Nolva (Tamoxifen) may affect muscle regeneration?!

[Jean-Claude]

Hey guys I just read a couple articles dexribing studies that had been conducted on mice and bascially saying Tamox/Nolva could destroy muscle satellite cells which could greatly affect muscle regenaration.. That would be extremely worrying as most ppl use it as part of PCT when their test levels are at their lowest.. I'd like to know you guys's thoughts about that..

 

[Mrrippedzilla]

As far as I'm aware, your not a mouse so those studies mean literally nothing to you

 

[Jean-Claude]

As far as I'm aware, your not a mouse so those studies mean literally nothing to you

I'm sure you know human's bodies and mice body's share A LOT of similarities in terms of function.. along with every other mammal. Why do you think we make these studies on animals in the first place?

 

[Teutonic]

I d bet that was more of a study for people coming back from serious emaciating trauma or some other very " non re start ur hpta" or for it s use in estro diverting properties for those who are seriously jacking up the bodies normal test production-like everyone on here.

Bear in mind the studies look for super small negative stuff a compound can cause and then they can extrapolate it to......whatever they want it to.

Statistics don t lie ( I took a 700 level stat class...have u ?)...statistician s do. Plus the masses of lawyer need another gd reason or more ammo to sue or ban something else. They got mortgages too.

In the 80 s they said saccharin, a sweetener in vogue, was touted by an alarmist media to cause cancer...fuck fuck fuck....ME.

They left out that the MICE were given the equivalent of 84 cases of soft drink s or such. We re bombarded by alarm bells , media s latest feeding frenzy based on little or zero overall presentation of the topics over facts and or it s relevance... or as my man Paul Harvey used to say " The rest of the story."

 

[Mrrippedzilla]

I'm sure you know human's bodies and mice body's share A LOT of similarities in terms of function.. along with every other mammal. Why do you think we make these studies on animals in the first place?

Because it's much easier, and cheaper, to care for mice/rats then it is for humans in a lab setting.
You cannot keep a human locked up in a lab 24/7 all year, or inject them with a bunch of new drugs with unknown side effects, etc, etc.

And no, our physiology is VERY different - that's why 99% of stuff tested out on them doesn't plan out when it comes to us.
It's also the reason why drugs are NEVER approved based off animal studies and ALWAYS require extensive human trials first.

Do you want me to give you a physiology lesson in the differences between a mouse/rat and a human? Seriously?
Accept the fact that your not a mouse and therefore the study is irrelevant to you or confirm that your a retard by thinking we're the same. Up to you.

 

[.Vision.]

I'm sure you know human's bodies and mice body's share A LOT of similarities in terms of function.. along with every other mammal. Why do you think we make these studies on animals in the first place?

Your correct per say; Mice/rodents are the gold standard for testing prior to pushing drugs into "human clinical trails"..Researchers relay on these mammals for a vast reason.. 1) convenience (in patient study) and the ability to adapt and reproduce fast (providing a next generation to analyze through passed genes/expression)..2) Not only are they docile and easy to handle, they can be genetically modified/inbred to be virtually IDENTICAL GENETICALLY minimizing any differences that could may effect the research (per request by National Human Genome Research Institute) as a strict requirement that all mice are to be the same purebred.. Over years scientists world wide have breed a genetically altered rodent that meets the standard, its known as "transgenic mice"..

These mice are even closer with sharing genes that are similar to those within humans, whether it's disease,chemical,or biological behavior characteristics that humans possess..These traits,symptoms and conditions can be replicated, yielding mice as the models for medical testing due to their original/existing and newly modified genetics..Besides chimps, mice are the closest Representative that humans have with pressing forward for further medical trails!

Because of these studies that have been conducted researchers are in fact PRESSING forward with human trail, its in transition from pre-clinical to clinical.. Data will not be avail for sometime..

There's research is being done at Dr. Urs Ruegg***8217;s laboratory by Dr. Olivier Dorchies at the University of Geneva using mdx mice (mice lacking dystrophin). They have shown that tamoxifen triggers substantial improvements in muscle quality and strength in mdx mice. Parent Project Muscular Dystrophy is helping to fund this research.

Below is a link with important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration.

