Endocrine system

Methadone Lowers Testosterone in Male Opioid Addicts

Methadone treatment significantly reduces testosterone levels in male opioid addicts but appears to have no effect on testosterone in female opioid users, according to a new study in Scientific Reports.

“Men on methadone treatment have about a quarter of the testosterone of men not using methadone, and this has not been considered in clinical practice,” say principal investigator Zena Samaan, MBChB, DMMD, MSc, PhD, MRCPsych, and first author Monica Bawor, BSc, of McMaster University in Ontario, Canada. “The fact that testosterone is suppressed by opioids is not a novel finding, but we were surprised by the extent of this suppression.”

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Samaan, Bawor, and colleagues conducted a multi-center, cross-sectional study to determine the prescise extent of testosterone suppression that occurs with opioid use and how it relates to methadone treatment for opioid dependence.

They recruited 231 patients with opioid dependence from methadone clinics across Ontario between June and December 2011, as well as a control group of 783 adults in Ontario who did not use opioids.

The average testosterone level in men receiving methadone treatment for opioid addiction was significantly lower than those in the control group. “Chronic use of opioids leads to significant hormone imbalances, especially sex hormones,” Bawor and Samaan say. When opioids (including methadone) bind to their respective opioid receptors in the hypothalamus of the brain, they interfere with the system that regulates hormone levels.

The researchers did not see any significant differences between the testosterone levels of women in the control group and those receiving methadone treatment. “We expect that this occurs for testosterone in men since it is the primary sex steroid,” Bawor and Samaan say. “For women, primary sex hormones include estrogen and progesterone; therefore, it is possible that these hormones are affected but not testosterone.”

They also found a positive correlation between methadone dose and testosterone suppression—the higher the dose the greater the suppression. “Any opioid, in general, causes suppression of testosterone and therefore, it is likely that individuals entering methadone treatment already have reduced testosterone levels,” Bawor and Samaan explain.

As a result, the researchers say it is difficult to determine at which dose or duration of opioid use that testosterone begins to drop and the consequences of the hormonal disruptions begin to affect the body.

“It is expected that testosterone levels may recover when opioids are stopped; however, the time and magnitude of recovery of testosterone level depend on the dose and duration methadone or other opioids were taken,” Bawor and Samaan say.

The researchers recommend that health care providers closely monitor testosterone levels before starting methadone and throughout the duration of treatment. They suggest tracking any symptoms of testosterone suppression:

• Specific symptoms may include sexual difficulties, reduced libido, loss of body hair, shrinking testes, and low bone density.

• Less specific symptoms may include low energy, poor concentration, depressed mood, increased weight, poor sleep, and poor work performance.

They say reducing methadone dose, when possible, may alleviate some of the suppression, and testosterone replacement therapy is an option in the absence of contraindications, such as prostate cancer.

If these patients do opt for testosterone therapy, health care providers should follow up with them and measure their testosterone level 3 to 6 months after initiating hormone therapy, as well as checking for symptoms and side effects and monitoring laboratory results such as prostate-specific antigen and hematocrit.


Bawor M, Dennis BB, Samaan MC, Plater C, Worster A, Varenbut M, et al. Methadone induces testosterone suppression in patients with opioid addiction. Sci Rep. 2014 Aug 26;4:6189.