Progesterone Shows Promise for Central Intractable Pain

PALM SPRINGS, CA — In a small pilot study of patients with central intractable pain reported at the 2012 American Academy of Pain Medicine Annual Meeting, progesterone was shown to have regenerative or ameliorative effects.

Forest S. Tennant, MD, DrPH, of Veract Intractable Pain Clinic, West Covina, CA, studied 34 patients (23 women, 13 men) between the ages of 29–69 years with high levels of pain. These subjects were noted to have low serum levels of allopregnanolone, the metabolite of progesterone. Animal studies have shown that progesterone has a regenerative effect on neural tissue.1,2 To determine if progesterone has a similar effect in humans, Dr. Tennant evaluated the efficacy of administration of oral or topical medroxyprogesterone to patients with presumed central, intractable pain who had been maintained on opioids ranging from three to twenty-five years.

Prior to the study, patients had constant pain for at least three years, a history of periodic allodynia and hyperalgesia, had failed multiple peripheral-pain treatments, demonstrated excess sympathetic discharge signs (e.g., tachycardia, hypertension, diaphoresis, mydriasis, vasoconstriction, hyperreflexia), and insomnia. All patients also were on ≥1 concomitant medications: bedtime sedative, neuropathic agent, stimulant, anti-inflammatory agent, antidepressant, or anxiolytic.

The patients were given medroxyprogesterone 10mg orally twice a day or 20mg/1mL topically ≥1 time a day. Patients receiving oral medroxyprogesterone could be titrated to 40mg/day if needed. If there was no response to medroxyprogesterone after 60 days, the therapy was discontinued.

After two months, 65% of patients reported that they felt better and wished to continue medroxyprogesterone. Patients reported feeling less pain and suffering or more happiness (71%); increased energy and more involvement in social activities (64%); improved memory, concentration, or reading ability (50%); less depression (43%), reduced need for polypharmacy (33%), and improved sleep or libido (21%).

Given the results of this small study suggesting that progesterone may have a regenerative or ameliorative effect on central, intractable pain, Dr. Tennant feels that further clinical trials are warranted. He states that “medroxyprogesterone was selected as a convenient, commercial preparation, but there may be more optimal progesterone agents or administration systems than those employed here.”

1. Roglio, et al. Neuroprotective effects of dihydroprogesterone and progesterone in an experimental model of nerve crush injury. Neuroscience. 2008;26:673-685.

2. Coronel MF, et al. Progesterone prevents allodynia after experimental spinal cord injury. J Pain. 2011;12:71-83.