Testosterone, women, and fibromyalgia? Could a male hormone  -or the lack of it – be causing trouble in FM? The primary male sex hormone, testosterone promotes the growth of the male sex organs and helps produce the increased muscle, bone mass, body hair, and deeper voices seen in men.

Could a male sex hormone play a role in fibromyalgia?

Testosterone may be responsible for many features associated with males but it’s also secreted in small amounts by the adrenal glands and the ovaries in females.  While males produce and use about 20’s the testosterone that females do, females are actually more sensitive to the hormone.  Women receive a spike in testosterone – not estrogen, but testosterone – endorphin and oxytocin levels, after intercourse.

The researchers of these two papers assert FM is an inflammatory nervous system disorder – and they believe testosterone plays a role in that inflammation.

A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients. Hillary D.White, Thomas D. Robinson. International Immunopharmacology xxx (2015) xxx–xxx

Treatment of pain in fibromyalgia patients with testosterone gel: Pharmacokinetics and clinical response. Hillary D. White, Lin A.J. Brown, Robert J. Gyurik, Paul D.Manganiello, Thomas D. Robinson, Linda S. Hallock, Lionel D. Lewis, Kiang-Teck J. Yeo.  International Immunopharmacology xxx (2015) xxx–xxx

The authors propose several mechanisms by which low testosterone might affect pain sensitization in fibromyalgia. They note that stressful situations usually reduce pain sensitization but that the opposite tends to occur in ME/CFS and FM.

A factor called substance P in the spinal cord usually, during stress, stimulates an enzyme (aromatase) that converts testosterone to estradiol. Estradiol then upregulates endogenous opioid production which in turn increases our tolerance of pain. The authors propose that low testosterone levels in FM and associated disorders prevent this from happening fully. They reported that several studies indicate that low testosterone levels are present in FM

In fact, they suggest that this inhibition of that inhibitory pain response allows the pain sensitization process to ramp up higher and higher: the outcome – instead of pain going down during stress it increases.

A lack of “inhibition” may spell increased pain in fibromyalgia

Faulty pain inhibition is increasingly being seen as a critical factor in FM. It seems that failed inhibitory processes are present across several systems in FM and ME/CFS.  The vagus nerve may not be toning down the sympathetic nervous system.  Microglial inhibiting factors may not be kicking in to stop them from over-activating. Activating under performing inhibitory processes may end up being key for treating these disorders.

The Multiple Sclerosis Connection

Fibromyalgia is not the only “women’s disorder” testosterone levels are being examined in.  Testosterone’s effects in multiple sclerosis are getting significant study. A recent review of hormonal related changes in MS asserted that there is “compelling evidence that estrogen, progesterone, and testosterone control MS pathology by influencing immune responses and by contributing to repair mechanisms in the nervous system”.

A recent study suggested lower testosterone levels in men with multiple sclerosis are associated with greater disability.  Another found a high association between reduced testicular functioning and the onset of MS in men.

Some similar findings have been found in women. Women with MS tend to have lower testosterone levels, and increased lesions were associated with reduced testosterone levels in one study.

Testosterone may have reparative factors.

Testosterone may be more than protective; it may even have reparative factors. Testosterone  treatment repaired damaged myelin in both male and female mice in an MS mouse model (autoimmune encephalomyelitis). The study suggested an androgen receptor on the nerves plays a critical role in myelin repair.

A very small clinical trial suggested testosterone supplementation might be able to increase white matter volume in the brains of men with MS.  If that finding is validated in larger studies, testosterone might be the first substance found that can reverse some of nervous system damage found in MS.

The Study

The authors tested out their hypothesis in a small, non-placebo controlled (12 person) pilot study that examined efficacy and safety of a transdermal testosterone gel a company they are associated with manufactures. (They propose this gel provides more effective release across time than other gels). All the participants were white females between the age of 40 and 55.

The gel was applied to the abdomen once a day. The amount of testosterone provided was modulated to produce just above normal blood testosterone levels. Hormone levels were monitored in  ten blood draws the first day and ten draws on the last day of the month-long study.

A questionnaire based on the Fibromyalgia Impact Questionnaire (FIQ) measured muscle pain, stiffness, fatigue upon awakening, tiredness, libido, depression and anxiety. Visual analogue pain scale and tender points rounded out the symptom testing portion of the trial.

Testosterone concentrations were determined by an immunoassay able to detect the lower testosterone levels in women.

Results

The test revealed the blood testosterone levels of the women entering the study  were in the lower half of the normal reference range for their ages.  Using the gel normalized and slightly increased their testosterone levels to just above the reference range.

A third of the women reported a 50% or greater decrease in pain. Forty-two percent were reported to have a 33% or greater decrease in pain.  Tender point sensitivity was significantly reduced. Libido was significantly increased. The treatment had no effect on headache severity, sleep, anxiety or depression.

The very small size of the trial and the lack of placebo controls undermined the ability to assess the effectiveness of the gel. The trend, however, was in the right direction.

Treatment

Testosterone treatment is somewhat controversial. The authors reported that the American Society for Reproductive Medicine’s Princeton Consensus Statement  recommends treating women  with gonadal hormones, if clinical symptoms such as diminished sense of well-being and chronic fatigue are present. The North American Menopause Society recommends treatment for symptoms of decreased sexual desire, if blood monitoring is done.  The Endocrine Society advises against androgen therapy in healthy women.

Findings suggesting that negative cardiovascular events may be associated with testosterone replacement therapy in older men lead the FDA to stop a testosterone trial.  Increasing the growth of pre-existing prostate cancer is another concern.  It may also exacerbate sleep apnea.

Several alternative MD’s reportedly use testosterone successfully in some of their FM and ME/CFS patients.

 Wrapup

The very high rates of gynecological disorders found in ME/CFS suggest female hormones play a role. They may not be the end of the hormonal story in fibromyalgia and ME/CFS.

Are both female and male hormones implicated in FM and ME/CFS?

Broderick’s models suggest women may be more susceptible to  ME/CFS because they don’t have large amounts of testosterone coursing through their systems. Low testosterone levels, on the other hand, may increase men’s susceptibility to some disorders.  Imbalances in both hormones may, in the end, contribute to fibromyalgia and ME/CFS.

If testosterone treatment ends up becoming part of the standard FM treatment protocol it will surely, like other therapies, be one part of a multi-dimensional treatment protocol: not a cure – but a help.