Mmm...didn't I just mention something in another thread about male neurologists and lack of progress in MS research
I never suspected that hormones and steroids were similar, and I look forward to Sharon's response to your comments.
I’m not at all certain what to say. I have no medical or scientific background. I’m quite certain I don’t really understand Tony’s points and objections to estrogen in people with MS. (or, why he thinks estrogen increases the risk of breast cancer since the estrogen only trial showed just the opposite).
I do think balancing estrogen and progesterone levels is important. I also think that neuroprotection and the prevention of neurodegeneration is important. I think estrogen, pre-clinically, exhibits neurprotective properties that might be applicable to people with MS. I definitely don’t have the impression estrogen and synthetic versions of “cortisol”, i.e., IVMP, etc. do the same things. I think the decline in hormone levels with age, including estrogen, increases the possibility for neurodegeneration in people with MS. So, with that…..some comments.
Estrogens and the Blood Brain Barrier
Based upon what I’ve read (and could understand a little), estrogens just don’t act directly after passing the blood-brain barrier as all other steroids do. Estrogens are also synthesized de novo in the CNS
, as are several other hormones (progesterone, DHEA). Glia-neuron crosstalk in the neuroprotective mechanisms of sex steroid hormones
These findings suggest that an increase in steroidogenesis is part of an overall mechanism used by the nervous tissue to cope with neurodegenerative conditions. Neural steroidogenesis is the result of a coordinated interaction of neurons and glia. To repeat,
In the central nervous system, the steroids produced by glia regulate synaptic function, affect anxiety, cognition, sleep and behavior, and exert neuroprotective and reparative roles.
some researchers are of the opinion that some steroids, including estrogen, are produced “de novo” in the CNS to cope with neurodegeneration, provide neuroprotection and support repair. Stable MS PM
Yes, I think most women with MS stabilize in the PM period if that means the absence of relapses. My guess would be that this is because many probably progressed from RRMS to SPMS when relapses are less frequent or cease. Personally, I don’t consider the SPMS phase of the disease to be better than the RRMS phase. Lesions, MS and Estrogen
With regard to estrogen, lesions and scarring, I have no idea how that process occurs. But some people and researchers don’t think lesions correlate well with disability, so I have to ask how relevant is that?
And, if it is relevant, there’s some information that estrogen has a positive impact on lesions in spinal cord injuries. (There may be some similarities between SCI and MS lesions). Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in rats
the only currently recommended pharmacotherapy is high-dose methylprednisolone, which has limited efficacy. Estrogen, Neurodegeneration and Neuroprotection
Estrogen is a multi-active steroid that has shown antiinflammatory and antioxidant effects, and estrogen may modulate intracellular Ca(2+) and attenuate apoptosis
Treatment of SCI rats with estrogen reduced edema and decreased inflammation and myelin loss in the lesion and penumbral areas, suggesting its potential as a therapeutic agent.
Two of the things it seems that researchers suggest may impact neurodegeneration in people with MS are mitochondrial dysfunction and glutamate toxicity. I have to resort to what Dignan once referred to as word matching, so, here’s some word matching about that as it pertains to properties of estrogen.
First, info about glutamate toxicity and estrogen. Equine estrogens differentially prevent neuronal cell death induced by glutamate
CONCLUSIONS: Our data indicate that the neurotoxic effects of glutamate can be inhibited differentially by various equine estrogens.
estrogens may provide compounds that are useful for preventing neurodegenerative diseases in both women and men.
Now, some info about estrogen and mitochondria. Mitochondria play a central role in estrogen-induced neuroprotection
The potent feminizing hormone, 17 beta-estradiol (E2), has shown cytoprotective activities in a host of cell and animal models of stroke, myocardial infarct and neurodegenerative diseases.
