Testosterone, dihydrotestosterone or 5ar2 antibodies.

[Oscar]

stay on topic FFS. viewtopic.php?f=27&t=5589&p=50159#p50159

[spstriken]

@Oscar

stay on topic FFS. viewtopic.php?f=27&t=5589&p=50159#p50159

how am I off topic?

[Oscar]

@spstriken

how am I off topic?

Your always off-topic. Please go away.

[spstriken]

@Oscar

@spstriken

how am I off topic?

Your always off-topic. Please go away.

you did not start this thread. I have already left your thread and don’t post there any more.

[Oscar]

[Size=4]Proof that enzyme inhbitors can cause a self-sustaining auto-immune reaction against the enzyme they inhibit that persists after the drug is stopped.[/size] Note that the study mentions the symptoms can get worse after stopping, it also mentions how this is a rare side effect of a commonly used enzyme inhbitor. These are all very strong coincidences with persistent side-effects from finasteride (although you have to imagine an effect against 5aR-2 and possibly 5aR-1, 3) and may mean that ‘PFS’ has scientific backing and is not an entirely new phenomenon.

Autoantibodies Against 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase in Patients With Statin-Associated Autoimmune Myopathy onlinelibrary.wiley.com/doi/10.1002/art.30156/pdf

Statins lower cholesterol levels by specifically inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a key enzyme in the cholesterol biosynthesis pathway… Musculoskeletal symptoms are a well-known complication of statin use and range from myalgias and cramps, which occur in 9–20% of statin users

In most cases, statin-induced myopathic events are self-limited, with complete recovery in the weeks or months after the statin is discontinued (6). However, 2 recent studies have described 33 patients who developed an autoimmune myopathy following statin exposure, which did not abate after discontinuing the statins… we concluded that these patients had an immune-mediated necrotizing myopathy (IMNM)

We reasoned that statin-associated autoimmune myopathy with anti–200/100-kd autoantibodies provides a model system for defining the mechanistic relationship between drug exposure and the development of a specific autoimmune response. Identification of the autoantigen(s) targeted by the immune response is a critical first step… These findings suggest that statins trigger an autoimmune response against HMGCR by upregulating the expression of this autoantigen. Even after discontinuing statins, the presence of high levels of HMGCR in regenerating muscle fibers may perpetuate the immune response.

In the present study, we demonstrated a plausible causal link between statin exposure and this distinct form of IMNM through identification of the autoantigen as HMGCR. Immunoprecipitation assays demonstrated the specificity of the autoantibodies for the carboxy-terminus of this enzyme, while competition experiments confirmed that anti-HMGCR autoantibodies immunoprecipitated both HMGCR and the 200-kd protein.

Press release for this study (already posted) that also confirms the conclusions drawn from this paper. theheart.org/article/1162047.do

[b]“In the vast majority of cases, in patients who develop muscle symptoms while taking statins, the symptoms resolve once you have the patient stop taking the statin, without any needed form of treatment,” lead investigator Dr Andrew Mammen (Johns Hopkins Medical Institute, Baltimore, MD) told heartwire. “But there is a rare group of patients who develop a sustained autoimmune process that actually requires immunosuppressive therapy to treat. Otherwise, they continue to get worse and worse, with many of our patients coming into the clinic in wheelchairs, even after having been off the statin for months.”

…

“When you talked to the patients, a very typical story was that they got put on a statin medication,” said Mammen. “It was recognized that it was causing some muscle problems, it was stopped, maybe switched to another one, and then finally the medication was discontinued. But instead of getting better, which is what usually happens with statin myopathy, it just continued to progress and get worse. It didn’t get better until they were put on immunosuppressive medications.”

…

With that background, the group then wanted to determine what the antibodies were recognizing. In this latest study, they learned the antibodies recognize HMG-CoA reductase, the target of statin therapy. After 750 patients with muscle symptoms at the clinic were screened, 45 patients, or 6%, were identified as having the HMG-CoA-reductase antibodies. Among patients 50 years of age and older, 92% of patients were exposed to statin therapy.

