Associations of sex-related steroid hormones and proteins with alcohol dependence: A United Kingdom Biobank study. (1st March 2023)

• Record Type: Journal Article
• Authors: Ho, Ada Man-Choi; Pozsonyiova, Sofia; Waller, T. Cameron; Song, Yilin; Geske, Jennifer R.; Karpyak, Victor M.; Winham, Stacey J.
• Is Part Of: Drug and alcohol dependence. Volume 244(2023)
• Publication Date: 2023-03-01
• Subjects: Alcohol dependence -- Alcohol consumption -- Steroid sex hormones -- Sex hormone binding globulin -- Males -- Females; Drug abuse -- Periodicals; Alcoholism -- Periodicals; 616.86
• DOI: 10.1016/j.drugalcdep.2023.109781
• Languages: English
• ISSNs: 0376-8716

Abstract

Abstract: Background: Sex-related steroid hormones and proteins may contribute to the sex differences in the characteristics and health consequences of alcohol use disorder. This study aimed to examine the associations between alcohol dependence (AD) and sex-related hormones/proteins using a population-based dataset. Methods: We retrieved serum total testosterone (TT) and estradiol (TE2), sex hormone binding globulin (SHBG), and albumin levels along with clinical data from the UK Biobank. Hormone/protein levels were compared between AD (lifetime AD and/or related diagnoses; 2218 males; 682 females) and control (no aforementioned diagnoses and AUDIT<8; 198, 058 males; 250, 830 females) groups with sex-dependent linear regression models adjusting for age and body mass index. Moderation and mediation analyses were performed to test whether SHBG was a moderator and/or mediator between hormones and AD or current drinking. Results: AD males had higher TT, TE2, and SHBG levels but lower bioavailable testosterone, bioavailable estradiol, and albumin levels than controls ( p adjusted <0.001). After adjusting for menopause, AD females had higher TT and lower albumin levels than controls ( p adjusted <0.001). These differences remained after accounting for current drinking frequency ( p < 0.001). SHBG moderated TT's effect on AD in males ( p interaction <0.001). SHBG was a positive mediator between TT and AD in both sexes and between TE2 and AD in males ( p < 0.001), but a negative mediator between TT and current drinking in controls (both sexes) and AD males ( p < 0.001). Conclusions: Testosterone and estradiol levels are altered in males and females with AD distinctly regardless of current drinking frequency. SHBG may play a critical role in these associations. Highlights: The associations of steroid sex hormones with alcohol dependence (AD) were unclear. Females with AD history have higher testosterone and lower albumin levels in serum. Males with AD history further have higher estradiol and SHBG levels in serum. Effects of AD history are independent of current drinking status. SHBG mediates the associations of the hormones with AD and with current drinking.