INTRODUCTION: Opioid use disorder (OUD) is a public health challenge globally. Few studies examine sex differences in opioid agonist therapy outcomes, especially in contexts of high potency opioid consumption. Clarifying these could inform personalized treatment strategies.

METHODS: We conducted exploratory sex-stratified analyses using data from a 24-week, multicentric, pragmatic, open-label randomized controlled trial. Participants with OUD (n male=179, n female=93) were randomized to flexible take-home dosing of buprenorphine/naloxone (n male=95, n female=43) or standard methadone (n male=84, n female=50) models of care. Retention was defined as having both an active prescription and a positive urine drug screen for the assigned treatment at week 24. Opioid use was assessed as the proportion of opioid-positive urine samples. Craving was measured using the Brief Substance Craving Scale and withdrawal using the Clinical Opiate Withdrawal Scale. Substance-use-related problems were evaluated via the Addiction Severity Index (ASI).

RESULTS: In sex-stratified analyses, retention appeared overall lower for females (buprenorphine/naloxone=11.6%, methadone=26.0%) than males (buprenorphine/naloxone =28.4%, methadone=38.1%). Females showed higher opioid use overall; there was no treatment group effect on opioid use in either sex (p > 0.05). Both sexes improved in drug and psychiatric ASI domains (p < 0.05), while family-related problems improved only in males (p = 0.036). Craving decreased in both sexes, with females reporting lower craving on buprenorphine/naloxone than on methadone (p < 0.001). Withdrawal scores were higher with buprenorphine/naloxone versus methadone in males only (p = 0.026).

CONCLUSIONS: We found potential sex differences in treatment outcomes, suggesting that these may benefit from sex-based adaptations. Future research into this possibility is warranted.