CUA 2018: The Opioid Epidemic and Testosterone Dysfunction – Current Challenges and a Future Roadmap for the Practicing Clinician

Halifax, Nova Scotia ( Hossein Sadeghi-Nejad, MD, from New Jersey provided a State-of-the-Art lecture at the CUA 2018 annual meeting discussing the opioid epidemic and its relation to testosterone dysfunction. Dr. Sadeghi-Nejad started with several important facts from the National Governor’s Association:

  • Every day, 78 people die from an overdose related to the prescription of opioids and heroin
  • In 2012, health care providers wrote enough opioid prescriptions for every American adult to have a bottle of pills
  • 4 out of 5 heroin users reported misusing prescription opioids before moving to heroin
  • Medicaid is the most common payer of opioid-related hospitalizations, the cost of which quadrupled between 2002-2012
  • Heroin seizure by U.S. law enforcement rose 81% between 2010-2014
  • 80% of people with an opioid use disorder are not receiving treatment
The problem, according to Dr. Sadeghi-Nejad, is that there has been a surge in prescription narcotics, which has led to the subsequent heroin addiction. Overdose deaths have increased to 64,000/year, having nearly reached AIDS peak crisis level. 

Part of the problem also is that synthetic opioids are flooding the US from Mexico and China. Furthermore, fentanyl, in particular, is a problem for professionals, with an upswing in fentanyl analogs and underground labs. One of these analogs is carfentanil, an elephant tranquilizer, which has been associated with several deaths in the US. Carfentanil is listed as a DEA occupational hazard, since it is 100x more powerful than fentanyl, 4,000x more than heroine and 10,000x more than morphine: 0.02 mg (a speck of dust) is enough to kill an adult!

Over the past several years, there has been a change in the addiction demographics, switching from the inner cities and minorities to the white middle-class men and women. Additionally, most heroin users have tried other drugs and most have tried prescription drugs. The medical system also has a role in the epidemic:

  • Medicine is a culture of pain relief and not addiction treatment
  • There is pressure to recognize pain as the “fifth vital sign”
  • 259 million opioid prescriptions were written in 2012
  • Opioids are the main-stay of post-operative pain control due to the rapid onset of action and multiple routes of administration
Dr. Sadeghi-Nejad then described the “oxycontin story”, which was first introduced in 1996 and hailed for its 12-hour duration of action. However, based on patient resistance, this often resulted in higher and more frequent doses, quickly becoming America’s best-selling painkiller, with $31 billion in revenue. More than 7 million Americans abused oxycontin over the last 20 years and it is widely blamed for setting off the opioid epidemic.

The economic burden of the opioid epidemic is also substantial:

  • 500,000 individuals were in jail at the end of 2013 secondary to opioid-related offenses
  • 2.5 million of 18 million Medicaid eligible adults have a substance abuse disorder
  • Illicit drug use costs $181 billion/year
  • $1 on treatment saves $7 dollars in criminal justice expenditures 
The opioid dependence in urologic surgery is not without blame. A retrospective analysis of 675,527 patients demonstrated that 0.09% were diagnosed with opioid dependence or overdose, with the highest rates in patients undergoing stone procedures (0.15%) or major kidney surgery (0.12%)1. Risk factors for opioid addiction in this study included: younger age, non-private insurance, inpatients procedure, longer length of stay, history of depression or COPD. 

A systematic review assessing testosterone suppression in opioid users looked at 17 studies (2,769 patients), finding that testosterone levels are suppressed with regular opioid use, with no differences in opioid type, however differences were noted between men and women2. Studies assessing testosterone induced suppression generally are low-quality studies, including several shortcomings such as methodology, statistics, and outcome measurements. As such the incidence is likely grossly underestimated. Furthermore, this systematic review found that 90% of patients on chronic opioids have oncologic related pain.

The pathophysiology of testosterone suppression is hypogonadotropic hypogonadism, with the opioid binding to the hypothalamic mu receptors, leading to GnRH inhibition and subsequent decreased pituitary LH, FSH and testosterone. The general treatment for opioid-induced testosterone suppression are to decrease the opiate dose, and to diet and exercise. To date, there are not direct comparisons of these interventions to various modalities of testosterone replacement therapy.

In summary, Dr. Sadeghi-Nejad concluded with several take-home messages:

  • In parts of the US, overuse of opioids is the leading cause of death in young adults
  • Inappropriate prescription habits is a key cause
  • Long-acting opioid use leads to addiction and opioid dependence
  • Testosterone therapy in the affected younger population may adversely affect fertility, but there are no good studies assessing these outcomes to date
Presented by: Hossein Sadeghi-Nejad, MD, Rutgers New Jersey, Newark, NJ

1. Shah AS, Blackwell RH, Kuo PH, et al. Rates and risk factors for opioid dependence and overdose after urological surgery. J Urol 2017;198(5):1130-1136.
2. Bawor M, Bami H, Dennis BB, et al. Testosterone suppression in opioid users: A systematic review and meta-analysis. Drug Alcohol Depend 2015;149:1-9.

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the 73rd Canadian Urological Association Annual Meeting - June 23 - 26, 2018 - Halifax, Nova Scotia

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