the choice of the progestagen component in combined HRT is of importance regarding breast cancer risk; it could be preferable to use progesterone or dydrogesterone.
The pathological correlate of clinical disability and progression in multiple sclerosis is neuronal and axonal loss; however, the underlying mechanisms are unknown.
Abnormal phosphorylation of tau is a common feature of some neurodegenerative disorders
We investigated the presence of tau hyperphosphorylation and its relationship with neuronal and axonal loss.......in brain samples from patients with secondary progressive multiple sclerosis.
Significantly, analysis of secondary progressive multiple sclerosis brain tissue also revealed abnormally phosphorylated tau and the formation of insoluble tau.
Together, these observations provide the first evidence implicating abnormal tau in the neurodegenerative phase of tissue injury in experimental and human demyelinating disease.
E2 inhibits tau hyperphosphorylation
Shayk, the choice of Provera (medroxyprogesterone) was made by my primary care doctor, to prevent endometrial hyperplasia.
In addition, estriol reduces the ability of immune cells to attack the brain, and it makes the brain more resistant to damage. Dr. Voskuhl calls this a two-pronged approach in which there’s an anti-inflammatory prong that reduces attacks on the brain and a neuroprotective plug that helps the brain heal in case of an attack.
ID# P162 Location: 220C Time of Presentation:
Sep 18 3:30 PM - 3:30 PM
Presentation Category: Experimental Disease Models
Estrogen and progesterone prevent demyelination and affect oligodendrocyte function in the cuprizone modelA. C. Braun1; A. Norkute1; S. Johann1; S. Komoly2; P. Acs2; C. Beyer1; M. Kipp1
1. Neuroanatomy, RWTH Aachen, Aachen, Germany.
2. University of Pecs, Neurology, Pecs, Hungary.
Sex hormones are thought to affect and delay progression of multiple sclerosis (MS) during pregnancy.
Both steroid hormones are regarded as neuroprotective factors in the brain.
Only the influence of estrogen supplementation on disease progression has so far been tested in clinical trials.
In this study, we focused on the underlying mechanisms of protective hormonal effects.
Adult male mice were fed with cuprizone for a defined time interval to induce demyelination of the corpus callosum. Animals were exposed to estrogen and progesterone by subcutaneous injection.
A combined treatment with both hormones nearly completely counteracted the process of demyelination. Furthermore, premature and mature oligodendrocyte markers were significantly increased.
These data support the concept that sex steroids can protect the brain from demyelination during MS.
Great to hear from you and learn that your symptoms have improved so much. Wonderful news.
Undoubtedly Provera (MPA) is the standard and most widely prescribed form of progesterone in the US to prevent endometrial hyperplasia in women who are taking estrogen. As far as I know bio-identical progesterone does that as well. It's just that I've also been interested in the potential of progesterone (not just estriol) to help manage MS too and from what I've been able to cobble together (I have no medical or scientific background), progesterone wins hands down over MPA in that category on multiple fronts.
I certainly have high regard and respect for Dr. Voskuhl. Per the link you posted (thanks for that updated info) Dr. Voskuhl stated:In addition, estriol reduces the ability of immune cells to attack the brain, and it makes the brain more resistant to damage. Dr. Voskuhl calls this a two-pronged approach in which there’s an anti-inflammatory prong that reduces attacks on the brain and a neuroprotective plug that helps the brain heal in case of an attack.
Since you're in contact with her periodically, do you happen to know what that "neuroprotective plug" is that Dr. Voskuhl is referring to that helps heal the brain in case of an attack? I'm really curious since estrogen (and progesterone) both impact glutamate excitotoxicity and BDNF levels and both have been implicated in neurodegeneration in MS. I'm just wondering if Dr. Voskuhl is referring to either one or both of those or something else being the "neuroprotective plug"?
So, I'm still sticking with estriol and progesterone. I've been diagnosed over 5 years now and so far, so good I think. My neuro only does MRIs if clinically indicated to consider any change in treatment and so far I've only had my diagnostic MRI, so can't report anything on that front.
