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11/12/2018 5:48 pm
Yes but Anadrol has to be given in bigger amounts due to its low binding affinity to the AR.
There are people making twice the gains on 100 mg a day anadrol than on 750 mg of testosterone. The difference in dose per day is barely 30%. While the RBA is undetectable in comparison to testosterone. There is clearly no real correlation between the RBA and the potency in vivo.
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But that's true, in vivo bioactivity of androgens could be influenced not only by binding affinity to receptors but also by factors such as absorption, binding to serum proteins and metabolism. However, the potency of 19-Nor is primarily related to its higher affinity to AR.
How can you state with any degree of accuracy ? You DON'T and CAN'T know what the result of increased potency of 19Nor is given the 20 or so different things that difference would be based on. In fact this very debate has actually exposed there is no reason to assume that 19Nor is necessarily more potent mg for mg, than C19.
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Yes, that data is not available. But i think that a simple study which compare LBM increase between a T and a N group, could be enough for most physical trainers and steroid users.
Only if you have a sufficiently large and diverse group, and sufficient means to control them 24/7. That would be a costly study.Can't imagine anyone undertaking a study that requires 200+ people from a diverse population to stay in a closed facility for 12 weeks, with a strict diet and training regimen. This is also the reason why you'll find such studies are rarely used as reference material, their unreliable nature.
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Endogenous nandrolone production is refered as a side reaction to enzymatic aromatisation, it can only be found in low amounts. Even in pregnant women whose are known to have higher 19-nor and its metabolites levels, the 2 ng/mL limit is unlikely reached.
I have not wanted to say that natural 19-nor is an unfuctionnal metabolite, only that its role is not major in the man endocrinal equilibrium.
About the role of endogenous nandrolone :
"To the best of our knowledge, these studies are the first to examine the effect of Nandrolone on endometrial mitogenesis and gene expression and to evaluate its possible actions during pregnancy. Although the concentrations of Nandrolone in uterine luminal fluids have not been accurately quantified, the recent report that a major steroid product of the stably expressed porcine P450arom type III (blastocyst) isoform is Nandrolone suggests physiological relevance for this androgen. Nandrolone can bind to the ER� isoform, albeit with low affinity. However, our findings that Nandrolone behaves more like an androgen than an estrogen and the limited ER� expression in the pig endometrium during early pregnancy (unpublished data), suggest that the functional effects of Nandrolone in vivo are likely to be mediated via AR."
That much we already know, since nandrolone only binds the ER sufficiently in the mM range, and exerts most of its estrogenic action via the AR.
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Gynecomastia and many other side effects have been reported by physicians, scientists and users at therapeutical doses of TE. Nandrolone is generally said to have less side effects.
Yes, usually in test subjects that weigh about 160 lbs, and never trained before, usually suffering from some pathology. And yes, over a wide range of therapeutic treatments, you are bound to find a few case reports that represent that 0,5% of the population that represents the people who are hypersensitive to aromatisation.
And nandrolone's reputation as a safe drug stems from its low androgenic potency, not its estrogenic mildness.
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I agree. But because real Deca-Durabolin (100mg/ml or less) has strongly been used by the past, it could have played a role in the nandrolone's bad reputation.
True, but in those days, because of the high injection volume, doses were lower as well, which evens out the balance.
[auote]Metabolites detection time is not a relevant information to compare steroids potency in term of HPT axes suppression. This detection time is linked to the ester which has been used in conjonction whith the parent drug. How long do you think we could find detectable metabolites after a Testosterone decanoate cycle in a castrated and adrenalectomized subject ?
My guess is, none of them quite as long, since deca is the only drug that is detected so long. Not even boldenone undecylenate is detectable half that long.
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There is no reason to think that slight steroid's traces are able to delay HPTA recovery.
Primobolan-depot is detectable for months too and no-one worries about its suppressive effect.
Well between 6 months and 24 months is a HUGE difference. And half-life does matter in supression. The principle of half-life states that of the dose in serum, over that time, half is removed. Assuming detection limits for steroid metabolites are roughly the same, given the metabolites looked for are usually those most stable and longest present, then you can state that nandrolone is removed over a 4 times longer period than Primo, and thus levels over a same amount of time are 4 times higher for a similar administered dose.
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And I hope they do, I wish other opinions too.
Not all who read will feel compelled to reply, some may just take your words to be true and run with them, with all consequences that brings.
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This remark disturbs me. When I have written that what I say is only for theoretic purpose, it's not only to preserve me against legal action, it's because it is the simple truth. I want to write with all my honesty and write what I think without to be scared by how people will interpret it. I think this board is made for adults, clevers and educated guys whoses are able to make their own opinions. When Nandi has written his excellent article about thyroid hormones and reveals the truth about the irrational fear commonly carried in the bodybuilding's world, it was not to promote their use. The same thing for me when I say that nandrolone is maybe not as suppressive as it is often believed.
And nandrolone's suppressive effect (like the other androgens) has been proven to be totally reversible.
... over a given period of time. There have been plenty of case reports from bodybuilders using steroids that failed to recuperate, many of them with nandrolone.
