"There are direct endocrine consequences of opioid use, including hypogonadism, that adversely impact men’s health," write Michael S. Leapman, MD, and Steven A. Kaplan, MD.
In recent years, the toll of opioid misuse on public health has increased dramatically and is now understood to be a major source of morbidity and mortality in the United States. Stories of premature death and misfortune are now chronicled on a near-daily basis and have upended families and communities across the country. Despite a decrease in the number of total opioids prescribed in the U.S. from a peak in 2012, some 33,000 people died of opioid overdoses in 2015, including 15,000 from prescription sources.
Most recently, on Oct. 26, 2017, President Trump formally declared the opioid crisis in the United States to be a public health emergency. In light of this declaration, FDA Commissioner Scott Gottlieb, MD, contextualized the efforts at primary prevention: “Lowering the rate of new addiction means also reducing overall exposure to opioids to prevent more people from becoming addicted to these drugs in the first place,” Dr. Gottlieb said in an Oct. 30 FDA statement.
Efforts to decrease the supply of opioids will require increasing commitment from all prescribers, including surgeons. As drug monitoring programs seek to offer greater scrutiny, urologists are tasked with improving their understanding of how opioids are dispensed to patients and how best to reduce over-prescription. Moreover, there are direct endocrine consequences of opioid use, including hypogonadism, that adversely impact men’s health.
To better understand the impact of opioids on urology and men’s health, we offer an overview of the burden and public health consequences of surgical over-prescription as well as the nature of opioid-induced hypogonadism.
The opioid epidemic in the United States is notable for the expansiveness of the problem, spanning divisions of gender, race, age, and income level. Although greater increases in prescription pain reliever opioid deaths were seen between 1999 and 2010 among women (400%) compared with men (273%), men are still significantly more likely to misuse, overdose, and die from opioids (MMWR Surveill Summ 2017; 66:1-12). The downstream consequences of opioid-related morbidity are complex and have been implicated as a key causative factor in the decline of the depressed labor force, according to a Brookings Institute report, which notes that roughly half of working-age American men who are out of the labor force are using painkillers daily.
Urologists can play an important role in limiting the supply of opioids. Currently, prescription practices following surgery are highly variable, with some providers routinely dispensing above recommended safety thresholds. Not only do these practices represent potential dangers to the patients receiving the prescriptions themselves, but they also are a source of risk for those in an individual’s family and community. Indeed, the majority of people who abuse prescription opioids obtain them for free from friends or relatives (JAMA Intern Med 2014; 174:802-3).
The potential supply of opioids is vast given that most patients report using far less than is prescribed by their surgeons (Am J Sports Med 2017; 45:636-41; Drug Alcohol Depend 2016; 168:328-34; Ann Surg 2017; 265:709-14). Moreover, a majority of patients report storage of unused opioids in unsecured locations following surgery (PLoS One 2016; 11:e0147972).
Recently, a growing body of literature has highlighted the risks of new-onset opioid use or overdose following general and urologic surgery (JAMA Surg 2017; 152:e170504; J Urol 2017; 198:1130-6). There has also been recent interest in understanding how undergoing cancer surgery affects subsequent patterns of opioid use. In a publication examining nearly 70,000 patients undergoing cancer surgery with curative intent, the risk of new persistent opioid use was 10.4% and more common in patients receiving adjuvant chemotherapy (J Clin Oncol 2017; Jco2017741363).
Seen together, a growing appreciation for the potential harm associated with high-dose prescribing appears to demand greater scrutiny in the quantities dispensed to patients in the postoperative period and increased attention to warning signs of transitions to chronic use.
Opioids have a profound effect on male gonadal function. By disrupting the pulsatile release of gonadotropin-releasing hormone, opioids suppress the hypothalamic-pituitary-gonadal axis and result in hypogonadism (Neuroscience 2006; 140:929-37) (figure). Among chronic users, sustained gonadal suppression is commonly noted and may have adverse effects on male sexual health, including low libido, fatigue, depression, anxiety, osteoporosis, and loss of muscle mass (BMJ 2010; 341:c4462; Psychoneuroendocrinology 2009; 34[suppl 1]:S162-8).
Because of the central role of testosterone on regulating bone mineral density and cardiovascular function, there are likely other downstream consequences of opioid misuse. For example, in a study of men receiving intrathecal opioids for chronic pain, uncorrected opioid-related hypogonadism was associated with lower bone mineral density and adverse cardiovascular outcomes (BMJ Open 2013; 3:e002856).
For some individuals, the identification of opioid-related endocrine dysfunction can serve as an opportunity to seek formal treatment. In light of the growing prevalence of opioid use, clinicians who treat hypogonadism should continue to take note of the potential contributions of chronic opioid use as a causative agent for symptomatic hypogonadism. Rather than venues for providing supplementation to address the symptoms of low testosterone, these may present chances for substance abuse treatment.
Nevertheless, with a growing population of opioid users-including those receiving chronic opioid substitution therapies such as methadone-exogenous androgen supplementation may have a potential role. For example, in a randomized, double-blind, placebo-controlled trial of testosterone replacement in men with opioid-induced androgen deficiency, patients receiving testosterone supplementation experienced greater improvements in pain sensitivity, sexual desire, body composition, and overall quality of life (Pain 2015; 156:280-8). These findings suggest that in selected patients who do have non-modifiable opioid use, consideration of supplementation may be warranted.
With increasing attention to a public health emergency, there is an evident need for urologists to foster greater awareness of the potential harms associated with even short courses of opioids (J Urol 2017; 198:990-2). Prescribers are encouraged to adopt responsible prescribing practices, such as initially prescribing the lowest effective dose and offering repeat assessments as needed, rather than upfront high-dose therapy. In addition to direct consequences of overdose and dependence, opioids can adversely impact men’s health by resulting in hypogonadism and should be regarded as a potential opportunity to primarily address chronic use.
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