Phenotypic and Genetic Effects of Endogenous Testosterone on Binge Eating in Women

About This Grant

PROJECT SUMMARY Gonadal hormones (testosterone, estrogen, progesterone) cause significant changes in food intake in animals, but until recently, were largely ignored in studies of binge eating (BE). Animal and human data now confirm that ovarian hormones (estrogen, progesterone) are critical risk factors for BE in females, and that natural changes in these hormones across the menstrual cycle substantially increase risk for BE via hormonally induced increases in genetic risk. However, a critical gap in this novel area of research remains - the impact of testosterone on BE risk in women. Testosterone is traditionally associated with male physiology, yet it is also present in females and is highly relevant to BE and women's health. Animal studies show higher testosterone levels have stimulatory effects on food intake and preferences for palatable food (PF). Elevated testosterone is associated with increased cravings for PF, and disorders characterized by elevated testosterone in women (e.g., PCOS) are marked by higher BE. Testosterone also exerts potent effects on gene transcription in systems critical for BE. Remarkably, no large-scale study has examined testosterone effects on BE risk in women. Our Specific Aims are to illuminate the critical and unique role of testosterone in risk for BE in women and identify etiologic mechanisms of individual differences in risk. We will capitalize on the availability of novel archival data from our NIMH-funded study that collected daily BE and ovarian hormones across 45 consecutive days (>100,000 datapoints) in a population-based sample of female twins (N = 520). We will assay archival saliva samples (15,000+) for daily testosterone levels and use our daily data to examine testosterone as a critical phenotypic risk factor for BE in women (Aim 1). We will substantially extend these findings by examining whether daily changes in testosterone impact genetic risk for BE (Aim 2) and serve as mechanisms of individual differences in risk. Finally, we will conduct secondary analyses to probe the interplay between testosterone and ovarian hormones to develop the most comprehensive models of gonadal hormone influences on BE in women to date. There is a compelling and urgent public health need to understand the role of testosterone in BE. Millions of women are prescribed hormonal contraceptives that stimulate testosterone/androgenic activity, and testosterone is used to treat health conditions in women. These treatments have proceeded with very little data on the potential adverse effects of testosterone on BE or other psychiatric symptoms. Our project’s integration of unique archival data with new testosterone measurements is a powerful strategy for studying these effects and addressing NIMH’s focus on isolating mechanisms and analyses that “incorporate genetic markers of risk, and leverage existing large, population-based cohorts… to advance understanding of complex etiologies.” Our findings will substantially advance etiologic models and inform precision medicine approaches that can reduce BE and improve women’s health.