Progesterone Treatment in Female Smokers - 12

Limited research has been done on the effects of gender and menstrual cycle in response to
drugs of abuse in humans. The main goal of this pilot study is to investigate the safety and
tolerability of progesterone treatment in female nicotine users. In addition, plasma
progesterone levels reached with a single 200 mg dose of progesterone treatment will be
measured. The study will be a double-blind placebo controlled, crossover trial in which 12
female smokers who are in the early follicular phase of their menstrual cycle will be
enrolled. Druing the experimental sessions, subjects will be given a single 200 mg dose of
micronized progesterone or placebo and multiple blood samples will be obtained to measure
the plasma levels of progesterone. Starting 2 hours after progesterone or placebo treatment,
subjects will have a self-administration period that will last around 2.5 hours. We
hypothesize that administration of 200 mg of progesterone will achieve plasma progesterone
concentrations similar to those found in the luteal phase of the menstrual cycle, 3-30
ng/ml.

Inclusion Criteria:

Female subjects aged 21-45 years with a smoking history of at least 20 cigarettes daily
for at least 1 year. In good health as verified by medical history, screening examination,
and screening laboratory tests. Not pregnant as determined by pregnancy screening nor
breast feeding, and using acceptable birth control methods other than hormonal
contraceptives.

Exclusion Criteria:

History of heart disease, peripheral vascular disease, COPD, liver diseases, abnormal
vaginal bleeding, suspected or known breast malignancy, or any other medical condition
which physician investigator deems inappropriate for subject participation. Use of regular
psychotropic medication (antidepressants, antipsychotics, or anxiolytics) and recent
psychiatric history. Amenorrhea. Current use of oral or other types of hormonal
contraceptives. Abuse of alcohol or any other recreational or prescription drug. Regular
use of any other tobacco products, including smokeless tobacco and nicotine products.
Known allergy to progesterone or peanuts.