analysis evaluating the effectiveness (in terms of sustained abstinence rates) and safety of NRT showed that 6.75% of smokers previously unable or unwilling to quit were able to achieve sustained abstinence for 6 months, compared with 2.06% of smokers receiving placebo.16 While there were no statistically significant differences in adverse events or discontinuation secondary to adverse events, nausea was more common with NRT. Nicotine replacement in the form of gum or patches does not target smoking behavior; however, the nicotine inhaler does.15 NRT should be initiated at the same time that the smoker abruptly quits, with the dose based on the number of cigarettes smoked. The dose is then tapered. NRT is considered safe to use in pregnancy and is possibly more effective than cognitive behavioral therapy.17

Antidepressants

Antidepressants are also effective in smoking cessation, particularly in female smokers, who are more likely to have concurrent depression that may be ameliorated by smoking.12 The atypical antidepressant bupropion, which has nicotine antagonist activity, and the tricyclic antidepressant nortriptyline are used for smoking cessation. Both have been shown to be more effective than placebo, and in one trial, bupropion was more effective than either the nicotine patch or inhaler.18 Antidepressants are generally started 1 week to 1 month prior to the intended quit date. While bupropion has fewer side effects than nortriptyline, it does carry a black box warning for serious neuropsychiatric events, including suicide. Nortriptyline causes significant sedation, has numerous drug interactions, and may cause fatal cardiac arrhythmias when overdosed. These adverse effects have prevented nortriptyline from being used as a first-line treatment.

Varenicline

Varenicline, approved for smoking cessation in 2006, is a partial agonist at the nicotine receptor that reduces cravings, withdrawal symptoms, and smoking satisfaction. In phase II and III clinical trials, continuous abstinence rates at 12 months were higher than for either placebo or bupropion.19-21 Treatment is initiated 7 days before the planned quit date and is typically continued for 12 weeks; however, treatment for an additional 12 weeks improves long-term abstinence rates.22 While prolonged treatment extends the period of abstinence, once the medication is stopped, as with other methods, the relapse rate approaches 50%.23 Varenicline has few side effects. The most common, nausea, may be prevented with dose titration up to the target dose of 1 mg twice daily. Like bupropion, varenicline has received a black box warning for neuropsychiatric events, even in patients without a prior psychiatric history. Patients on varenicline should be monitored for behavioral changes.6

Clonidine

Clonidine is a centrally acting antihypertensive agent that has been used in the treatment of alcohol and opioid addiction, and more recently tobacco dependence. It ameliorates withdrawal symptoms. In a meta-analysis evaluating the effectiveness of clonidine alone compared to placebo, the pooled quit rate was 23% for clonidine compared to 14% for placebo. Clonidine therapy is not without significant side effects (Table), which have prevented its widespread use as a first-line treatment. Clonidine may, however, have utility in patients whose treatment has failed with NRT alone, antidepressants, or nicotine antagonists.24

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TABLE. Pharmacologic Smoking Cessation Therapies6,24

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CONCLUSION

All women should be screened for smoking at every clinician visit, and all smokers should be offered cessation aids. Those who are smoking more than 10 cigarettes per day and are not pregnant should be offered a pharmacologic cessation aid. Patients should be followed closely after initiating medications to monitor for potential adverse effects.

The authors report no actual or potential conflict of interest in relationship to this article.

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Vijaya Galic, MD, is Resident, Obstetrics and Gynecology, and Martin Martino, MD, is Gynecologic Oncologist, both at Lehigh Valley Health Network, Allentown, PA.

References

1. CDC. Smoking prevalence among women of reproductive age—United States, 2006. MMWR Morb Mortal Wkly Rep. 2008;57(31):849-852.
2. CDC. Smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 2000-2004. MMWR Morb Mortal Wkly Rep. 2008;57(45):1226-1228.
3. CDC, National Center for Health Statistics. Mortality tables. Available at: www.cdc.gov/nchs/datawh/statab/unpubd/mortabs.htm. Accessed October 14, 2009.
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17. Pollak KI, Oncken CA, Lipkus IM, et al. Nicotine replacement and behavioral therapy for smoking cessation in pregnancy. Am J Prev Med. 2007;33(4):297-305.
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19. Garrison GD, Dugan SE. Varenicline: a first-line treatment option for smoking cessation. Clin Ther. 2009;31(3): 463-491.
20. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2008;(3):CD006103.
21. Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006;296(1):56-63.
22. Lee JH, Jones PG, Bybee K, O’Keefe JH. A longer course of varenicline therapy improves smoking cessation rates. Prev Cardiol. 2008;11(4):210-214.
23. Tonstad S, Tønnesen P, Hajek P, Williams KE, Billing CB, Reeves KR. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA. 2006;296(1):64-71.
24. Gourlay SG, Stead LF, Benowitz NL. Clonidine for smoking cessation. Cochrane Database Syst Rev. 2004;(3): CD000058.

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