You are right, we shouldn't be scared shitless as was the habit in the late '80's and the '90's, but at the same time we have to consider the merit of suggesting there isless risk when there is no explicit data to back that up, and there are better alternatives at hand
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
11/12/2018 6:40 pm
I know it and I have read it many and many times, and so what ?
In this study we can see that an injection of 100mg nandrolone decanoate lowers endogenous T from 18 nM (baseline) to 5nM at day five. Then the recovery processus starts at day ten and total recovery is achieved between days 25 and 30.
That's mean that nandrolone is suppressive ... someone has claimed the opposite ? When we speak about the suppressive effect of androgens, we deal with a relative concept, that's mean to learn comparative datas.
Nandrolone is suppressive but in the light of this thread we can think that its potency in this regard could be comparable to testosterone (or slighty lesser, slighty greater), not the terrifying stuff sometimes described.
Terrifying is overboard. Among all the pharmaceutically used drugs, there isn't one that is monsterously supressive or harmful. What has been suggested many times in the past half a decade is that comparatively, which is what you are saying, nandrolone is more supressive than these other drugs, and given its lack of real benefit, and other shortcomings, over other drugs, that there are better, more efficient and safer alternatives. That is after the idea, to promote the most efficient and safe use of steroids, by those who make that choice.
No one is out to demonize nandrolone, as I said, its a good drug in a therapeutic setting, merely pointing out its flaws and suggesting there are better alternatives. Surely you could agree with that ?
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
11/12/2018 7:35 pm
when i first entered the scene deca was a mainstay, lately it seems to have lost some of the attraction.jb
I guess because people are more conscious shoppers, looking for both bang for their buck, as well as something they can freely use to experiment in relative safety.
In the past fear of androgenic side-effects, that are very rare in healthy men using normal doses, was all the rage, and in that background, deca was a godsend. Now we are debunking some of the scaremongering and some people stick to deca but aren't so afraid to try other things, while others seem to realize that there is better things out there than deca entirely, that aren't as harmful as they thought, and in turn realizing that deca was more harmful than they thought.
Its a strange time now, with some people awakening still from those dark ages, and others who are just starting, thinking these old myths are the new gospel. It becomes hard to know when you are playing the devil's advocate and when not, as sometimes its better to preach caution (always use test, always use proper PCT, avoid orals where possible) and sometimes its better to preach a little more open-mindedness (androgenic sides are relatively rare, gyno is relatively rare, you don't need an anti-estrogen with every cycle).
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
Topic starter 11/12/2018 8:09 pm
There are people making twice the gains on 100 mg a day anadrol than on 750 mg of testosterone. The difference in dose per day is barely 30%. While the RBA is undetectable in comparison to testosterone. There is clearly no real correlation between the RBA and the potency in vivo.
I disagree. RBA alone cannot be taken as a perfect measuring value to estimate AAS potency but it remains a very important notion in pharmacology. When you compare AA17 and non-AA17 steroids you must take into account the great difference in their resistance to metabolism.
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How can you state with any degree of accuracy ? You DON'T and CAN'T know what the result of increased potency of 19Nor is given the 20 or so different things that difference would be based on. In fact this very debate has actually exposed there is no reason to assume that 19Nor is necessarily more potent mg for mg, than C19.
It is not really my statement but the statement of all the scientists and researchers. Here, we compare steroids with comparable resistance (low) to metabolism. So, their respective RBA are relevant to estimate their potencies. Except in tissues with 5-a reductase, nandrolone has a greater affinity for the AR, and this information is correlate by a superior capacity to induce growth in these tissues.
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Only if you have a sufficiently large and diverse group, and sufficient means to control them 24/7. That would be a costly study.Can't imagine anyone undertaking a study that requires 200+ people from a diverse population to stay in a closed facility for 12 weeks, with a strict diet and training regimen. This is also the reason why you'll find such studies are rarely used as reference material, their unreliable nature.
Do you agree to say that we can say the same thing from the users reports you give as support to your statement that T is more anabolic and safer than nandrolone ?
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That much we already know, since nandrolone only binds the ER sufficiently in the mM range, and exerts most of its estrogenic action via the AR.
We know that nandrolone can exert estrogenic effects via the AR. But, actually, we do not know the relevance of this information and its involvements.
I quote from the study :"predicts the possibility of some troublesome feminizing effects in males, which still await examination.'
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My guess is, none of them quite as long, since deca is the only drug that is detected so long. Not even boldenone undecylenate is detectable half that long.
Well between 6 months and 24 months is a HUGE difference. And half-life does matter in supression. The principle of half-life states that of the dose in serum, over that time, half is removed. Assuming detection limits for steroid metabolites are roughly the same, given the metabolites looked for are usually those most stable and longest present, then you can state that nandrolone is removed over a 4 times longer period than Primo, and thus levels over a same amount of time are 4 times higher for a similar administered dose.
Other things have to be taken into account. Some AAS have more metabolic's pathways than others and some are more well-known and identified than others. And Nandrolone has been extensively studied. I repeat that to find inactive/weak metabolites does not mean that these (low to very low amount) metabolites are able to delay the recovery processus.
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Not all who read will feel compelled to reply, some may just take your words to be true and run with them, with all consequences that brings.
And the same thing for you.
