Testosterone Replacement in Chronic Pain Patients

Testosterone Replacement in Chronic Pain Patients

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

  1. Opioid receptor binding
  2. Dopamine-norepinephrine activity
  3. Maintenance of blood-brain barrier
  4. Androgenic-healing/tissue growth
  5. Libido
  6. Erectile activity (males)
  7. Maintenance of muscle and bone mass
  8. 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

  1. Lack of energy
  2. Loss of libido
  3. Depression
  4. Poor healing
  5. Diminished opioid affects
  6. Loss of motivation
  7. Apathy
  8. Weakness

Treatment Recommendations

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

  1. Dehydroepiandrosterone (DHEA) 50 to 100mg
  2. Pregnenolone 50 to 100mg Androstenedione 50 to 100mg
  3. 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.


13 thoughts on “Testosterone Replacement in Chronic Pain Patients

  1. Alexandra

    HI I totally believe testosterone keeps EDS ” at bay” I have polyovarian syndrome and underwent IVF a year ago. I was a runner and never had issues. After starting IVF my normally very high testosterone levels were lowered. What transpired after this was lung collapse, then prolapsed discs within my thoracic spine neck and annular tears. I did not put 2 and 2 together as the IVF went on over a year and half. I was weight lifting and I believed the testosterone protected me but the minute it was removed the EDS took over and the tissues weakened.
    I stop IVF, I am damaged but the joint strength is returning and the issues stop. I absolutely believe this has been “falsely” keeping me strong all these years. I have done a lot of research now into what areas of the brain are affected in EDS patients. I suffered from cluster headaches for years but got a terrible pressure headaches on GNRH medications during IVF which were brand new. I always knew the hypothalamus was engaged during migraines but reading the above I always believed sudden hormone or fluid shifts affected the brain/my migraines. I now have been diagnosed with a Chiari 0 Malformation. Just after IVF and the inhibitor drug again I had the most horrendous pressure migraine (never get these) and was in hospital for 2 days. I see so many links to how EDS functions and hormone levels and IVF taught me some of it. My mother says her back deteriorated after having children for a multitude of reasons but I also think the body’s natural lowering of testosterone during pregnancy can be part of this plus additional pressure on the tissues. She probably had EDS but just thought she was “falling apart.”
    I used to think high testosterone was a curse due to my acne and scarring and I wish I had known I had EDS to curb all activities involving weights during IVF. I MAY not have damaged myself but I still believe I am stronger and the skin is a LITTLE less lax due to testosterone. I might have looser skin but the sebum production counteracts it but keeping it very oily and moist and more supple.
    I really really see the links…..

    Liked by 1 person

    1. Zyp Czyk Post author

      This is very interesting. I’ve been taking DHEA for decades because my levels were a little low and it gives me energy. I have the super-high sebum production as well and believe it’s from higher testosterone, but I have also retained my musculature from my athletic days before EDS put an end to such activity.

      DHEA levels tend to decline with age, and this is a precursor for both testosterone and estrogen. I figure I’ll let my body decide how much of each it wants to make, even though my testosterone might be a bit high. I’m also extremely “estrogen dominant”, but over my whole life, any amount of progesterone (even supposedly bio identical) gives me PMS symptoms within 12 hours.

      After what you’ve said, I think I’ll keep taking the DHEA.


    2. Meg

      During IVF do they give you progesterone? I was prescribed that once and instantly felt like a blob that had no body structure to hold myself together. It laxes connective tissue and well…we already have a problem with that. Anyways, if that also increased they may be another reason for the flare up of EDS.


      1. Zyp Czyk Post author

        Yes! Progesterone has that effect on me as well, which also tied my pain to a certain time in my menstrual cycle when progesterone peaks. I’ve heard about multiple people who felt exactly this kind of joint “loosening” from it.


  2. Mark

    A close friend of mine with EDS developed a varicocele. His testosterone levels have been consistently low but occasionally increase to the lower end of the normal reference range. He is having a terrible time convincing his doctors that testosterone is the culprit of his decreased energy, lack of motivation, lack of sex drive etc. It seems crazy that there is not more knowledge in general about testosterone in the medical community.


      1. Zyp Czyk Post author

        Dr. Tenant is one of the few docs willing to prescribe “whatever works” for his patients and I admire his outspoken support for our cause.

        He has explored all kinds of treatments and has unconventional ideas for pain management, several of which I’ve annotated in this blog.

        The links at the top of my posts always go to the original article.


  3. garry

    As with most medical treatments, testosterone therapy for men is not without its risks. While this treatment is considered safe in general, the common testosterone therapy contraindications for men include:

    Acne or increased oil in the skin
    Fluid retention
    Stimulation of the prostate, with associated issues, such as increased urination symptoms and or decreased flow or frequency
    Increased risk of prostate cancer
    Breast enlargement
    Increased risk of blood clots
    Worsening sleep apnea
    Decreased testicular size
    Increased aggression
    Mood swings
    Increased risk of heart attack and stroke
    Source: https://hrtguru.com/testosterone-therapy-for-men/

    Liked by 1 person

  4. hcgbestdiet.com

    HCG, or human chorionic gonadotropin, is a hormone produced by pregnant women. It’s essential for the progression of a normal pregnancy. You’re probably wondering what a pregnancy hormone could possibly have to do with a male hormone such as testosterone. The answer lies in another hormone called luteinizing hormone, or LH. LH is produced by a tiny gland in the brain that is called the pituitary gland. LH has a direct causal effect on the testicles, where most testosterone is produced. LH monitors the amount of testosterone present in the bloodstream and works to keep this amount at optimal levels. It does this by signaling special cells in the testicles to produce more testosterone whenever it’s needed.

    Liked by 1 person

  5. Cathy Straus

    Who wrote this summary of the original article? This goes much further than the original article in saying it should be treated and I would like to share this with my doctors (Pain Management, Gynecologist, PCP and endocrinologist) who refused to treat my tested low testosterone levels. However it needs to be from a professional, not an individuals “interpretation” of the article

    Liked by 1 person


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