Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review

Hippocampal gray matter volume in young adulthood varies with adolescent alcohol use.

“…Prior work suggests that models including both chronological age and pubertal status provide the best fit to data describing subcortical gray matter development (Goddings et al, 2014; Herting et al, 2014). Furthermore, recent work suggests that the hormones associated with puberty (e.g., estrogen, testosterone) may be linked with substance use outcomes (Santos-Toscano et al, 2023). Thus, adolescents who initiate substance use at the same chronological age, but different pubertal stage, may have different neural outcomes in young adulthood.…”

Epigenetic and sex differences in opioid use disorder in chronic pain: A real‐world study linked with OPRM1 DNA methylation

“… 2 Findings from the literature suggest that women are more likely to use prescription opioids 3 with faster progression of abuse after their first substance use, unlike men who show higher overdose death rates. 4 Taking into account the higher chronic pain prevalence in older women, 5 the socio‐cultural influence in pain response, 6 and the existing gender inequalities in pain management, 7 understanding sex differences seems essential for effective OUD prevention. 8 , 9 …”

“…2 Findings from the literature suggest that women are more likely to use prescription opioids 3 with faster progression of abuse after their first substance use, unlike men who show higher overdose death rates. 4 Taking into account the higher chronic pain prevalence in older women, 5 the socio-cultural influence in pain response, 6 and the existing gender inequalities in pain management, 7 understanding sex differences seems essential for effective OUD prevention. 8,9 Some genetic markers and epigenetic modifications have been widely studied for their association in a variety of drug addiction 10,11 and pain sensitivity phenotypes, 12 most notably μ-opioid receptor 1 (OPRM1, A118G, rs1799971-G allele).…”