The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) integrates the two distinct DSM-IV disorders, alcohol abuse and alcohol dependence, into a single disorder that is called alcohol use disorder (AUD; NIAAA, 2021). According to the 2019 National Survey on Drug Use and Health, approximately 9 million men and 5.5 million women in the United States aged 12 and older have AUD, representing 6.8% of men and 3.9% of women in this age group (NIAAA, 2022a). Prevalence of binge drinking, defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) as a pattern of drinking that brings blood alcohol concentration to 80 mg/dl or higher (NIAAA, 2004), is reported in 29.7% of men and 22.2% of women aged 18 and older (NIAAA, 2022a). There are numerous negative health consequences in individuals with AUD, making alcohol the fourth leading preventable cause of death in the United States (NIAAA, 2022a). Notably, prevalence of binge drinking has been increasing in women, but not in men, that were between the ages of 31 – 65, when data were analyzed across studies during a 2000-2016 observation period (Grucza et al., 2018). In addition to this narrowing of the previous sex difference in rate of AUD (males > females), it should be considered that negative health consequences have been reported to be worse in females versus (vs) males with fewer years of heavy drinking (Erol & Karpyak, 2015 and references therein; NIAAA, 2022b; Wiren, 2013 and references therein). It is possible that telescoping, a phenomenon that refers to the amount of time between initial alcohol consumption and the onset of dependence, is more pronounced in women than in men (see Erol & Karpyak, 2015 and references therein). Overall, there are likely multiple reasons contributing to the above sex differences, including biological and psychological factors, with suggestions that the increased rate of AUD among women may reflect drinking to regulate negative affect and/or stress reactivity in females (Becker & Koob, 2016; Logrip et al., 2018, Peltier et al., 2019).

Function of the endocrine system is influenced by biological sex and is disrupted by acute and chronic alcohol exposure (Rachdaoui & Sarkar, 2017). Glands in the endocrine system secrete steroid hormones that influence and facilitate numerous physiological functions as well as the ability to respond to stress and to changes in the environment in order to maintain homeostasis (Oyola & Handa, 2017; Rachdaoui & Sarker, 2017). Sex steroids regulate sexual differentiation and secondary sex characteristics as well as sex differences in behavior via organizational and activational effects in the brain (Arnold & Gorski, 1984; Becker & Koob, 2016; Erol et al., 2019, McCarthy et al., 2012). Moreover, due to interactions and cross-talk between the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes, gonadal steroids influence the response to stress via the HPA axis, and elevated stress steroids negatively impact the reproductive or HPG axis (Oyola & Handa, 2017). Consequently, when considering the influence of sex and stress steroids on various effects of alcohol, it is important to bear in mind the interaction between the effects of alcohol exposure on the endocrine system as well as the reciprocal interaction between the HPA and HPG axes.

It is well documented that sex and stress hormones influence alcohol consumption, alcohol withdrawal, and behavior in models of addiction (Becker & Koob, 2016; Devaud et al., 2006, Erol et al., 2019, Flores-Bonilla and Richardson, 2020, Lenz et al., 2012, Logrip et al., 2018). The purpose of the current review is to update (Finn, 2020) and expand upon preclinical research related to the contributions of the endocrine system to alcohol drinking and withdrawal in females, with a focus on animal models. It will concentrate on steroids important in the HPG and HPA axes, the effects of alcohol exposure on steroid levels, and the influence of steroid administration on alcohol drinking, withdrawal, and other select addiction-related behaviors. Genomic effects and rapid membrane-associated effects of steroids and neurosteroids are considered. Comparisons of pertinent results between females and males highlight sex differences in steroid effects on alcohol drinking- and withdrawal-related behaviors. These comparisons and the sexually divergent responses emphasize the importance of considering sex in the development of novel pharmacotherapies for the treatment of AUD.