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10 Articles in Volume 10, Issue #1
An Overview of CRPS
Balancing Evidence, Efficacy and Stakeholder Values in Practical Pain Care
Biopsychosocial Approach to Management of Total Joint Arthroplasty Patients
Dextrose Prolotherapy Injections for Chronic Ankle Pain
Genetic Influences on Pain Perception and Treatment
Headache in Children and Adolescents
Hormone Replacements and Treatments in Chronic Pain: Update 2010
Opioid Treatment 10-year Longevity Survey Final Report
Therapeutic Laser in the Treatment of Herpes Zoster
Use and Effectiveness of Spinal Cord Stimulation

Hormone Replacements and Treatments in Chronic Pain: Update 2010

When severe pain and stimulation of the pituitary-adrenal-gonadal axis goes unabated for a considerable time period, exhaustion of some adrenal compounds may develop and, left untreated, may pose a combination of a serious, life-threatening condition, a vegetative state with incapacitation, mental disturbance, and a house- or bed-bound state.
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The Problem of Opioid Supression of Hormones

When pain is severe enough to require regular treatment with opioids, the practitioner must be aware that opioids may suppress one or more hormones of the axis.3,6,11,27 The understanding of opioid suppression is poorly understood at this time, but it is clear that hormone suppression is a major opioid complication.

First, opioid suppression may apparently occur at one of these sites: (1) pituitary; (2) adrenals; (3) ovary or testicle. There is no convincing evidence at this time that opioids cause suppression of any biologic pathways in the thyroid, pancreas, parathyroid, or pineal glands. Although somewhat uncertain, opioids are probably more likely to suppress some hormones if the opioid is constantly in the blood of a patient for several continuous days. It is unknown if some opioids produce more hormone suppression than others, and it is unknown if short-acting opioids are more or less likely than long-acting opioids to produce suppression.

What is known is that the major hormone suppressed by opioids is testosterone in males and females. Most of the suppression is due to suppression of follicle stimulation hormone (FSH) in the posterior pituitary. For example, intrathecal opioids don’t enter the general blood circulation to reach the adrenals or gonads, but they suppress testosterone production via the pituitary route.27

It is known that opioids may, in a few select patients, suppress ACTH or directly impact the adrenals.3,11 In these cases, it may be necessary to replace preg-nenolone, cortisol, and possibly other compounds. Other than testosterone, however, there is little data published on opioid hormone suppression. One common suppression may be aldosterone in the adrenal.3 This is apparently the cause of opioid edema. It can usually be relieved by a corticoid injection that probably converts to aldosterone (see Figure 2), which is the adrenal compound involved in fluid retention

Treatment With Hormonal Compounds

Replacement and restoration of hormonal homeostasis must become a cornerstone of modern day pain management. Pain practitioners routinely observe patient in treatment who progressively deteriorate. Common deterioration conditions include severe dental erosion, spine degeneration, decrease in mental function, and joint degeneration. Hormonal homeostasis with natural hormone replacement or synthetic analogues may hopefully prevent the progressive deterioration observed in chronic pain patients. Indeed, there is nothing more new and exciting in pain management than treatment with hor-monal compounds. While some of the current hormonal compounds may not prove to have long-term staying power in practical pain management, some hormones or their analogues are now being used by pain practitioners and are summarized in Table 6.

Human growth hormone (HGH) and human chorionic gonadotropin (HCG) are birthing a number of very positive reports. Both of these compounds are produced in the pituitary of males and females.28,29 Both are anabolic and grow tissue. HCG activates a number of adrenal-gonadal compounds such as estrogen, progesterone, and testosterone, and so it helps prevent opioid suppression of hormones in the adrenal and gonads.12 Besides activating hormones, HCG causes tissue growth by increasing blood flow and activating cyclic adenosinemonophosphate (CAMP). HGH is well known to cause tissue growth and has recently had great success in treating fibromyalgia.13-15 Its only drawback is cost that is too expensive for practical clinical use in all but a few settings. In contrast, the cost of HCG is a fraction of HGH, and so it is within reach for most patients. Some intermediaries in the steroidogenesic pathway (see Figure 2) may have great merit. Included here are progesterone, androstenedione, and dehydroepiandrosterone (DHEA).24-26

The author has received several positive reports on the use of progesterone used topically over pain sites. In some cases, it is being used under ultrasound or infrared light to achieve deep penetration into pain sites. Other hormones may also be beneficial when used topically over pain sites. Oxandrolone is an oral anabolic steroid classified under the Uniform Controlled Substances as a Schedule III Drug. Its package insert lists its indication for osteoporosis, which is a most common complication in severe, chronic pain patients who have hormonal disturbances.

To date, I have found good use for all the hormonal compounds listed in Table 6. I highly encourage practitioners to try these compounds and share the results. Chronic pain patients eagerly like to try hormone treatments because they are aware that this approach likely offers them their best hope for a permanent reduction in pain and possibly even cure.


Severe pain, acute and chronic, is a potent stressor that stimulates the pituitary-adrenal-gonadal axis to release and raise serum levels of catecholamines (adrenalin) and glucocorticoids (cortisol, preg-nenolone). If severe pain and stimulation of the axis goes unabated for a considerable time period, exhaustion of some adrenal compounds may develop which results in low serum levels of cortisol and pregnenolone. Very low cortisol levels below 2ug/dl may pose a serious, life-threatening condition. Chronic hormonal disturbances may cause a vegetative state with incapacitation, mental disturbance and a house– or bed–bound state. Severe chronic pain patients who require daily analgesic medication and demonstrate poor function should be screened with a baseline, early morning, fasting cortisol, pregnenolone and testosterone. Not only will this screen provide a diagnosis of adrenal overstimulation or exhaustion, the testosterone level can serve as a baseline or diagnosis of gonadal suppression and an indication for testosterone replacement. Pain patients on opioids maintenance will have to be periodically screened for testosterone deficiency. At present, there is a great deal of clinical investigation into replacement and treatment using a variety of hormones or their analogues. Some topical hormones applied over pain sites appear promising. In summary, hormone replacement and treatment is taking pain management to an exciting, new level of care.


Last updated on: February 25, 2011