Hormone level side effects in prolonged painkiller usage

Many individuals that contact us have been on long-term medications to manage their chronic pain. Many times these medications were prescribed to help the patient manage until a surgery could be performed. More recently, as elective surgeries have become less available and longer wait times are being given, doctors may find it necessary to prescribe medications as “no other option.”

In over two decades of service helping patients with chronic pain, we have seen our fair share of patients who were put into the “tween” group. These patients have advancing osteoarthritis but are too young for joint replacement. They come into to see us complaining that they are being pain managed along until the deterioration of their joint is sufficient enough to warrant surgery or they simply become old enough that their doctors will feel that they will not outlive the prosthesis. While these people wait for surgery, they will be suffering from increasingly lower levels of activity and chronic pain. They will likely develop obesity, and despite all warnings about opioid addiction and challenges, they will be on pain medications. What is worse, for many people this cascade of degenerative joint disease will play a role in their diminishing hormones and make their health challenges that much more significant. The patient is not in a good place for healing.

Low hormones associated with the need for knee and hip replacements

Diminished hormone levels cause a myriad of health related problems, not the least of which is an acceleration of joint damage. Painkillers therefore, by way of reducing hormone levels, increase the need for these joint replacements. Often we will see people who are trying to balance hormonal levels and the need to function with knee or hip pain. Many times these people have to resort to painkillers to help them get through their day. These people are in our office because they are seeking a more long-term solution to their pain issues than the daily management of pain and eventual succumbing to joint replacement surgery.

In a study published in the journal Osteoarthritis Cartilage, [1] doctors in Australia confirmed that low testosterone is associated with an increased risk of both knee and hip replacement in overweight and obese men. The findings suggest that circulating sex steroids may play a role in the origins and acceleration of osteoarthritis in men.. Supporting this idea, another study lead by an international team of doctors and published by the Arab Association of Urology [2] found that restoring testosterone levels helped aging men with their joint problems, physical activity, and quality of life.

Of course these are not the only two studies to suggest that low levels of testosterone negatively impact joint pain and that providing testosterone replacement therapy may help the situation. They are however among the most recent to specifically test the theory that low testosterone levels do cause joint pain and joint pain causes low testosterone levels.

A June 2020 study (3) from Odense University Hospital in Denmark updated this research. In this study it is acknowledged that men suffer from low testosterone levels during opioid treatment, but it is unclear what impact testosterone supplementation will have on restoring correct body composition, pain perception, and adrenal function.

  • This study examined 41 men with an age range of 46 to to 59 years old.
  • Scores and measurements were taken for body composition (lean body mass and fat mass assessed), clinical pain intensity (numerical rating scale), and experimental pain perception (quantitative sensory assessment), quality of life, and adrenocorticotrophic hormone (ACTH) test (adrenal function).

When testosterone replacement therapy was introduced the following results were noted:

  • Increased lean body mass
  • Decreased total fat mass.

However, testosterone alone could not fix chronic pain problems.

  • The men still had the same pains
  • Quality of life did not dramatically improve
  • Cortisol levels did not improve. (In cases of low cortisol levels, increase in blood sugar, weight gain and greater risk for Type 2 Diabetes are seen.

Conclusions: “Six months of testosterone replacement therapy improved body composition in men with opioid-induced hypogonadism without significant changes in outcomes of pain perception, quality of life, or adrenal function.”

Low estrogen is associated with joint pain in women

Doctors have been investigating low hormone levels in women and its effect on chronic joint pain. Here are some of the findings.

  • In the journal Ultrasound in medicine & biology, researchers found that post-menopausal reduction or low levels of estrogen can accelerate cartilage loss and joint deterioration in the hip and knee.(4)
  • In the medical journal Menopause, researchers produced finding that estrogen supplementation in postmenopausal women resulted in a modest but sustained reduction in the frequency of joint pain.(5)

Painkiller use makes hormonal imbalances worse and disrupts healing cycles
How bad are the effects of painkillers be on hormone levels?

A recent study in the medical journal Pain Management suggests that even after only 30 days, patients on opioid (narcotic) medication for pain management suffer from reduced levels of testosterone.[6]

Research has shown us opioids have a number of adverse effects including hormonal imbalances. These imbalances have been reported to primarily involve testosterone and affect both males and females to the point of interfering with successful treatment of pain management.

