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Curr Urol Rep. 2016 Oct;17(10):76. doi: 10.1007/s11934-016-0634-y.

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

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Frank H. Netter MD School of Medicine, Quinnipiac University, 370 Bassett Road, North Haven, CT, 06473, USA.
Northeast Medical Group Urology / Male Reproductive Medicine and Surgery, Yale New Haven Health, 425 Post Road, Fairfield, CT, 06824, USA.


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.


Chronic pain; Hypogonadism; Low testosterone; Opioid-induced androgen deficiency; Testosterone replacement therapy

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