Role of progesterone in nicotine addiction: evidence from initiation to relapse

Nicotine addiction continues to be the main cause of preventable death in developed countries. Women and teen girls appear to be more vulnerable on certain aspects of nicotine addiction compared with men and boys. While the mechanism of gender differences in nicotine addiction is not yet clear, evidence suggests that while estrogen may underlie enhanced vulnerability in females, progesterone may protect females. Thus, progesterone may have therapeutic use for tobacco addiction, especially in female smokers. A greater understanding of the role of progesterone in nicotine addiction is important not only from a treatment standpoint, but also from a prevention standpoint: hormone transition phases, such as those that occur at adolescence, and during pregnancy and following birth, as well as following hormonal manipulation (e.g., using methods of hormonal birth control), may all contribute to changes in vulnerability to nicotine addiction. In this review, we summarize recent evidence from clinical and preclinical studies examining the role of progesterone in nicotine addiction focusing on its role during initiation of use and during later phases of the addiction process as a potential relapse prevention treatment. We conclude with future directions including further examination of progesterone as a potential intervention and treatment of nicotine addiction.