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Women & Addiction: Why is it more difficult for women to quit smoking?

Women & Addiction: Why is it more difficult for women to quit smoking?. Nora D. Volkow, M.D. Director National Institute on Drug Abuse National Institutes of Health. frontal cortex. FOOD. 200. nucleus accumbens. VTA/SN. 150. 100. % of Basal Release. Empty. 1. 2. 3 hr. 0. 50.

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Women & Addiction: Why is it more difficult for women to quit smoking?

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  1. Women & Addiction: Why is it more difficult for women to quit smoking? Nora D. Volkow, M.D. Director National Institute on Drug Abuse National Institutes of Health

  2. frontal cortex FOOD 200 nucleus accumbens VTA/SN 150 100 % of Basal Release Empty 1 2 3 hr 0 50 Feeding Box 0 0 60 120 180 Time (min) Di Chiara et al. Natural & Drug Reinforcers Increase Dopamine in NAc NICOTINE 250 200 Accumbens 150 % of Basal Release 100 0 Time After Nicotine Accumbens Drugs of abuse increase DA in the Nucleus Accumbens, which is believed to trigger the neuroadaptions that result in addiction

  3. Long term effects of nicotine differs in males and females and this is influenced by age • Prevalence Rate Smokers: • Men -- 25.4% • Women -- 20.7% • 2010 National Survey on Drug Use & Health (NSDUH), SAMHSA, 2011. Menopause Menarche

  4. Tobacco Addiction is a Developmental Disease that Starts in Adolescence and Earlier in Girls than Boys 1.8% 1.6% 1.4% 1.2% 1.0% % in each age group who develop first time dependence 0.8% White et al. (2002) 0.6% 0.4% Time from onset to dependence: Girls: 3 weeks Boys: 6 months 0.2% 0.0% 5 10 15 21 25 30 35 40 45 50 55 60 65 Age Age at tobaccouse dependence as per DSM IV DiFranza et al. (2002) NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003.

  5. Rates of Nicotine Clearance (ml/min/kg) Rates of CotinineClearance(ml/min/kg) * * * * * * OC: oral contraceptives Benowitz et al., 2006, ClinPharmTher

  6. O H O H C H C H 3 3 a r o m a t a s e C H 3 H O t e s t o s t e r o n e 1 7 - e s t r a d i o l b Nicotine:More than Dopamine O Aromatase* (Estrogen synthase, CYP19A1) • Mediates sexual differentiation of the brain during development • (Wu et al., Cell 2009) Acute nicotine inhibits aromatase in the Brain (Biegon et al., Biological Psychiatry , 2010) Baseline 0.015 mg/kg 0.03 mg/kg

  7. Smoking has Adverse Effects on Womens’ Endocrinology and Reproductive Health • Female smokers show hypo-estrogenic effects including • early menopause, dysmenorrhea, menstrual irregularity • Lower bone mineral density (osteoporosis) • Conception delay, primary/secondary infertility • Pregnancy & delivery complications • Stillborn, neonatal death Surgeon General’s Report 2001, Women & Smoking

  8. Smoking During Pregnancy… • Affects prenatal and • postnatal growth • Increases the risk of • developmental and • behavioral deficits

  9. Use of Drugs During Pregnancy Not Only Affects the Physiology of the Mother But Also that of the Fetus Nicotine Gets into the Fetus’ Brain Nicotine gets into the fetal brain [11C]Nicotine and metabolites Placenta Fetal brain Maternal Brain Fetal brain Fetal Liver Source: Benveniste et al. Unpublished data

  10. Effect of Secondhand Smoke on Occupancy of Nicotinic Acetylcholine Receptors in Brain Control Second Hand Smoke Secondhand smoke (SHS) exposure decreased 2-FA binding in brain demonstrating α4β2* nicotinic acetylcholine receptor occupancy Secondhand smoke (SHS) leads to significant α4β2* nicotinic acetylcholine receptor occupancy (18-22%) Brody et al. Arch General Psych 2011.

  11. Second Hand Smoke (SHS) Exposure • Increases risk of pregnancy complications and affects • fetal health • Worldwide, 50% of men smoke and particularly in • developing countries, there are few proscriptions • against smoking in the home • Children exposed to SHS have increased risk of: • -- Sudden Infant Death Syndrome • -- Lower respiratory tract infections • -- Ear infections • -- Asthma • -- Becoming smokers

  12. Women have a harder time quitting… • Factors control smoking • -- Women are less sensitive to • nicotine as a pharmacologic • agent • -- Women are more sensitive • to non-nicotine factors • Greater role in women • --stress & negative affect • -- depression • -- weight concerns

  13. The Smoker’s Body Smokers have a 35-45% reduction in MAO B in heart, lungs, kidneys and spleen

  14. As Women Age, the Medical Consequences from Smoking are Greater than for Males • Lung cancer • risk is2 x greater in womenthan in • men; women develop lung cancer • with less time than men • Heart attacks • relative risk for smokers vs non-smokers • Men: 1.43 -- Women: 2.24 • Breast cancer • risk dose-dependently increases with exposure • risk of breast cancer spreading to lungs is 2x than in • nonsmokers

  15. Smoking Causes Cancer in Organs Throughout the Body Throat Larynx (voice box) Mouth Esophagus Leukemia (blood) Lung Stomach Kidney Pancreas Bladder Cervix

  16. Less attention to NRTs (except the inhaler) • More attention to • CBT to deal with the non-nicotine aspects of smoking • -- environmental cues, mood • Cognitive restructuring regarding risks • -- weight gain • Non-NRT pharmacotherapies • --bupropion: M=F; F only with CYP2BG polymorphism • --varenicline: M=F • --naltrexone: effective only in F • Menstrual cycle Clinical Implications

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