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No one is out to demonize nandrolone, as I said, its a good drug in a therapeutic setting, merely pointing out its flaws and suggesting there are better alternatives. Surely you could agree with that ?
I can agree with the idea that users must use the drugs they are most comfortable with, by the way the (rational/irational) reasons.
11/12/2018 8:59 pm
I don't know if it's relevent to your discussion or even if it was a well conducted study but Nandi had posted a study here showing nandrolone yielded greater muscle tissue gorwth where testosterone yielded similar gains in terms of subject weight but testosterone yielded greater increase in bone density and less in muscle tissue compared to nandrolone.
I can't contribute much on the research end but this prompted me to switch 600mg's of testosterone with 300mg's of nandrolone per week in my current cycles and thus far I've gotten much better results with less sides. Now that could be on account that I'm stacking 2 drugs but I am getting better results from 400mg test and 300mg/deca per week than 1000mg's of testosterone per week.
Not very scientific and I'm only one individual but just thought I'd share.
11/12/2018 9:38 pm
I don't know if it's relevent to your discussion or even if it was a well conducted study but Nandi had posted a study here showing nandrolone yielded greater muscle tissue gorwth where testosterone yielded similar gains in terms of subject weight but testosterone yielded greater increase in bone density and less in muscle tissue compared to nandrolone.I can't contribute much on the research end but this prompted me to switch 600mg's of testosterone with 300mg's of nandrolone per week in my current cycles and thus far I've gotten much better results with less sides. Now that could be on account that I'm stacking 2 drugs but I am getting better results from 400mg test and 300mg/deca per week than 1000mg's of testosterone per week.
Not very scientific and I'm only one individual but just thought I'd share.
Don't worry, your input is considered Level 5 according to Oxford-Centre for Evidence-Based Medicine which consider this kind of opinion an expert opinion without explicit critical appraisal. So every individual's opinion is important and valued to build knowledge bases.
"The medals don't mean anything and the glory doesn't last. It's all about your happiness. The rewards are going to come, but my happiness is just loving the sport and having fun performing" ~ Jackie Joyner Kersee.
11/12/2018 10:13 pm
well put.
jb
11/12/2018 11:01 pm
[B]I disagree. RBA alone cannot be taken as a perfect measuring value to estimate AAS potency but it remains a very important notion in pharmacology. When you compare AA17 and non-AA17 steroids you must take into account the great difference in their resistance to metabolism.
There, metabolism, that's the first thing you need to take into account on top of RBA. But don't stop there, you also need to take into account the pharmacodynamics, the metabolism into active and inactive compounds, the ability to stimulate non-genomic and non-AR pathways, ability to block glucocorticoids, to block other enzymes like aromatase, 11bHSD, etc, but most importantly you need to take into account the ability of a steroid to make the AR fold so there is an N/C interaction, that can activate the activation domains, and then the ability of the created activation domains to recruit either co-repressors or co-activators.
So if you are suggesting, for even one minute, that RBA is an important measure of anabolic activity, then I suggest you start bulking on hydroxyflutamide, since that has a bigger RBA than test ...
Do you see how foolish this notion is ? The only correct estimate of anabolic activity is the ability to fold the AR, recruit cofactors, and bind and transcribe target genes.
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It is not really my statement but the statement of all the scientists and researchers. Here, we compare steroids with comparable resistance (low) to metabolism. So, their respective RBA are relevant to estimate their potencies. Except in tissues with 5-a reductase, nandrolone has a greater affinity for the AR, and this information is correlate by a superior capacity to induce growth in these tissues.
It is your statement, researchers aren't so blunt. I refer to the Holterhus study, look up the activation caused at normal doses for AAS users, and examine the difference in target gene activation between testosterone and nandrolone. even if nandrolone has a higher RBA (which I sincerly doubt, I've seen numbers between 0,8 and 2,4, none of them with adequate backing) then it would still be only as, or likely less potent than testosterone. Several decades of steroid use have demonstrated the same.
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Do you agree to say that we can say the same thing from the users reports you give as support to your statement that T is more anabolic and safer than nandrolone ?
No, but I didn't say it for nandrolone either, you did. I think the most accurate measure requires identification of target genes and quantification of output of those genes after AR activation by a certain steroid. I think studies like the one you suggested are impossible to set up, unless you married Paris Hilton and took her for every cent she had.
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We know that nandrolone can exert estrogenic effects via the AR. But, actually, we do not know the relevance of this information and its involvements.
I quote from the study :"predicts the possibility of some troublesome feminizing effects in males, which still await examination.'
Indeed, and now lets set that opposed to other steroids that "do not have the possibility of troublesome feminizing effects". I would classify that as safer.
Score 1 against nandrolone
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Other things have to be taken into account. Some AAS have more metabolic's pathways than others and some are more well-known and identified than others. And Nandrolone has been extensively studied. I repeat that to find inactive/weak metabolites does not mean that these (low to very low amount) metabolites are able to delay the recovery processus.
To clear the body of steroids, they are transformed into more soluble and glucuronidatable metabolites. The fact that a steroid has trouble clearing the body, means that it resides there in a form that isn't cleared to easily, so you certainly can't assume that it is there in a weak or inactive form, on the contrary.
