Short answer: Yes, long-term opioid use can lower testosterone in men. Researchers call this opioid-induced androgen deficiency (OPIAD): opioids act on the brain’s hormone control centers and reduce the signals that tell the testes to make testosterone. Reviews of men on long-term opioids for chronic non-cancer pain report rates from 19% to 86%, depending on how low testosterone is defined.[2] If you take opioids and notice low sex drive, erection changes, fatigue or mood changes, talk to your prescriber about testing, and never stop or change your opioid dose on your own.
Key Takeaways
- The mechanism is central: opioids suppress gonadotropin-releasing hormone (GnRH) in the hypothalamus, which lowers luteinizing hormone (LH) and then testosterone.[2]
- Risk depends on the drug, the dose and the duration: long-acting opioids and higher daily doses are associated with more risk; brief use is a different situation.[1][2]
- The FDA requires opioid labels to warn about it: since 2016, labels note that long-term use may be associated with decreased sex hormone levels, and prescribers are told to run lab tests when symptoms appear.[3]
- Diagnosis needs proper testing: symptoms plus consistently low fasting morning testosterone on two separate days, with LH and FSH to find the cause.[6]
- Never stop opioids abruptly: the FDA has reported serious harm, including withdrawal, uncontrolled pain and suicide, after sudden discontinuation or rapid dose cuts.[4]
- Treatment is the clinician’s decision: options are individualized, and no supplement is a substitute for that evaluation.[2][5]
What Is Opioid-Induced Androgen Deficiency (OPIAD)?
Opioid-induced androgen deficiency is low testosterone (hypogonadism) caused or worsened by opioid medicines. It is not new: a 2016 review in Current Urology Reports notes that it was first recognized roughly four decades earlier, and that long-acting opioids can cause hypogonadotropic hypogonadism, meaning the testes are underproducing because the brain is not sending enough of a signal.[1]
The Endocrine Society’s clinical practice guideline on testosterone therapy lists opioid use among the “functional” causes of secondary hypogonadism. Functional means the problem comes from something that may be reversible, such as a medication, rather than permanent damage to the testes or pituitary gland.[6]
OPIAD matters because it is common, it is under-recognized, and its symptoms are easy to blame on pain, poor sleep, stress or simply getting older. A 2020 review in Cureus points out that patients often under-report symptoms and that there are no established guidelines specifically for evaluating and managing it, which makes it easy to miss.[5] For a general overview of what low testosterone looks like, see our guide to the signs of low testosterone.
How Opioids Lower Testosterone
The hypothalamic-pituitary-gonadal (HPG) axis
Testosterone production runs on a chain of signals. The hypothalamus releases GnRH, GnRH tells the pituitary to release LH and follicle-stimulating hormone (FSH), and LH tells the Leydig cells in the testes to make testosterone. This chain is called the HPG axis.
According to a 2018 review in the Journal of Endocrinological Investigation, the main pathway in OPIAD is suppression of GnRH through mu-opioid receptors. Less GnRH means less LH, and less LH means less testosterone.[2] The authors note that tapentadol, which has a lower affinity for the mu receptor, appears to have minimal effects on testosterone, which supports the role of that receptor.[2]
Other proposed effects
The 2016 review also describes proposed direct effects on the testes and on the hypothalamic-pituitary-adrenal (stress hormone) axis.[1] Some of the extra mechanisms, such as changes in feedback sensitivity and peripheral testosterone metabolism, come mainly from animal data, so they are less certain than the GnRH pathway seen in humans.[2]
Which Opioids, Doses and Durations Carry More Risk?
Not every man who takes an opioid will develop low testosterone. The evidence points to a few patterns, summarized from the 2018 review of non-cancer opioid-treated patients:[2]
| Factor | What the review reports | What it means for you |
|---|---|---|
| Formulation | At equivalent doses, long-acting opioids are more likely to cause androgen deficiency | Ask whether your regimen is long-acting |
| Daily dose | Doses above about 100 mg oral morphine equivalent per day may be more likely to trigger OPIAD, though not all studies confirm this | Higher doses deserve closer monitoring |
| Specific drugs | Risk appeared highest with fentanyl, then methadone and oxycodone; tapentadol had minimal effects and buprenorphine had limited endocrine effects | The drug choice is your prescriber’s call, based on your whole picture |
| Example data | In one study, 45.5% of patients on oxycodone (mean 75 mg per day) fell below the reference range after 12 weeks | Changes can appear within months |
| Maintenance therapy | Hypogonadism was reported in 75% of men on high-dose methadone maintenance | Men in treatment programs should also ask about testing |
These are research findings in specific groups, not predictions for any individual. They are also not a reason to switch drugs on your own: changing an opioid involves pain control, dependence and safety issues that only your prescriber can weigh.
Symptoms of Low Testosterone From Opioids
The FDA’s 2016 safety communication lists symptoms patients should report, including low interest in sex, impotence, erectile dysfunction and infertility.[3] The research reviews describe a wider picture:[2][5]
- Sexual function: low libido and erection problems. In one study cited by the 2018 review, 78% of men on long-term opioids reported sexual dysfunction.[2]
- Energy and mood: fatigue, low mood and reduced quality of life.
- Body composition: weight gain and changes in muscle and fat.
- Bone health: osteopenia was found in 50% of men in one study, and opioid use has been associated with a 50% to 60% increase in osteoporotic fracture risk.[2]
- Fertility: androgen insufficiency may contribute to infertility.[5]
- Pain itself: both reviews note that low testosterone may be linked to hyperalgesia (increased pain sensitivity) and poorer pain control.[2][5]
Many of these symptoms overlap with chronic pain, depression, sleep problems and the side effects of other medicines. That overlap is exactly why testing, not guessing, is the right next step.
