Abstract Introduction Opioid-induced androgen deficiency (OPIAD) is a common yet underrecognized complication of chronic opioid therapy. By inhibiting hypothalamic gonadotropin-releasing hormone, opioids cause inappropriately low luteinizing hormone (LH) and follicle-stimulating hormone (FSH) with reduced sex steroids. Prevalence is substantial across formulations and is particularly high in patients treated with intrathecal drug delivery systems (IDDS). Contemporary syntheses also describe effects on the hypothalamic-pituitary-adrenal (HPA) axis that merit clinical attention. Objective To summarize high-quality evidence on hypogonadotropic hypogonadism during treatment with major opioids, including intrathecal morphine, and to contextualize the evidence through a representative clinical case. Methods We present and characterize a de-identified clinical case diagnosed and managed at a tertiary care center, illustrating the endocrine consequences associated with intrathecal drug delivery system therapy. He had long-standing spine-related pain with prior lumbar surgeries, and a variable-flow intrathecal pump was implanted in mid-2023 (catheter + pump) delivering morphine plus bupivacaine. A remote history of perianal abscess/fistula was noted but pain was predominantly spinal. We conducted a focused PubMed review through September 2025 prioritizing cohort and comparative studies and systematic reviews addressing: (i) endocrine consequences of intrathecal opioids; (ii) prevalence and determinants of OPIAD with oral or transdermal regimens; and (iii) management implications. Findings are anchored to a prototypical adult male with an IDDS for nonmalignant back pain who developed erectile dysfunction (ED) and biochemical hypogonadotropic hypogonadism. Results After IDDS initiation, our patient reported ED unresponsive to a phosphodiesterase type 5 inhibitor. At the initial specialist assessment, beyond ED he reported cardinal hypogonadal symptoms-fatigue, low motivation, and loss of libido-prompting initiation of testosterone replacement therapy (TRT) alongside endocrine evaluation. Laboratory testing showed total testosterone 66 ng/dL with LH 0.4 mIU/mL and FSH 2.5 mIU/mL; estradiol was low and prolactin initially normal. Topical TRT produced partial symptomatic and biochemical improvement (total testosterone 173 ng/dL after several months), with transition to long-acting intramuscular testosterone due to suboptimal levels. Gradual opioid dose reduction coincided with further symptomatic gains, and routine safety monitoring tracked prostate-specific antigen, hematocrit, and lipid and liver profiles. Conclusions OPIAD is highly prevalent in men receiving chronic opioids and is especially pronounced with intrathecal administration. Patients using IDDS or long-acting formulations who present with sexual dysfunction, fatigue, or infertility should be proactively screened for hypogonadotropic hypogonadism and, when indicated, evaluated for HPA axis suppression. Management should combine analgesic optimization with evidence-based TRT when appropriate, alongside ongoing monitoring of efficacy and safety. Disclosure No
Fernández et al. (Mon,) studied this question.