But lets for a minute follow your logic. It doesn't mean that there is supression, but it does mean that there COULD BE supression. Something that use of the product confirms. Set that opposed to steroids that don't have metabolites that reside that long, then it is a very safe statement to call those products safer in that regard.
Score two against nandrolone
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And the same thing for you.
Of course.
That is why I state it in my signature, why I prefer to err on the safe side, and when I do on occassion play the devils advocate I take to explicitly state it in every post that I'm just theorizing. See my point ?
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I can agree with the idea that users must use the drugs they are most comfortable with, by the way the (rational/irational) reasons. []
I suggest they use what they know to be safest and most effective, that happens to be testosterone for all the reasons discussed and many, many more.
But I doubt there will be more research into it, after the studies on AR mediated estrogenic effects on top of all the other stuff, taken together with the heavy development of SARMS, deca will be buried on a therapeutic front.
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
11/12/2018 11:43 pm
I don't know if it's relevent to your discussion or even if it was a well conducted study but Nandi had posted a study here showing nandrolone yielded greater muscle tissue gorwth where testosterone yielded similar gains in terms of subject weight but testosterone yielded greater increase in bone density and less in muscle tissue compared to nandrolone.I can't contribute much on the research end but this prompted me to switch 600mg's of testosterone with 300mg's of nandrolone per week in my current cycles and thus far I've gotten much better results with less sides. Now that could be on account that I'm stacking 2 drugs but I am getting better results from 400mg test and 300mg/deca per week than 1000mg's of testosterone per week.
Not very scientific and I'm only one individual but just thought I'd share.
Like the other guys said, opinions much welcomed. And you are right. of course, doses of higher than 750 a week of testosterone seem t no longer linearly increase results, as opposed to most other steroids.
I also see less objection to using deca with testosterone, rather than suggesting deca is just as safe and using it instead of testosterone as BB suggests.
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
Topic starter 12/12/2018 12:28 am
There, metabolism, that's the first thing you need to take into account on top of RBA.
Not sure to understand your remark. RBA are based on Kd values (aka dissociation constant), i will not detail the equation and the method of determination here, but Kd is the ligand's concentration needed to achieve an occupation of half the receptors. It follows that the smaller Kd, the stronger the binding.
This is a useful measure to describe the strength of binding between receptors and their ligands.
After, we must know if the ligand acts as an agonist or an antagonist, but I think here we deal with agonists refered as "analogs", so to compare agonists from a same family (AAS), RBA is an important factor to estimate their respective potencies.
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But don't stop there, you also need to take into account the pharmacodynamics, the metabolism into active and inactive compounds, the ability to stimulate non-genomic and non-AR pathways, ability to block glucocorticoids, to block other enzymes like aromatase, 11bHSD, etc, but most importantly you need to take into account the ability of a steroid to make the AR fold so there is an N/C interaction, that can activate the activation domains, and then the ability of the created activation domains to recruit either co-repressors or co-activators.
Yes ... but I do not see how it argues against what I have said in previous answers.
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So if you are suggesting, for even one minute, that RBA is an important measure of anabolic activity, then I suggest you start bulking on hydroxyflutamide, since that has a bigger RBA than test ...
I confirm that RBA is an important measure to estimate anabolic potency in terms of doses-concentrations/receptors/effects relationship. But, please keep serious, I speak about agonists from the same family, not antagonists like hydroxyflutamide ...
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Do you see how foolish this notion is ?
No, sorry I don't.
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The only correct estimate of anabolic activity is the ability to fold the AR, recruit cofactors, and bind and transcribe target genes.
Okay, and do you have informations about differences between AAS in terms of AR folding, cofactors recruitement, target genes binding and transcription ? Actually, we do not know how much AAS are different in these regards. Now, it is the easy explanation : AAS are different because they bind and transcribe different (or in a different manner) target genes ... In fact, we know little to nothing about that. Maybe future studies will give us more informations and describe great differences in this regard ... and maybe not. What we know for sure : all AAS are able to promote muscle or prostatic tissues growth, that's mean that they are able to bind and transcribe the involved genes. For example, it has been described that DHT is required for the development of external sex organs, but is has also been demonstrated that greater amounts of T can compensate for the lack of DHT.
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It is your statement, researchers aren't so blunt. I refer to the Holterhus study, look up the activation caused at normal doses for AAS users, and examine the difference in target gene activation between testosterone and nandrolone. even if nandrolone has a higher RBA (which I sincerly doubt, I've seen numbers between 0,8 and 2,4, none of them with adequate backing) then it would still be only as, or likely less potent than testosterone. Several decades of steroid use have demonstrated the same.
Not my statement, I can quote many studies where 19-nor is claimed to be at least as potent and often more (twice ?) potent than T.
I can't argue against "several decades of steroid use" ... but I have noticed that AAS with weak potencies reputations are often those whose are only availabe in low concentrations. Because the limits linked to injection's volumes, these AAS have been used in lower amounts. I have often read reports with 1000mg/week of T and rarely with 1000mg/week of nandrolone or methenolone. Because it's easier to inject 4ml of sustanon than 10ml of Deca-durabolin or Primobolan (and we know that 1000mg/4ml will give a greater maximal AAS concentration, "peak", than 1000mg/10ml) . Users often compare vials to vials (or tabs to tabs) and not real amounts (mg).
