Opioids and Low Testosterone: How Long-Term Painkiller Use Suppresses the Hormone in Men, and What the Trials Show About Treating It

Opioids and low testosterone go together far more often than most men are told. Long-term opioid use suppresses testosterone in 20% to 80% of men, long-acting drugs carry the highest odds, and testosterone therapy trials show gains in libido and body composition but not in day-to-day pain.

Do opioids lower testosterone? Yes. Regular opioid use lowers testosterone in men, and the link between opioids and low testosterone is one of the most consistent drug side effects in the hormone literature. A 2015 meta-analysis by Bawor and colleagues in Drug and Alcohol Dependence pooled 17 studies with 2,769 participants and concluded that testosterone is suppressed in men with regular opioid use regardless of opioid type.

Doctors call the problem opioid-induced androgen deficiency, and a 2025 review in Andrology by Kafel, Braga-Basaria and Basaria described it as common but underappreciated by clinicians. This guide covers how opioids shut the hormone down, which drugs carry the highest odds, how to test properly while on a painkiller, and what the randomized trials of testosterone therapy in opioid users actually found. Every figure comes from studies opened and checked for this article.

Opioids lower testosterone by acting on the brain, not mainly on the testicles. The Kafel 2025 review states that opioids suppress the gonadal axis mainly by inhibiting GnRH, the hypothalamic hormone that starts the chain of signals ending in testosterone production. Without enough GnRH, the pituitary releases less LH, and the testicles receive less instruction to make testosterone.

That pattern is called secondary hypogonadism, because the testicles themselves are usually healthy. In the Hallinan study of 103 men on methadone or buprenorphine maintenance, published in the International Journal of Andrology in 2009, men on both drugs had lower free testosterone and LH than age-matched reference groups, and primary testicular failure was an uncommon cause. A 2026 JAMA review by Anawalt and colleagues lists opioids among the most common potentially reversible causes of secondary hypogonadism.

Low testosterone affects somewhere between 20% and 80% of men on long-term opioids, according to the Kafel 2025 review. The range is wide because studies used different drugs, durations, age groups and cutoffs for what counts as low. Even the lower end of that range is far above the background rate in men of the same age.

Individual studies sit toward the high end. Daniell measured hormones in 54 men taking sustained-action oral opioids for nonmalignant pain and 27 similar men taking none, published in the Journal of Pain in 2002. Total testosterone was subnormal in 74% of the opioid users and free testosterone in 56%. In a Kaiser Permanente chronic pain clinic, Rubinstein and colleagues found that 53% of 81 men on daily opioids for at least 3 months had a morning testosterone below 250 ng/dL.

Long-acting opioids lower testosterone more than short-acting ones. In the 2013 Rubinstein study in the Clinical Journal of Pain, 74% of men on long-acting opioids were hypogonadal, compared with 34% of men using only short-acting hydrocodone or oxycodone. Median morning testosterone was 126 ng/dL in the long-acting group and 283 ng/dL in the short-acting group.

After adjusting for daily dose and BMI, men on long-acting opioids had 4.78 times the odds of low testosterone. Daily dose itself was not a significant factor in that study (odds ratio 1.02), while each step up in BMI added to the odds (odds ratio 1.13). Body weight therefore stacks on top of the drug effect, a point covered in our guide to whether losing weight raises testosterone.

The specific drug also matters. In a larger 2017 follow-up in Pain Medicine, Rubinstein and Carpenter studied 1,159 men who had taken a single opioid for at least 90 days, using hydrocodone as the comparison. Transdermal fentanyl, methadone and oxycodone were all linked to higher odds of androgen deficiency after adjustment for dose, obesity, age, hypertension, hyperlipidemia and diabetes.

The fentanyl estimate is the least precise of the three, with a confidence interval running from 2.82 to 234.97, so the true figure could be much lower or higher. The direction is consistent across studies: steady, around-the-clock opioid exposure tends to suppress testosterone more than intermittent use. Dose can still matter for individual drugs; each 10-mg increase in hydrocodone raised the odds by a factor of 1.18.

Buprenorphine appears to lower testosterone less than methadone in men treated for opioid dependence. Hallinan and colleagues found that 65% of men on methadone had total testosterone below 12.0 nmol/L, against 28% of men on buprenorphine. In a smaller German study in the Journal of Clinical Endocrinology and Metabolism, Bliesener and colleagues measured average testosterone of 17.7 nmol/L in 17 men on buprenorphine and 9.7 nmol/L in 37 men on high-dose methadone.

These were observational studies of small groups, and the buprenorphine samples numbered 19 and 17 men. The Bawor meta-analysis did not find that methadone affected testosterone differently from other opioids, and the Hallinan authors wrote that the hormonal effect of buprenorphine needs larger studies. Any switch between opioid treatments is a decision for the prescriber, never a self-directed change.

The most reported symptoms of opioid-induced low testosterone are lower sex drive and erectile problems. In the Daniell 2002 study, 87% of opioid users who had normal erectile function before treatment (39 of 45 men) reported severe erectile dysfunction or diminished libido after starting opioids. The 2026 JAMA review lists decreased libido and fewer spontaneous erections as the most common signs of hypogonadism in general.

Fatigue, low mood, loss of muscle and weight gain can also appear, but chronic pain, poor sleep and the opioid itself cause many of the same complaints. That overlap is the reason a blood test, rather than symptoms alone, has to make the diagnosis. Our article on low testosterone and depression covers how the two conditions are separated.