There is a growing body of evidence which makes it clear that the long-term treatment of chronic pain with opioid pain-killer medications puts the patient at great risk for hormonal abnormalities including lowering the testosterone in both male and female patients which in turn prevents healing among other health concerns.

The evidence of the above cited research demonstrates that opioids effect testosterone levels differently in men and women and that severity of symptoms must be carefully weighed as they will manifest themselves differently. A man’s joint pain may be much more severe than a woman’s despite similar problems.[7]

In a new October 2018 study doctors found that the use of opioids in patients with chronic non-cancer pain is common and can be associated with opioid-induced androgen deficiency (OPIAD) in men. “OPIAD is a common adverse effect of opioid treatment and contributes to sexual dysfunction, impairs pain relief and reduces overall quality of life.” [8]

Investigators researching opioids say some patients with severe and chronic pain fail to obtain adequate pain relief with standard pharmacologic treatment agents, including low to moderate dosages of opioid. Understandably, physicians might not believe patients who claim that a standard opioid dosage is an ineffective treatment. These patients may be severely impaired, nonfunctional, and bedridden or housebound.

To help characterize these individuals and develop treatment strategies for them, a serum hormone profile consisting of adrenocorticotropin, cortisol, pregnenolone, progesterone, dehydroepiandrosterone, and testosterone was obtained on 61 chronic pain patients who failed standard treatments; 49 patients (80.3%) demonstrated hormone abnormality.(9) To manage this problem the researchers suggested enhanced analgesia (more painkillers) is required and that hormone replacement may be indicated.

Years of chronic pain require a broad understanding that in many patients, pain and function problems are more than a hole in the cartilage. Hormones can be involved, weight can be an issue, lifestyle choices can be an issue. The path to healing crosses many roads.

Hussain SM, Cicuttini FM, Giles GG, Graves SE, Wang Y. Relationship between circulating sex steroid hormone concentrations and incidence of total knee and hip arthroplasty due to osteoarthritis in men. Osteoarthritis Cartilage. 2016 Apr 12. pii: S1063-4584(16)30024-3. doi: 10.1016/j.joca.2016.04.008.
2. Almehmadi Y, Yassin AA, Nettleship JE, Saad F. Testosterone replacement therapy improves the health-related quality of life of men diagnosed with late-onset hypogonadism. Arab J Urol. 2016 Mar;14(1):31-6. doi: 10.1016/j.aju.2015.10.002.
3 Glintborg D, Vaegter HB, Christensen LL, 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. Eur J Endocrinol. 2020;182(6):539‐548. doi:10.1530/EJE-19-0979
4 Wang Q, Liu Z, Wang Y, Pan Q, Feng Q, Huang Q, Chen W. Quantitative Ultrasound Assessment of Cartilage Degeneration in Ovariectomized Rats with Low Estrogen Levels. Ultrasound Med Biol. 2016 Jan;42(1):290-8. doi: 10.1016/j.ultrasmedbio.2015.08.004. Epub 2015 Oct 21.
5 Chlebowski RT, Cirillo DJ, Eaton CB, Stefanick ML, Pettinger M, Carbone LD, Johnson KC, Simon MS, Woods NF, Wactawski-Wende J. Estrogen alone and joint symptoms in the Women’s Health Initiative randomized trial. Menopause. 2013 Jun;20(6):600-8. doi: 10.1097/GME.0b013e31828392c4.
6. Cepeda MS, Zhu V, Vorsanger G, Eichenbaum G. Effect of Opioids on Testosterone Levels: Cross-Sectional Study using NHANES. Pain Med. 2015 Jul 14. doi: 10.1111/pme.12843.
7. Bawor M, Bami H, Dennis B, et al, Testosterone suppression in opioid users: a systematic review and meta-analysis. Drug Alcohol Depend. 2015 Apr 1;149:1-9. doi: 10.1016/j.drugalcdep.2015.01.038.
8 Coluzzi F, Billeci D, Maggi M, Corona G. Testosterone deficiency in non-cancer opioid-treated patients. J Endocrinol Invest. 2018;41(12):1377-1388.
9. Tennant F. Hormone abnormalities in patients with severe and chronic pain who fail standard treatments. Postgrad Med. 2015 Jan;127(1):1-4. Epub 2014 Dec 15.

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