Kryptocur: Completely prevent HPG suppression?

[Structure]

Why don't you provide anecdotal links to all of the BB using or implementing your theory? This will help us have an added laugh.

[Kryptocur has been on the market for 30+ years. Where is the use of your theory put to practice anywhere? [LH-RH nasal spray (Kryptocur), a new aspect in th... [Klin Padiatr. 1981] - PubMed result ]

You realize that at no point did I claim to have proof that kryptocur use while on steroids would prevent HPG axis, right? You do recall all the times I've already explicitly state that this was a theory right?

And you realize that anyone reading this post can see that you repeatedly claimed that the reason it wouldn't work was because using Kryptocur would unavoidably result in hypogonadism?

If you had just admitted that you were wrong, we could move on. But you still aren't interested in addressing that. I'm not particularly impressed with you, to say the least.

 

[Michael Scally MD]

What does what I think about GnRH (as Kryptocur or otherwise) have to do with your theory? Produce ANY study that you believe supports your theory. ANY STUDY. Also, even though Kryptocur is the same as GnRH, this does NOT support your theory. Provide evidence that it supports your theory. You are trying in desperation to change the OP topic to GnRH induced hypogonadism. GnRH induced hypogonadism is a well documented effect. As for GnRH itself, I will wait for your studies. The reply will quickly reveal the use of GnRH fantasy. This is your thread! Produce (or SHUT UP) ANY study that you believe supports your theory. ANY STUDY.

Why don't you provide anecdotal links to all of the BB using or implementing your theory? This will help us have an added laugh.

[Kryptocur has been on the market for 30+ years. Where is the use of your theory put to practice anywhere? [LH-RH nasal spray (Kryptocur), a new aspect in th... [Klin Padiatr. 1981] - PubMed result ]

You fail to even understand HPTA feedback or the GnRH pulse generator. This alone kills your "theory." GnRH induced hypogonadism is well documented with chronic use. Did you FAIL to read. The use of GnRH (any form) itself will not help your "theory." If so, one could theorize for intermittent GnRH use to avoid the induced hypogonadism. The bottom line is no matter how much you uselessly argue, there is NO evidence for your "theory." On the market for over 30+ years and no evidence to support your theory. You can not even produce BB talk for support. I can guarantee that no BB (or anyone else) will try your theory and produce satisfactory results. NOBODY. And BB are know to try almost anything, particularly to avoid PCT.

I do NOT need to produce evidence for your theory, you do. You can protest all you want. You have NO support for your theory. All that read this thread will know there is NO support for the "theory" you propose. And what is with NOT producing a SINGLE study. I am done. Go at it. You FAIL. LMAO The thread is all yours. EOM.

 

[Structure]

You fail to even understand HPTA feedback or the GnRH pulse generator. This alone kills your "theory." GnRH induced hypogonadism is well documented with chronic use. Did you FAIL to read. The use of GnRH (any form) itself will not help your "theory." If so, one could theorize for intermittent GnRH use to avoid the induced hypogonadism. The bottom line is no matter how much you uselessly argue, there is NO evidence for your "theory." On the market for over 30+ years and no evidence to support your theory. You can not even produce BB talk for support. I can guarantee that no BB (or anyone else) will try your theory and produce satisfactory results. NOBODY. And BB are know to try almost anything, particularly to avoid PCT.

I do NOT need to produce evidence for your theory, you do. You can protest all you want. You have NO support for your theory. All that read this thread will know there is NO support for the "theory" you propose. And what is with NOT producing a SINGLE study. I am done. Go at it. You FAIL. LMAO The thread is all yours. EOM.

Very impressive, Scally --- your discussion skills are top notch. Your presence in this thread has really furthered everyone's knowledge.

Here are the studies I promised. However, they shouldn't have been necessary --- its obvious that if there is no difference between GnRH as it appears in the body and gonadorelin, then there is no reason to think that frequent, physiologically appropriate doses of gondorelin would cause hypogonadism, be it in the short-term, the long-term, and in between. If its the same chemical, its the same chemical, and its no more likely to induce hypogonadism than our own hypothalamus glands. For what its worth, the studies below show usage ranging from three weeks to longer, and the benefit is maintained throughout.