An other reason why mice are frequently used and genetically modified to assist in a particular study!
Effective fiber hypertrophy in satellite cell-depleted skeletal muscle



Here is some momentum for human trails in which I believe is derived from studies similar to that posted above!

TAMOXIFEN - Using tamoxifen to improve muscle strength in Duchenne and Becker

What stage is this research?

This research in Duchenne is currently at the transition from pre-clinical to clinical, meaning that pre-clinical data and previous experience with this drug are sufficient to start clinical trials involving people. Tamoxifen is the generic name for an approved drug (Nolvadex) that is used to treat estrogen-dependent breast cancer.


What is the goal or purpose of this research?

The main goal is to collect pre-clinical data that are convincing to take tamoxifen into a clinical trial in Duchenne and perhaps Becker. Low doses (threshold 0.3 mg/kg body weight per day) were effective to improve muscle function. This very low dose suggests that the drug acts on a high-affinity target, probably one of the nuclear estrogen receptors, ERa and ERb. Studies are ongoing to investigate the exact mechanism of action using mice deleted of either ERa or ERb and antagonists of these receptors
Ultimately, tamoxifen may be part of a ***8220;cocktail***8221; along with other treatments that slow or stop the loss of strength in Duchenne or Becker. It is also possible that tamoxifen could take the place of prednisone as an alternative with fewer side effects or that lower prednisone doses could be used in combination with tamoxifen.


What is the current state of this research?

Drs. Ruegg and Dorchies have tested various doses of tamoxifen in both young and old mice. Benefits of treatment included lower creatine kinase levels, 40% less fibrosis (scarring) than in untreated mice, and near normal improvements in muscle strength. Although mice are not humans and it is never entirely certain how results will translate, a robust treatment response in mice that lack dystrophin is the gold standard for moving drugs into human clinical trials for Duchenne.
The laboratory of Dr. Dominic Wells at the University of London has recently shown that there is good reproducibility and that the combination of tamoxifen plus prednisolone gives a slightly stronger effect than tamoxifen alone.

What steps need to be completed before moving into a clinical trial?

While current data are encouraging, we don***8217;t yet know if tamoxifen will have the same positive effects in Duchenne and Becker. We need to understand more about how tamoxifen may work in Duchenne. In particular, we need to determine if tamoxifen prevents muscle necrosis and enhances muscle regeneration. This would be an additional benefit. These experiments can go on in parallel with a clinical trial.
Noteworthy, the pharmacological profile of tamoxifen is well known; it has also been given as an anti-tumor agent to children ages 5-12 and no undesired effects have been noted.

What is your best estimate for the length of time it will take to move this research into clinical trials?

There are two points of view: Some think that it should be tested in dystrophic dogs before a clinical trial, whereas others don't see the benefit of a canine study, given that tamoxifen has been used for more than 30 years to treat breast cancer. Without a study in dogs, a clinical trial with Duchenne patients may start around the end of 2015. If a study in dogs is required, a clinical trial would start 2-3 years later.


Where would a clinical trial take place?

It is too early to know where a clinical trial for this research would be located. Many complex factors go into determining the right location(s) for a clinical trial. It is likely that Dr. Lee Sweeney will be the coordinator of a first pilot trial and that PPMD will provide funding.

 

[Jean-Claude]

Because it's much easier, and cheaper, to care for mice/rats then it is for humans in a lab setting.
You cannot keep a human locked up in a lab 24/7 all year, or inject them with a bunch of new drugs with unknown side effects, etc, etc.

And no, our physiology is VERY different - that's why 99% of stuff tested out on them doesn't plan out when it comes to us.
It's also the reason why drugs are NEVER approved based off animal studies and ALWAYS require extensive human trials first.

Do you want me to give you a physiology lesson in the differences between a mouse/rat and a human? Seriously?
Accept the fact that your not a mouse and therefore the study is irrelevant to you or confirm that your a retard by thinking we're the same. Up to you.

Obviously the reasons you named explain partly why we do these reaserches on animal.. But why do you think we pay millions of dollars in the first place to do them? Do you think it is to be able to warn all the other mice that Nolva can be detrimental to their muscle regeneration? It is because often times phenomena that are discoevered in animals are also at least partly applicable in humans dumb ass.

