1. Introduction
A large body of literature reveals significant sex and gender differences in opioid-mediated effects. Many of these differences are clinically meaningful and have public health implications. For instance, sex differences in sensitivity to opioid-mediated analgesia contribute to significant differences in the potency and efficacy of opioid analgesics between men and women treated for acute and chronic pain (Craft, 2008; Neisters et al., 2010; Loyd & Murphy, 2014; Lee & Ho, 2013). Similarly, sex differences in opioid-mediated reward contributes to differences in the risk of developing an opioid use disorder in men and women prescribed opioids or using opioids recreationally (Lopresti et al, 2020; Kokane & Perotti, 2020; Becker & Chartoff, 2019). These sex differences are apparent at preclinical, clinical, and epidemiological levels of analysis, and a number of mechanisms that may contribute to these differences have been explored.
One area that has received significant research attention concerns the role of gonadal hormones in opioid-mediated effects. Gonadal hormones are an obvious target for investigation given their known role in determining the potency and efficacy of drugs from many pharmacological classes. In regard to opioids, much of the prior research has focused on the role of ovarian hormones, particularly estrogen and progesterone, in the modulation of opioid-mediated effects, and a number of review articles have described their effects on opioid-related outcomes (Becker and Koob, 2016; Fillingim, 2009; Kokane & Perotti, 2020; Huhn, Berry, & Dunn, 2018). A smaller body of literature has described the role of androgens in opioid-mediated effects, and we are not aware of any comprehensive attempts to synthesize this literature. The goal of this review is to describe the research examining the effects of androgens on opioid-mediated effects, and how androgens may contribute to clinically relevant sex differences, especially in areas of opioid analgesia and reward.