Hormone Abnormalities in Uncontrolled Chronic Pain Patients: Use of Hormone Profiles
The emergence of hormone testing and treatment in pain management, to a great extent, has been caused by a rapid access to hormone panels or profiles. Compared to the recent past, a panel of 6 to 10 hormones now can be determined rapidly from a single tube of blood, giving the practitioner a broad-based hormone profile to improve management of pain patients. Due to this technological advance, some specialty laboratories that offer body fluid toxicology and pharmacogenetic testing to pain practitioners are beginning to add hormone panel testing to their portfolio of services.
One of the best uses of hormone profiles is for the chronic pain patient who has not responded to a standard treatment regimen and continues to have uncontrolled pain. Keep in mind that today’s standard pain control regimens are extremely effective in the vast majority of chronic pain patients, so non-responders are somewhat uncommon. A hormone profile can measure multiple hormones simultaneously. This usually will give the practitioner some clues as to why the treatment regimen is not effective and provide enough information so the clinician can take measures to help the patient adjust, or modify, their regimen to attain better pain control.
To illustrate the value of hormone profiles, I report here a case series of hormone abnormalities in a group of 61 consecutive, chronic pain patients who were referred to my clinic because they were not responding well to a standard pain control regimen, which included opioids and a variety of non-opioid pharmaceuticals. This group was tested with a 6-hormone panel and demonstrated an array of hormone abnormalities, which would be typical of what a pain practitioner might find when testing poorly controlled, chronic pain patients. A few of the abnormalities were of a most serious nature. Guidelines for interpretation and actions to take after a hormone profile is done and abnormalities are detected are included.
Benefits of Hormone Testing
There are 4 major benefits or attributes of hormone profiles (Table 1). When hormone panel testing is performed on a chronic pain patient who has poor pain control, the practitioner primarily is interested in knowing if the patient requires additional analgesia, including opioids, and/or requires hormone replacement.1-6 Low levels of any one of several different hormones may cause poor pain control.
Contents of Hormone Profile
Modern day laboratory technology makes it possible to have a large number of hormones assayed in a single blood test, and pain practitioners can design their own profiles. Table 2 outlines the basic profile I use routinely and which was used in the case series described here.
The 6 hormones included in the basic profile provide a good picture of hypothalamic, pituitary, adrenal, and gonadal functions (HPAG axis). Pregnenolone, dehydroepiandrosterone (DHEA), and progesterone are produced not only in the adrenal and gonads but also in the brain. This class of hormones is referred to as neurosteroids.9-11 Their natural brain functions are neuroprotection and neurogenesis.11 Low serum levels of pregnenolone, DHEA, and progesterone likely reflect suppression of adrenal, gonadal, and brain production. All the hormones in the panel can be replaced easily with the exception of adrenocorticotropic hormone (ACTH), which, like human growth hormone, is cost prohibitive. All the hormones in the panel can be elevated or depressed and serve as biomarkers of uncontrolled pain.
There are options that can be added to the basic panel that I routinely use. These include thyroid, estradiol, and vitamin D. Note that many pain practitioners consider vitamin D to be a hormone because it has receptors throughout the body and its chemical structure is similar to pregnenolone and progesterone.12
Physiologic Effects of Pain
The analysis and interpretation of hormone serum levels primarily is based on the effect of pain on the endocrine system.1 Uncontrolled pain is a stressor that stimulates the hypothalamus and pituitary glands to secrete trophic hormones that cause release of adrenal, thyroid, and gonadal hormones (Figure 1).13-17 For example, a chronic pain patient who is not getting enough pain relief may show elevated serum levels of ACTH from the pituitary, cortisol and pregnenolone from the adrenal, and testosterone from the gonad glands. If pain goes unabated for an extended period of time, various hormones may become depleted.1,15-17 In this case, serum levels of ACTH from the pituitary, pregnenolone from the adrenals, and progesterone from the gonads may be lowered. These 2 phases—stimulation and depletion—provide an excellent set of biomarkers to diagnose uncontrolled pain. The normalization of serum hormones, as determined by sequential profile testing, provides an excellent determinant of pain treatment success.
To interpret a hormone panel, the pain practitioner must know that opioids can suppress one or more components of the endocrine system.18-20 For reasons that are unclear, when opioids are given to male and female pain patients, they primarily and preferentially suppress gonadal-releasing hormone (GRH) in the hypothalamus.18-20 This, in turn, suppresses trophic hormones in the pituitary, resulting in gonadal suppression of testosterone and estrogen.21 Opioid therapy sometimes will cause suppression of other hormones, including DHEA, progesterone, pregnenolone, and cortisol.18,22-25 Since uncontrolled pain and opioid therapy both can suppress hormones, a low hormone serum level of testosterone and cortisol, for example, may be a combination of both pain and opioid use.
Who Should Have a Hormone Profile?
Not every chronic pain patient should go through the time and expense of obtaining a hormone profile. Only patients who have severe chronic pain will stimulate the HPAG axis enough to secrete hormones to raise serum levels. The average patient with arthritis or neuropathic pain will not have increased serum levels of hormones.4,26 However, chronic pain patients who demonstrate hormone abnormalities tend to be those who have severe, chronic painful conditions with multiple contributing factors.27,28 Pain that is constant, as seen with centralized pain, is a major factor in causing hormone abnormalities. If the pain remits or subsides on an intermittent basis, the endocrine system seems to recover.