Investigating the Influence of Prenatal Androgen Exposure and Sibling Effects on Alcohol Use and Alcohol Use Disorder in Females from Opposite-Sex Twin Pairs

Background There are robust sex differences for alcohol phenotypes, with men reporting more drinking and alcohol use disorder (AUD) symptoms than women. However, the sources of these effects are not completely understood. Sex hormones, a substantial biological sex difference, exert neurobehavioral influences and are candidates for influencing sex differences in alcohol phenotypes. This study investigated the effects of prenatal androgens based on the hypothesis of prenatal hormone transfer, which posits that hormones from one twin influence the development of a cotwin. Methods This study compared female twins from opposite-sex (OSF) and same-sex (SSF) pairs to investigate associations between prenatal androgens and alcohol phenotypes. Additional analyses distinguished prenatal and postnatal effects by comparing OSFs and SSFs with a close-in-age older (CAO) brother. Results OSFs endorsed more lifetime AUD symptoms than SSFs (d=0.14). Females with a CAO brother reported greater intoxication frequency (d=0.35), hangover frequency (d=0.24), typical drinking quantity (d=0.33), and max drinks (i.e., the most drinks ever consumed in a 24-hour period; d=0.29). Controlling for postnatal effects, OSFs still endorsed more lifetime AUD symptoms than SSFs with a CAO brother (d=0.16). Conclusions Prenatal exposure to a male cotwin was associated with increases in AUD symptoms, above the effect of postnatal exposure to a male sibling. Prenatal exposure to a male cotwin was not associated with increases in other alcohol-related phenotypes, but postnatal exposure to older male siblings produced medium effect sizes for indicators of alcohol consumption. Sex differences in AUDs, but not alcohol use, may be partially due to the neurodevelopmental effects of prenatal androgens. However, sibling effects may be larger than any effect of prenatal androgen exposure.