Gonadal Hormone Contribution to Substance Use Disorders and Neurodegenerative Diseases in Female

Sex differences have been long recognized to influence multiple systems in the human body, ranging from the cardiovascular system to the neurological system, and these differences have been attributed primarily to the influence of the gonadal hormone, estrogen. In most cases, estrogen functions as a protective agent against multiple diseases, e.g., neurodegenerative diseases, thereby making women generally less vulnerable than men. However, research studies have also shown that estrogen contributes to increased vulnerability in developing substance use disorders (SUD), where because women have higher concentration of circulating estrogen, setting them at a higher risk for development of SUD. While extensive research has revealed some of the underlying mechanisms through which estrogen influences both substance use disorders (SUD) and neurodegenerative diseases, current studies have yet to investigate situations in which these diseases coexist. Such investigations could potentially illuminate the nuanced relationship between the two conditions. In this comprehensive review paper, the mechanisms underlying gender-dependent vulnerability are discussed, along with more real-life dilemmas and questions that are posed. To address these questions, some potential preclinical and clinical experimental proposals are explored and discussed