My research on Testosterone and GBS
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November 25, 2007 at 1:31 pm
Note:
If, after reading this paper, any men are interested in being part of a clinical trial please send me a personal message. Perhaps if we act as a group, we could persuade one of the neurologists on the advisory board to conduct that trial which will have to be well documented and monitored so it can be used in future research.
Thank you!=====================================================================================
Could testosterone be the key to curing Guillan-Barre Syndrome?
By Dino JerkovichI have spent my professional career working in the research department of a major pharmaceutical company. In 2003, I became seriously afflicted with Guillain-Barré. Like many GBS sufferers, my recovery has been limited and I have not yet regained the ability to walk. But I have been able to conduct independent medical research on the subject – to me, this is the most important research I have ever done.
This research has led me to believe that testosterone may hold the key to unlocking the mystery of GBS (and possibly MS as well). It appears to provide significant relief to long-term GBS symptoms and may be an effective treatment to prevent symptoms from taking hold if administered promptly when GBS is first diagnosed.
Although the scientist may be working on finding what may cause the attack on the nervous system or how to prevent GBS, not much has been done to find the actual cure of the resulting symptoms, the demyelination of the Peripheral Nervous System (PNS). Myelin is a substance rich in protein and lipids (fatty substances) that forms layers around the nerve fibers that help make sure the nerve impulse is conducted efficiently.
Myelin is present in both the central nervous system (CNS) and the peripheral nervous system (PNS). It is the destruction of CNS myelin that produces the symptoms of MS and the destruction of PNS myelin that produces the symptoms of GBS. It is known that CNS myelin is produced by special cells called oligodendrocytes and PNS myelin is produced by Schwann cells. Therefore finding a way to stimulate these cells to produce myelin sheath is the critical piece in the puzzle to find the cure for MS, GBS and other PNS disorders such as Miller-Fisher variant of GBS.
It is also known that GBS patients do recover with time, indicating that the body heals naturally by repairing the myelin sheath in PNS. This would therefore suggest that the body has or manufactures the chemical that stimulates the Schwann cells to produce myelin sheath. Identifying this chemical and introducing it to the body in greater or appropriate amounts could speed up the production of myelin and therefore shorten the time to recovery for GBS patients.
It has been reported that GBS patients’ speed of recovery is often associated with age and with the severity of the attack. Specifically, younger patients recover more quickly than older ones. After discussion with four other GBS patients between 50 and 60 years of age, I discovered that all have exhibited symptoms of low libido and inability to have erection in addition to those symptoms associated with classic GBS. This led me to believe that the testosterone level may be the key to recovery. My own testosterone level at 36 months post onset was 361ng/dl. Although this is considered within the normal limits of 300-1100 ng/dl, since this is at the lower end of the range, I theorized that increasing my testosterone level, specifically the free testosterone level, may help in my recovery. Although I tried to convince my doctors to give me an injection of testosterone, they all refused because testosterone is not indicated for GBS.
I shared my theory with my friend Bob Shea , a 53-year-old GBS patient whom I met while in rehab. Bob recalled that at the outset of his rehab, in January 2003, a doctor gave him an injection of testosterone (Testosterone Cypionate, 100 mg, Depo) for the purpose of preventing muscle weakness. Bob remembers that for about two weeks after the injection, he experienced a sudden burst of recovery. At the time, he believed that this was a part of the normal recovery process for GBS. In retrospect, however, by his personal observation, that initial burst is the most dramatic surge of recovery he has experienced over a period of four years.
Last March, at 54 months post onset, Bob began receiving treatment, under the supervision of a neurologist and endocrinologist, with a very low dosage level of testosterone (1% Androgel, 5 gm dose). Within a few weeks, he began to perceive gains. In September, at 60 months post onset, an EMG indicated objectively verifiable gains. Bob’s experience, albeit limited, seemed to validate my theory, and I have pursued additional literature search to find a connection between testosterone and myelin sheath regeneration.
There has been some research done by a group (Magnaghi, Leonelli, Melcagni, et.al.) at the University of Milan, Italy, that has indicated (using laboratory rats) that the neuroactive steroids (e.g. testosterone, progesterone and their derivatives) are able to influence, through the action of steroid receptors, some parameters of the PNS such as Schwann cells. Peripheral Nervous System possesses steroid receptors that may represent the target of action for these neuroactive steroids, which, their data indicates, stimulate the expression of two important proteins of the myelin of peripheral nerves: the glycoprotein P0 (P0) and the peripheral myelin protein 22 (PMP22).
Magnaghi, et.al have also shown that Glycoprotein Po (Po) and peripheral myelin protein 22 (PMP22) are two proteins playing a crucial physiological role in the maintenance of the multilamellar structure of peripheral myelin. They demonstrated that the removal of circulating androgens by orchidectomy (castration) induces a significant decrease of the synthesis of Po and PMP22 in the rat sciatic nerve. It is their conclusion that neuroactive steroids therefore not only control the expression of these specific myelin proteins, but also influence the morphology of myelin sheaths and axons, suggesting that these molecules may represent a new therapeutic approach where rebuilding of myelin is necessary.