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Indeed, and now lets set that opposed to other steroids that "do not have the possibility of troublesome feminizing effects". I would classify that as safer.
But actually we do not know all about that. And even DHT (or its metabolite) is implicated.
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To clear the body of steroids, they are transformed into more soluble and glucuronidatable metabolites. The fact that a steroid has trouble clearing the body, means that it resides there in a form that isn't cleared to easily, so you certainly can't assume that it is there in a weak or inactive form, on the contrary.
But lets for a minute follow your logic. It doesn't mean that there is supression, but it does mean that there COULD BE supression. Something that use of the product confirms. Set that opposed to steroids that don't have metabolites that reside that long, then it is a very safe statement to call those products safer in that regard.
I find this reasonning shaky. Nandrolone's pharmacokinetic is not special as we can see in the Minto or other studies and linked to the ester used with the parent drug. The same thing for T and the others.
How can you believe that traces of nandrolone or metabolites are able to delay the recovery processus ? In the Minto study, natural T has returned to the baseline in one month. I'm sure a doping-test in day 30 would be able to detect nandrolone or metabolites despite the fact that T levels are restored.
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I suggest they use what they know to be safest and most effective
100% agree.
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that happens to be testosterone for all the reasons discussed and many, many more.
Your statement.
During years, scientists have tried to create other AAS because they were not satisfied by testosterone.
Now, to be clear I am not against T, for me AAS are mostly interchangeable to promote muscle, you have just to adapt the doses to their potencies.
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Its a strange time now, with some people awakening still from those dark ages, and others who are just starting, thinking these old myths are the new gospel.
When we fight myths we must take caution to don't create new ...
12/12/2018 1:21 am
I also see less objection to using deca with testosterone, rather than suggesting deca is just as safe and using it instead of testosterone as BB suggests.
That's an important point here. Maybe in order to avoid long term supression due to Deca administration, one might want to do the following procedures (please let me know what you think):
1) When using Deca always use it with Test, never use it alone. Down here in S�o Paulo I've heard silly yound men using Deca without test and proper PCT, and having trouble with keeping strength and muscle gains after cycle and libido for many many months.
2) Limit the amount of Deca for anything between 200-400 mg/week in order to avoid strong and long-term supression. In Brazil, recreational athletes use Deca at 200 mg/week stacked with test at 500 week. On top of that, it's not easy to effort Deca for more than 200 mg/week.
3) Use it with HCG at maybe 250-500 IU/week since week-1 in order to avoid further supression and optimize PCT.
4) Stop nandrolone maybe 2 weeks before test in order to optimize PCT.
5) Never use it without proper PCT.
6) Do strictly monitoring blood work before, during and after cycle.
7) In order to monitor testicular volume and atrophy maybe it might be a good idea to use a Prader's Orchidometer.
"The medals don't mean anything and the glory doesn't last. It's all about your happiness. The rewards are going to come, but my happiness is just loving the sport and having fun performing" ~ Jackie Joyner Kersee.
12/12/2018 2:11 am
[B]Not sure to understand your remark. RBA are based on Kd values (aka dissociation constant), i will not detail the equation and the method of determination here, but Kd is the ligand's concentration needed to achieve an occupation of half the receptors. It follows that the smaller Kd, the stronger the binding.
This is a useful measure to describe the strength of binding between receptors and their ligands.
After, we must know if the ligand acts as an agonist or an antagonist, but I think here we deal with agonists refered as "analogs", so to compare agonists from a same family (AAS), RBA is an important factor to estimate their respective potencies.
I'm pretty sure you didn't understand my remark :
BEFORE, you must first determine how much unchanged ligand reaches your designated receptors, hence my remark about pharmacodynamics, secondly the appearance of metabolites, either inactove (reducing potency) or active (increasing potency) or active at another receptor (safety, interference downstream of the receptor, etc) Then you determine your RBA, only then do you determine if it is an agonist or antagonist, and THEN you still need to determine how good of an antagonist it is, REGARDLESS of RBA ...
Hence RBA is only a very small piece of the puzzle in determining anabolic effect.
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Yes ... but I do not see how it argues against what I have said in previous answers.
See above, it argues against the use of RBA as a predictor of anabolic efficacy, as you did suggest repeatedly in previous answers. Both upstream and downstream effectors, especially the downstream (since they determine whether a ligand has anywhere from 0 to 100% efficacy regardless of RBA), affect the potency of a drug.
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I confirm that RBA is an important measure to estimate anabolic potency in terms of doses-concentrations/receptors/effects relationship. But, please keep serious, I speak about agonists from the same family, not antagonists like hydroxyflutamide ...
This is serious, some antagonists, like flutamide, do cause the N/C fold in the AR and CAN act as agonists if there is an overexpression of co-activators or a shortage of co-repressors. The only complete antagonists are those that do not cause the N/C fold and hence cannot activate the AF2 when ligand binds.
i'm sorry, but this is a pointless discussion if you don't know the intricacies of Androgen receptor function.
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No, sorry I don't.
Ok, perhaps you will allow me to recommend some reading on androgen receptor functionality so you can better grasp the notion ? I have some reviews if you want them.
