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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Di Chiara et al.

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nucleus accumbens

frontalcortex

Drugs of abuse increase DA in the Nucleus Accumbens, which is believed to trigger the neuroadaptions that result in addiction

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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

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White et al. (2002)

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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)

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Nicotine: More than Dopamine

Aromatase* (Estrogen synthase, CYP19A1)

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CH3

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aromatase

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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