Did you know that 75% of mouse genes have equivalents in humans, 90% of the mouse genome could be lined up with a region on the human genome, 99% of mouse genes turn out to have analogues in humans? Obviously you're the one who needs a physiology lesson bud.

 

[Jean-Claude]

Your correct per say; Mice/rodents are the gold standard for testing prior to pushing drugs into "human clinical trails"..Researchers relay on these mammals for a vast reason.. 1) convenience (in patient study) and the ability to adapt and reproduce fast (providing a next generation to analyze through passed genes/expression)..2) Not only are they docile and easy to handle, they can be genetically modified/inbred to be virtually IDENTICAL GENETICALLY minimizing any differences that could may effect the research (per request by National Human Genome Research Institute) as a strict requirement that all mice are to be the same purebred.. Over years scientists world wide have breed a genetically altered rodent that meets the standard, its known as "transgenic mice"..

These mice are even closer with sharing genes that are similar to those within humans, whether it's disease,chemical,or biological behavior characteristics that humans possess..These traits,symptoms and conditions can be replicated, yielding mice as the models for medical testing due to their original/existing and newly modified genetics..Besides chimps, mice are the closest Representative that humans have with pressing forward for further medical trails!

Because of these studies that have been conducted researchers are in fact PRESSING forward with human trail, its in transition from pre-clinical to clinical.. Data will not be avail for sometime..

There's research is being done at Dr. Urs Ruegg***8217;s laboratory by Dr. Olivier Dorchies at the University of Geneva using mdx mice (mice lacking dystrophin). They have shown that tamoxifen triggers substantial improvements in muscle quality and strength in mdx mice. Parent Project Muscular Dystrophy is helping to fund this research.

Below is a link with important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration.

An other reason why mice are frequently used and genetically modified to assist in a particular study!
Effective fiber hypertrophy in satellite cell-depleted skeletal muscle



Here is some momentum for human trails in which I believe is derived from studies similar to that posted above!

TAMOXIFEN - Using tamoxifen to improve muscle strength in Duchenne and Becker

What stage is this research?

This research in Duchenne is currently at the transition from pre-clinical to clinical, meaning that pre-clinical data and previous experience with this drug are sufficient to start clinical trials involving people. Tamoxifen is the generic name for an approved drug (Nolvadex) that is used to treat estrogen-dependent breast cancer.


What is the goal or purpose of this research?

The main goal is to collect pre-clinical data that are convincing to take tamoxifen into a clinical trial in Duchenne and perhaps Becker. Low doses (threshold 0.3 mg/kg body weight per day) were effective to improve muscle function. This very low dose suggests that the drug acts on a high-affinity target, probably one of the nuclear estrogen receptors, ERa and ERb. Studies are ongoing to investigate the exact mechanism of action using mice deleted of either ERa or ERb and antagonists of these receptors
Ultimately, tamoxifen may be part of a ***8220;cocktail***8221; along with other treatments that slow or stop the loss of strength in Duchenne or Becker. It is also possible that tamoxifen could take the place of prednisone as an alternative with fewer side effects or that lower prednisone doses could be used in combination with tamoxifen.


What is the current state of this research?

Drs. Ruegg and Dorchies have tested various doses of tamoxifen in both young and old mice. Benefits of treatment included lower creatine kinase levels, 40% less fibrosis (scarring) than in untreated mice, and near normal improvements in muscle strength. Although mice are not humans and it is never entirely certain how results will translate, a robust treatment response in mice that lack dystrophin is the gold standard for moving drugs into human clinical trials for Duchenne.
The laboratory of Dr. Dominic Wells at the University of London has recently shown that there is good reproducibility and that the combination of tamoxifen plus prednisolone gives a slightly stronger effect than tamoxifen alone.

What steps need to be completed before moving into a clinical trial?

While current data are encouraging, we don***8217;t yet know if tamoxifen will have the same positive effects in Duchenne and Becker. We need to understand more about how tamoxifen may work in Duchenne. In particular, we need to determine if tamoxifen prevents muscle necrosis and enhances muscle regeneration. This would be an additional benefit. These experiments can go on in parallel with a clinical trial.
Noteworthy, the pharmacological profile of tamoxifen is well known; it has also been given as an anti-tumor agent to children ages 5-12 and no undesired effects have been noted.