At present, we do not have any treatment for GBS other than initial plasmapheresis and/or IVIg. Once these treatments are completed, patients are not treated further for GBS and the focus of attention is placed on physical therapy and how to cope with the disorder. Because only about 1% of the population may contract GBS with varying degrees of severity, GBS is an “orphan” illness for which few researchers are doing any specific work. Health professionals are understandably reluctant to employ any treatment that has not been tried or written about, due to fear of liability.
I believe that testosterone as treatment does not present significant side effects, especially when weighed against the possible benefits of relief from a condition that I can personally attest is devastating. I believe that testosterone should be tried as treatment for rebuilding myelin in GBS patients. Based on Bob Shea’s recovery gains after using testosterone and the supportive evidence by studies conducted by the research group at the University of Milan, I appeal to GBS International to sponsor a clinical trial, using testosterone injection as treatment on GBS volunteers. We, the GBS patients, do not have many options and are therefore ready and willing to explore new treatments. Let me be the first on the list of volunteers to test testosterone as a possible cure for Guillain Barre Syndrome.References:
1. Melcangi RC, et al, J Neurocytol. 2000 May-Jun.; 29 (5-6):327-39
2. Magnaghi V, et al, Brain Res.: Brain Res. Rev. 2001 Nov.; 37 (1-3):360-71 -
November 25, 2007 at 10:13 pm
Dino,
The first time I got GBS it was fairly mild. I could walk – but slowly and not well. Since you are oding research on this, I wanted to add that I took 12 pills of adrenal extract daily and it turned the GBS around. When I asked my doctor, he said that he would have given me that intrarvenously had I been hospitalized. Doesn’t this sorta tie in with hormones? I also attribute the fact that I was able to NOT been hospitalized both times I had GBS to taking 16-20 grams of vitamin C a day. WHen I stopped for a 24 hour urine collection, I felt like I was hit by a Mack truck. There has to be some reason why these supplements worked. The adrenal extract took my blood pressure down and really turned it around. But I had to take twelve for it to work. My doctor said that I needed such a huge amount because it was difficult for the body to absorb. I adlso took 150 mg ob B complex. I have not needed any pain medication. Hope this helps. -
November 25, 2007 at 10:37 pm
Dino,
I remember being interested in neuroactive steroids last year when my daughter was in a chronic state of cidp. After a day of looking at the reviews, considering if birth-control pills/patches would deliver enough substance (estrogens), I decided it would not be an answer to our situation. Since you brought up the subject, I decided to take a second look from the perspective of testosterone. Here are my thoughts and findings – while both testosterone and estrogen can modulate immune actions, it,in my mind, is not demonstrated to be a clear solution to resolve autoimmune mediated damage. Each person will have to weigh the evidence for themselves.
One of my first thoughts was that steroids are not advised in (acute onset) Guillain Barre. Some papers suggest they may be potentially harmful. Oth, steroids are considered helpful in the treatment of chronic immune-mediated neurological conditions (such as cidp, multiple sclerosis).
I’m curious what could cause the different outcomes between corticosteriods and anabolic/sex steroids (in the event that testosterone were useful for gbs)? I have had a quick look at the study you refered to on healthy males that were medically castrated – and it suggests that testosterone has a dampening effect on pro-inflammatory immune activity. This could be one of those chicken and egg situations: for example – at the time of onset, could it be that low testosterone reduced the capacity of the immune system to fully respond to antigenic challenge; or was reduced testosterone a result of pro-inflammatory activity after onset? I don’t think the cited article digs that deep into cause and effect.
[QUOTE=article]Deficiency in either the number or function of CD4+CD25+ T cells has been implicated in a number of human autoimmune diseases. ….., although subjects treated with acyline alone experienced a >90% reduction in circulating T and an 80% reduction in DHT, they also experienced a 55% reduction in serum E2 concentrations. Therefore, although the changes in lymphocyte subsets and function that we observed in this study are clearly related to alterations in sex steroids, whether they resulted from androgen deprivation, estrogen deprivation, or a combination of these is not clear from our data.
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[QUOTE=Dino]
It appears to provide significant relief to long-term GBS symptoms and may be an effective treatment to prevent symptoms from taking hold if administered promptly when GBS is first diagnosed.
