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13 Articles in Volume 11, Issue #4
Diagnosing and Managing Hand Osteoarthritis
Difficult Migraine Patient
Electromagnetic Applications In Biology and Medicine
Excerpt from the Book Avoiding Opioid Abuse While Managing Pain
Hormone Therapies: Newest Advance in Pain Care
Make the Family Your Best Friend
Medications for Chronic Pain—Opioid Analgesics
Nonpharmacologic Remedies for Back Pain During Pregnancy
Reconsidering and Revising Evidence-Based Practice in Pain Medicine: Steps Toward Sustaining the Profession?
The Value of Blood Analysis for Compliance Monitoring
Treatment of Neuropathic Pain: The Role of Unique Opioid Agents
Understanding Potential Complications Of Epidural Steroid Injections
Unmasking Post-traumatic Headache

Hormone Therapies: Newest Advance in Pain Care

Severe, uncontrolled pain may exhaust the adrenal gland, resulting in low levels of pregnenolone and cortisol. While adequate pain control will usually normalize serum hormone levels, opioid-induced suppression of the system may require additional treatment.
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A 30-year-old man had Lyme-induced arthritis and fibromyalgia. His opioid treatment consisted of transdermal fentanyl with oxycodone, and hydromorphone for breakthrough pain. He complained of impotence, insomnia, lethargy, and poor pain control. Serum testing revealed a low testosterone concentration of 59 ng/dL. His FSH and LH were below normal, but his serum cortisol, ACTH, and TSH were normal.

Pregnenolone Deficiency

Pregnenolone is not a well-known hormone, but it is critical for adequate pain control and many mental functions.21-25 Patients with pregnenolone deficiency tend to complain of anxiety, poor mental concentration, and inadequate pain control, probably related to pregnenolone’s effects on GABA and NMDA receptors.24,25 Replacement dosage is extremely variable and ranges from 50 to 800 mg per day.


This hormone is the newest to find its way into pain treatment. General knowledge suggests that progesterone is a female hormone that helps to regulate the menstrual cycle and maintain pregnancy. We now know that progesterone has critical anabolic and immunologic functions in women and men. Progesterone levels may decrease in chronic pain. A recent study of US soldiers in Iraq showed that a metabolite of progesterone, allopregnanolone, was lowered in soldiers with pain.26 This study suggests that progesterone is required for pain control and that supplementation with progesterone may be beneficial. To this end, the author has begun trials with low-dose oral and topical progesterone, as the agent is rapidly absorbed through the skin. Early results are highly encouraging. A glance at Figure 1 shows that progesterone is a precursor of cortisol, estrogen, and testosterone. Few side effects have been reported with progesterone.

The following case illustrates that progesterone administration requires further investigation.

A 52-year-old man sustained a back injury 24 years prior that required multiple surgeries, vertebral fusion, and implanted metal rods. In his twenty-second year on opioids, he was maintained on 100 mcg daily of transdermal fentanyl, 9,600 mcg daily of transmucosal fentanyl, and 60 mg daily of oxycodone. He had a testosterone deficiency of 154 ng/dL, and was taking a systemic testosterone replacement. He was given a topical soluble cream preparation of medroxyprogesterone 10 mg per ounce to apply over his pain site. He received good relief with topical progesterone, so he was prescribed oral medroxyprogesterone at 10 mg twice daily. Within 1 month, he reported a dramatic reduction in pain and reduction in his opioid dosage by 50% and halted his systemic testosterone replacement, claiming that medroxyprogesterone gave him more libido and ability to engage in sexual activity than testosterone. He has maintained his reduced pain, lower opioid dosage, and increased libido for 6 months.

Human Chorionic Gonadotropin

The author first became aware of the potential pain-reducing effect of HCG when a weight reduction clinic noted that its obese patients with fibromyalgia and osteoarthritis had reduced pain when HCG was prescribed for weight loss. The dosage of HCG used was about 10 to 30 units 1 to 3 times per week. Personal interviews with some of these patients convinced the author that HCG should be investigated as a possible adjunct for pain treatment.

HCG is a poorly understood hormone. It isn’t just a compound secreted in pregnant women to maintain placenta and produce a positive pregnancy test. It is constantly secreted by the pituitary in women and men, as it has major hormone stimulation and androgenic effects.28,29 The HCG molecule is composed of two amino acid subunits. One is identical to FSH, LH, and TSH. The other is an androgenic unit that activates cyclic adenosine monophosphate (c-AMP) and produces nitric oxide, which is known to increase blood flow.

The hormone-stimulating component accounts for its labeled indication for hypogonadism. The adrogenic component accounts for its use in athletes and bodybuilders, who apparently take it to build bigger blood vessels on their upper torso. Athletes who episodically use (cycle) anabolic steroids like to use HCG when they stop steroids and want to revive their own testosterone and libido.

To date, the author and colleagues have given HCG to about 30 patients with intractable pain who are maintained on opioids. One group of 8 has taken it for more than a year. The others have used it in various dosages for various lengths of time. Our dosages have been 500 to 1,000 units subcutaneously or 250 to 500 units as a sublingual liquid, 1 to 3 times per week. The only side effect has been acne in one woman.

To date, clinical results reflect, we believe, HCG’s two base mechanisms: gonadal and thyroid stimulation; and anabolic regeneration. Almost all patients report, as with testosterone and progesterone, increased energy, pain control, and libido. Almost all patients have reduced opioid dosages and improved sleep.

Can HCG and Other Hormones Produce Neuronal Regeneration?

Our early experience with HCG, pregnenolone, progesterone, and testosterone suggests that these hormones may directly or indirectly produce regeneration of neural tissue. The anecdotal clinical evidence is less pain, lowered opioid dosages, less insomnia, and elevated libido. Studies of the past two decades clearly show that severe pain may cause reorganization (neuroplasticity) of neurons and glial cells as well as loss of brain tissue. Intermittent, excess cortisol in the blood is a known cause of central brain tissue loss.20,27 We clinically need to find hormones to ameliorate the neural changes that pain may cause. HCG appears to be a relatively harmless and inexpensive approach that can be easily adopted by any pain practitioner. Other hormones, such as pregnenolone, progesterone, or testosterone, may prove to be better agents or agents that can be simultaneously administered with HCG.


Pain is a stressor, just as fright, shock, trauma, and surgery are. When pain begins, the pituitary and adrenal glands attempt to provide a healing, immune response by secreting extra cortisol, pregnenolone, adrenalin, and other hormones into the general blood circulation. If severe pain goes uncontrolled, the adrenal glands may become exhausted, resulting in low serum levels of pregnenolone and cortisol. Although adequate pain control will usually normalize or balance serum hormone levels, supplementation may have to be given. Daily opioid administration frequently causes suppression of testosterone and pregnenolone, which can simply and easily be replaced. Some adrenal and gonadal hormones are secreted into the bloodstream and travel to the brain and spinal cord, where they have profound effects on pain control, mood, sleep, and mental capacity. The term “neurosteroid” is frequently applied to these compounds, which include pregnenolone, estrogen, progesterone, and testosterone. If any of these hormones is deficient, pain control is impaired, and the patient will complain of such symptoms as insomnia, ineffective medication, depression, fatigue, allodynia, and hyperalgesia.

Last updated on: September 6, 2011