Menstrual Cycle Effects on Smoking Cessation and Cue Reactivity

This component builds directly upon the results of the previously funded project in
systematically investigating the impact of short-term ovarian hormone fluctuation on females
as they try to quit smoking with the aid of either transdermal nicotine patch (TNP) or
varenicline. Each participant will receive a standardized impulsivity evaluation and a
laboratory-based cue reactivity assessment before the initiation of smoking cessation.
Progesterone and estrogen levels will be measured at each of nine visits, thereby providing
an index of reproductive hormone variation over the course of each participant's quit
attempt. This novel approach of integrating a human laboratory cue reactivity paradigm
directly with a treatment outcome study will permit us to assess whether or not smoking cue
reactivity has predictive utility with respect to cessation outcome. Subjects will be
randomized to receive one of two active pharmacotherapeutic interventions for smoking
cessation: TNP vs. varenicline in a randomized, single-blind, double dummy design. While TNP
has demonstrated modest efficacy in improving smoking cessation outcomes, there is some
evidence that its efficacy may be more robust in men as compared to women. This project will
provide important information about a) the impact of ovarian hormone levels on smoking
cessation outcomes, b) the relationship between smoking cue reactivity and smoking cessation,
and c) comparison between a new pharmacotherapeutic agent and TNP in women.

Inclusion Criteria:

- Age 18-45. Individuals over the age of 45 will not be included as we are examining the
effects of menstrual cycle and ovarian hormones.

- Daily smokers who smoke at least 10 cigarettes per day for at least past 6 months.

- Post menarche and pre menopausal

- Regular menstrual cycle between 25 and 35 days

- At least three months post delivery and breast feeding

- Desire to quit smoking and willingness to participate in a research study.

- Women with a history of depression (but not current MDE) and current PMDD will be
included. Excluding women with these diagnoses would have a major impact on
feasibility, but because both disorders might impact treatment outcome, individuals
will be stratified across randomization groups.

Exclusion Criteria:

- Any unstable major axis I psychiatric disorder in the past month

- Current substance use disorders other than nicotine and caffeine use, in the past 30
days.

- Any medication that may interfere with psychophysiological monitoring

- Unstable medical or serious medical condition in the past 6 months

- Hypersensitivity to varenicline or TNP

- Use of other tobacco products

- Use of other medications with smoking cessation efficacy within 30 days prior to
enrollment

- BMI less than 15 since this could alter hormone levels that affect menstrual phase

- Pregnancy

- Breast feeding

- Status post hysterectomy

- Birth control or HRT medication that would effect the menstrual cycle. Currently
available oral contraceptives contain either a combination of a synthetic estrogen and
synthetic progestin, or a progestin alone. Estrogen and/or progestin inhibit ovulation
and alter cervical mucus and the endometrium by suppressing the production of
follicle-stimulating hormone and the luteinizing hormone surge (Bucci & Carson, 1997)