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
Natural & Drug Reinforcers Increase Dopamine in NAc
NICOTINE
% of Basal Release
250
frontal
cortex
nucleus
accumbens
200
Accumbens
150
100
0
1
0
VTA/SN
2
Time After Nicotine
FOOD
% of Basal Release
200
Drugs of abuse increase DA in the Nucleus
Accumbens, which is believed to trigger the
neuroadaptions that result in addiction
3 hr
Accumbens
150
100
50
0
Empty
Box Feeding
0
60
120
180
Time (min)
Di Chiara et al.
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
Tobacco Addiction is a Developmental Disease that
Starts in Adolescence and Earlier in Girls than Boys
17.5
% in each age group who develop
first time dependence
1.8%
17
1.6%
16.5
1.4%
16
Male
Female
15.5
1.2%
15
1.0%
14.5
0.8%
14
Onset of Daily Smoking
White et al. (2002)
0.6%
0.4%
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
NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003.
Time from onset to
dependence:
Girls: 3 weeks
Boys: 6 months
DiFranza et al. (2002)
Rates of Cotinine Clearance
Rates of Nicotine Clearance
(ml/min/kg)
(ml/min/kg)
*
*
*
*
*
*
OC: oral contraceptives
Benowitz et al., 2006, Clin Pharm Ther
Nicotine: More than Dopamine
Aromatase* (Estrogen synthase, CYP19A1)
C H3 O H
CH3 O H
CH3
aromatase
HO
O
testosterone
•
17 b -estradiol
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
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
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
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.
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
As Women Age, the Medical Consequences
from Smoking are Greater than for Males
Lung cancer
risk is 2 x greater in women than 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
Smoking Causes Cancer in Organs Throughout the Body
Throat
Larynx (voice box)
Mouth
Esophagus
Lung
Leukemia (blood)
Stomach
Kidney
Bladder
Pancreas
Cervix
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