The cytoprotective and mitoprotective potencies for 14 of these analogs are significantly correlated, suggesting that these compounds prevent cell death in large measure by maintaining functionally intact mitochondria. This therapeutic strategy is germane not only to sudden mitochondrial failure in acute circumstances, such as during a stroke or myocardial infarction, but also to gradual mitochondrial dysfunction associated with chronic degenerative disorders such as AD, PD and HD.
Is MS a chronic degenerative disorder that should be added to that list, or, to the list in the following abstract? Estrogen is being developed as a neuroprotective agent for degenerative neurological diseases.Development of 17alpha-estradiol as a neuroprotective therapeutic agent: rationale and results from a phase I clinical study
Maintaining membrane integrity is critical to mitochondrial function, where loss of impermeability of the inner membrane initiates both necrotic and apoptotic pathways. Thus, by serving as a mitoprotectant, 17alpha-E2 forestalls cell death and could correspondingly provide therapeutic benefit in a host of degenerative diseases, including AD, PD, Friedreich's ataxia, and amyotrophic lateral sclerosis,
If you want to read more about estrogen and neuroprotection, there’s more….. From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens Mechanisms of neuroprotection by estrogen
Accumulating evidence from basic science studies demonstrates that estrogens exert profound protective actions against various forms of neurodegenerative diseases and injury.Are estrogens protective or risk factors in brain injury and neurodegeneration? Reevaluation after the Women's health initiative.
recent work demonstrating that estradiol may additionally enhance the ability of the adult brain to undergo repair by influencing the production of new neurons under neuropathological conditions, as well as by promoting an anti-inflammatory response.
we increasingly appreciate that the mechanisms by which estrogens achieve these effects are diverse and complex.
work that we have done during the past 6 yr that strongly suggests that low levels of estradiol therapy exert dramatic protective actions in the adult injured brain. Neuroendocrine modulation and repercussions of female reproductive aging
Our results reveal that 17beta-estradiol slows the progression of this injury and diminishes the extent of cell death by suppressing apoptotic cell death pathways and enhancing expression of genes that optimize cell survival. Furthermore, we have found that estrogen receptors play a pivotal functional role in neuroprotection. Together, these results carry broad implications for the selective targeting of estrogen receptors in the treatment of neurodegenerative conditions resulting from disease or injury, particularly for aging, postmenopausal women.
Furthermore, we have shown that the lack of estradiol increases the vulnerability of the brain to injury and neurodegeneration.Estrogen, estrogen treatment and the post-reproductive woman's brain
From early embryonic life to death, estrogen is a primary regulator of brain neurogenesis and cell number, synaptogenesis and synaptolysis, multiple cognitive and autonomic functions, vascular function, immune responses and defense measures against brain lesions and dystrophy.Estrogens, progestins, menopause and neurodegeneration: basic and clinical studies
While the mechanisms of this potent neuroprotection are currently unresolved, a mitochondrial mechanism is involved
Collectively, results of these animal and tissue culture models suggest that the loss of both estrogens and progestins at the menopause makes the brain more vulnerable to acute insults and chronic neurodegenerative diseases.
That’s way more than enough. Like I said, my interest in utilizing "estrogen" to help manage MS is for it's potential to increase neuroprotection and to prevent neurodegeneration.
I’ll post some info about why I’m not fond of other steroids (namely synthetic cortisol, methylprednisolone) to treat MS at another time. Here’s just one reason why I think it’s not exactly comparable to estrogen. Methylprednisolone increases neuronal apoptosis during autoimmune CNS inflammation by inhibition of an endogenous neuroprotective pathway
To investigate the influence of methylprednisolone therapy on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the ON, we used a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced EAE.
Methylprednisolone treatment significantly increased RGC apoptosis during MOG-EAE.
we provide evidence for negative effects of steroid treatment on neuronal survival during chronic inflammatory autoimmune disease of the CNS, which should result in a reevaluation of the current therapy regimen
I understand some people equate estrogen with methylprednisolone. Clearly, I'm not one of them. And, I do understand many people find "steroids" helpful for relapses.
Take care all...the beat definitely goes on.