4.1. Implications for Opioid Analgesia
Converging evidence from preclinical, clinical, and epidemiological
studies strongly indicate that women are more sensitive to pain and are
more likely to suffer from pain disorders (Section 2.2.1). Some
additional evidence also indicates that men are more sensitive to opioid
analgesics and typically need lower doses (at least as a function of
body weight) to obtain comparable levels of analgesia. A sizeable but
underappreciated body of evidence suggests that these sex differences
are due, in part, to greater androgenic activity in males. Indeed,
preclinical and clinical data suggest that sex differences can be
minimized by androgenic blockade in males or androgenic stimulation in
females.
One obvious implication of androgen-induced enhancement opioid analgesia
is that the effectiveness of opioid analgesics could be increased by
direct or indirect activation of androgen receptors. Although clinically
intriguing, this practice would have clinically limiting drawbacks for
both men and women. In women, for instance, androgens produce
masculinizing and anti-feminizing effects, whereas in men, exogenous
androgens suppress endogenous androgenic activity, leading to problems
with fertility and hypogonadism (Christou et al., 2017; de Souza &
Hallak, 2011; Vorona & Nieschlag, 2018). Regardless, low levels of
endogenous androgenic activity may be an unrecognized contributor to
both chronic pain disorders and diminished sensitivity to opioid
analgesics. Hypogonadism can quickly be diagnosed by simple blood tests
measuring free and total testosterone. Testosterone levels could guide
initial dose determinations and subsequent dose adjustments. Moreover,
in cases where hypogonadism is detected, opioid treatment could be
augmented by androgen treatment to simultaneously decrease pain
sensitivity and enhance opioid analgesia.