Digital and hormonal biomarkers: identifying novel targets for a personalized medicine approach for smoking cessation in women of reproductive age

The National Institutes of Health Office of the Director awarded Arkansas Children's Research Institute $1,451,548 on July 1, 2026, under the Trans-NIH Research Support program (CFDA 93.310) to conduct a national, fully-remote natural-experiment study identifying hormonal and digital biomarkers predictive of smoking cessation outcomes in women of reproductive age.

The research addresses the lower efficacy of evidence-based smoking cessation interventions in women compared to men and the greater vulnerability of women to smoking-related morbidity and mortality. The study will investigate how ovarian hormonal fluctuations—including progesterone and estradiol—contribute to smoking behavior and can inform personalized medicine approaches to cessation. The project will enroll a diverse sample of biological females and collect four types of data including ovarian hormone measurement via urinalysis and identification of digital biomarkers that vary with hormonal fluctuation, such as body temperature changes during ovulation. The research addresses documented gaps in clinical literature by including women using hormonal contraceptives and those with irregular menstrual cycles, expanding hormone measurement to include ethinyl estradiol, and examining digital biomarkers previously absent from smoking cessation research.

Performance takes place in Little Rock, Arkansas, with a period of performance extending from July 1, 2026, through April 30, 2031. The assistance type is a project grant.

Abstract

Evidenced-based cigarette smoking cessation interventions are less efficacious in women as compared to men. Women are also more vulnerable to smoking-related morbidity and mortality compared to men. The role of ovarian hormones (e.g., progesterone, estradiol) in cigarette smoking in women of reproductive age remains unknown, despite ample compelling evidence from preclinical literature. Utilizing today's technology, we can gain a better understanding how ovarian hormonal fluctuations contribute to smoking behavior, as well as how they can be used to create effective smoking cessation interventions. Specifically, three major outstanding limitations exist in the clinical literature on ovarian hormones and smoking cessation that need to be addressed to improve generalizability (i.e., inclusion of women who are using hormonal contraceptives and/or have irregular menstrual cycles), increase scientific rigor (i.e., expansion to measurement of other hormones; e.g., ethinyl estradiol), and expand scientific knowledge. Beyond these limitations, an additional GAP includes a lack of research on the identification of digital biomarkers that are known to vary with hormonal fluctuation (e.g., increase in body temperature during ovulation). Overall, these existing limitations and gaps in knowledge severely limit the opportunities to apply hormonal and/or digital biomarkers to personalized medicine approaches in smoking cessation for women of reproductive age. The overall goal of his national fully-remote natural-experiment study is to identify hormonal and/or digital biomarkers that are predictive of smoking cessation outcomes in a diverse sample of biological females utilizing innovative methodology. Participants will complete four types of data collection: (a) measurement ovarian hormone measurement via urine DIP stick testing (e.g., progesterone) and dried blood spot testing (e.g., ethinyl estradiol), (b) monitoring of physiological changes (e.g. distal body temperature) via sensor measurement, (c) self-administered validated surveys, and (d) measurement of expired carbon monoxide. Our primary outcome will be cigarette smoking cessation, with secondary outcomes including level of use (e.g., cigarettes/day), motives for use (e.g., craving), and smoking cessation intervention engagement (e.g., completion of coaching sessions). Upon completion of this project, regardless of outcome, the data collected here will advance the knowledge on how female physiology influences smoking. Further, the identification of novel hormonal and/or digital biomarkers will inform the development of personalized medicine approaches for smoking cessation tailored to the needs of women of reproductive age in direct response to not-OD-24-079.