• Gonadorelin is the same as the GnRH that is released from the hypothalamus. See Gonadorelin (Intravenous Route, Injection Route) - MayoClinic.com
• Kryptocur and Lutrepulse both use the same active: gonadorelin. See Experiences with Kryptocur in the treatment of cry... [Acta Chir Hung. 1987] - PubMed result and ScienceDirect - Advanced Drug Delivery Reviews : Endocrine/reproductive pulsatile delivery systems
• Studies show that gonadorelin (in physiologically appropriate doses) stimulates the HPG axis, and can therefore used to make women fertile See Getting pregnant & staying pregnant ... - Google Books search for lutrepulse (see image, below), treat hypothalamic hypogonadism See Successful GnRH Treatment in a Patient with Kallmann's Syndrome, who previously failed HMG/HCG Treatment/Erfolgreiche GnRH-Behandlung bei einem Mann mit Kallmann-Syndrom bei vorher erfolgloser HMG-HCG-Behandlung - Berezin - 2009 - Andrologia - Wiley , and treat cryptorchidism See any of the results at kryptocur - Google Scholar.

And whatever knowledge it is that I don't understand about the HPG axis, you have contributed exactly nothing to help me learn. What a fantastic help you are. Perhaps it would be different if I had paid you? Maybe that's the real reason you are here --- not to help any of us, rather its to troll for business. Good for you. Not so much for the rest of us.

Again: very nice. You're a class act, Scally.

 

[Millard]

HCG helps maintain testicular function during a steroid cycle but when it's stopped there's still the problem of getting the pituitary going.

Kryptocur sounds like it'd help maintain pituitary function during a steroid cycle, but wouldn't you still have the problem of getting the hypothalamus going again?

Won't Kryptocur suppress natural release of GnRH as part of HPT feedback loop?

I admittedly don't have a detailed understanding of GnRH pulse generator but it doesn't seem like it completely solves the problem any more than HCG use on-cycle.

It just changes the focus of PCT.

 

[someanddone]

HCG helps maintain testicular function during a steroid cycle but when it's stopped there's still the problem of getting the pituitary going.

Kryptocur sounds like it'd help maintain pituitary function during a steroid cycle, but wouldn't you still have the problem of getting the hypothalamus going again?

Won't Kryptocur suppress GnRH as part of HPT feedback loop?

I admittedly don't have a detailed understanding of GnRH pulse generator but it doesn't seem like it completely solves the problem any more than HCG use on-cycle.

It just changes the focus of PCT.

Finally we're getting somewhere.......
opcorn:

 

[Structure]

HCG helps maintain testicular function during a steroid cycle but when it's stopped there's still the problem of getting the pituitary going.

Kryptocur sounds like it'd help maintain pituitary function during a steroid cycle, but wouldn't you still have the problem of getting the hypothalamus going again?

This is a very good question, and I've been unable to answer it. From what I understand, suppression happens because of overstimulation or understimulation of receptors.

For example, testicular atrophy happens when there's a lack of LH and FSH --- the LH receptors don't get any stimulation, and the leydig cells die. This is an example of understimulation. On the other hand, if you inject very large, frequent doses of HCG, the LH receptors on your testes can get overstimulated. Thus, when you try to go natural, the testes are insensitive to the normal levels of LH produced by the pituitary, and low T results. This is an example of suppression from overstimulation.

The question becomes: will the hypothalamus experience bad effects from having its androgen receptors (or ERs for that matter) overstimulated? If these receptors became desensitized, would not the hypothalamus become insensitive to T, and thus "think" that T was low? From what I understand, high levels of T result in AR upregulation, so hypothalamic desensitization from elevated T doesn't seem likely. However, could there be other deleterious effects from the hypothalamus having not secreted GnRH for long periods of time? Given that this lack of GnRH secretion is not a result of the hypothalamus being understimulated, I don't have a good understanding of whether or not the hypothalamus will have a hard time coming back online.

One thing seems true though: if the hypothalamus would have a hard time coming back online after a steroid cycle involving GnRH, it would also have a hard time coming back online after an ordinary steroid cycle. I say this because from the hypothalamus' perspective, the situations look the same: too much T and E2. I don't think the hypothalamus would change its behavior based on the presence of exogenous GnRH, because I don't think the hypothalamus can directly detect the GnRH. Thus, we should be seeing some cases of steroid-induced hypothalamic hypogonadism, despite the dearth of athletes using Kryptocur. The fact that we're not seeing these cases makes me think that the hypothalamus doesn't typically suffer from steroid use. However, I can't say this with any certainty...

Won't Kryptocur suppress natural release of GnRH as part of HPT feedback loop?

I admittedly don't have a detailed understanding of GnRH pulse generator but it doesn't seem like it completely solves the problem any more than HCG use on-cycle.

It just changes the focus of PCT.