What is your best estimate for the length of time it will take to move this research into clinical trials?

There are two points of view: Some think that it should be tested in dystrophic dogs before a clinical trial, whereas others don't see the benefit of a canine study, given that tamoxifen has been used for more than 30 years to treat breast cancer. Without a study in dogs, a clinical trial with Duchenne patients may start around the end of 2015. If a study in dogs is required, a clinical trial would start 2-3 years later.


Where would a clinical trial take place?

It is too early to know where a clinical trial for this research would be located. Many complex factors go into determining the right location(s) for a clinical trial. It is likely that Dr. Lee Sweeney will be the coordinator of a first pilot trial and that PPMD will provide funding.

Thanks for the constructive input!

 

[omgmike1]

Because it's much easier, and cheaper, to care for mice/rats then it is for humans in a lab setting.
You cannot keep a human locked up in a lab 24/7 all year, or inject them with a bunch of new drugs with unknown side effects, etc, etc.

And no, our physiology is VERY different - that's why 99% of stuff tested out on them doesn't plan out when it comes to us.
It's also the reason why drugs are NEVER approved based off animal studies and ALWAYS require extensive human trials first.

Do you want me to give you a physiology lesson in the differences between a mouse/rat and a human? Seriously?
Accept the fact that your not a mouse and therefore the study is irrelevant to you or confirm that your a retard by thinking we're the same. Up to you.

I have heard this before. Can u confirm that using Nolva to PREVENT or REMOVE gyno/Itchy Nips during a mid-start cycle is fine and that it does not affect muscle gains/growth at all?

I don't know if it was broscience or something, but someone said to use Nolva during cycles for gyno as a last resort only. Do u not agree and say that it's fine to use anytime?

I know of course why it's important to use for PCT though.

It's not liver toxic too?

 

[Mrrippedzilla]

Obviously the reasons you named are explain partly why we do these reaserches on animal.. But why do you think we pay millions of dollars in the first place to do them? Do you think it is to be able to warn all the other mice that Nolva can be detrimental to their muscle regeneration? It is because it oten times phenomena that are discoevred in animals are also at least partly applicable in humans dumb ass.

Did you know that 75% of mouse genes have equivalents in humans, 90% of the mouse genome could be lined up with a region on the human genome, 99% of mouse genes turn out to have analogues in humans? Obviously you're the one who needs a physiology lesson bud.

LOL congrats on confirming your status as a retard and here is a lesson on the physiological differences between us and mice as promised


- Animal studies are used to generate an HYPOTHESIS (an educated guess) that can be tested out at a later date in humans.
I actually know a fair few researchers and even they admit that the results are interesting but have ZERO applicability to humans in reality UNTIL the results can be confirmed via human trials. So your completely wrong about it being "applicable" to us.

- Mice live, on average for about 2 years. That means 1 day = 1 month, 1 month = 28 years, etc.
IMMEDIATELY there is a massive issue of the data being applicable to humans since NONE of the studies apply to a short time period such as PCT and NOBODY takes Nolva continuously for years on end.

- Most studies use completely irrelevant doses because, for example, 20mg is a shit load for a tiny mouse compred to human on an mg/kg basis. Another reason why the studies simply are not applicable to us because NO ONE uses crazy high doses of Nolva.

- The DNL contribution to triglyceride levels in rodents is around 60-70% where as it only contributes <5% in humans, which illustrates the COMPLETELY different metabolisms that we have.
In fact we have more in common with COWS and PIGS when it comes to some aspects of our metabolism:
Stable isotope methods for the in vivo measurement of lipogenesis and triglyceride metabolism. - PubMed - NCBI

- Human GKRP has a much greater inhibition of glucokinase than rodent GKRP and we also have a much higher affinity for fructose-6-phosphate & s*****ol-6-phosphate. These are key difference that illustrate why researcher have REPEATEDLY observed the fact that rodents are much more sensitive to & less capable of metabolizing certain things compared to us:
Differences in regulatory properties between human and rat glucokinase regulatory protein. - PubMed - NCBI

