1. SEX DIFFERENCES IN NICOTINE USE
Reagan Wetherill, Ph.D.
Perelman School of Medicine
University of Pennsylvania
© AMSP 2017

2. 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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3. 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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4. 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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5. Quitting Smoking is Challenging
Withdrawal
Triggers
Ambivalence
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6. This Lecture Will Cover:
Definitions
Course of nicotine use disorder (NUD)
Factors underlying sex differences in NUD
Treatment options for NUD & response
© AMSP 2017

7. This Lecture Will Cover:
Definitions
Course of nicotine use disorder (NUD)
Factors underlying sex differences in NUD
Treatment options for NUD & response
© AMSP 2017

8. Cigarettes and Cigarette Smoke
Complex mix of chemicals
Fungicides and pesticides
Cadmium
Benzene
Formaldehyde
Nicotine → stimulant
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9. 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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10. DSM-5 Nicotine Use Disorder
> Amount, longer time smoking
↑ Time obtain/use
Failure to fulfill life obligations
Giving up important activities
Use despite social problems
Use despite health problems
Craving
Use in hazardous situations
Tolerance
Withdrawal (WD)
Desire/unable to ↓/control
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11. Nicotine Withdrawal Physical symptoms Weight gain (~10 lbs) Headaches
Tingling in hands and feet
Sweating
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12. Nicotine Withdrawal (2)
Cognitive/emotional symptoms
Craving
↑ Irritability
↑ Anxiety & depression symptoms
↓ Concentration
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13. Sex Versus Gender Sex  biological sex Gender  socially constructed
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14. Ovarian Hormones Ovulation Follicular Phase Luteal Phase Early Late
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15. 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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16. Progesterone (P) Stimulates and regulates Maintains pregnancy
P levels low during FP
P ↑ during LP, ↓↓ just before menses
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17. Hypothalamic-Pituitary-Adrenal Axis
Central control & regulatory system
Digestion
Immune system
Mood and emotions
Energy
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18. Hypothalamic-Pituitary-Adrenal Axis (2)
Helps adapt and respond
Cortisol  mobilizes for energy
Sex differences in cortisol levels/stress response
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19. This Lecture Will Cover:
Definitions
Course of nicotine use disorder (NUD)
Factors underlying sex differences in NUD
Treatment options for NUD & response
© AMSP 2017

20. Age of First Use
Females  16.7 yrs
Males  15.6 yrs
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21. 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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22. 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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23. Lapse vs. Relapse for ♀ Lapse – 21% greater risk
Relapse – 29% greater risk
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24. ♀ ↑ 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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25. ♀ ↑ 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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26. This Lecture Will Cover:
Definitions
Course of nicotine use disorder (NUD)
Factors underlying sex differences in NUD
Treatment options for NUD & response
© AMSP 2017

27. Nicotine Action ♀ More sensitive to nicotine effects
♀ Dopamine (DA) varies with hormones
P → inhibits the nicotinic receptor
E → ↑ DA release
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28. 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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29. Ovarian Hormones in ♀ > Smoking/craving < Smoking/craving
Ovulation
Early
Late
Follicular Phase
Luteal Phase
> Smoking/craving
< Smoking/craving
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30. Smoking Cessation Quit rates → decline less pronounced in ♀
♀ Less successful
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31. This Lecture Will Cover:
Definitions
Course of nicotine use disorder (NUD)
Key factors underlying sex differences in NUD
Treatment options for NUD & response
© AMSP 2017

32. Overview of Treatment Options
Psychotherapy
FDA-approved medications
Nicotine Replacement Therapy
Bupropion (Wellbutrin, Zyban)
Varenicline (Chantix)
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33. 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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34. 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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35. 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
© AMSP 2017

36. 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
© AMSP 2017

37. 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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38. 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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39. 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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40. 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
© AMSP 2017