Modifying Progesterone and Estradiol Levels to Prevent Postpartum Cigarette Smoking Relapse and Reduce Secondhand Smoke Exposure in Infants and Children

Project Summary/Abstract
Postpartum smoking relapse rates have remained stagnant for over a decade with more than 50% of those
who are able to achieve smoking abstinence during pregnancy relapsing within the first few months after
childbirth. Maternal cigarette smoking results in significant increases in a variety of negative health
consequences for both mother and child. Second-hand smoke exposure to newborns and infants increases
their risk of both acute and chronic illness. Therefore, research to identify safe and novel postpartum smoking
relapse prevention intervention is warranted. Our preliminary data indicates that the delivery of exogenous
progesterone (Prog) in the early postpartum period reduces several smoking relapse related risk factors (e.g.,
craving) and was also associated with a higher prevalence of smoking abstinence at 12-weeks postpartum.
These observations concur with a wealth of prior literature that demonstrates the protective effects of
progesterone on a variety of addictive behaviors. In our other preliminary work looking at non-pregnant
premenopausal women, depot medroxyprogesterone acetate or DMPA, which blocks ovulation for 12-weeks
which subsequently decreases estradiol levels, was associated with longer previous quit attempts and reduced
smoking motives. These observations have shaped our central hypothesis which is that the combination of
Prog + DMPA; i.e., increased progesterone and decreased estradiol will prevent postpartum smoking relapse.
To examine this hypothesis, we will conduct a double-blind, placebo-controlled, randomized clinical trial that
will be implemented by an experienced, transdisciplinary, and productive team of investigators from two sites
to enhance the diversity of the study sample and generalizability of the results. We will enroll healthy pregnant
women (n=320) who have recently quit smoking and intend to stay abstinent postpartum. Using a 2×2 factorial
design, participants will be randomized into one of four assignments: (1) Prog + DMPA, (2) Prog + placebo, (3)
placebo + DMPA, and (4) placebo + placebo. Participants will be followed for days to smoking relapse (primary
outcome), smoking relapse-related risk factors (e.g., craving), and infant health outcomes from gestational
week 36 through 9 months postpartum. This study proposes a safe and innovative intervention to examine the
impact of manipulating postpartum physiological to influence the behavior of a new mother which will lead to
improved health outcomes for her and her infant. The implications of this novel study will directly advance the
current state of the science by expanding on the role of Prog and DMPA in addressing smoking-related
behaviors within this highly vulnerable population. Further, should our central hypothesis be supported, the
clinical translatability of this intervention is high and may be immediately pursued.

Grant Number: 5R01HD100418-05
NIH Institute/Center: NIH
Principal Investigator: SHARON ALLEN