Managing Opioid-Induced Androgen Deficiency

Illustration of the hypothalamus. The hypothalamus controls body temperature, hunger, thirst, fatigue, sleep, and the circadian cycles. The hypothalamus links the nervous system tothe endocrine system via the pituitary gland.
The increased opioid use has been associated with a rising incidence of opioid-induced endocrinopathy, most commonly in the form of androgen deficiency.

Although the overall trend of illicit drug use has decreased in the United States, the abuse of prescription opioids has increased by 81% since the 1990s.1 The opioid epidemic has become a national crisis, bringing with it a myriad of complications, including the rise of opioid-induced androgen deficiency (OPIAD). Although OPIAD can significantly impact men’s sexual function and quality of life, it is thought to often be overlooked and poorly understood by the medical community.

Understanding Androgen Deficiency

The increased opioid use has been associated with a rising incidence of opioid-induced endocrinopathy, most commonly in the form of androgen deficiency.1 In a recent review of research on the topic, it was estimated that sexual dysfunction rates range from 34% to 85% in heroin addicts, from 14% to 81% in men on methadone maintenance treatment, and from 36% to 83% in individuals on buprenorphine maintenance treatment.2

Chronic opioid use inhibits the hypothalamic pituitary gonadal (HPG) axis, resulting in a secondary testosterone deficiency known as OPIAD.3 Activation of opioid receptors in the hypothalamus and the pituitary is associated with inhibition of the HPG axis, leading to hypogonadotropic hypogonadism.3 Persistently low levels of testosterone can affect the musculoskeletal, metabolic, and neuropsychiatric functions and reduce sexual function in men.1,3

The true incidence of OPIAD is difficult to evaluate, as associated symptoms are often nonspecific, if present at all.1 However, small-scale studies have estimated the prevalence of OPIAD at approximately 90% and 53% and at 53% in symptomatic and asymptomatic men on chronic opioid therapy, respectively.1 The risk for androgen deficiency increases with opioid doses, usually when the morphine-equivalent dose exceeds 60 mg and to a greater extent when the dose exceeds 100 mg.3  In addition, the effect of opioids on the HPG axis differs with the type and preparation of the opioid.3 Among opioid users, men taking hydrocodone and hydromorphone were found to be the least affected by androgen deficiency, while men taking fentanyl, methadone, or oxycodone (long- and short-acting formulations) were found to have higher odds of being androgen-deficient, particularly those taking fentanyl.3

Related Articles

“Because of the scale of the opioid epidemic, the concomitant rise in OPIAD, and its effects on the quality of life of patients, the urologic and sexual health communities need to be aware of this condition and how to treat it,” explained Alan Hsieh, MD, a cardiologist in Morristown, New Jersey.1

Diagnosing OPIAD

Hypogonadism, perhaps the least known and investigated effect of chronic opioid use, has been increasingly reported in both men and women on chronic opioid treatment.1 Hypogonadism is traditionally categorized as primary, secondary, or tertiary. As OPIAD origninates at the hypothalamic level, it is classified as tertiary hypogonadism. Testosterone levels have been found to drop within hours of opioid administration, with effects last for weeks after opioid discontinuation, but eventually returning to baseline levels.3

According to researchers, there are no definitive guidelines for diagnosing OPIAD. During the history and physical examination, patients with hypogonadism may complain of increased fatigue, reduced sense of vitality, depression, weight gain, and decreased muscle mass.