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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 severe chronic pain patient who has axis exhaustion and abnormal serum levels of hormones will likely be in a vegetative state. It is highly recommended that pain practitioners recognize the hormone-induced vegetative state (see Table 2). If hormone exhaustion is severe, the patient will likely be bed– or house–bound. They will appear apathetic, depressed, and have difficulty providing a coherent history or performing normal daily tasks of living such as eating, working, or sleeping. They often sit with a straight-ahead stare and may falsely appear unmotivated or uncooperative. In fact, their overall mentation is grossly disturbed. They may move slowly and demonstrate facial creasing and muscle wasting. Adrenal exhaustion in a severe chronic pain patient must be considered a serious, life-threatening condition.

Figure 1. Overstimulation of the pituitary-adrenal axis followed by adrenal exhaustion. Figure 1. The steroidogenic pathway is the major metabolic pathway in the adrenals and gonads; it is incorrect to state some hormones are “male” or “female.” Adapted from Kronenberg M et al. (eds). Williams Textbook of Endocrinology, 11th Edition. Saunders. 2007.

Table 3. Candidates For Hormone Screening
  • Patient with chronic, persistent, or intractable pain who requires daily analgesic medication
  • Patients who require opioids for treatment
  • Patients who demonstrate tachycardia, hypertension, or vegetative symptoms
  • Patients who complain their current pain-control regimen is ineffective
  • Patient with musculoskeletal pain at a distance from the primary pain site
  • Patients who demonstrate marked dental erosion or osteoporosis

Blood Screening for Hormone Deficiencies

Not every pain patient needs to be tested for hormone deficiencies. Only those that have severe chronic, persistent, or intractable pain and require regular analgesic medications are candidates for hormone screening. Table 3 lists candidates for hormonal screening. I recommend a simple, short screening panel: cortisol, pregnenolone and testosterone (summarized in Table 4). This screening panel can be done by any licensed clinical laboratory on an 8:00 am, fasting, whole blood specimen. These three serum hormone levels will give a pain practitioner enough information to know if severe overstimulation or exhaustion is present.

Additional endocrine testing can be done if this screen shows an abnormality. Also, pain practitioners may wish to obtain an endocrine consult. I recommend a total serum testosterone rather than any free or sub-total test. Testosterone is critical for pain control, libido, and proper mental function.17,18 Although some of testosterone’s functions (e.g., libido) may rely on the non-protein bound serum fraction, testosterone has other functions critical to pain management that may require the protein-bound component.17,18

Management of Serum Cortisol Levels

Some severe chronic pain patients may demonstrate serum cortisol levels that range 2 to 3 times above the upper normal level (about 20-25 ug/dl).8 If the patient is in the exhaustion phase, serum cortisol levels will be under 5ug/dl. The key to normalizing high or low serum cortisol levels is aggressive opioid management. Opioid dosage should be raised from any current daily dosage or initiated if the patient is not taking opioids. Normalization of serum cortisol will almost always take place within 4 to 6 weeks.8

Cortisol replacement is rarely necessary. I recommend plain hydrocortisone or prednisone administration for 1 to 2 weeks if the serum cortisol is below 2 ug/dl. This is a precautionary measure done as a potential life-saving procedure as serum cortisol levels this low pose grave danger to the patient.

Management of Serum Pregnenolone Levels

Few physicians are even aware of pregnenolone and its biologic roles. First, pregnenolone is the primary precursor in the steroidogenic pathway (see Figure 2). A low serum pregnenolone represents a potential, problematic situation in that there may not be enough substrate for the major metabolic pathway in the adrenals and gonads.

Pregnenolone is, itself, a critical hormone.19-21 It is probably the most plentiful hormone in the human brain. Normal levels are necessary for gamma amino butyric acid (GABA) neurotransmission and helps stabilize the NMDA receptor.22,23 If serum concentrations are below 20ng/dl, I recommend a daily supplement dosage of 100 to 200mg a day. At this time, pregnenolone, due to its high safety and non-abuse profile, is available without prescription in health food stores.

Serum pregnenolone may drop to subnormal levels when patients are maintained on opioids. In these cases, patients complain that their medication is “no longer working.” Opioids may suppress pregnenolone production and require replacement as is the case with testosterone.

Table 4. Recommended Basic Screening Hormone Panel
  • Cortisol
  • Pregnenolone
  • Testosterone-total
Done at 8:00 am and with a fasting blood specimen.
Table 5. Some Symptoms Of Testosterone Deficiency
  • Lack of energy
  • Loss of libido
  • Depression
  • Poor healing
  • Diminished opioid affects
  • Loss of motivation
  • Apathy
Table 6. Hormonal Compounds Which Are Clinically Used And Indicate Potential Promise
  • Human chorionic gonadotropin (HCG)
  • Human growth hormone (HGH)
  • Progesterone
  • Androstenedione
  • Dihydroepiandrostenedione (DHEA)
  • Oxandrolone
The hormonal compounds listed in this table are being clinically used by practitioners throughout the Country. Reports are anecdotal but promising. All are anabolic compounds which promote tissue development. Some are being used topically over pain sites.

Management of Low Serum Testosterone

Commercial laboratories now report normal levels for males and females making it easy for the practitioner to make a diagnosis of “low serum testosterone.” Patients with low serum testosterone usually present with a number of symptoms that are outlined in Table 5.

If the serum testosterone is low, several testosterone products are available including injectable, patch, buccal tablet, and gel formulations. I recommend a female starting dose of about 20 to 25% of the male dose.10 In addition to plain testosterone, the use of human chorionic gonadotropin (HCG), androstenedione, or dehydroepiandrosterone (DHEA) may assist or enhance testosterone activity.24-26

Last updated on: February 25, 2011
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