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Okay, and do you have informations about differences between AAS in terms of AR folding, cofactors recruitement, target genes binding and transcription ? Actually, we do not know how much AAS are different in these regards. Now, it is the easy explanation : AAS are different because they bind and transcribe different (or in a different manner) target genes ... In fact, we know little to nothing about that. Maybe future studies will give us more informations and describe great differences in this regard ... and maybe not. What we know for sure : all AAS are able to promote muscle or prostatic tissues growth, that's mean that they are able to bind and transcribe the involved genes. For example, it has been described that DHT is required for the development of external sex organs, but is has also been demonstrated that greater amounts of T can compensate for the lack of DHT.
What we know is that AAS do activate different genes to different extents. The Holterhus study proves, as does the fact that nandrolone can activate ERE's with a 3 times higher efficiency than test or DHT. There is no doubt that even with commonly used AAS there is a distinct difference in their activation of target genes. Period.
If you want to further establish that fact take into account the difference in potency of two drugs that are fairly resistant to metabolization (so that only the parent compound plays a nominal role) and with similar RBA's. As well as their difference in anabolic and androgenic ratio's. This proves not only different levels of activation, but differentiation in levels of activation in different tissues, such as the prostate and the muscle.
If you wish to dismiss the function of the AR entirely and continue to convince yourself that the RBA is the only or even the best predictor of anabolic potency, then I'm sorry, but I cannot contend with that unscientific position.
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Not my statement, I can quote many studies where 19-nor is claimed to be at least as potent and often more (twice ?) potent than T.
I can't argue against "several decades of steroid use" ... but I have noticed that AAS with weak potencies reputations are often those whose are only availabe in low concentrations. Because the limits linked to injection's volumes, these AAS have been used in lower amounts. I have often read reports with 1000mg/week of T and rarely with 1000mg/week of nandrolone or methenolone. Because it's easier to inject 4ml of Sustanon than 10ml of Deca-durabolin or Primobolan (and we know that 1000mg/4ml will give a greater maximal AAS concentration, "peak", than 1000mg/10ml) . Users often compare vials to vials (or tabs to tabs) and not real amounts (mg).
These days there is no such thing as a steroid that is available only in low quantities. Look at oxandrolone. You still require 80 mg a day to see a really decent anabolic effect, and that effect is nowhere near as efficient as testosterone, despite the fact that it is extremely resistent to metabolism. Look at methenolone. It has a higher RBA than testosterone. Yet even at 1g a week, it is nowhere near as anabolic ...
Second point, and for the third time IT IS your statement. you may have a zillion studies that say nandrolone does this more than T, and that nandrolone has a higher RBA than T (but the variance in that number alone across studies demonstrates the idiocy of using that as a measure) and that those findings may suggest nandrolone is stronger, or even that they find nandrolone to be stronger in a certain assay. It is you who determined that meant that "nandrolone is stronger than testosterone"
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But actually we do not know all about that. And even DHT (or its metabolite) is implicated.
We know that the possibility of testosterone or DHT, unchanged, causing the same effects are three times lower, since it was a comparative study. Now if you want to talk about metabolites, that's a different story, because nandrolone has very similar metabolites, such as 3beta-19Nor-androstanediol, which is structurally even more like estradiol and likely a stronger estrogen as well.
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I find this reasonning shaky. Nandrolone's pharmacokinetic is not special as we can see in the Minto or other studies and linked to the ester used with the parent drug. The same thing for T and the others.
How can you believe that traces of nandrolone or metabolites are able to delay the recovery processus ? In the Minto study, natural T has returned to the baseline in one month. I'm sure a doping-test in day 30 would be able to detect nandrolone or metabolites despite the fact that T levels are restored.
For christ's sake, get with the argument. The argument does not concern trace levels. The argument was that if trace levels of nandrolone can be detected 4 times longer than any other known steroid that nandrolone, by comparison halves at a 4 times slower rate. That means the minimal supressive amount present in the body will be there for a period 4 times longer than for any other steroid. Do you understand that ?
Plus, if you contention remains that nandrolone's RBA is higher and therefor is so much stronger than other steroids, then you must also concede that it is more supressive. If it is not, then your whole argument dismissing post-receptor events goes down the drain with it, so its time to make a choice : either nandrolone is more supressive, or you have to accept that there is differential regulation of target genes. You can't continue to deny both.
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Your statement.
During years, scientists have tried to create other AAS because they were not satisfied by testosterone.
Now, to be clear I am not against T, for me AAS are mostly interchangeable to promote muscle, you have just to adapt the doses to their potencies.
My well-founded statement. Scientist have long searched for AAS with a greater androgenic/anabolic dissociation because they sought to treat a wide variety of people, like children, elderly and women. In AAS use, if we are the least bit ethical at least, we are talking about healthy men. In which case such a thing is not a necessity, as virilization is not an issue. On the contrary.
My most important argument for testosterone is in fact that we know so little about AAS and how they function individually. testosterone is an extremely versatile hormone, with millions of functions, and metabolites that have millions of functions. When you use steroids without testosterone, you essentially replace your own testosterone with those AAS, and those AAS do not fulfill those millions of functions and do not metabolize into products with those same millions of functions. Long term exposure to such depriving conditions can only be regarded as unsafe and unethical at best.
quote:
When we fight myths we must take caution to don't create new ...