DIM wrote:I have bought some Emerita bio-intedical progesterone creams for my wife and when I give her DHEA (increases estrogen levels) she uses also the progesterone cream as both hormones work much better than progesterone or estriol alone or at least this is what I believe from what have read!
But, who knows?
Concerning progestin vs. progesterone, Dr. Voskuhl's response to me was "no evidence that a progesterone is more neuroprotective. Go with what the gyn wants you to use to protect your uterus from "unopposed" estrogens".
Here, we review the data from various laboratories including our own that support the protective role of progesterone and describe the multiplicity of mechanisms by which progesterone elicits these protective effects.
Finally, we contrast the neurobiology of progesterone with that of the clinically used progestin, medroxyprogesterone acetate (MPA), and suggest that the "natural" progesterone may be the better choice when considering which progestin to use for future therapeutic/ palliative purposes in CNS-related disorders.
And though additional research is certainly needed to explore the neurobiology of progesterone and its related progestins more completely, we provide evidence that, at least with respect to the brain, not all progestins are created equal.
The ovarian hormone progesterone is neuroprotective in different experimental models of neurodegeneration.
In conclusion, our findings indicate that progesterone is neuroprotective against kainic acid excitotoxicity in vivo while the synthetic progestin MPA is not and suggest that progesterone metabolism to its reduced derivatives DHP and THP is necessary for the neuroprotective effect of the hormone.
We previously demonstrated that progesterone functions as a neuroprotective agent whereas medroxyprogesterone acetate (MPA; Provera) does not.
Moreover, MPA antagonized the neuroprotective and neurotrophic outcomes induced by 17beta-estradiol (E2).
Results of these analyses indicated that both crystalline MPA and a pharmaceutical formulation (Depo-Provera) lacked neuroprotective efficacy, indicating that the effects were not dependent upon MPA formulation.
Likewise, MPA in the prevention and treatment paradigms were equally ineffective at promoting neuronal survival, indicating that timing of MPA administration was not a factor.
Further, the detrimental effects of MPA were not due to the presence of the acetate group, as medroxyprogesterone was as ineffective as MPA in promoting neuronal survival.
Moreover, MPA pretreatment exacerbated neuron death induced by glutamate excitotoxicity as indicated by a 40% increase in neuron death
Collectively these results predict that the progestin formulation of hormone therapy will affect the vulnerability of the central nervous system to degenerative insults.
Menstrual cycle and menopause in patients with multiple sclerosis. How do these affect the symptoms of disease?
M. Avila1; G. A. Suarez1; D. Brandt1; J. Ramirez1; G. J. Hutton1; V. M. Rivera1
1. Baylor College of Medicine-MMMS Clinic, Houston, TX, USA.
To document clinical changes in MS symptoms during the menstrual cycle, menopause and pregnancy.
A total of 100 patients will be evaluated. At the present time 71 patient have been included (94% relapsing-remitting MS, 6% secondary progressive MS) mean age of 41, 66% Caucasians, 17% Hispanic, 12% African American and 5% other ethnic background.
42% complained of worsening of symptoms while menstruating,
and 21% worsening prior to the menstrual period.
Twenty-eight patients had at least one pregnancy after their MS diagnosis; of these 57% reported improvement of symptoms during pregnancy, 19% had a relapse in a 12-month period after delivery and one patient had a relapse during pregnancy.
In our menopausal group of patients (n=13), 77% had worsening after menopause and 46% had increase in their number of clinical relapses after menopause.
Female hormones play an important role in MS. This may have therapeutic implications in the future.
11 premenopausal and 19 postmenopausal women
Eighty-two per cent of menopausal women reported an increase in severity premenstrually.
Of the postmenopausal women 54% reported a worsening of symptoms with the menopause,
and 75% of those who had tried hormone replacement therapy reported an improvement.
The results of this pilot study indicate the need for further research to clarify the effects of the menopause and hormone replacement therapy upon multiple sclerosis.
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