May 2012 Letters to the Editor
Pain and Bilateral Oophectomy
Dear Dr. Tennant,
I am writing to inquire about the relationship of chronic pain with bilateral oophorectomy. My patient is a 44-year-old white female who is experiencing uncontrolled joint pain since having a hysterectomy and bilateral oophorectomy. If that is the case, what do you suggest regarding hormone replacement?
—Azza Kenawy, MD
West Chester, Pennsylvania
Dear Dr. Kenawy,
Your patient, who had a bilateral oophorectomy and later developed uncontrolled joint pain, is an example of a patient who has heretofore been a mystery. Also, astute observers have often seen women develop worse pain following menopause. I suspect you are correct when you believe that her pain is related to a lowering of some serum hormone resulting from gonadal tissue loss.
One thing is abundantly clear: some hormones are pain protective and a deficiency results in pain. I recommend
your patients have their progesterone, pregnenolone, cortisol, and testosterone levels tested. Simply order an early morning, non-fasting blood specimen at your local lab. Testing results will help target therapy.
The most likely causative hormone for her increased pain is progesterone. My first encounter with progesterone’s pain relief occurred a few years ago when I visited a nurse practitioner and her pharmacist husband near Indio, California. They were successfully treating farm workers who had arthritis, particularly of the knee, with topical progesterone.
Several animal studies document progesterone’s pain protection and neurogenic effects.1-3 In addition to peripheral targets, progesterone has receptors in the central nervous system. Soldiers with pain who have returned from Iraq and Afghanistan show low levels of the progesterone metabolite allopregnanolone.4 I just presented my preliminary investigation with the use of progesterone in patients who have severe centralized pain. These were patients who had various peripheral pain conditions and required opioids. The majority of patients reduced their pain and opioid dosages when given the progestin medroxyprogesterone, either in topical or oral form.5,6
Progesterone, besides having its own neurogenic and pain-protective effects, metabolizes to dehydroepiandrosterone (DHEA), estrogen, and testosterone. These properties make it a prime, safe choice, particularly when used topically. My progesterone therapy is simple: I use the inexpensive and widely available progestin medroxyprogesterone, which metabolizes to plain progesterone.
In topical form, I mix 20 to 30 mg in 1 oz of a cream base. Patients can use it for pain flares or on a regular basis such as before bedtime. Orally, I start with 10 mg twice per day and work up to as much as 50 mg per day. I use it in men and women. If I don’t get a response within 60 days, I stop the treatment. The only side effect I’ve seen is menstrual bleeding in premenopausal women.
Besides progesterone, it may be that your patient would respond to any one of these hormones: pregnenolone,
testosterone, DHEA, or human chorionic gonadotropin (HCG). Pregnenolone has its own pain-protective effects and receptors throughout the body. It also metabolizes to progesterone and testosterone. HCG stimulates production of progesterone, estrogen, thyroid, and testosterone.
It is my early observation that some adjunctive hormone therapies will allow us to minimize the use of drugs prone to side effects and toxicity including the opioids and neuropathic agents. Also, I believe the early use of hormones such as progesterone may prevent the centralization of peripheral pain.
If you find some hormonal success with your patient, please share your experience.
—Forest Tennant, MD, DrPH
Replacing Stimulants in Pain Treatment
Dear Dr. Tennant,
I was impressed with your article on stimulants and opioids.7 This is frowned upon by the medical community, but I must admit, it makes a lot of sense. Many of my chronic pain patients (I am a human immunodeficiency virus specialist, too) have gained a lot of weight, have sleep apnea, are developing diabetes and hypertension from being overweight, have lower testosterone from obesity, and are not able to work out.
Stimulants would help them lose weight, get rid of the apnea, hypertension, and diabetes, I presume, based on your article. Stimulants would also help with reducing the opioid dose, perhaps?
My question, besides the amphetamines (I understand that the norepinephrine hormone is key. Is that right?), are there other medications that would have a similar effect (ie, venlafaxine [Effexor], a norepinephrine reuptake inhibitor, duloxetine [Cymbalta], which hasn’t had that great a track record with my patients, milnacipran [Savella])? Do they even come close to being as effective as the stimulants? Do you have any other suggestions for these metabolic syndrome patients who basically have become that way due to the opioids and inactivity? Do testosterone shots increase the weight gain? Is there any benefit from caffeine, gingko, or thyroid hormone?
(I think these may disrupt the pituitary axis, more than help, but I’m not sure.)
You seem to have a lot of experience. I need some wisdom and knowledge.
—Robert Shankerman, MD
Chief Medical Officer
Clinica Sierra Vista
Dear Dr. Shankerman,
The simultaneous use of stimulants and opioids dates back to the 1890s when physicians at the Royal Brompton Hospital in London believed that opioids without stimulants were less effective.8 Only later did hard science support the concomitant use of stimulants and opioids when double-blind clinical trials in humans showed heightened analgesia when the two were combined. 9 Also, animal studies show that endogenous opioids and amphetamines operate independently to provide enhanced analgesia.10
You well describe why stimulants make a lot of sense. In early historical writings, there is mention that stimulants may counter the sedative effects of opioids.11 The problem with stimulants is that the ones that best potentiate analgesia and neutralize opioid side effects are abusable; they are amphetamine, dextroamphetamine, methamphetamine, and methylphenidate. In my experience, old-fashioned dextroamphetamine best minimizes opioid complications while enhancing analgesia. Given the potential abuse problem with stimulants that truly potentiate analgesia and reduce opioid complications, they can only be given to very trustworthy patients who are being monitored quite closely. Given the abuse potential of many stimulants, a number of compounds have been tried to substitute for the “real McCoy.” They usually fall short, however, in providing long-term stimulant activity.