Methadone Treatment Lowers Testosterone Levels in Opioid-addicted Men

New research finds that a common treatment for opioid addiction significantly reduces testosterone levels in many male patients and suggests that supplementary testosterone might improve outcomes.

The study, which appears in the journal Scientific Reports, recruited 231 patients from methadone clinics across Ontario and found that testosterone levels among men — but not women — were lower, on average, than those from a control group of 781 adults who did not use opioids.

Given that low testosterone levels in men have repeatedly been associated with erectile dysfunction, fatigue, mood disturbances, and other symptoms that reduce quality of life, the study authors recommend that doctors monitor the testosterone levels of male patients before and after methadone treatment and prescribe supplements where necessary.

“We expect that treating testosterone deficiency will improve outcomes of methadone treatment for patients, including treatment response and retention,” said the principal investigator, Zena Samaan, MD, PhD, an assistant professor in the Department of Psychiatry and Behavioral Neurosciences at McMaster University, in a news release that accompanied publication of the study results.

“Doctors should also ensure the patients are being prescribed the lowest dose of opioids including methadone for effective treatment to minimize testosterone suppression,” Samaan said.

Overall, testosterone levels among men in the study group averaged 100.10 ng/dl (3.47 nmol/L) and the standard deviation was 72.21 ng/dl (2.51 nmol/L). Testosterone levels among men in the control group were, on average, more than four times as high: 414.74 ng/dl (14.39 nmol/L), with a standard deviation of 141.81 ng/dl (4.92 nmol/L).

Testosterone levels among women in the study group, however, were actually higher than those in the control group, though the difference did not rise to the level of statistical significance. The average was 36.61ng/dl for the former pool and 25.93 ng/dl for the latter.

Among men in the study group, testosterone levels were inversely associated with the dose of methadone each man received (estimated β = −0.003; 95% CI −0.005 to −0.001; p = 0.003) (Figure 2) and positively associated with the number of cigarettes each man smoked per day (estimated β = 0.011; 95% CI 0.000, 0.021; p = 0.046).

To estimate the magnitude of the effect, the researchers used the exponentiated beta coefficient to reverse the logarithmic transformation and multiplied by 10. They found that for each 10 mg increase in methadone dose, there is a 0.97 ng/dL (0.03 nmol/L) decrease in testosterone level (estimated exp(β) = 0.969; 95% CI 0.950, 0.989; p = 0.003).

The researchers hypothesized that cigarette usage increased testosterone levels by speeding the metabolism of methadone and thus reducing its impact on the hormone. They also speculated that the effect may explain the common observation that men struggle especially hard to quit smoking during methadone treatment.

Reported limitations of the study include the relatively small size of the study group for gender specific analyses. The study team calculated that there was adequate power to support the associations found for the 131 men but that the power for the female group (100 patients) was not large enough to assert that any detected correlations were significant.

“Larger sample sizes with more sex hormones investigated,” the authors wrote, “would be ideal for future study, as well as implementing a prospective follow-up study design to observe whether testosterone levels change throughout the course of treatment with methadone.”