Contributions of testosterone to excessive alcohol drinking in males: Potential role for interactions with the HPA axis

Excessive alcohol drinking and alcohol use disorders (AUDs) are a significant and increasing public health concern in the United States and worldwide, with men historically having higher rates of alcohol consumption and AUD diagnoses. Despite this, the biological mechanisms underlying sex differences in these outcomes are not fully understood. Endocrine systems are critical regulators of behavior and testosterone has a bidirectional relationship with alcohol in males. Baseline levels of testosterone (T) may bias males toward approach behaviors that increase the tendency to engage in risky drinking behaviors in adolescent and adult men. At the same time, T appears to protect males (particularly rodents) against elevated levels of initial alcohol consumption. T levels also change with alcohol exposure, decreasing with acute and chronic use. This review synthesizes findings from both human and animal studies, highlighting how interactions between the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes may underlie male-specific patterns of alcohol use and risk for AUD. Understanding these mechanisms is essential for preclinical and clinical researchers conducting research in males and for the development of more effective interventions for AUD in men.