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Keep in mind that these experiments were performed on healthy males, which leaves unanswered the question of testosterone’s influence upon “effector” T-cells (the ones that signal a ramping up of immune activity) in patients w/acute onset illness. In my mind’s eye, I visualize autoimmune lymphocytes “on steroids” potentiating a cytokine storm in an enviroment absent of cd4+cd25+ regulatory t-cells.J Neuroimmunol. 2007 Jan 17; : 17239444
Reduced circulating CD4+CD25+ cell populations in Guillain-Barré syndrome.I’ve got a wild immagination – that is probably a overly dramatic description of unexpected events, but it does convey the need for caution when suggesting (already immune-compromised) patients volunteer for such a study. Since gbs has a self-limiting progression, testosterone may prove useful in speeding up myelin growth once immune responses have returned to normal levels – i.e. treatment for residual damage caused by gbs – which is different from a “cure for GBS”. The issue of how to turn off the auto-reactive self-antigens is not addressed by testosterone treatment – possibly an important consideration for those hoping to lessen the impact of acute onset.
Here is a study on the effects of androgen decline on autoimmune disease in aging males. These experiments are on rats – I haven’t found any similar human studies. Again, it demonstrates suppression of inflammatory cytokines, but only in young subjects. Testosterone benefits are described as ineffective in middle-aged subjects (human equivalent of 35-40 yr old).
[url]http://www.jimmunol.org/cgi/content/full/174/4/2387[/url]
[QUOTE=article]
Surprisingly, middle-age males were unresponsive to the EAE-protective effects of T4 and had only a transient benefit from E2 treatment; young males were almost completely protected by both hormone treatments.
[/QUOTE]Here is the complete title to the article along with summary statements from the abstract by Magnaghi V: (emphasis mine)
[url]http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T07-4C9HRMK-3&_user=10&_coverDate=07%2F05%2F2004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=1ebce33dc71e3b3de716b942497e3799[/url]
[QUOTE=article]
The synthesis of glycoprotein Po and peripheral myelin protein 22 in sciatic nerve of male rats is [COLOR=”Red”]modulated[/COLOR] by testosterone [COLOR=”Red”]metabolites[/COLOR]In case of Po, this effect may be counteracted by the subsequent treatment with testosterone metabolites, dihydrotestosterone or 5α-androstan-3α,17β-diol (3α-diol)……On the contrary, PMP22 seems not to be under the control of AR, but a role for GABAA receptor may be proposed.
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Elsewhere I have read that both testosterone and estradiol can have a weak effect upon myelin regeneration, but this article indicates that metabolites (progesterone) is effective – only on PO. PMP22 is not affected by testosterone metabolites on androgen receptors. Progesterone also activates mammary tumor virus – probably not a fair trade-off in terms of risk.Abstracts from Melcangi RC echoed similar results for age-related degeneration of myelin. Progesterone & derivatives can improve abnormalities (nothing about autoimmune related damage), but testosterone did not have significant effects on myelin growth parameters.
[url]http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12927767&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus[/url]
In summary, Testosterone reduces pro-inflammatory cytokine production while Estrogen contributes to the expansion of regulatory T-cells. The answer may lie somewhere in the balance.
best wishes,
cd -
December 3, 2007 at 3:07 pm
CD,
Thank you for taking the time to read the article. I had pointed out that the referenced studies were done on rats and I am sure the rats did not have GBS. The reference was made simply to point out that the studies suggesat that testosterone and progesterone in seem to have stimulatory influence on the Schwann cells to produce myelin proteins. I believe that the cure for GBS rests simply in that…repair of the myelin sheath.
Your analysis, I must admit, has gone way beyond my comprehension and understanding, so I can not refute or agree to anything you wrote. It is too confusing for me.
However, I would like to point out that two men, who are members of the discussion group have been treated by testosterone and both have experienced a surge in recovery. One so much that he is running now. I don’t think that we should dismiss this so lightly. I stand by my original theory that testsoterone may stimulate the Scwann cells to regenerate the myelin sheath as supported by the testimonials of the two discussion group members who have recovered using testosterone (testosterone cypionate) at high dose.
Dino
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December 7, 2007 at 9:59 am
I would be most interested in participating in a clinical trial if I qualifed. I was hit with GBS in 2005 at age 53. I’m walking, but not normally, and continue to have pain, weakness, poor balance,energy issues, and not much libido. I’m dealing with it, but it’s a diminished life. I avoid the public because people are so careless and I could fall so easily–a setback I don’t need. Is there no danger that the shock of a testosterone injection could actually set GBS off again? In my case we’re not sure if it was triggered by the trauma of three heart surgeries in as many weeks or the Epogen I was prescribed to address anemia. Thanks.
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December 8, 2007 at 3:38 pm
Russ,
I don’t believe that testosterone would cause a shock to the system. Testosterone is present and necessary for a normal functioning of our body. We, at our age, have a much lower level than what we had when we were younger. I believe that probably stress, more than shock, contributes to the disfunction of the autoimmune system. In my case, bacterial infection and high stress during the same period were the basis of GBS onset.
