Prolonged opioid use linked to low testosterone

By Dr. Liji Thomas, MDSep 9 2019

A new study has confirmed that a major effect of opioid overuse in adults is hypogonadism, or the abnormally low secretion of testosterone. This is associated with low sexual interest, loss of muscle and bone mass, increase in fatty tissue and infertility. However, less than six in a hundred receive testosterone supplementation. These findings come from a study on over 50,000 men on prescription long-term opioid therapy.

The current study is the first large-scale national study on opioid-linked hypogonadism. High hypogonadism rates were expected due to the increase in opioid use over the last two decades.

Image Credit: Kimberly Boyles / Shutterstock

How was the study done?

It was performed on 53,888 men aged 20 years or older matched with the same number of controls. The subjects had all taken opioids by prescription for 90 days or more over a period of 12 months, between 2010 and 2017, but none had experienced testosterone deficiency or had testosterone treatment for 12 months prior to this. The indications for testosterone use included back pain, muscular or bone pain, nerve pain, wound pain, fracture and other intensely painful chronic conditions.

The controls had received opioids for 14 days or less, to enable a better matching for opioid use indication. The aim was to find out whether those who had taken opioids long-term had been diagnosed for testosterone deficiency, had ever had a serum testosterone test, or been prescribed testosterone starting 14 days after the beginning of the course.

What did the study show?

Patients on prolonged opioid use were generally sicker and had more prior hospitalizations and other diseases such as heart failure and peripheral vascular disease, diabetes and high blood pressure. In the control group, about 4%, 9% and 12% reported having their serum testosterone tested at one, three and five years from the date of opioid initiation despite the known association of hypogonadism with opioid use. In the user group, the corresponding rates were 6%, 14% and 17% respectively.

Another measurement was the number of hypogonadism diagnoses in each group over the last five years. They found that in the one-, three- and five-year groups of short-term opioid users, the rates of new diagnosis included 1 %, 6% and 5%, compared to 3%, 7% and 9% respectively in the prolonged user group. This indicates a very low rate of screening for hypogonadism despite being aware of the associated risk, perhaps because the patient is already on several medications and have complex diseases. Another possible reason could be the relative unimportance of this adverse effect of opioids in the patient’s eyes, compared to kidney dysfunction, muscle wasting and increased fat deposition. This would reduce the chances of reporting such a condition or having it tested.

Meanwhile, only 2.2% received testosterone at five years compared to 5.7% in the short-term and long-term user groups respectively. This shows significant under-treatment of opioid-induced hypogonadism, perhaps due to fear of cardiovascular side effects of testosterone supplementation.

After adjusting for numerous confounding factors, the chronic opioid group had a 46% increase in serum testosterone testing, a 74% higher incidence of diagnosed hypogonadism, and were almost 2.5 times as likely to receive testosterone therapy. The study thus established the risk of hypogonadism with exposure to opioids over a long period: the surprise here was the reduced magnitude of risk compared to earlier studies which looked only at serum testosterone levels. About 9.5% of men in this study had hypogonadism, compared to a prevalence of 35% to 90% in earlier studies. The researchers attribute this to their report on incidence (or new cases arising over the five years of the study) rather than prevalence, as well as on their collection of data from administrative claims database which is known to produce an underestimate of the prevalence of chronic conditions.

The study also shows up the need for increased or even routine screening for hypogonadism among this group of opioid users, by increasing the awareness of this adverse effect among physicians and patients alike. Another important conclusion is the need to treat this complication, given the very low rate of testosterone therapy in this group at only 1.5% at one year, and less than 6% at five years.

Researcher Yong-Fang Kuo says, “As policy experts and medical professionals move forward in their search for the proper balance between pain control and opioid over-prescribing, it will be important to keep high-risk groups in mind when refining public policy and medical practice.” Regarding the study on hypogonadism, the report concludes, “Prolonged opioid users—in comparison to short-term users—had an increased incidence of serum testosterone screening, hypogonadism diagnosis, and receipt of testosterone therapy. Given the scale of the opioid epidemic in the United States, clinicians should be aware of this condition and monitor patients accordingly.”

The study is published in the Mayo Clinic Proceedings.