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Heroin Addiction and Related Clinical Problems: 2025, 27, 7

Pharmacogenomic predictors of sexual dysfunction in Malaysian male opioid users on methadone maintenance treatment

Sim Maw Shin, Shahrzad Riahi, Muhammad Fazril Mohamad Razif, Loh Huai Seng, and Anne Yee

Digital Object Identifier:
https://doi.org/10.62401/2531-4122-2025-7

Summary: Background: Opioid Use Disorder (OUD) continues to pose a significant public health challenge globally, including in Malaysia, where methadone maintenance therapy (MMT) is a primary treatment. While MMT is effective in managing OUD, it is frequently associated with sexual dysfunction (SD), which can negatively impact both treatment adherence and the overall quality of life. Pharmacogenomics presents a promising approach for understanding individual differences in treatment responses, including the development of SD. This study aims to explore the relationship between specific genetic polymorphisms and the occurrence of sexual dysfunction in Malaysian male opioid users undergoing MMT. Methods: A cross-sectional genetic association study was conducted with 121 male participants aged 18-60, all of whom had been on stable methadone doses for at least three months. Sexual function was assessed using the International Index of Erectile Function (IIEF-15) and the Sexual Desire Inventory (SDI-2). Additionally, blood samples were collected to measure testosterone and prolactin levels. Forty-six single nucleotide polymorphisms (SNPs) in OPRM1, ABCB1, COMT, and SHBG genes were genotyped to investigate potential associations with sexual dysfunction (SD) and hormone levels. Multivariate regression models were employed to adjust for potential confounders, and Bonferroni correction was applied to adjust for multiple comparisons. Results: Among the 121 MMT patients, 40 (33.06%) had low testosterone levels, while 81 (66.94%) had normal levels. Genotyping analysis revealed significant associations between specific SNPs and testosterone levels, including ABCB1 (rs2235067, rs2032583, rs2235040), OPRM1 (rs2075572, rs1074287), SHBG (rs727428), and COMT (rs6269, rs165722). Additionally, significant associations were identified between MMT-induced sexual dysfunction and SNPs in OPRM1 (rs12209447, rs3778152, rs165722, rs499796), DRD4 (rs12720390, rs3758653), ABCB1 (rs2235015, rs2235040), SHBG (rs1799941), and COMT (rs165722, rs165774, rs4680). Conclusions: This study underscores the impact of genetic variability on methadone-induced sexual dysfunction, offering valuable insights for personalized treatment approaches in opioid dependence. By integrating pharmacogenomic profiling, clinicians may be better equipped to identify individuals at higher risk for adverse side effects, paving the way for more tailored and effective therapeutic interventions that could improve treatment outcomes.

Keywords: Methadone; Sexual Dysfunction; Pharmacogenomic; Testosterone; genetic polymorphism