- Human adipose tissue has a much lower lipogenic capacity due to lower levels of a transcription factor known as SREBP-1c as seen in this study where they reached this conclusive by measuring GENE expression:
Genetic control of de novo lipogenesis: role in diet-induced obesity. - PubMed - NCBI

- We have "unprecedented major differences" as quoted in this study regarding liver X receptors (key regulators of genes involved in hepaticaly mediated homeostasis):
Physiological differences between human and rat primary hepatocytes in response to liver X receptor activation by 3-[3-[N-(2-chloro-3-trifluorometh... - PubMed - NCBI

- We have vastly different distributions of BCAT, a key enzyme involved in protein metabolism, with rodents having 3x less BCAT activity in the liver and 13x more activity in muscle. This, along with major differences in BCKD capacity, explains why they have greater rates of BCAA oxidation compared to us:
A molecular model of human branched-chain amino acid metabolism. - PubMed - NCBI

- Here is a review where the researchers themselves admit that they have NO IDEA whether we even have the same skeletal muscle satellite cell activity as mice. This completely and utterly nullifies the data you found regarding Nolva:
Are Human and Mouse Satellite Cells Really the Same?

- And finally, a nice little paper with the discussion section showing the marked differences between us & mice:
Human and Mouse Skeletal Muscle Stem Cells: Convergent and Divergent Mechanisms of Myogenesis

"The study of human satellite cells has lagged and thus little is known about how the biology of mouse and human satellite cells compare... not all mechanisms regulating mouse satellite cell activation are conserved in human satellite cells and that such differences may impact the clinical translation of therapeutics validated in mouse models."

Wow....would you look at that....the researchers themselves admit that mice & humans have different satellite cell activity...


Who needs the physiology lesson now hmm?

 

[Megatron28]

I have heard this before. Can u confirm that using Nolva to PREVENT or REMOVE gyno/Itchy Nips during a mid-start cycle is fine and that it does not affect muscle gains/growth at all?

I don't know if it was broscience or something, but someone said to use Nolva during cycles for gyno as a last resort only. Do u not agree and say that it's fine to use anytime?

I know of course why it's important to use for PCT though.

It's not liver toxic too?

How many times do we have to recommend Raloxifene to you as a better choice for combatting gyno?

 

[Megatron28]

Did you also know that 70% of the human genes are a match for worm genes? 70%!!!

Understanding A Worm's Genetic Code May Improve Human Health

 

[omgmike1]

How many times do we have to recommend Raloxifene to you as a better choice for combatting gyno?

Other than last night (which no one responded), this would be the first time me asking about anything for gyno. I'd like to use what I have on hand and thats nolva, either way it should work and I asked the question just wondering.

 

[Mrrippedzilla]

I have heard this before. Can u confirm that using Nolva to PREVENT or REMOVE gyno/Itchy Nips during a mid-start cycle is fine and that it does not affect muscle gains/growth at all?

I don't know if it was broscience or something, but someone said to use Nolva during cycles for gyno as a last resort only. Do u not agree and say that it's fine to use anytime?

I know of course why it's important to use for PCT though.

It's not liver toxic too?

Mega's right - Ralox is superior to other SERMS because it has a stronger binding affinity to the e2 receptor in breast tissue. It also reduces IGF-1, GH, etc less than Nolva so you don't have to worry about that potential side effect.
Nolva is a fine second choice if your not willing to spend the cash on ralox provided you adjust the dosage/duration appropriately.

Of course surgery is the only real fool proof solution is you have legit full on gyno but I understand that, financially, it isn't always a viable option for some people

 

[Megatron28]

Other than last night (which no one responded), this would be the first time me asking about anything for gyno. I'd like to use what I have on hand and thats nolva, either way it should work and I asked the question just wondering.

http://www.steroidology.com/forum/anabolic-steroid-forum/677911-500mg-test-e-no-sex-drive.html

Raloxifene was recommended in this thread.

 

[omgmike1]

Mega's right - Ralox is superior to other SERMS because it has a stronger binding affinity to the e2 receptor in breast tissue. It also reduces IGF-1, GH, etc less than Nolva so you don't have to worry about that potential side effect.
Nolva is a fine second choice if your not willing to spend the cash on ralox provided you adjust the dosage/duration appropriately.