Yes, I agree that natural release of GnRH would be suppressed, but from my understanding, the rest of the HPG axis would be stimulated from the exogenous GnRH, which seems like it would prevent secondary and primary hypogonadism. Without the GnRH stimulation from Kryptocur, secondary hypogonadism remains a possibility, even with HCG use...

Scally brought up the feedback path to the pituitary. Exactly what the pituitary will do given these conflicting signals (GnRH tells the pituitary to increase gonadotropins, while elevated T/E2 tells the pituitary to decrease gonadotropins), I cannot say (and he chose not to illucidate). My assumption was that the pituitary would secrete gonadotropins if either one of these signals was positive. However, this is speculation on my part. Any ideas?

 

[CubbieBlue]

This is a very good question, and I've been unable to answer it. From what I understand, suppression happens because of overstimulation or understimulation of receptors.

For example, testicular atrophy happens when there's a lack of LH and FSH --- the LH receptors don't get any stimulation, and the leydig cells die. This is an example of understimulation. On the other hand, if you inject very large, frequent doses of HCG, the LH receptors on your testes can get overstimulated. Thus, when you try to go natural, the testes are insensitive to the normal levels of LH produced by the pituitary, and low T results. This is an example of suppression from overstimulation.

The question becomes: will the hypothalamus experience bad effects from having its androgen receptors (or ERs for that matter) overstimulated? If these receptors became desensitized, would not the hypothalamus become insensitive to T, and thus "think" that T was low? From what I understand, high levels of T result in AR upregulation, so hypothalamic desensitization from elevated T doesn't seem likely. However, could there be other deleterious effects from the hypothalamus having not secreted GnRH for long periods of time? Given that this lack of GnRH secretion is not a result of the hypothalamus being understimulated, I don't have a good understanding of whether or not the hypothalamus will have a hard time coming back online.

One thing seems true though: if the hypothalamus would have a hard time coming back online after a steroid cycle involving GnRH, it would also have a hard time coming back online after an ordinary steroid cycle. I say this because from the hypothalamus' perspective, the situations look the same: too much T and E2. I don't think the hypothalamus would change its behavior based on the presence of exogenous GnRH, because I don't think the hypothalamus can directly detect the GnRH. Thus, we should be seeing some cases of steroid-induced hypothalamic hypogonadism, despite the dearth of athletes using Kryptocur. The fact that we're not seeing these cases makes me think that the hypothalamus doesn't typically suffer from steroid use. However, I can't say this with any certainty...



Yes, I agree that natural release of GnRH would be suppressed, but from my understanding, the rest of the HPG axis would be stimulated from the exogenous GnRH, which seems like it would prevent secondary and primary hypogonadism. Without the GnRH stimulation from Kryptocur, secondary hypogonadism remains a possibility, even with HCG use...

Scally brought up the feedback path to the pituitary. Exactly what the pituitary will do given these conflicting signals (GnRH tells the pituitary to increase gonadotropins, while elevated T/E2 tells the pituitary to decrease gonadotropins), I cannot say (and he chose not to illucidate). My assumption was that the pituitary would secrete gonadotropins if either one of these signals was positive. However, this is speculation on my part. Any ideas?

This thread is giving me a fucking headache...and every time I try to post someone else ends up chiming in so I back up.

Structure, I think the hold up here is on semantics.

Essentially, this is Scally's answer, and I agree with him:

There was a very small chance (very small) to provide support for mimicking the GnRH pulse generator, but now you have completely disregarded the HPTA feedback loop at the pituitary level.

He's saying the GnRH is suppressive in itself. It is disrupting another feedback loop, just further upstream. Either way, you are suppressing something.

 

[CubbieBlue]

Yes, I agree that natural release of GnRH would be suppressed, but from my understanding, the rest of the HPG axis would be stimulated from the exogenous GnRH, which seems like it would prevent secondary and primary hypogonadism.

Any problem that does not lie in the gonads is still secondary hypogonadism. Again, you are suppressing something else, just moving the problem further upstream.

 

[Structure]

Scally brought up the feedback path to the pituitary. Exactly what the pituitary will do given these conflicting signals (GnRH tells the pituitary to increase gonadotropins, while elevated T/E2 tells the pituitary to decrease gonadotropins), I cannot say (and he chose not to illucidate). My assumption was that the pituitary would secrete gonadotropins if either one of these signals was positive. However, this is speculation on my part. Any ideas?

He's saying the GnRH is suppressive in itself. It is disrupting another feedback loop, just further upstream. Either way, you are suppressing something.

