Gender differences in mortality among treated opioid dependent patients

Highlights

• We assess gender-specific mortality risks suffered by opioid-dependent individuals.

• Women have a higher mortality risk compared to the general population than men.

• Women have a lower mortality risk than men, controlling for other factors.

• Employment, heroin use, and health problems uniquely impact men's mortality risk.

• Stimulant use increases mortality risk among women and decreases it among men.

Abstract

Aims

To assess gender differences in characteristics, mortality rates, and the causes and predictors of death among treated opioid-dependent individuals.

Methods

Linked vital statistics data were obtained for all individuals first enrolled in publicly funded pharmacological treatment for opioid dependence in California from 2006 to 2010. Standardized mortality ratios (SMR) were calculated by gender. Cox proportional hazards models with time-varying covariates were fitted to determine the effect of gender on the hazard of all-cause mortality, controlling for covariates.

Results

Over a median 2.6 years (interquartile range: 1.4–3.7), 1.031 deaths were observed, including 2.2% (259/11,564) of women and 3.7% (772/20,758) of men. Women had a greater increased risk of mortality compared to the general population (SMR 5.1 95% CI: 4.5, 5.7) than men (SMR 4.3 95% CI: 4.0, 4.6). The relative risk of death for women compared with men was 1.18 (95% CI: 1.02, 1.36). Women had a lower instantaneous hazard of all-cause mortality than men (HR 0.58, 95% CI 0.50, 0.68), controlling for other factors. Significant interaction effects indicated that among men, mortality risk was decreased by full-time employment and increased by non-daily heroin use (relative to daily use) and medical problems. Concurrent opioid and methamphetamine/cocaine use increased mortality risk among women and decreased it among men.

Conclusions

Treatment for opioid dependence is likely to reduce mortality risk among men by addressing employment and medical problems, and via interventions to reduce overdose risk after heroin abstinence, and among women by attending to the concurrent use of methamphetamine/cocaine and opioids.

Introduction

National prevalence data indicate that from 2009 to 2011, women in the USA were less likely than men to use heroin (SAMHSA, 2013). At the same time, however, rates of prescribed opioid abuse have escalated dramatically, particularly among women (Mack, 2013, SAMHSA, 2014). These increases are alarming because opioid-dependent individuals face mortality risks that are 6–20 times higher than the general population (Darke et al., 2011, Degenhardt et al., 2011). This context helps to explain why since 2007, more adult women of all ages have died each year from drug overdoses than from motor vehicle-related injuries, and in 2010, 4 times as many women died from drug overdose as were homicide victims (CDC, 2013a, CDC, 2013b). Opioid overdose deaths among women have increased fivefold in the past decade and this problem is now recognized to be a national epidemic among both women and men (CDC, 2013a, CDC, 2013b). Despite the rapid growth of this epidemic, women are typically outnumbered by men in opioid treatment settings by approximately 3 to 1 (Brady and Ashley, 2005, Nosyk et al., 2014). This phenomenon highlights the need to consider if and how opioid mortality outcomes are impacted by gender. Understanding factors that influence mortality risk differentially by gender has important implications for addressing gender-specific treatment needs, thereby aiding efforts to eliminate gender disparities in opioid-related mortality.

There are substantial differences by gender in the course of opioid use disorders, engagement in treatment for these disorders, and related health outcomes. A key finding is that more women than men rapidly decrease their heroin use over time (Grella and Lovinger, 2011), women remain engaged in maintenance treatment for a longer period of time (Nosyk et al., 2014), and women and men encounter different risk and protective factors that alter the course of the disorder (Hser et al., 2015). Few studies have examined gender differences in mortality among treated opioid-dependent populations. These studies have mostly focused on documenting mortality rates by gender, and have typically reported lower crude mortality rates for women compared with men, but higher standardized mortality ratios (SMRs; Degenhardt et al., 2009, 2010). This pattern likely reflects, in part, less risk-taking behavior among women in the general population than men that, in turn, results in fewer accidents and traumatic deaths for women and therefore a longer life expectancy for women.

Less is known regarding the potential for gender-specificity in the way that demographic characteristics, substance use, and treatment may affect mortality risk among individuals with opioid use disorders (Bawor et al., 2014). In studies of opioid-dependent populations that have not specifically examined gender differences, it is clear that older age is a key risk factor for mortality (Peles et al., 2010, Stoové et al., 2009), as is injection drug use (Brugal et al., 2005), alcohol use (Degenhardt et al., 2014, Larney et al., 2013, Shah et al., 2008), benzodiazepine use (Cousins et al., 2011, McCowan et al., 2009, Peles et al., 2010), chronic illness (e.g., positive for HIV or hepatitis B or C; Brugal et al., 2005, Muga et al., 2014, Peles et al., 2010), mental illness (Cousins et al., 2011, McCowan et al., 2009), and inadequate exposure to methadone maintenance treatment (Amato et al., 2005, Degenhardt et al., 2011, Degenhardt et al., 2014, Evans et al., 2015). The few studies of opioid-dependent populations that have focused on gender and mortality have revealed significant gender differences. For example, an examination of gender differences in opioid/cocaine fatal overdoses in Luxembourg between 1985 and 2011 found that the time between the onset of drug use and death was shorter for women than for men (Origer et al., 2014). A study of injection drug users in Norway reported that the risk of death was heightened among women by sex work and among men by experiences of being incarcerated in prison (Gjersing and Bretteville-Jensen, 2014). Findings are consistent with those generated by other studies that have attributed gender differences in the course of addiction to both socio-cultural (Cloud and Granfield, 2008, Roberts et al., 2010) and biological (Lynch et al., 2002) factors. In other health-related research, gender differences in health are thought to reflect intertwined social and biological factors that vary over the life course (Short et al., 2013).

Despite these advances in knowledge, little empirical evidence has been generated regarding whether gender modifies the effects of factors known to influence mortality among populations with opioid use disorders. Lacking information on gender-specific effects, incorrect conclusions may be drawn about the underlying causes of mortality and the optimal methods to treat opioid use disorders. Knowing about gender differences in the causes and predictors of mortality can contribute to discussions regarding whether gender-focused treatment is desirable and how it may be performed. In the present paper, we aim to build on our prior research (Evans et al., 2015, Nosyk et al., 2014) to assess gender differences in characteristics at treatment entry, mortality rates, causes of death, and predictors of death. A broader goal is to better understand the factors and experiences that elevate mortality risks among treated opioid-dependent individuals in ways that may be unique to each gender.