Of course surgery is the only real fool proof solution is you have legit full on gyno but I understand that, financially, it isn't always a viable option for some people

I'll have to remember to get ralox during my next batch. How much diff would u say ralox compared to nolva in terms of lowering IGF1, GH is? Is it just a little bit or a major diff... that it would REALLY be worth going out of my way to purchase ralox over nolva?

Even so though, I was looking at a lot of old threads in the past talking about this and they say that using ralox or nolva during cycle is fine, it does lower IGF1 and GH, but not nearly as bad as people make it out to be and that it's over rated? Opinions/thoughts Mr?

500mg test e, no sex drive..?

Raloxifene was recommended in this thread.

that was over a year ago man and that was when I was clueless about 90% of stuff. Go ahead and pull up a lot of other guys threads when they started and I'm sure they over reacted like me.

PS: I don't know how u specifically find my old threads lol. U must have them saved on a notepad or something man, hilarious..

 

[Megatron28]

I'll have to remember to get ralox during my next batch. How much diff would u say ralox compared to nolva in terms of lowering IGF1, GH is? Is it just a little bit or a major diff... that it would REALLY be worth going out of my way to purchase ralox over nolva?

Even so though, I was looking at a lot of old threads in the past talking about this and they say that using ralox or nolva during cycle is fine, it does lower IGF1 and GH, but not nearly as bad as people make it out to be and that it's over rated? Opinions/thoughts Mr?

This is covered in the FAQs thread found in my signature. Austinite had a great writeup on it.

 

[Mrrippedzilla]

Posted this study in the Nolva to increase test thread but here it is again:
Neuroendocrine regulation of growth hormone and androgen axes by selective estrogen receptor modulators in healthy men. - PubMed - NCBI

20mg Nolva caused a 25% reduction in IGF-1 levels while ralox only caused an insignificant decrease (approx. 2%) with 120mg - IMO this difference is enough to pay attention to when your using high-ish doses for longer periods of time (treating gyno, etc).
The fact is Ralox is better at combatting gyno than Nolva therefore yes - its worth purchasing if you want to give yourself the best possible chance of dealing with the issue.

I'm no gyno expert so I also recommend reading Austinite's thread on this like Mega suggested.
I have no idea why that was removed as a sticky....but I digress.

 

[omgmike1]

Posted this study in the Nolva to increase test thread but here it is again:
Neuroendocrine regulation of growth hormone and androgen axes by selective estrogen receptor modulators in healthy men. - PubMed - NCBI

20mg Nolva caused a 25% reduction in IGF-1 levels while ralox only caused an insignificant decrease (approx. 2%) with 120mg - IMO this difference is enough to pay attention to when your using high-ish doses for longer periods of time (treating gyno, etc).
The fact is Ralox is better at combatting gyno than Nolva therefore yes - its worth purchasing if you want to give yourself the best possible chance of dealing with the issue.

I'm no gyno expert so I also recommend reading Austinite's thread on this like Mega suggested.
I have no idea why that was removed as a sticky....but I digress.

Dang 25% vs 2%? That defo is worth going out of the way to buy that stuff.
Thanks

PS: I read the sticky, it gives dosages and details, but it doesn't say how they compare in TERMS of reduction in IGF and GH, just that ralox in general is better.

 

[Jean-Claude]

- Animal studies are used to generate an HYPOTHESIS (an educated guess) that can be tested out at a later date in humans.
I actually know a fair few researchers and even they admit that the results are interesting but have ZERO applicability to humans in reality UNTIL the results can be confirmed via human trials. So your completely wrong about it being "applicable" to us.

Who needs the physiology lesson now hmm?

Wow the first paragraph is basically pretty much exactly what I said before as to why we do these studies on animals just said in different words. At the end of the day A SHITLOAD of discoveries have been made in medicine, physiology, biology etc. because of reasearches that had first been made on animals. Obviously more often than not, there are nuances to be made and that is why I said "partly".. It is still very possible that Nolva could have similar effects in humans on the long run.

Well appearantly you know a bit more than I thought, you do need a lesson on how to fucking read though, pretty much everything you wrote isn't in contradiction to what I said. And another lesson on how not to express yourself like an arrogant asshole maybe! You know you could have posted all this constructive information without being a little bitch in the first place!