Access to the PPM Journal and newsletters is FREE for clinicians.
11 Articles in Volume 13, Issue #8
Ask the Expert: Intranasal Ketamine for Migraine Therapy
Assessment and Treatment of Neuropathic Pain
Diabetes & PAD: Diagnosis, Prevention, and Treatment Paradigms
Editor's Memo: Chronic Low Back Pain: Bringing Back A Forgotten Treatment
Evaluation and Treatment of Chemo- or Radiation-Induced Painful Complications
Guide to Implantable Devices for Intrathecal Therapy
Is Buprenorphine a ‘Partial Agonist’? Preclinical and Clinical Evidence
Letters to the Editor: Hormones and Genetic Testing
Pain Management in Kenya: A Team Experience
PROP versus PROMPT: FDA Speaks
Use of Ultrasound in Detection Of Rotator Cuff Tears

Letters to the Editor: Hormones and Genetic Testing

September 2013

Hormone Levels Addressed, But No Decrease in Opioids

I have been amazed at how many patients in my pain management practice have low levels of pregnenolone when measured. Constitutional symptoms including fatigue, insomnia, lowered libido, and depression improve significantly with supplementation. However, although quality of life is improved, I have not seen the decrease in opioid requirements that I expected.

I have a few questions about the management of these patients. What is the optimal interval for injections? When during that interval is the most appropriate time to retest serum pregnenolone, or is there another way to objectively gauge
adequate dosing?

Charles Walker, MD

Dear Dr. Walker,

Your observations with pregnenolone pretty well parallel mine. The high prevalence of severe chronic pain patients who show low serum levels is rather astounding. This is of particular concern since we now know that pregnenolone is not only the precursor of all adrenal and gonadal hormones but is a neurosteroid produced in the brain.1-3

I too have been somewhat disappointed in that it dramatically improves constitutional symptoms but doesn’t lower opioid dosages very much, if at all. I have had opioid-maintained patients who developed apparent opioid hyperalgesia and/or non-responsiveness to their opioid regimen. Their pregnenolone serum levels were below normal, and when pregnenolone was replaced, opioid responsiveness returned to normal.

Despite little ability to reduce opioid dosages in existing patients, pregnenolone replacement in patients with low serum levels may really, as you well point out, improve their quality of life. I’m just now evaluating pregnenolone dosage and effectiveness after 1 year of therapy, so I’ll keep you posted.

Forest Tennant, MD, DrPH


HCG for Pain

Recently, I read your article in Practical Pain Management regarding the use of human chorionic gonadotropin (hCG) in pain treatment. Are you aware of any additional studies or reports regarding the use of hCG in chronic pain?

In the article you mention a dosing regimen of 500-1,000 units 1-3 times per week. Typically, how long a period of treatment is recommended before determining if the hCG is effective? Also, is there any evidence that hCG is effective for pain if given sublingually as a liquid or a tablet?

Anthony T. March, DO

Dear Dr. March,

I have used hCG on two types of patients: centralized pain patients who have "gone as far" as possible with a standard regimen of antidepressant, neuropathic, stimulant, and opioid agents; and patients not on opioids, but who have mild to moderate arthritis or muscular pains.

Due to cost and the obvious objections of patients to injections, I now primarily use a sublingual preparations of hCG (250 units/mL). The usual starting dose is 125 units/mL bid. My maximal dose is 750 units/mL per day. Compounding pharmacists can now make the preparations.

I have just finished a periodic update on 26 patients with intractable pain who were originally on standard therapy as described above. They have been on hCG for 1 to 6 years. All claim hCG provides energy and endurance. Subgroups report increases in intellectual function, sleep, and libido. All reported decreases in opioid use ranging from 30% to 100%. Two patients have stopped opioids. Some type of pain relief is reported by all patients including some pain-free hours, lengthening of time between flares, or reduction of baseline pain.

At this juncture I view hCG as an aid worth trying when your menu of options for a pain patient grows slim. As a closing thought, the basic science studies of hCG involving neurogenesis and hormonal stimulation are compelling.4,5 One has to look beyond its controversial roles in weight loss and athletic performance to objectively evaluate hCG.