…

Mammen said that normal muscle has very low levels of HMG-CoA reductase, but regenerating muscle, muscle that has been previously damaged, has very high levels. As a result, that damaged muscle continues to serve as a rich source of the HMG-CoA-reductase protein even after the statin is discontinued, which helps explain why an autoimmune muscle disease process started with the statin continues after the drugs have been stopped.
[/b]

Note that the scientists believe that the auto-immune reaction is caused by the ‘upregulation’ of the enzyme, however this idea has already been critisized by a leading expert in the field. arthritis-research.com/content/13/6/138

[b]While myalgias and cramps are frequent among statin users, some patients may develop an inflammatory myopathy or inclusion body myositis. Given the frequency of statin use, such occurrence may coincidence. Some patients, however, present with a newly recognized form of myopathy that appears to be genuinely associated with statin use and has a fascinating serological profile that may provide a clue to etiology. Thus, as described in a lecture from Dr Lisa Christopher-Stine from Johns Hopkins, statin users are prone to immune-mediated necrotizing myopathy (IMMS) that has a distinct set of clinical and histopathological findings. This condition presents with widespread muscle pain and weakness, with biopsies showing evidence of myocyte necrosis.

Intriguingly, patients with IMMS express antibodies to the target of statin action, the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). This serological feature was defined originally by Western blots showing antibodies to proteins with molecular weights of 100 kDa and 200 kDa; molecular techniques established the identity of the 100 kDa protein as HMGCR; the 200 kDa band may result from a dimer or associated protein. The link between antibodies to HMGCR and statin use suggests a scenario in which statin use decreases cholesterol levels, which in turn induces HMGCR production. This up-regulation somehow may increase immunogenicity and drive the production of autoantibodies that may damage myocytes. Furthermore, since regenerating muscle can also show HMGCR up-regulation, a repair response to an initial injury may exacerbate autoimmunity, fueling the fire with an ever increasing supply of autoantigen to stimulate pathogenic B and T cell responses.

This model, while attractive and consistent with the data, may be insufficient to explain an anti-HMGCR response since it suggests that the immune system is exquisitely sensitive to even small changes in the expression levels of protein. Other mechanisms may therefore be at play. Thus, binding of a statin to the enzyme could create structural change that alters the enzyme’s conformation or intracellular metabolism to promote autoimmunization. Perhaps muscle has an unusual sensitivity to the effects of cholesterol and is predisposed to injury as the cholesterol levels drop.[/b]

[tim1911]

1. What have we got on this forum so far as in how people responded to immunosuppressive medication?
   Personally prednisone did nothing for me, although i was on it for a very short time and experienced undesirable side effects.
   Others have had benefits, some have even recovered, maybe?

Either way it is strikingly similar to our situation and is a very good theory and does need to be tested, someone must be interested in this considering the papers that have been presented in this thread.

2. Wondering what you think about the mechinism behind brain fog as you believe there is no 5ar2 in the brain?

[martinM]

@tim1911

1. What have we got on this forum so far as in how people responded to immunosuppressive medication?

Boston2009 didn’t have much luck replacing cortisol, he got quite sick.

@tim1911

2. Wondering what you think about the mechinism behind brain fog as you believe there is no 5ar2 in the brain?

I’d like to know Oscar’s opinion here too. Do you think the enzyme isn’t active in the brain but the substrates are already acted upon before crossing the blood/brain barrier into the brain?

[tim1911]

ncbi.nlm.nih.gov/pubmed/15458455

bloodjournal.hematologylibrary.org/content/90/1/43.full.pdf

nejm.org/doi/full/10.1056/NEJMc0806809

mendeley.com/research/neutralizing-antibodies-to-therapeutic-enzymes-considerations-for-testing-prevention-and-treatment/

4 Papers where an antibody has developed against an introduce enzyme.

[spstriken]

good fine Oscar but how would we find these anti bodies in our serum. is there any tests?

[Oscar]

@tim1911

1. What have we got on this forum so far as in how people responded to immunosuppressive medication?

People have claimed different things, ‘Cytochrome?’ actually claimed to have recovered with Dexamthasone after 12 months, also that brazilian guy ‘Corvip-something’ and even that story from from ‘robocopp’. But you are more believable. Maybe it takes more forceful medication, as corticosteroids arent usually used to treat hashimotos or graves disease (two autoimmune illnesses directed towards an enzyme). Recently i have been reading about successes with Rituximab that disrupts the immune system in a different way to corticosteroids.

@martinM

@tim1911

2. Wondering what you think about the mechinism behind brain fog as you believe there is no 5ar2 in the brain?

I’d like to know Oscar’s opinion here too. Do you think the enzyme isn’t active in the brain but the substrates are already acted upon before crossing the blood/brain barrier into the brain?