A man on opioids should be tested the same careful way as any man with suspected hypogonadism, and the result should be read in light of the drug. The 2026 JAMA review confirms hypogonadism only when testosterone is below 264 to 300 ng/dL in at least 2 fasting samples collected between 7 and 10 am, using an accurate assay. The review also advises measuring LH and FSH, which in opioid users usually point to a secondary cause.

Timing and technique are covered in more detail in our guide to testing testosterone accurately. For opioid users the extra step is simple: make sure the doctor reading the result knows which opioid you take, in what form, and for how long.

Testosterone therapy in men on opioids improved sex drive and body composition in randomized trials, but it did not reduce day-to-day pain scores. Basaria and colleagues, publishing in Pain in 2015, randomized 84 men aged 18 to 64 on opioids for chronic noncancer pain, with total testosterone below 350 ng/dL, to 14 weeks of 5 g testosterone gel daily or placebo. Median baseline testosterone was 243 and 251 ng/dL in the two groups, and the mean age was 49.

Compared with placebo, men on testosterone in the Basaria trial had greater improvements in pressure and mechanical pain sensitivity, sexual desire, body composition and role limitation from emotional problems. There were no between-group differences in self-reported pain. A companion analysis of 64 men from the trial, published by Huang and colleagues in Clinical Endocrinology in 2016, found that the gel did not worsen metabolic or inflammatory markers over the same 14 weeks.

A Danish trial tested injections for longer. Glintborg and colleagues randomized 41 opioid-treated men with total testosterone below 12 nmol/L to 24 weeks of testosterone undecanoate injections or placebo, published in the European Journal of Endocrinology in 2020. Median age was 55 and baseline testosterone was 6.8 nmol/L. Lean body mass rose 3.6 kg on testosterone versus 0.1 kg on placebo, and fat mass changed by -1.2 kg versus +1.2 kg. Pain perception, quality of life and cortisol response were not significantly changed compared with placebo.

The extra lean mass in the Danish trial did not turn into measurable strength. A 2022 analysis of the same men by Kolind and colleagues in Andrology found that 24 weeks of testosterone did not improve leg press strength, leg power, grip strength or walking speed compared with placebo.

The 2026 JAMA review states that men unable to discontinue medications that cause hypogonadism may be treated with testosterone. The Kafel 2025 review adds that therapy could be considered in men with unequivocal androgen deficiency after a thorough clinical evaluation. Both conditions matter: a confirmed low level on repeat testing, and an opioid that cannot reasonably be stopped or reduced.

Testosterone therapy carries its own monitoring needs, including hematocrit and, in some men, PSA, and it suppresses sperm production in men who still want children. Our guides to hematocrit on TRT and to enclomiphene as a fertility-sparing alternative cover those trade-offs.

Testosterone is expected to recover in many men after opioids are reduced or stopped, because the testicles are usually not damaged. The 2026 JAMA review classes opioid-related hypogonadism as potentially reversible. Controlled studies tracking how fast and how fully testosterone returns after an opioid taper are limited, so no reliable timeline can be given.

This article is for educational purposes only and is not medical advice. It does not diagnose, treat, cure or prevent any disease. Speak with a doctor before changing any pain medication or starting testosterone therapy.

• Bawor M et al. Testosterone suppression in opioid users: a systematic review and meta-analysis. Drug and Alcohol Dependence, 2015. https://doi.org/10.1016/j.drugalcdep.2015.01.038
• Kafel H, Braga-Basaria M, Basaria S. Opioid-induced androgen deficiency in men: Prevalence, pathophysiology, and efficacy of testosterone therapy. Andrology, 2025. https://doi.org/10.1111/andr.70013
• Anawalt BD et al. Adult Male Hypogonadism: A Review. JAMA, 2026. https://doi.org/10.1001/jama.2026.8526
• Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. The Journal of Pain, 2002. https://doi.org/10.1054/jpai.2002.126790
• Rubinstein AL, Carpenter DM, Minkoff JR. Hypogonadism in men with chronic pain linked to the use of long-acting rather than short-acting opioids. The Clinical Journal of Pain, 2013. https://doi.org/10.1097/AJP.0b013e31827c7b5d
• Rubinstein AL, Carpenter DM. Association Between Commonly Prescribed Opioids and Androgen Deficiency in Men: A Retrospective Cohort Analysis. Pain Medicine, 2017. https://doi.org/10.1093/pm/pnw182
• Hallinan R et al. Hypogonadism in men receiving methadone and buprenorphine maintenance treatment. International Journal of Andrology, 2009. https://doi.org/10.1111/j.1365-2605.2007.00824.x
• Bliesener N et al. Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence. The Journal of Clinical Endocrinology and Metabolism, 2005. https://doi.org/10.1210/jc.2004-0929
• Basaria S et al. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial. Pain, 2015. https://doi.org/10.1097/01.j.pain.0000460308.86819.aa
• Glintborg D et al. Testosterone replacement therapy of opioid-induced male hypogonadism improved body composition but not pain perception: a double-blind, randomized, and placebo-controlled trial. European Journal of Endocrinology, 2020. https://doi.org/10.1530/EJE-19-0979
• Huang G et al. Effects of testosterone replacement on metabolic and inflammatory markers in men with opioid-induced androgen deficiency. Clinical Endocrinology, 2016. https://doi.org/10.1111/cen.13049
• Kolind MI et al. Muscle function following testosterone replacement in men on opioid therapy for chronic non-cancer pain: A randomized controlled trial. Andrology, 2022. https://doi.org/10.1111/andr.13147

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