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Laurance Johnston, Ph.D.

Quality-of-life compromising pain affects at least two-thirds of individuals with spinal cord injury (SCI). This pain can manifest in numerous forms, ranging from overuse-related shoulder pain to the insidious neuropathic pain resulting from nervous-tissue damage.

Recently, this series highlighted a variety of non-pharmaceutical approaches for reducing SCI pain, in part, because many pain-relieving drugs have adverse side effects. For example, commonly used opioid drugs can knock out the body’s production of testosterone, a physiologically vital hormone that is all ready compromised after SCI.


As discussed elsewhere, testosterone is produced by the testes in men and, to a lesser degree, the ovaries in women. It promotes the development of reproductive tissue, sex organs, secondary sexual characteristics, sexual function, muscle mass/strength, and bone density. The hormone also helps to maintain neuronal health and inhibits various post-injury neuron-damaging processes. Testosterone production is regulated by the secretion of hormones (called gonadotropins) from the brain’s pituitary. Because it is a central-nervous-system-driven process, CNS insults like SCI can decrease testosterone levels, often substantially.

For example, in 2011, investigators at the Milwaukee VA Medical Center and affiliated institutions demonstrated that 43% of study participants with chronic SCI had low testosterone levels. Those Individuals with complete injuries and those taking narcotic pain medications or opioids were especially affected.


Opioids are molecules that bind to certain receptors on the surface of neurons, including those in the spinal cord. This binding alters communication between neurons, in turn, muting pain perception. Isolated from the poppy, opium is the most well-known example of a naturally occurring opioid-containing material. It is the source of many painkilling and substance-abuse drugs, such as morphine and its derivative heroin. In an effort to tailor specific neurological responses, numerous synthetic opioids have been created. 

In addition, the body produces its own opioid-like molecules, such as the endorphins associated with the feel-good, endorphin rush or runner’s high generated by exercise, etc. 

Opioids & Pain

Opioids have been extensively used to treat moderate to severe chronic pain.  Although not a panacea, evidence indicates that some opioid drugs can lessen SCI pain, including morphine, alfentanil, tramadol, fentanyl, hydromorphone (Dilaudid), methadone, and levorphanol.

Many side effects are associated with opioid use, including sedation, nausea, dizziness, headaches, dry mouth, mood, vision, and hearing changes, constipation, bladder dysfunction, and addiction. Considerable mortality is associated with their use. Specifically, a 2012 article entitled “Opioid Epidemic in the United States,” noted that there are now more overdose deaths from opioid pain relievers [My sister became one of these statistics in 2012.] than deaths from both suicide and car accidents, or deaths from cocaine and heroin combined. The majority of these deaths resulted from using opioids exactly as prescribed.

Opioids & Testosterone

An exceedingly important issue is the impact of these drugs on testosterone levels, especially in a SCI population already suffering the deleterious effects of compromised testosterone. Testosterone-depleting effects are often underappreciated by primary-care physicians, the doctors doing most of the prescribing. In the case of the most studied opioid morphine, the drug causes a dramatic reduction in testosterone. Fortunately, once treatment is discontinued, levels recover.

Scientists speculate that opioids shut-down testosterone production by inhibiting the release of the brain gonadotropin hormones that stimulate testosterone production and accelerating the enzymatic degradation of existing testosterone. So to speak, a wrench has been thrown in the testosterone assembly line, and the testosterone already in circulation has been broken down for parts.

Ironically, low testosterone is correlated with increased pain levels. Hence, if opioids are given to fight pain, the ensuing low testosterone may actually increase pain.

Because many opioid painkillers are used, it is difficult to overgeneralize. Furthermore, testosterone-depleting effects are affected by pharmacological considerations, such as the formulation used, route of administration, dose, and treatment duration.

Given this problem, experts suggest that testosterone levels be measured before and periodically after opioid treatment has been initiated. Finally, it is recommended that those with treatment-induced low testosterone contemplate testosterone replacement therapy, although this will not reverse the opioid suppression of the pituitary gonadotropins.


An internal medicine, board-certified SCI-staff physician at the Palo Alto VA Medical Center, Steven Linder, MD has served on the VA-Department of Defense Health Executive Council Pain Management Work Subgroup, focusing on pain systems of care for returning combat veterans. He is strongly interested in developing “more enlightened approaches to managing…chronic pain in patients with SCI.” He believes that the issue of opioid-induced testosterone depletion in SCI patients requires more investigation so that the scientific community and, in turn, prescribing physicians can develop a better, big-picture appreciation of the consequences of and better strategies for using these drugs. He feels we need validated questionnaires or structured-interview assessments for screening opioid-induced, low-testosterone symptoms through testosterone replacement therapy.


Given their widespread use, this discussion is relevant to anyone considering opioid painkillers, but it is especially germane for pain-inclined individuals with SCI already suffering from the health-compromising consequences of low testosterone. If you understand the tradeoffs and believe you must take an opioid, monitor your testosterone levels and consider replacement therapy.

Adapted from article appearing in June 2013 Paraplegia News (For subscriptions, call 602-224-0500) or go to www.pn-magazine.com