You seem to be much better off than many of us who were hit much harder than you and who are taking much longer to recover. Although the life may be diminished for you right now, I believe that you will continue to get better and, if we get to use the testosterone as treatment, I believe that it will speed that process and improve the quality of life. Good luck to you and to us all.
Dino -
October 9, 2010 at 9:07 pm
If contact me, [email]rdpfun@earthlink.net[/email] mine went down to 150 and I have CIDP now after GBS
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October 10, 2010 at 6:53 am
interesting article. I happen to know a couple of people who have fallen for the Low T thing and have become extremely difficult to live with. They are miserable and so are their families. Not sure if this would have the same effect.
Also, I know, as a woman, that female hormones (and almost every damn hormone) plays a large role in the flare up of residuals and misery. I wrote to dr. Parry about this and he confirmed my suspicions that hormones do indeed have a negative affect on our symptoms. Why would testosterone actually help? Don’t mean to sound negative and am definitely one to try just about anything (well maybe not this considering my sex and I really hate shaving my legs), but my post is more out of curiosity.
I sure hope this helps someone. I also know that taking colostrum and other supplements during my active phase helped. Stopped the colostrum because of the growth factor in it that could cause cancer cells to feed and grow. As if I needed that on top of everything else.
The Low T thing I am sure has a ton to do with all the estrogen in our foods (soy), chemicals we use, and the air we breathe. We are slowly but surely changing our males into effeminate beings and raising cancer rates in women dramatically. Just a thought.
Will be keeping an eye on this in hopes that is shows promise 🙂
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May 24, 2018 at 10:49 pm
Dino –
There is no post on this testosterone subject for eight years. May I ask for an update. Was any new research done and what is the latest scientific opinion on the use of testosterone supplements for GBS-CIDP patients. I have been diagnosed with CIDP since 2011 and have extremely low testosterone at age 72 now. I went off the testosterone but now wonder if I should continue. I am having IVIG every four weeks and expect this to continue indefinitely.
Thanks
cidpLog.com editor -
August 13, 2018 at 7:04 pm
I too first read this post last year (2017) as well as the two related posts. After doing additional research I decided to simply try for myself.
First some background: I was 51 at DX. GBS for me was a very rapid progression in that 36 hours from beginning symptoms, I was in an ICU, fully paralyzed, and mechanically ventilated. I stayed on a ventilator via a trache for the next few weeks. I wound up staying in hospitals for 8 weeks, a nursing home for 6 months, and an acute rehab for six weeks. A grand total of nine months. When I returned home I was still in a wheelchair and using a walker for transfer.
I’ve been on transdermal testosterone (5%-125ml daily) now for five weeks. I’m in no way advising or advocating anyone to try this but here are my results thus far. My strength has vastly improved as well as endurance. I went from wheelchair to cane in that short time period. Neuropathy has went down to just my feet and feels more like a sunburn than any sharp pains. My libido returned after three weeks to pre GBS levels. My balance has also improved significantly.
I wish to also mention I did have my testosterone levels checked prior to doing this and although in the normal range they were just barely.
Once again allow me to say I’m not advising or advocating this just sharing my results.
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August 14, 2018 at 10:54 am
Edayle – I assume your testosterone therapy was with the concurrence of your doctor (?) – I am surprized this would be recommended given your normal testosterone levels? That dose is pretty too but with encouraging results so it is really too bad there is not more research being done in its use for GBS and CIDP. I hope you continue to post the impact of this treatment including what happens with your testosterone level.
My trial with testosterone was less dramatic but certainly positive on my tolerance of my CIDP symptoms. I am now in a quandary though as I have a slight risk of prostate cancer (I had one needle precancerous out of 13 in a prostate biopsy) and testosterone therapy can increase that risk. My testosterone was originally virtually non-existence so I was prescribed Androgel but was taken off the testosterone because of this risk. I am now completely deficient in testosterone and my CIDP remains pretty challenging but at least stable with IVIG. I and my doctors are going to re-assess the testosterone though and by year end 2018 I may give it another try.
CIDPlog.com
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August 14, 2018 at 4:22 pm
It admittedly took some persuading on my part. My beginning levels were around 300 ng/dl. This last check they were around 1000! My application method is within five minutes of showering plus going over the area with moisturizer after an hour. Application sites are alternating shoulders coupled with a dab “down under”.
Now has the sudden progression in my recovery been due to trt? We will never truly know. It may have just coincided with a recovery phase that would’ve happened anyway. I had just been intrigued by this post since reading it last year which prompted me to research futhur. As you mentioned there has been hardly any detailed studies just a lot of observations and hypotheses!
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August 20, 2018 at 3:58 pm
I would be interested in clinical test. I’ve had the same problems after GBS 2 years ago. My improvement has slowed drastically, which seems to be normal, but I would love to get back more of what I lost quicker.
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