Download Sex Differences in Nicotine Use - Alcohol Medical Scholars Program

SEX DIFFERENCES IN
NICOTINE USE
Reagan Wetherill, Ph.D.
Perelman School of Medicine
University of Pennsylvania
© AMSP 2017
CC: Background
• Demographics and substance use Hx:
– 48yo, Caucasian female
– M.A.-psychology, realtor
– 20 cigarettes/day for 15 yrs
– Fagerström Test for Nicotine Dependence: 6
– No other substance use
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CC: Psychiatric Hx
• Smoking cessation Rx Hx
– Bupropion
– Nicotine replacement therapy
• No other significant clinical symptoms
• Reason for Rx  pneumonia 2x, health
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Smoking – Leading Cause of Death
• ~500,000 deaths/year in U.S.
• >16 million w/smoking-related diseases
• Women ↑↑ severe health consequences
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Quitting Smoking is Challenging
• Withdrawal
• Triggers
• Ambivalence
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This Lecture Will Cover:
• Definitions
• Course of nicotine use disorder (NUD)
• Factors underlying sex differences in NUD
• Treatment options for NUD & response
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This Lecture Will Cover:
• Definitions
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Cigarettes and Cigarette Smoke
• Complex mix of chemicals
– Fungicides and pesticides
– Cadmium
– Benzene
– Formaldehyde
• Nicotine → stimulant
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Brain Effects of Nicotine
•  Neurotransmitters and hormone release
• Alters cognitive and mood states
– ↑ Attention, learning and memory
– ↑ Pleasure
– Improves mood
– ↓ Appetite
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DSM-5 Nicotine Use Disorder
> Amount, longer time smoking
Craving
↑ Time obtain/use
Use in hazardous situations
Failure to fulfill life obligations
Tolerance
Giving up important activities
Withdrawal (WD)
Use despite social problems
Desire/unable to ↓/control
Use despite health problems
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Nicotine Withdrawal
• Physical symptoms
– Weight gain (~10 lbs)
– Headaches
– Tingling in hands and feet
– Sweating
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Nicotine Withdrawal (2)
• Cognitive/emotional symptoms
– Craving
– ↑ Irritability
– ↑ Anxiety & depression symptoms
– ↓ Concentration
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Sex Versus Gender
• Sex  biological sex
• Gender  socially constructed
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Ovulation
Ovarian Hormones
Follicular Phase
Early
0
Late
7
Luteal Phase
14
Estradiol
21
28
Progesterone
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Estrogen
• Female features & reproduction
• 3 types of estrogen: estradiol (E) is focus
• E levels low during menstruation
• E ↑ during follicular phase (FP)
• E ↓↑ during luteal phase (LP) then ↓
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Progesterone (P)
• Stimulates and regulates
• Maintains pregnancy
• P levels low during FP
• P ↑ during LP, ↓↓ just before menses
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Hypothalamic-Pituitary-Adrenal Axis
• Central control & regulatory system
– Digestion
– Immune system
– Mood and emotions
– Energy
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Hypothalamic-Pituitary-Adrenal Axis (2)
• Helps adapt and respond
• Cortisol  mobilizes for energy
– Sex differences in cortisol levels/stress response
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This Lecture Will Cover:
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Age of First Use
• Females  16.7 yrs
• Males  15.6 yrs
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Escalation of Use & Progression to NUD
• NUD sxs w/i days-weeks of use
– Urge/desire to smoke upon waking
– Smoking to help stay alert/concentrate
– Urge/desire to smoke when exposed to cues
• ♀ Escalate use and progress faster
• Onset of dependence for ♀ → 21 days
• Onset of dependence for ♂ → 183 days
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Withdrawal (WD) & Relapse
• WD sxs after monitored overnight abstinence
– ♀ → More severe sxs of negative mood
• ♀ → 6.5 pt ↑ in tension-anxiety
• ♂ → 2.9 pt ↑ in tension-anxiety
