Women & Addiction:Why is it more difficult for women to quit smoking?
Nora D. Volkow, M.D.Director
National Institute on Drug AbuseNational Institutes of Health
Natural & Drug Reinforcers Increase Dopamine in NAc
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Time (min)%
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EmptyBox Feeding
Di Chiara et al.
FOOD
VTA/SNVTA/SNnucleus accumbensnucleus accumbens
frontalcortexfrontalcortex
Drugs of abuse increase DA in the Nucleus Accumbens, which is believed to trigger the neuroadaptions that result in addiction
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Time After Nicotine
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Accumbens
NICOTINE
Accumbens
Long term effects of nicotine differs in males and females and this is influenced by age
Menarche
Menopause
Prevalence Rate Smokers:Men -- 25.4%Women -- 20.7%
2010 National Survey on Drug Use & Health (NSDUH), SAMHSA, 2011.
Tobacco Addiction is a Developmental Disease that Starts in Adolescence and Earlier in Girls than Boys
NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003.
Age at tobaccouse dependence as per DSM IV
Age
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0.2%
0.4%
0.6%
0.8%
1.0%
1.2%
1.4%
1.6%
1.8%
5 10 15 21 25 30 35 40 45 50 55 60 65
% in
eac
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oup
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o de
velo
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t ti
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White et al. (2002)
14
14.5
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15.5
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16.5
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17.5
Onset of Daily Smoking
Male
Female
Time from onset to dependence:Girls: 3 weeksBoys: 6 months
DiFranza et al. (2002)
Rates of Cotinine Clearance(ml/min/kg)
Benowitz et al., 2006, Clin Pharm Ther
*
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OC: oral contraceptives
Rates of Nicotine Clearance(ml/min/kg)
**
*
Nicotine: More than Dopamine
Aromatase* (Estrogen synthase, CYP19A1)
HO
CH3
CH3
CH3
O
aromatase
O H O H
testosterone 17b-estradiol
• Mediates sexual differentiation of the brain during development (Wu et al., Cell 2009)
Baseline 0.015 mg/kg 0.03 mg/kg
Acute nicotine inhibits aromatase in the Brain (Biegon et al., Biological Psychiatry , 2010)
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
Smoking During Pregnancy…
• Affects prenatal and postnatal growth
• Increases the risk of developmental and behavioral deficits
Nicotine Gets into the Fetus’ Brain
Fetal brainPlacenta
Fetal Liver
Maternal Brain
Fetal brain
Nicotine gets into
the fetal brain
Source: Benveniste et al. Unpublished data
[11C]Nicotine and metabolites
Use of Drugs During Pregnancy Not Only Affects the Physiology of the Mother But Also that of the Fetus
Secondhand smoke (SHS) exposure decreased 2-FA binding in brain demonstrating α4β2* nicotinic acetylcholine receptor occupancy
Control
Second Hand Smoke
Secondhand smoke (SHS) leads to significant α4β2* nicotinic acetylcholine receptor occupancy (18-22%)
Effect of Secondhand Smoke on Occupancy of Nicotinic Acetylcholine Receptors in Brain
Brody et al. Arch General Psych 2011.
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
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
The Smoker’s Body
Smokers have a 35-45% reduction in MAO B in heart, lungs, kidneys and spleen
Lung cancer risk is 2 x greater in women than in men; women develop lung cancerwith less time than men
Heart attacks relative risk for smokers vs non-smokersMen: 1.43 -- Women: 2.24
As Women Age, the Medical Consequencesfrom Smoking are Greater than for Males
Breast cancer risk dose-dependently increases with exposurerisk of breast cancer spreading to lungs is 2x than innonsmokers
Throat
Lung
Kidney
Bladder
Stomach
Leukemia (blood)
MouthEsophagus
Larynx (voice box)
Pancreas
Cervix
Smoking Causes Cancer in Organs Throughout the Body
Clinical Implications
• 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
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