True enough, which is why I think it is very unsafe to dismiss nandrolone's supressive nature, when this discussion has revealed you do not have all the facts.
Mind you, neither do I , nor will anyone in the next twenty years, but that is why i take caution not to make such bold statements. I refer to testosterone as safer because its an endogenous hormone that can at the very least maintain its own function inside the body. Something no other AAS can guarantee ...
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
12/12/2018 2:43 am
That's an important point here. Maybe in order to avoid long term supression due to Deca administration, one might want to do the following procedures (please let me know what you think):1) When using Deca always use it with Test, never use it alone. Down here in S�o Paulo I've heard silly yound men using Deca without test and proper PCT, and having trouble with keeping strength and muscle gains after cycle and libido for many many months.
2) Limit the amount of Deca for anything between 200-400 mg/week in order to avoid strong and long-term supression. In Brazil, recreational athletes use Deca at 200 mg/week stacked with test at 500 week. On top of that, it's not easy to effort Deca for more than 200 mg/week.
3) Use it with HCG at maybe 250-500 IU/week since week-1 in order to avoid further supression and optimize PCT.
4) Stop nandrolone maybe 2 weeks before test in order to optimize PCT.
5) Never use it without proper PCT.
6) Do strictly monitoring blood work before, during and after cycle.
7) In order to monitor testicular volume and atrophy maybe it might be a good idea to use a Prader's Orchidometer.
All very good points, especially number 4.
Point 1 has been supported by users throughout the last 4 decades. Difficulty in maintaining mass and strength, even with good PCT, prolonged libido problems, more after than during a cycle and so on.
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
Topic starter 12/12/2018 3:17 am
BEFORE, you must first determine how much unchanged ligand reaches your designated receptors, hence my remark about pharmacodynamics, secondly the appearance of metabolites, either inactove (reducing potency) or active (increasing potency) or active at another receptor (safety, interference downstream of the receptor, etc) Then you determine your RBA, only then do you determine if it is an agonist or antagonist, and THEN you still need to determine how good of an antagonist it is, REGARDLESS of RBA ...
Yes ... and ? Nandrolone is not an agonist ? It is not able to promote virilization and muscle growth ?
quote:
Hence RBA is only a very small piece of the puzzle in determining anabolic effect.
True, but when you make a comparison, you have to speak about the main factor. If I compare T and stanozolol, I will not speak so much about RBA, if I compare T and N, I do.
quote:
See above, it argues against the use of RBA as a predictor of anabolic efficacy, as you did suggest repeatedly in previous answers. Both upstream and downstream effectors, especially the downstream (since they determine whether a ligand has anywhere from 0 to 100% efficacy regardless of RBA), affect the potency of a drug.
No, it argues against the use of RBA as a sole predictor. I have never said that RBA is always the relevant point to compare all AAS. And yes other factors have to be taken into account too (never said the contrary ...). But RBA remains an important notion, especially when you compare T and N.
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This is serious, some antagonists, like flutamide, do cause the N/C fold in the AR and CAN act as agonists if there is an overexpression of co-activators or a shortage of co-repressors. The only complete antagonists are those that do not cause the N/C fold and hence cannot activate the AF2 when ligand binds.
Yes ... and ? This thread is about T analogs or derivatives, not about other chemical compounds, AR agonists/antagonists. Because their closely chemical structures AAS have closely biological activities.
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i'm sorry, but this is a pointless discussion if you don't know the intricacies of Androgen receptor function.
I prefer smile ... I think unpacking our degrees has nothing to do on a board, but plz do not think that I am not aware with the notions we deal in this thread. I am not fluent in english and it's sometimes difficult to me to explain my ideas and I prefer argue on the "hot point" than to do a school lesson.
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Ok, perhaps you will allow me to recommend some reading on androgen receptor functionality so you can better grasp the notion ? I have some reviews if you want them.
Of course. My mind is always open. I have a lot in my filing cases, but yours are welcome too.
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What we know is that AAS do activate different genes to different extents.
Yes, we know that they could activate different genes to different extents, nothing more. For me, more questions than answers.
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If you wish to dismiss the function of the AR entirely and continue to convince yourself that the RBA is the only or even the best predictor of anabolic potency, then I'm sorry, but I cannot contend with that unscientific position.
No it's not my reasonning. But before to activate genes, an AAS must bind ... Kd and RBA values are informatives, especially when you want to compare the potency (meaning dose-concentration/receptors/effects relationship) of two almost similar compounds. If nandrolone has a lesser Kd, that's mean that you need a lesser concentration to bind half the receptors. If for you it is not an important value to estimate a drug potency, I cannot argue more ... but it is in pharmacologic's books.
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These days there is no such thing as a steroid that is available only in low quantities. Look at oxandrolone. You still require 80 mg a day to see a really decent anabolic effect, and that effect is nowhere near as efficient as testosterone, despite the fact that it is extremely resistent to metabolism. Look at methenolone. It has a higher RBA than testosterone. Yet even at 1g a week, it is nowhere near as anabolic ...
