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.