Any problem that does not lie in the gonads is still secondary hypogonadism. Again, you are suppressing something else, just moving the problem further upstream.

Does GnRH suppress the pituitary? I was under the impression that GnRH stimulates LH and FSH release from the pituitary. I thought the point about the pituitary feedback was in regards to T / E2; specifically, that the pituitary would sense the abundance of T / E2, and would thereby make less LH and FSH.

If this is the case, the part that I'm unsure about is this: what does the pituitary do when it receives conflicting instructions? On one hand, the GnRH is telling it to make more LH and FSH. On the other hand, the T / E2 levels are high, and tell the pituitary to make less LH and FSH. I speculated that the pituitary would make LH and FSH if either path told it to do so. This is why I assumed that the pituitary would produce LH and FSH, despite the high circulating levels of T and E2: because the GnRH tells it to do so. Again, I'm just speculating here. Do you know of any text (studies, books, etc.) that can say what the pituitary will do in this situation?

 

[Millard]

Yes, I agree that natural release of GnRH would be suppressed, but from my understanding, the rest of the HPG axis would be stimulated from the exogenous GnRH,

Maybe "can kyrptocur prevent HPT suppression during AAS cycle?" isn't really the question but "can kryptocur make it easier to recover from HPT suppression during AAS cycle?"

Will HPTA recovery be quicker from AAS + krytocur > AAS + hCG > AAS alone?

 

[Bill Roberts]

I have to admit I did not read through the brawl-fest, but only skimmed it.

With regard to the subject matter:

GnRH agonist drugs, and GnRH itself would work the same way, are used to achieve a long-term suppression of LH production whether for chemical castration or treatment of endometriosis via their sustained, intense effect.

At first they act exactly as one would expect: their GnRH agonist activity causes increased LH production.

But on the pituitary receiving constant, saturation-level agonist effect for an extended time such as weeks, then the effect reverses and becomes shutdown.

Accordingly, I agree with the OP that quite likely production of LH could continue via use of the drug, provided dosing was far lower than is used for treatment of endometriosis or for chemical castration.

I agree with Dr Scally that this is not going to achieve the desired aim of maintaining proper HPTA function.

Keeping the pituitary producing LH is fine but it is doing nothing whatsoever towards maintaining hypothalamic function.

 

[CubbieBlue]

I have to admit I did not read through the brawl-fest, but only skimmed it.

With regard to the subject matter:

GnRH agonist drugs, and GnRH itself would work the same way, are used to achieve a long-term suppression of LH production whether for chemical castration or treatment of endometriosis via their sustained, intense effect.

At first they act exactly as one would expect: their GnRH agonist activity causes increased LH production.

But on the pituitary receiving constant, saturation-level agonist effect for an extended time such as weeks, then the effect reverses and becomes shutdown.

Accordingly, I agree with the OP that quite likely production of LH could continue via use of the drug, provided dosing was far lower than is used for treatment of endometriosis or for chemical castration.

I agree with Dr Scally that this is not going to achieve the desired aim of maintaining proper HPTA function.

Keeping the pituitary producing LH is fine but it is doing nothing whatsoever towards maintaining hypothalamic function.

Did this get moved from Men's Health or am I crazy? If so some notice would be good.

 

[Structure]

Accordingly, I agree with the OP that quite likely production of LH could continue via use of the drug, provided dosing was far lower than is used for treatment of endometriosis or for chemical castration.

I agree with Dr Scally that this is not going to achieve the desired aim of maintaining proper HPTA function.

Keeping the pituitary producing LH is fine but it is doing nothing whatsoever towards maintaining hypothalamic function.

Given what you and others have said so far, it seems that there are two main issues with Kryptocur: resilience of the hypothalamus, and whether or not the pituitary will shut down.

(regarding resilience of the hypothalamus:) I know that AAS abusers have a blunted response to a GnRH stimulation test, but I know nothing about how common it is for them to experience tertiary hypogonadism (GnRH deficiency). This is pertinent to this discussion because hypothalamic shutdown would occur similarly with or without Kryptocur:

• The hypothalamus detects high androgens and estrogens, but (from what I understand) it does not directly sense the presence of GnRH.
• Thus it does not draw a distinction between a cycle of steroids with Kryptocur vs. a cycle of steroids without Kryptocur.
• If hypothalamic shutdown is a problem in one scenario, then it will be a problem in both.

Unfortunately, I don't have any data regarding how long it takes for the hypothalamus in particular to resume generating GnRH pulses after steroid use.