Difficult to argue because it's unverifiable datas.
quote:
Second point, and for the third time IT IS your statement. you may have a zillion studies that say nandrolone does this more than T, and that nandrolone has a higher RBA than T (but the variance in that number alone across studies demonstrates the idiocy of using that as a measure) and that those findings may suggest nandrolone is stronger, or even that they find nandrolone to be stronger in a certain assay. It is you who determined that meant that "nandrolone is stronger than testosterone"
Again it is not my statement. I do not speak here about RBA but about studies where nandrolone is said to be more potent than T for different purposes. In fact, except by its 5-a reducted metabolites, I do not remember any study where T was said to be more potent than nandrolone, never mind the field.
Effects of nandrolone decanoate compared with placebo or testosterone on HIV-associated wasting.
"Conclusions Treatment with nandrolone decanoate increased body weight when compared with placebo and testosterone. Nandrolone decanoate treatment resulted in greater increases in fat-free mass than placebo and demonstrated a trend for a significant increase when compared with testosterone."
In fact we can generally see a good correlation between bioactivity and binding affinity to AR, even if like we have said before other factors such as absorption, binding to serum proteins and metabolism have to be taken into account too.
quote:
We know that the possibility of testosterone or DHT, unchanged, causing the same effects are three times lower, since it was a comparative study. Now if you want to talk about metabolites, that's a different story, because nandrolone has very similar metabolites, such as 3beta-19Nor-androstanediol, which is structurally even more like estradiol and likely a stronger estrogen as well.
Yes, it is true. But is it relevant when we compare T and N anabolic's effect ?
quote:
For christ's sake, get with the argument. The argument does not concern trace levels. The argument was that if trace levels of nandrolone can be detected 4 times longer than any other known steroid that nandrolone, by comparison halves at a 4 times slower rate. That means the minimal supressive amount present in the body will be there for a period 4 times longer than for any other steroid. Do you understand that ?
Please can you quote some datas because I do not see the things like you. The fact that nandrolone could be detected 4 times longer than another AAS does not mean that the minimal supressive amount stay in the body for a period 4 times longer.
The pharmacokinetic studies about nandrolone have not shown anything special.
Sorry but I do not see any logic in this reasonning.
quote:
Plus, if you contention remains that nandrolone's RBA is higher and therefor is so much stronger than other steroids, then you must also concede that it is more supressive. If it is not, then your whole argument dismissing post-receptor events goes down the drain with it, so its time to make a choice : either nandrolone is more supressive, or you have to accept that there is differential regulation of target genes. You can't continue to deny both.
It sounds like you have missed the thread ... the subject was about nandrolone suppressive effect and I have pointed up the importance of aromatisation in LH inhibition as a first step (but of course not the sole) in AAS suppressive effect.
Because nandrolone is a weaker substrate for aromatisation, it could be less inhibitory in this regard. Of course, in the regard of the other regulation mechanisms, it is certainly more potent than T. That is what I have said in this thread, not that nandrolone is not suppressive, not that nandrolone is perfectly safe, not that nandrolone is the best drug to use ...
quote:
My well-founded statement. Scientist have long searched for AAS with a greater androgenic/anabolic dissociation because they sought to treat a wide variety of people, like children, elderly and women. In AAS use, if we are the least bit ethical at least, we are talking about healthy men. In which case such a thing is not a necessity, as virilization is not an issue. On the contrary.
Right.
quote:
My most important argument for testosterone is in fact that we know so little about AAS and how they function individually. testosterone is an extremely versatile hormone, with millions of functions, and metabolites that have millions of functions. When you use steroids without testosterone, you essentially replace your own testosterone with those AAS, and those AAS do not fulfill those millions of functions and do not metabolize into products with those same millions of functions. Long term exposure to such depriving conditions can only be regarded as unsafe and unethical at best.
Mind you, neither do I , nor will anyone in the next twenty years, but that is why i take caution not to make such bold statements. I refer to testosterone as safer because its an endogenous hormone that can at the very least maintain its own function inside the body. Something no other AAS can guarantee ...
Right too. But to say that T is the best drug to replace T is not an amazing discovery. But I think here we do not speak about HRT but about the administration of AAS for an athletic performance enhancement purpose. It is not because T is the natural androgen than it is the safest when you administer it exogenously and in supraphysiological amounts.
quote:
True enough, which is why I think it is very unsafe to dismiss nandrolone's supressive nature, when this discussion has revealed you do not have all the facts.
I have not dismissed nandrolone's suppressive nature, this is only your opinion and I refute. I have said what I think in all integrity. If we consider the studies, I see no reason to believe that nandrolone is suppressive in a very different extent than T.
I am not a big fan of neverending discussions and I don't want this thread become an arm-wrestling match. This is absolutely not my goal. I hope some have consider my ideas, but I am not the guy who want to convince the others.
12/12/2018 4:05 am
You doing good Big Cat and Black Baccara, don't take to the personal side, it's part of the human nature to get a little angry while on in a scientific debate, but we have to remember that it's all in the name of science. Keep up the good work.
"The medals don't mean anything and the glory doesn't last. It's all about your happiness. The rewards are going to come, but my happiness is just loving the sport and having fun performing" ~ Jackie Joyner Kersee.
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