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What is the best way to manage opioid-induced hypogonadism without disregard for pain relief?
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Some patients — but not all — will feel better with testosterone replacement.
It is well known that opioids suppress the pituitary gland, so that the hormones controlling the testicles tend to be low, causing testosterone to fall. The question is, do you replace testosterone or not? Generally, the answer depends on the patient’s testosterone level. If it is mildly depressed, then there is no great urgency in correcting it. If it is very depressed, then some patients will feel better with replacement. Not all, but some. I replace testosterone when levels are below 200 ng/dL, and I do not for levels above 300 ng/dL. For a level in between, I discuss replacement with the patient.
There has been some hesitancy regarding testosterone replacement due to reports of risks for increased cardiovascular events. The data on this are very poor. There may be an association if a patient has advanced heart disease, particularly with high doses of testosterone. But for everybody else, there does not seem to be any danger. There are also data suggesting an increased risk for blood clots in men undergoing testosterone replacement therapy, but again, the data are not very good and are typically associated with high levels of replacement.
The common preparations for testosterone therapy are a patch or gel. The patch is very convenient, but it does cause irritation in a large proportion of patients. If the patch does not work well, the gel is very good and provides a relatively steady level of testosterone throughout the day.
A recent study shows that, in older men, many of them do feel better with testosterone replacement (Cunningham GR, et al. J Clin Endocrinol Metab. 2016;doi:10.1210/jc.2016-1645). But, testosterone therapy will not work as an antidepressant, and these patients on opioid therapy are often depressed.
Other options to manage opioid-induced hypogonadism include rotating opioids or tapering therapy. However, for these patients, rotating opioids will not work, as any opioid will still affect the same brain receptors. In addition, many of these patients also have PTSD. If you taper opioid therapy, there is still the underlying stress, and stress is a tremendous depressor of testosterone. Pain and stress on their own will push testosterone down.
Terry F. Davies, MD, FRCP, is professor of medicine, diabetes, endocrinology and bone disease at the Icahn School of Medicine at Mount Sinai. Disclosure: Davies reports no relevant financial disclosures.
Testosterone replacement is not the answer.
The current thinking is that we should rarely be using opioids for chronic, noncancer pain. We have a multitude of people nationwide on opioids for chronic, noncancer pain, who have not had any significant improvements in pain score or function, or lifestyle. If you look at what you would want as an outcome for yourself and see that this medicine is clearly not producing the desired outcome, then the first thing to do is get rid of it. When men are on chronic opioid therapy, they frequently have no libido, they have erectile dysfunction, loss of muscle mass and osteoporosis. When they are given testosterone replacement therapy, they do not suddenly have all of the endocrine side effects reversed and become a pain-free, highly functional individual. The reality is that although the measurable outcome or measurable level of testosterone is the thing we’re looking at, there are so many other endocrine abnormalities and growth hormone abnormalities that result from chronic administration of opioids that we do not address. It’s not as simple as saying, “Well, I can find low testosterone and I can treat low testosterone.” That’s probably not the answer to the question.
Any opioid that interacts with the mu receptor is going to have that impact on endocrine function. Endocrine dysfunction is a universal effect of opioid therapy.
Depending on the fundamental underlying reason for the pain, nonopioid treatments should always be the first line of therapy. For neuropathic pain, first-line therapy should be antidepressants or anticonvulsants; for muscular-related pain, physical activity. Sometimes there are interventional procedures that might be appropriate, such as individual nerve blocks, steroid injections or spinal cord stimulation. There are also other alternatives, including mindfulness-based therapies. If you can address the underlying cause of the pain with these options, that should be the first approach.
Richard W. Rosenquist, MD, is chair of the department of pain management at the Cleveland Clinic. Disclosure: Rosenquist reports no relevant financial disclosures.