2.1.1. Human Studies
Opioids were involved in approximately 70% of all drug-related overdoses in the United States in 2018 (Wilson et al., 2020). Although men are more likely to experience an opioid overdose, the risk of overdose has increased more rapidly in women than men since 2000 (Lopresti et al., 2020). There are also notable sex differences in the use of licit vs. illicit opioids. For instance, men are more likely to use heroin, use heroin in larger quantities, and use heroin for a longer period of time than women (Back et al., 2010; Back et al., 2011; Kuhn, 2016; NIDA, 2020). In contrast, women are more likely to use prescription opioids (Back et al., 2011; Green et al., 2009), are more likely to have their first opioid experience with prescription opioids (Bawor et al., 2015a; see reviews by Lee & Ho, 2013; Kokane & Perotti, 2020), are more likely to be prescribed opioids, and are more likely to have opioid prescriptions filled than men (Schieber et al., 2020). These findings may be related to the observation that women report more general bodily pain and are more likely to suffer from pain disorders than men (Fillingim et al., 2009; Cepeda & Carr, 2003; Darnell et al., 2012; NIDA, 2020). Women are also more likely to meet diagnostic criteria for opioid abuse and have a substance use disorder attributed to prescription opioids than men (NIDA, 2020; Green et al., 2009; Serdarevic et al., 2017; see review by Kokane & Perotti, 2020).
Women are also more likely to experience negative consequences related to opioid use compared to men. For example, women meet the diagnostic criteria for addiction quicker (Anglin, Hser, & McGlothin, 1987; Hser, Anglin, & Booth, 1897), escalate to higher doses faster (for review, see Back et al., 2011; Becker & Chartoff, 2019; Kokane & Perotti, 2020; Lopresti, et al., 2020; but see Kaplovich et al., 2015), report more physical and socioeconomic negative side effects (Cepeda et al., 2003; Back et al., 2011; McHugh et al., 2013; Bawor et al., 2015a; Huhn et al., 2019), report more withdrawal symptoms (Kokane & Perotti, 2020; Giacomuzzi et al., 2005, Dunn et al., 2018), experience more craving (Yu et al., 2007; Back et al., 2011; Lee & Ho, 2013), and are less likely to seek treatment over their lifetime (for review, see Greenfield et al., 2007; Kokane & Perotti, 2020) than men. These negative consequences are associated with greater levels of stress, and women experience more opioid craving during stressful situations then men (Moran et al., 2018).
Remarkably, there have been very few studies examining the possible influence of gonadal hormones on sex differences in opioid use/abuse in human populations, and we could not find any experimental studies that systematically addressed the potential role of androgens in abuse-related effects in humans. There are a few reports describing testosterone-induced increases in positive affect in opioid users (Blick et al., 2012; Roantree & Zylicz, 2009), but these studies have small sample sizes and lack relevant control conditions. Consequently, the role of androgens in opioid intake is mostly unknown at this time.