– ♀ → Greater relief from WD after smoking
• ♀ → 1.4 pt ↓ in psychological sxs
• ♂ → 0.5 pt ↓ in psychological sxs
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Lapse vs. Relapse for ♀
• Lapse – 21% greater risk
• Relapse – 29% greater risk
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♀ ↑ Severe Health Problems
• Risks to children
– Smoking during pregnancy:
• ↑ Risk of miscarriage
• Placenta problems
• Premature birth
• Low birth weight
• ↑ Risk of birth defects
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♀ ↑ Severe Health Problems (2)
• Lung cancer: 2x more likely than ♂
• Coronary heart disease: 25% > risk than ♂
• Chronic obstructive pulmonary disease: 2-3x
more likely hospitalization/death than ♂
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This Lecture Will Cover:
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Nicotine Action
• ♀ More sensitive to nicotine effects
• ♀ Dopamine (DA) varies with hormones
– P → inhibits the nicotinic receptor
– E → ↑ DA release
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Once NUD is Established
• ♂ Use → maintain nicotine levels
– Able to identify difference in nicotine levels
– Increased number of nicotinic receptors
• ♀ Use → non-nicotine factors
– Experience relief from denicotinized cigarette
– Smoke less when taste/smell cues blocked
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Ovarian Hormones in ♀
<
Smoking/crav
ng
Ovulation
>
Smoking/cravi
ng
Follicular Phase
Early
0
Late
7
Luteal Phase
14
Estradiol
21
28
Progesterone
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Smoking Cessation
• Quit rates → decline less pronounced in
♀
• ♀ Less successful
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This Lecture Will Cover:
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Overview of Treatment Options
• Psychotherapy
• FDA-approved medications
– Nicotine Replacement Therapy
– Bupropion (Wellbutrin, Zyban)
– Varenicline (Chantix)
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Cognitive Behavioral Therapy (CBT)
• Basic idea: thoughts → feelings & behaviors
• Teach pt. to identify & correct thoughts
• Explore +/- consequences
• Identify craving quickly to avoid smoking
• Relapse prevention
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Relapse Prevention
• Identify & avoid high-risk situations
• ↑ Effective non-smoking coping skills
• Pt’s belief that he/she can change
• Keep smoking “lapses” short
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FDA-Approved Medications
• Nicotine Replacement or NRT
– Nicotine w/o negative effects of smoking
– Taper amount of nicotine until discontinue
– NRT better than placebo
– 70-80% who use NRT relapse w/i 6 mos
– ♀ Show poor response
– Patient CC  not effective
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FDA-Approved Medications (2)
• Bupropion (BUP; Wellbutrin, Zyban)
– Reduces craving
– Reduces withdrawal symptoms
– ♂ Show similar efficacy to NRT and varenicline
– ♀ Show poor response
– Patient CC  not effective
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FDA-Approved Medications (3)
• Varenicline (VAR; Chantix)
– Reduces craving
– Decreases rewarding/pleasure effects of nicotine
– No sex differences
– Patient CC  ↓ smoking from 20 to 0 in 9 weeks
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Sex Differences in Rx Response
• Head-to-head comparisons of meds in ♀
– VAR superior to NRT and BUP
– ♀ on VAR 41% more likely abstinent at 6-mo f-u
• Head-to-head comparisons of meds in ♂
– No statistically significant differences
– ♂ on VAR 16% more likely abstinent at 6-mo f-u
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Conclusions
• Sex differences in all phases of NUD
• ♀ have > vulnerability to and more severe:
– Health-related consequences
– Lapses and relapses
• VAR most effective Rx for all smokers
• Several areas for needed inquiry
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Future Directions
• Consideration of biological sex in analyses
• ↑ Collection of hormone levels in research
• ↑ Number of women in studies
• Evaluate sex differences in psychosocial Rx
• Consider hormonal milieu when planning Rx
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