Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review

Abstract

Opioid-induced androgen deficiency (OPIAD) was initially recognized as a possible consequence of opioid use roughly four decades ago. Long-acting opioid use carries risks of addiction, tolerance, and systemic side effects including hypogonadotropic hypogonadism with consequent testosterone depletion leading to multiple central and peripheral effects. Hypogonadism is induced through direct inhibitory action of opioids on receptors within the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes as well as testosterone production within the testes. Few studies have systematically investigated hormonal changes induced by long-term opioid administration or the effects of testosterone replacement therapy (TRT) in patients with OPIAD. Clomiphene citrate, a selective estrogen receptor modulator (SERM), is a testosterone enhancement treatment which upregulates endogenous hypothalamic function. This review will focus on the pathophysiology, diagnosis, and management of OPIAD, including summary of literature evaluating OPIAD treatment with TRT, and areas of future investigation.

Opioid‐induced hypogonadism: Pathophysiology, clinical and therapeutics review

“…In a recent clinical study, testosterone replacement therapy is found to be beneficial in improving patient's tolerance to pain and hence they required less therapeutic doses of opioids . The use of testosterone as a hormonal replacement is still not conclusive; more clinical studies with bigger patient samples and designs minimizing bias are still required to build an evidence‐based model . Additionally, the use of opioid antagonist naltrexone in low dose (1–4.5 mg/d) is reported as an anti‐inflammatory and analgesic therapy of chronic pain conditions .…”

An Internet‐Based Survey to Assess Clinicians’ Knowledge and Attitudes Towards Opioid‐Induced Hypogonadism

“…An often forgotten or neglected side effect of opioid treatment is the impairment of endocrine systems, most notably its effect on pituitary hormone pathways and bone metabolism. Of those metabolic disturbances, hypogonadism is the best described, with occurrence varying from 21% to 95% of patients on chronic opioid therapy …”

“…The time to develop OIH after initiation of the therapy has been described as within the first week, yet inhibition as early as within the first 24 hours has been reported in patients on methadone replacement . Discontinuation of opioids can improve symptoms of hypogonadism and allow restoration of testosterone levels, but symptoms may continue for months or years after treatment is stopped …”

“…Of those metabolic disturbances, hypogonadism is the best described, 3 with occurrence varying from 21% to 95% of patients on chronic opioid therapy. 4,5 The most common signs and symptoms of hypogonadism include decreased libido, impaired vitality and mood, erectile dysfunction, gynecomastia, loss of body hair, and changes in body composition, with sarcopenia, osteoporosis, and increase in fat tissue. 6 Additionally, declines in cognitive function, 7 as well as associations with metabolic syndrome 8 and increased cardiovascular-related morbidity and mortality, have been demonstrated.…”

“…16 Discontinuation of opioids can improve symptoms of hypogonadism and allow restoration of testosterone levels, 17 but symptoms may continue for months or years after treatment is stopped. 4 Opioid-induced hypogonadism is under-recognized and undertreated. 18 Pain physicians are possibly the clinicians with the highest likelihood of prescribing opioids as part of an analgesic plan and certainly the most expert.…”