Opioid‐induced hypogonadism: Pathophysiology, clinical and therapeutics review

Abstract

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.

Anxiety and Fear Avoidance Beliefs and Behavior May Be Significant Risk Factors for Chronic Opioid Analgesic Therapy Reliance for Patients with Chronic Pain—Results from a Preliminary Study

“…Even when used as prescribed, COAT use is associated with significant negative clinical outcomes for the individual patient. Long-term side effects include hypogonadism [ 4 ] and immunocompromise [ 5 ]. A myriad of adverse immediate effects are also common [ 6 ], such as constipation, dry mouth, urinary retention, emotional blunting and cognitive impairment.…”

European clinical practice recommendations on opioids for chronic noncancer pain – Part 2: Special situations*

“…Comment: Long-term opioid therapy can lead to central hypogonadism in women and in men. Clinically, patients with opioid-induced hypogonadism mainly suffer from sexual dysfunction and infertility (Antony et al, 2020). The prevalence of patients with opioid-induced hypogonadism ranges from 19% to 86%, depending on the criteria for diagnosis of hypogonadism (Coluzzi et al, 2018).…”

Gender Differences in Depression and Sex Hormones among Patients Receiving Long-Term Opioid Treatment for Chronic Noncancer Pain in Taiwan—A Multicenter Cross-Sectional Study

“…The prevalence of low total testosterone levels in aging men is, on average, 20% to 30% in the United States [34] and 24% in Taiwan based on the criterion of total testosterone level <300 ng/dL [18]. Following long-term opioid therapy (≥4 weeks), the suppression of the gonadotropin-releasing hormone in the hypothalamic-pituitary-gonadal axis causes a luteinizing hormone, a follicle-stimulating hormone, estradiol, and testosterone deficiencies [3]. Prolonged opioid exposure is associated with increased rates of screening, diagnosis, and treatment for hypogonadism [2,8].…”

“…In addition to chronic pain, patients with opioid-induced hypogonadism also present symptoms of depression, muscle wasting, and sexual dysfunction [3]. The only evidencebased indication for testosterone therapy in women is hypoactive sexual desire disorder, which involves a full clinical assessment and cannot be determined according to blood testosterone level alone [36].…”

“…The drastic increase in opioid prescription and prolonged use over the past two decades has led to an "opioid crisis" in the United States, manifested by prescription opioids involved in 32% of opioid-related overdose deaths in 2018 [1]. Long-term use of opioids contributes to the increased diagnosis and treatment of opioid-induced hypogonadism [2] with clinical presentation of fatigue, depression, sexual dysfunction, and infertility [3]. Meanwhile, reduced gonadal function in menopausal women and older men is associated with sleep disturbances and cognitive decline [4].…”