Adequate testosterone serum levels are required in males and females not just for libido and sexual function but also for cellular growth, healing, maintenance of muscle mass and bone, and central nervous system maintenance of opioid receptors, blood- brain barrier, and dopamine-norepinephrine activity.
Due to its critical biologic functions in pain control, testosterone testing and replacement (TR) should now become a mandatory component in the treatment of chronic pain. This paper summarizes the physiologic actions of testosterone relative to pain management and lays out practical guidelines for testing and treatment that can easily be adapted to pain practice.
Why the Necessity of Testosterone?
First, adequate testosterone levels are needed for satisfactory pain control as this hormone is intricately involved in endogenous opioid activity. Testosterone is also necessary for opioid receptor binding, maintenance of blood-brain barrier transport, and activation of dopamine and norepinephrine activity.1
Consequently, a lack of testosterone activity in the CNS may result in poor pain control, depression, sleep disturbances, and lack of energy and motivation.
Table 1. Testosterone Functions in Chronic Pain Patients
- Opioid receptor binding
- Dopamine-norepinephrine activity
- Maintenance of blood-brain barrier
- Androgenic-healing/tissue growth
- Erectile activity (males)
- Maintenance of muscle and bone mass
- Exercise tolerance
all of testosterone’s CNS and androgenic-immunologic functions apply equally to females.
Although testosterone was previously thought to be only produced in the testicles, it is now clear that it can be produced in the adrenal and ovary
Of considerable importance is the fact that testosterone converts to estradiol and dihydrotestosterone in peripheral tissue.
Hormonal therapy is emerging as critical to adequately treat an altered CNS that develops in response to severe chronic pain
Mechanism of Testosterone Depletion
There may be two reasons for testosterone depletion in a chronic pain patient.
One is pituitary insufficiency caused by severe pain, per se. Constant, persistent, uncontrolled pain will, over time, exert enough stress on the hypothalamus and pituitary (GnRH, LH, FSH) to cause the inadequate secretion of testosterone from the adrenal and gonads. When the cause of hypotestosteronemia is hypothalamic-pituitary insufficiency, other hormones such as cortisol, pregnenolone, or thyroid may likely show serum deficiencies.
The second and most common cause of testosterone deficiency is opioid administration. Low testosterone levels have been observed with essentially all oral and intrathecal opioids. Low testosterone serum levels are primarily caused by opioid suppression of GnRH in the hypothalamus. Opioids may also directly impair testosterone production in the adrenal or gonads.
If financial resources are available, all chronic pain patients who require opioid administration, including those patients who are currently taking opioids, should be screened. Those patients currently in opioid treatment and who complain of lethargy, inadequate pain control, depression, weakness, and lack of libido, are obvious candidates for serum testing (see Tables 3 and 4).
Table 3. Symptoms of Testosterone Deficiency in Males and Females
- Lack of energy
- Loss of libido
- Poor healing
- Diminished opioid affects
- Loss of motivation
There are several commercial testosterone products from which to choose (see Table 5). Each has pros and cons and all are relatively expensive. Third party payment is extremely variable and may dictate your selection. Due to cost considerations, patients without insurance coverage will usually be forced to use injectable testosterone. Some compounding pharmacies will now make a topical testosterone cream or gel for a cost similar to that of injectable testosterone. If you use a compounding pharmacy, we recommend you order a testosterone concentration similar to that found in the commercial gels which is a 1% testosterone concentration. For example, 50mg in 5gms (Testim
Testosterone is a Schedule III drug under the U.S. Controlled Substance Act and is classified as an “anabolic steroid.” Indeed its anabolic (tissue building) affects are desired in pain management.
Precursor therapy with testosterone replacement is reported by many pain patients to be a useful adjunct. There are four precursors of testosterone that can be given therapeutic trials: dehydro-epiandrosterone (DHEA), pregnenolone, progesterone, and androstenedione
Table 6. Testosterone Precursors Precursor Daily Dosage
- Dehydroepiandrosterone (DHEA) 50 to 100mg
- Pregnenolone 50 to 100mg Androstenedione 50 to 100mg
- Medroxyprogesterone 10 to 20mg
Note: Intermittent, rather than daily, administration is recommended.
Precursors are quite safe and appear quite free of side-effects. To be cautious, we do not recommend they be used on a daily basis but rather on an intermittent basis.