Do Painkillers Cause Lower Testosterone Levels?

We see many “masters” aged athletes and men who continue to do physically demanding work well into their 40s, 50s, 60s and 70s and some beyond.

What we see these men for are their problems with chronic joint and back pain. These men will tell us that to get themselves through the day they will take painkillers and anti-inflammatory medications. Sometimes before, during, or after activities. Sometimes when they know the activities will be extra strenuous they take extra medications. These men are in a difficult situation. They want to continue on, they are trying to manage themselves with medication, braces, wraps, what ever they can buy on the internet that offers them some hope of relief.  Most have already been told that they should consider surgery now.

Another set of problems that these men report are problems of fatigue and lack of energy. They may drink more coffee or try an “energy boost” drink or vitamin mixture. With fatigue comes a sense of weakness and the sense that they are not well. Sometimes, they will report sexual dysfunction as a new and obviously concerning symptom. For those regularly seeing a doctor, they will tell us that they were initially surprised when their doctor told them that painkillers may alter their testosterone levels and that fatigue, weakness and sexual or erectile dysfunction are common side-effects.

Does low testosterone cause opioid craving?

A 2021 study suggested (1)  “opioid dependence is a severe disease which is associated with a high risk of relapse, even in cases of successful withdrawal therapy. Studies have shown alterations of the hypothalamic-pituitary-gonadal axis in opioid-dependent patients, such as decreased testosterone serum levels in affected males.” The findings of this paper seemed to indicate: “a possible role of testosterone metabolism (low testosterone causing) opioid dependence, which may be relevant for the establishment of future treatment strategies.”

In some men, testosterone replacement therapy may be recommended

A July 2021 paper (2) demonstrated the high prevalence of depression diagnosis, low sex hormone levels, and reduced sexual function among  patients with chronic noncancer pain receiving prolonged opioid therapy. Regular hypogonadal screenings are recommended for further management.

A March 2022 paper wrote: (3) “Chronic pain and opioid treatment are associated with increased risk of male hypogonadism and subsequently decreased muscle function. . . The effect of testosterone replacement therapy on muscle function in men with chronic pain and low total testosterone remains to be investigated.”

Testosterone supplementation or replacement can be considered a controversial treatment. This would explain the vast amounts of research investigator the testosterone pain-killer connection. In this paper researchers found 24 weeks testosterone replacement therapy in opioid-treated men with pain-related male hypogonadism did not improve muscle function although it appeared to improve lean muscle mass. The question here is was the opioid damage too far gone for 24 weeks of therapy to repair?

“The clinical significance of opioid-induced androgen deficiency and the diagnostic techniques to recognize and credible treatment alternatives, including testosterone replacement therapy”

An October 2020 study (4) offered a different opinion: “Opioids play a pivotal role in managing chronic pain with increasing prescription rates over the last few years. Hence, it is crucial to focus on the adverse effects of narcotics, and one of the lesser-known side effects is hypogonadism (low testosterone). Opioids act on the hypothalamus, pituitary, and directly on the gonads affecting serum testosterone levels. Narcotic-induced androgen insufficiency contributes to sexual dysfunction, infertility, hyperalgesia (higher sensitivity to pain), and involving various body functions overall, affecting the quality of life. Opioid-induced hypogonadism is very challenging to diagnose for the clinicians, as the patients often under-report the symptoms . . .This study aims to highlight the clinical significance of opioid-induced androgen deficiency and the diagnostic techniques to recognize and credible treatment alternatives, including testosterone replacement therapy.”

1 Janke E, Groh A, Mühle C, Dürsteler-MacFarland KM, Wiesbeck GA, Kornhuber J, Jahn K, Groeschl M, Lichtinghagen R, Frieling H, Bleich S. Association of Testosterone Levels and Steroid 5-Alpha-Reductase 2 Polymorphisms with Opioid Craving. Neuropsychobiology. 2021;80(1):64-73.
2
Ho ST, Lin TC, Yeh CC, Cheng KI, Sun WZ, Sung CS, Wen YR, Hsieh YJ, Wang PK, Liu YC, Tsai YC. Gender Differences in Depression and Sex Hormones among Patients Receiving Long-Term Opioid Treatment for Chronic Noncancer Pain in Taiwan—A Multicenter Cross-Sectional Study. International journal of environmental research and public health. 2021 Jan;18(15):7837.
3 Kolind MI, Christensen LL, Caserotti P, Andersen MS, Glintborg D. Muscle function following testosterone replacement in men on opioid therapy for chronic non‐cancer pain‐a randomized controlled trial. Andrology. 2021 Dec 21.
4 Marudhai S, Patel M, Subas SV, Ghani MR, Busa V, Dardeir A, Cancarevic I. Long-term opioids linked to hypogonadism and the role of testosterone supplementation therapy. Cureus. 2020 Oct 5;12(10).

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