Opioids are pivotal therapeutics in the management of escalated chronic pain (moderate–severe). In the last two decades, the increased prescription rate and the prolonged usage of opioids shed light on opioid‐induced endocrinopathy. Opioid‐induced hypogonadism (OHG) results upon long‐term opioid therapy. Clinically, patients with OHG are presented mainly by sexual dysfunction and infertility. Opioid clinical use in pain therapy is indispensable. However, the resultant sexual endocrinopathy cannot be overlooked and hence hormonal replacement therapy with regular monitoring of the patients represents a potential therapeutic strategy while avoiding opioids in patients with guaranteed long therapeutic exposure and switching to using low‐dose naltrexone as alternative represents a possible prophylactic measure to ensure therapeutic compliance and secure a good life quality of patients.