3.2.1. Human Studies
Circulating levels of free testosterone are positively associated with greater pain thresholds (i.e., decreases in pain sensitivity) in normal men (Apkhazava et al., 2018) and men with hypogonadism receiving testosterone therapy (Glintborg et al., 2020). Circulating levels of estradiol are inversely associated with greater pain thresholds in women (Bartley et al., 2015); however, circulating levels of testosterone are positively associated with greater pain thresholds in women, just as they are in men (Bartley et al., 2015; Teepker et al., 2010). Studies examining men with hypogonadism report that testosterone replacement therapy increases pain thresholds and decreases pain sensitivity relative to either placebo controls or their own baselines (Raheem et al., 2017; Basaria et al., 2015; Aloisi et al., 2011; Daniell et al., 2006; AminiLari et al., 2019; Roantree & Zylicz, 2009, but see Glintborg et al., 2020). Finally, transgender individuals transitioning from female to male typically demonstrate a decrease in pain sensitivity upon treatment with testosterone (Aloisi et al., 2007).
Coinciding with reductions in pain sensitivity, testosterone treatment generally decreases the need for opioid analgesia, allowing for reductions in dose or frequency of use. For instance, men with hypogonadism typically reduce their intake of opioid analgesics upon the initiation of testosterone replacement therapy relative to their own baseline and to a control population (Raheem et al., 2017; Roantree & Zylicz, 2009). There are several exceptions to these findings (e.g., Basaria et al., 2015; Aloisi et al., 2011; Daniell et al., 2006), but much of that literature is limited by small sample sizes and heterogenous populations.