Forest Tennant, MD, DrPH


Denial of Testosterone Replacement

I have a dilemma: my patient has low testosterone from opioid use, but the Workers Compensation utilization review physician is denying his claim for treatment. Do you have any articles to reference that may work?

Timothy Hooper, MD

Dear Dr. Hooper,

Patients who take long-acting or intrathecal opioids almost always have some hormone suppression including testosterone. Periodic serum hormone screening at least twice a year is necessary when opioids have to be used. The screen should consist of testosterone, pregnenolone, cortisol, dehydroepiandrosterone (DHEA), and progesterone as these hormones can now be screened on a single blood draw. Here are some of my tips and experiences, since I, like you, am having difficulty getting commercial testosterone preparations covered:

The injectable form of testosterone is usually the cheapest, but I hate to use it since it alternatively overshoots and undershoots the normal serum range.

I have my local compounding pharmacists make a 50-gram jar of 10% testosterone. It costs about $50 for a month’s supply. The problem is that it won’t hold a 24-hour blood level like the commercial preparations. It needs twice a day application.

Tell the insurance carrier and patient that testosterone is a cofactor in pain relief, and the patient may have to take more opioids and engage in other costly measures if he can’t obtain testosterone replacement.1,6-10

Another option that I use when I can’t get commercial testosterone is hCG 125-250 units/mL; sublingual each day. I supplement hCG with DHEA, 100-200 mg/d.

Here are some additional tips regarding testosterone. I use the hormone combination described above in women. If the serum testosterone doesn’t come up to normal, I will use a commercial or compounded testosterone preparation starting at ¼ the male dosage. I recommend that serum testosterone levels be followed in patients who take a testosterone preparation. It’s my belief that cancer and benign prostatic hyperplasia (BPH) risk occurs when serum testosterone, over time, is too high or too low. Without testosterone some patients don’t achieve decent pain control or quality of life, so the benefits outweigh the risks. The practitioner can easily replace any hormones found to be deficient.

Forest Tennant, MD, DrPH


Genetic Testing Denials

We have been getting denials for saliva genetic testing from certain health insurance companies, especially MCOs, stating that the technology is still in its infancy and not accurate. How do you deal with these insurance coverage determinations and what, if any, strong literature is out there that would help us to deal with these denials?

Roland F. Chalifoux, Jr., DO

Dear Dr. Chalifoux,

Admittedly, genetic testing of cytochrome (CYP) 450 is relatively new and its value is poorly understood. Some commercial laboratories have tried to promote it as testing that should be done on every pain patient, and that it will tell you which antidepressant, benzodiazepine, and opioid you should prescribe. This concept is overstated.

The proper use of CYP 450 testing in pain patients is to primarily help find an effective opioid in a patient who isn’t responding to the standard low-dose regimens in use today. For example, physicians usually start an opioid regimen with low dosages of tramadol, buprenorphine, or an acetaminophen- or ibuprofen-hydrocodone or oxycodone combination. If this standard regimen isn’t working, a CYP 450 test may be warranted.

The other use, and the one that I personally utilize, is the patient who is referred and is taking a multitude of opioids, antidepressants, benzodiazepines, and neuropathic agents but isn’t responding well. For example, a patient referred to my clinical takes an average of 8 to 11 pharmaceutical agents. These are patients who physicians have attempted, over time, to find an effective treatment regimen to no avail.

In summary, CYP 450 testing is for those patients who aren’t responding to a standard treatment regimen. When you submit a claim, you must explain that the reason for the test is "Non-Responsive to Standard Therapy."

Also, patients with multiple CYP 450 defects may not respond to any oral opioid because normal CYP metabolism of the drug is necessary for gastrointestinal absorption and possibly passage across the blood brain barrier. For example, if you find that a patient has 2 or 3 defects in CYP 450 2D6, 2C9, 3A4, or 2C19, you can predict that oral opioids may not be very effective, and you may have to go to an alternate administration route such as sublingual, topical, injection, or intrathecal. You also can list as a reason to an insurance company "Determination of Route of Administration."

I list some references, which may hopefully assist.11-14

Forest Tennant, MD, DrPH
Last updated on: October 28, 2014
close X