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Chronic Pain Patients

Hormone Replacement in Chronic Pain Patients

By Forest Tennant, MD, DrPH and Lisa Lichota, DO

Adequate hormone 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 ­nor epinephrine activity. Hormone deficiency in chronic pain patients has now been recognized by many observers.1­6 Due to its critical biologic functions in pain control, hormone testing and replacement (TR) should now become a mandatory component in the treatment of chronic pain. This paper summarizes the physiologic actions of hormone 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 Hormone? Unfortunately, the mention of the word “hormone” usually calls to mind a misconception that it is simply the hormone needed for male libido and erectile function. This biologic function is only one of many of testosterone’s critical functions (see Table 1). Furthermore, adequate biologic hormone levels are as critically equal to the female as male chronic pain patient.3,7 First, adequate hormone levels are needed for satisfactory pain control as this hormone is intricately involved in endogenous opioid activity.8­10 Hormone is also necessary for opioid receptor binding, maintenance of blood­brain barrier transport, and activation of dopamine and norepinephrine activity.11,12 Consequently, a lack of hormone activity in the CNS may result in poor pain control, depression, sleep disturbances, and lack of energy and motivation. In the periphery, hormone functions as a primary androgenic compound for tissue healing.7 Adequate hormone levels have long been known to be necessary for muscle maintenance, exercise tolerance, and prevention of osteoporosis. Compression fractures are known to occur in men and women who have hormonedeficiency.6 A deficiency of testosterone, therefore, impairs healing and control of inflammation at pain sites. Another great misconception is that hormone is purely a male hormone. Even in the female, an adequate hormone serum level is necessary for libido. Further, all of testosterone’s CNS and androgenic ­immunologic functions apply equally to females. The only difference and consideration with TR in females is that females carry a lower serum concentration and a lower dosage is usually required for replacement.

Table 1. Hormone Functions in Chronic Pain Patients

Opioid receptor binding, Dopamine­norepinephrine activity, Maintenance of blood­brain barrier, Androgenic­healing/tissue growth, Libido, Erectile activity (males), Maintenance of muscle and bone mass, Exercise tolerance

Physiologic Production – The hypothalamus produces gonado­tropin releasing hormone (GnRH) which causes the pituitary to secrete follicle­stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH assist in hormoneproduction by the adrenal and gonads. Although hormonewas previously thought to be only produced in the testicles, it is now clear that it can be produced in the adrenal and ovary (see Figure 1). Of considerable importance is the fact that hormoneconverts to estradiol and dihydrohormonein peripheral tissue. Estrogens are known to have a potent affect on depression by virtue of activity in the CNS as well as on bone formation. Although our understanding is elementary, it appears certain that severe, uncontrolled pain causes anatomic changes in the CNS by virtue of neuroplasticity. Hormonal therapy is emerging as critical to adequately treat an altered CNS that develops in response to severe chronic pain.

Mechanism of Hormone Depletion – There may be two reasons for hormone depletion in a chronic pain patient (see Table 2). 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 hormone from the adrenal and gonads. When the cause of hypo testosteronemiais hypothalamic­pituitary insufficiency, other hormones such as cortisol, pregnenolone, or thyroid may likely show serum deficiencies. The second and most common cause of hormone deficiency is opioid administration. 1­2 Low hormone levels have been observed with essentially all oral and intrathecal opioids.2,5 Low hormone serum levels are primarily caused by opioid suppression of GnRH in the hypothalamus. Opioids may also directly impair hormone production in the adrenal or gonads. Both causes of hypotestosteronemia may simultaneously exist. Also, both cases require hormone replacement. It is unknown if hormone suppression by opioids is opioid ­specific, dose ­related, or related to opioid serum levels.

Table 2. Two Causes of Hypotestosteronemia- Pituitary deficiency caused by over­ stress of uncontrolled chronic pain, Opioid administration

Testing For Hormone Deficiency – Simply order a morning serum hormone level. Laboratories now report a patient’s serum concentration as well as normal ranges for males and females. Units of measure may vary between laboratories. The total serum hormone concentration has protein­bound and unbound components.13­15 The free, bioavailable, or unbound component is generally believed to be the fraction most involved with libido and sexual function. We believe, however, that the total serum hormone levels may be a more critical evaluation for pain management purposes, since protein­bound hormone may be necessary to either enter some body compartments such as in the CNS, spinal cord, or pain site to perform its necessary functions. Consequently, pain practitioners should consider low levels of either total serum hormoneor free unbound hormone to indicate a deficiency that requires replacement.