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|Title:||SEX AND GENDER DIFFERENCES IN THE MANAGEMENT AND TREATMENT OF OPIOID ADDICTION|
|Abstract:||Background and Objectives: Opioid addiction is a major contributor to the global burden of disease and carries a significant risk of morbidity and mortality. Individuals with opioid addiction are subject to numerous adverse consequences including infectious diseases, medical complications, psychiatric disorders, and social disintegration. Women especially experience a heightened vulnerability to the adverse medical and social consequences of opioid addiction as a result of biological sex characteristics and socially-defined gender roles, which increases their risk for poor treatment outcomes. The general objective of this thesis if to investigate sex and gender differences in the management and treatment of opioid addiction with a focus on hormonal influences, genetic variation, and sociobehavioral characteristics including substance use behavior, health status, and social functioning. Methods: Using various methodologies, we compared the biological and social characteristics of men and women with opioid addiction in the context of methadone treatment. We assessed sex and gender differences in methadone treatment outcomes using a systematic review of the literature and a meta-analysis, which was developed based on published protocol. Next, we used data from the multi-centre GENOA cross-sectional study including 250 patients with opioid addiction recruited from Ontario methadone clinics to measure testosterone levels among men and women compared to non-opioid using controls; total serum testosterone was assayed using ELISA and RIA techniques. Following this study, we conducted a systematic review and meta-analysis to test the effect of opioid use on testosterone levels, performing subgroup analyses by sex and type of opioid used. Using the previous GENOA sample, we then completed genotype analysis on variants of BDNF and DRD2 genes to test the genetic effect on continued opioid use, measured through urine drug screening. Finally, we recruited an additional 503 participants meeting criteria for opioid use disorder who were receiving treatment with methadone, from which we obtained information on drug use patterns and addiction severity using the Maudsley Addiction Profile (MAP) tool to evaluate sex and gender differences. Results: In our initial systematic review, we found 20 studies collectively showing that women were less likely than men to report alcohol use, employment, or legal involvement, but were more likely to misuse amphetamines. Using the GENOA dataset of methadone patients, we found a significant reduction in testosterone level among men but not women, which was associated with methadone dose. We also determined that testosterone did not fluctuate significantly between menstrual cycle phases. In line with these findings, our systematic review showed a significant suppression in mean testosterone level among men that use opioids compared to controls, but not in women. Our results also showed that methadone did not affect testosterone differently than other opioids. Among GENOA participants, BDNF rs6265 and DRD2 rs1799978 genetic variants were not significantly associated with continued opioid use while in methadone maintenance treatment. Our final study identified sex and gender differences in substance use, health status, and social functioning. Women were younger, had children, were current smokers, had higher rates of benzodiazepine use, more frequent physical and psychological health problems, family history of psychiatric disorders, more partner conflict, and began regular use of opioids through a physician prescription. In comparison, men were more likely to be employed and to report cannabis and amphetamine use. Conclusions: This thesis has demonstrated that men and women are differentially affected by opioid addiction and experience sex- and gender-specific challenges throughout the course of methadone treatment that are likely to impact treatment outcomes. The identification of clinically-relevant sex and gender differences is important to our understanding of the addiction profile, and can therefore be used to promote strategies for effective treatment and management of opioid addiction among men and women incorporating both biological and social perspectives.|
|Appears in Collections:||Open Access Dissertations and Theses|
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|Bawor_Monica_September2015_PhD_Neuroscience.pdf||Full thesis, 8 chapters||5.58 MB||Adobe PDF||View/Open|
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