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.