How Doctors Test for Opioid-Related Low Testosterone
Who should be tested
The FDA tells health professionals to perform a laboratory evaluation in opioid users who show signs or symptoms of low sex hormones.[3] The 2018 review goes further and suggests that serum testosterone should be considered in male chronic opioid users, with expert opinion favoring monitoring in men on more than 100 mg morphine equivalent per day.[2] The Cureus review recommends routine symptom screening and periodic hormone monitoring.[5]
How the tests are done
The Endocrine Society guideline recommends diagnosing hypogonadism only in men who have symptoms or signs and consistently low testosterone. In practice, that means:[6]
- Fasting, morning total testosterone measured on two separate mornings with an accurate assay.
- Free testosterone when total testosterone is near the lower limit or when SHBG may be abnormal.
- LH and FSH to tell primary (testicular) from secondary (brain-level) hypogonadism. OPIAD typically shows the secondary pattern.
The guideline also advises against testing during short-term opioid use or acute illness, because results then may not reflect your usual levels.[6] Timing matters a lot with this hormone; our article on the best time to check testosterone levels explains why, and free vs total testosterone explains the two main numbers on your report. For context on lab ranges, see normal testosterone levels.
Treatment Options: Decided With Your Prescriber
Do not stop or change opioids on your own
This is the most important safety point in this article. In 2019 the FDA reported serious harm in physically dependent patients after opioids were stopped suddenly or the dose was cut quickly, including serious withdrawal, uncontrolled pain, psychological distress and suicide.[4] The FDA tells prescribers not to stop opioids abruptly in a dependent patient and to build an individualized taper with ongoing monitoring when a reduction is appropriate.[4] If low testosterone worries you, raise it at your next appointment; do not adjust your medicine to “fix” it.
What clinicians may consider
Because opioid-related hypogonadism is a functional cause, the Endocrine Society notes it may be reversible when the medication is discontinued, but that decision depends on your pain, your diagnosis and your safety.[6] The reviews describe several approaches a clinician may weigh:[1][2][5]
- Reassessing the pain plan, including dose, formulation or a different medicine, only under medical supervision.
- Testosterone replacement therapy in carefully selected men with confirmed deficiency. The reviews stress individualized decisions made with the patient.[2][5]
- Medicines that stimulate the body’s own production, such as clomiphene citrate, which the 2016 review discusses as an option that works on hypothalamic function.[1]
Fertility changes the plan. The Endocrine Society recommends against starting testosterone therapy in men planning fertility in the near term, because testosterone therapy suppresses sperm production.[6] Tell your doctor if you hope to have children.
Bone health, mood and sleep may also need attention. Healthy habits such as regular activity within your limits, good sleep and adequate protein support overall health, but they are not a replacement for the medical evaluation described above.
Supplements and Opioids: Tell Your Prescriber Everything
No supplement has been shown to correct opioid-induced androgen deficiency, and none should be used in place of testing or medical care. Men on opioids also take other medicines that can interact with herbs. The safe rule is simple: tell your prescriber and pharmacist about every supplement you take, including Ultra Bann, and bring the bottle or label to your appointment. Ultra Bann’s full ingredient list and amounts are published on our ingredients page, so your clinician can review it in a minute.
Frequently Asked Questions
Do opioids lower testosterone in every man who takes them?
No. Studies report a wide range, from 19% to 86% of men on long-term opioids for non-cancer pain, depending on the definition used, with most studies above 50%.[2] Dose, drug type, formulation and duration all play a role, so the only way to know your own status is testing.
How long does it take for opioids to affect testosterone?
It can happen within weeks to months. In one study cited by the 2018 review, 45.5% of men on oxycodone fell below the reference range after 12 weeks.[2] Short-term use for an injury or surgery is a different situation, and guidelines advise against testing during short-term use.[6]
Will my testosterone come back if I stop opioids?
The Endocrine Society classifies opioid use as a functional cause of low testosterone that may be reversible after the medication is discontinued.[6] However, stopping must be planned with your prescriber, because sudden discontinuation can cause serious harm.[4]
Can I take testosterone while on opioids?
Some men with confirmed deficiency receive testosterone therapy, but the reviews emphasize careful patient selection and individualized decisions.[2][5] It is not recommended for men planning fertility soon.[6] Only your clinician can decide whether it fits you.
Does buprenorphine or methadone lower testosterone?
The 2018 review reports that methadone carries a relatively high risk, with hypogonadism found in 75% of men on high-dose methadone maintenance, while buprenorphine showed more limited endocrine effects.[2] Do not switch medicines on your own; discuss it with your treatment team.
References
- O’Rourke TK, Wosnitzer MS. Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review. Current Urology Reports, 2016. Abstract (UroToday)
- Coluzzi F, Billeci D, Maggi M, Corona G, et al. Testosterone deficiency in non-cancer opioid-treated patients. Journal of Endocrinological Investigation, 2018;41:1377 to 1388. Full text (Springer)
- U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. March 22, 2016. fda.gov
- U.S. Food and Drug Administration. FDA identifies harm reported from sudden discontinuation of opioid pain medicines and requires label changes. April 2019. fda.gov
- Long-term Opioids Linked to Hypogonadism and the Role of Testosterone Supplementation Therapy. Cureus, 2020;12(10):e10813. PubMed
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism, 2018;103(5):1715 to 1744. PDF
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease. This article is for information only and is not medical advice.
Ultra Bann natural male vitality support
1 capsule every 2 days. Free US shipping and a 60-day money-back guarantee on your first order.
See Ultra BannThese statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