I think the variety of symtoms are due to some people having a reaction against just 5aR-2 and some people a reaction against 5aR-1 and 5aR-2 (or maybe just 5aR-1). Finasteride will interact with type 1 long before it reaches levels sufficient to fully inhibit it. There are also probably other varibles like strength of reaction, individual physiology, etc.

In fact thats CLUE NO.1 isnt it? If Finasteride has persisitently effected the CNS it really must have done so via 5aR-1; therefore the enzymes in our bodies have reacted in an unusual way to finasteride.

It also explains why even men on Dutasteride dont get this - the ‘PFS’ is not based on the inhibition of neurosteroids caused by the drug!!!

[spstriken]

will we take this discussion to next level?
I mean we should contact labs and request them to test our bloods for the presence ABs. Actually I called one today but no success.

[Oscar]

@spstriken

will we take this discussion to next level?
I mean we should contact labs and request them to test our bloods for the presence ABs. Actually I called one today but no success.

if you think this has happened to you take a copy of the papers I have just posted and try and convince the doctor/hospital to run a special blood test for you. This is my plan!!! I have no idea what chance of success I have.

[spstriken]

@Oscar

@spstriken

will we take this discussion to next level?
I mean we should contact labs and request them to test our bloods for the presence ABs. Actually I called one today but no success.

if you think this has happened to you take a copy of the papers I have just posted and try and convince the doctor/hospital to run a special blood test for you. This is my plan!!! I have no idea what chance of success I have.

Trust me I am doing all the possible and have taken many printouts to my doctor and other doctors. My doctor has written very disturbing notes about me (I read my file while waiting for him in the waiting room) basically tried to prove me mentally unstable. I am scared there are good chances that health Canada will put me in mental hospital now.
I am trying to focus outside of Canada.
The attitude is very arrogant and disgusting. It is very hard to explain your point your doctor.

[spstriken]

Got Protein electrophorsis test. all looks normal

Total protein 68 60 - 80 g/L
Albumin 46 35 - 50 g/L
alpha 1 globulin 2 1-3 g/L
alpha 2 glubulin 6 5 - 10 g/L
Beta gluobulin 7 5 - 12 g/L
Gamma globulin 8 6 - 14 g/L

any comments?

[Oscar]

Funnily enough i was tested with this just today. I dont really understand the test, nor can I find raised results from this test associated with hashimoto’s or graves disease.

[spstriken]

the reason I put these test result is that I told doctor about auto immune and antibodies and she wrote me this test. I don’t know how it tells about auto immune.

[spstriken]

I think I messed up my tests by not stopping my supplements so my test results mean nothing.

[lil_squirt]

@Second Amendment

snip

Has anyone else noticed this connection?

2. in some instances, the immune system takes over where finasteride left off. And therein lies the PFS. Either DHT or 5-alpha-reductase II antibodies locked in critical spaces.

There’s been some success with immune suppressants. And some failures. My guess why some have failed is because their hormones were suboptimal; they never sorted out the hormonal mess finasteride caused.

snip

This may be relevant: when I was in the 2nd ER of the night the day i crashed (first ER thought I was just another guy who couldn’t get it up) my white blood cell count was up. 12.2 where 5-10 is normal.

[xfinuser]

I can directly relate to this topic… I have been feeling random muscle pain and had blood tests that revealed that I am low in Vitamin D and low in Testosterone along elevated levels of CPK(711) and Aldolase.

My doctor is telling me that its indicative of myositis an autoimune disease. I work out often so I was really hoping that the CPK and Aldolase levels were from that. Very nervous…

[Oscar]

I am suffering from continual muscle loss since stopping finasteride. I actually got my Creatine Kinase checked and it was normal (89, 38-201). This is actually the standard test for autoimmune myopathies which i really do think is causing my muscle loss at the moment.

Its possible CK will be normal with autoimmune muscle loss see; ncbi.nlm.nih.gov/pmc/articles/PMC170091/pdf/020001.pdf

the tendency to low CPK values in connective tissue disease may offset the high levels found in
myositis and thus account for the normal level of CPK found in some
patients with active myositis associated with connective tissue disorders.

Dont know if im grabbing at straws though, or even if im pinpointing the cause. Ill push for more tests in this area. Muscle biopsy, urine test?