(regarding pituitary suppression:) I don't know what the pituitary will do when it receives conflicting directions. Specifically, GnRH tells the pituitary to produce gonadotropins. However, high levels of androgens and estrogens tells the pituitary to stop producing gonadotropins. Its like having one foot on the gas and the other on the break. I've assumed that the pituitary would produce gonadotropins, but I have no direct knowledge to support this assumption.

The feasability of using Kryptocur to prevent shutdown depends on these two points. Specifically, it would only be feasible if the hypothalamus can come back online faster than a GnRH deprived pituitary, and if the pituitary will still produce gonadotropins due to the presence of GnRH despite elevated T and E2.

Any thoughts?

 

[zkt]

Given what you and others have said so far, it seems that there are two main issues with Kryptocur: resilience of the hypothalamus, and whether or not the pituitary will shut down.

(regarding resilience of the hypothalamus:) I know that AAS abusers have a blunted response to a GnRH stimulation test, but I know nothing about how common it is for them to experience tertiary hypogonadism (GnRH deficiency). This is pertinent to this discussion because hypothalamic shutdown would occur similarly with or without Kryptocur:

• The hypothalamus detects high androgens and estrogens, but (from what I understand) it does not directly sense the presence of GnRH.
• Thus it does not draw a distinction between a cycle of steroids with Kryptocur vs. a cycle of steroids without Kryptocur.
• If hypothalamic shutdown is a problem in one scenario, then it will be a problem in both.

Unfortunately, I don't have any data regarding how long it takes for the hypothalamus in particular to resume generating GnRH pulses after steroid use.

(regarding pituitary suppression:) I don't know what the pituitary will do when it receives conflicting directions. Specifically, GnRH tells the pituitary to produce gonadotropins. However, high levels of androgens and estrogens tells the pituitary to stop producing gonadotropins. Its like having one foot on the gas and the other on the break. I've assumed that the pituitary would produce gonadotropins, but I have no direct knowledge to support this assumption.

The feasability of using Kryptocur to prevent shutdown depends on these two points. Specifically, it would only be feasible if the hypothalamus can come back online faster than a GnRH deprived pituitary, and if the pituitary will still produce gonadotropins due to the presence of GnRH despite elevated T and E2.

Any thoughts?

I cant find any evidence at the moment that circulating androgens and estrogens exert more of an inhibitory effect that the secretory effect of GnRH but I strongly suspect that they do, especially in the long term. We would need to examine the exact mechanism of the androgens and estrogen on their pituitary receptors and the effects on the LH and FSH secretory cells.
You sure brought up a good one here !

 

[Michael Scally MD]

[ame="http://www.youtube.com/watch?v=UPw-3e_pzqU"]YouTube - Just when I thought I was out...they pull me back in.[/ame]

 

[zkt]

Thats a classic allrite. Is there a hidden relevant meaning?

 

[Structure]

Given what you and others have said so far, it seems that there are two main issues with Kryptocur: resilience of the hypothalamus, and whether or not the pituitary will shut down.

(regarding resilience of the hypothalamus:) I know that AAS abusers have a blunted response to a GnRH stimulation test, but I know nothing about how common it is for them to experience tertiary hypogonadism (GnRH deficiency). This is pertinent to this discussion because hypothalamic shutdown would occur similarly with or without Kryptocur:

• The hypothalamus detects high androgens and estrogens, but (from what I understand) it does not directly sense the presence of GnRH.
• Thus it does not draw a distinction between a cycle of steroids with Kryptocur vs. a cycle of steroids without Kryptocur.
• If hypothalamic shutdown is a problem in one scenario, then it will be a problem in both.

Unfortunately, I don't have any data regarding how long it takes for the hypothalamus in particular to resume generating GnRH pulses after steroid use.

(regarding pituitary suppression:) I don't know what the pituitary will do when it receives conflicting directions. Specifically, GnRH tells the pituitary to produce gonadotropins. However, high levels of androgens and estrogens tells the pituitary to stop producing gonadotropins. Its like having one foot on the gas and the other on the break. I've assumed that the pituitary would produce gonadotropins, but I have no direct knowledge to support this assumption.

The feasability of using Kryptocur to prevent shutdown depends on these two points. Specifically, it would only be feasible if the hypothalamus can come back online faster than a GnRH deprived pituitary, and if the pituitary will still produce gonadotropins due to the presence of GnRH despite elevated T and E2.

Any thoughts?

I cant find any evidence at the moment that circulating androgens and estrogens exert more of an inhibitory effect that the secretory effect of GnRH but I strongly suspect that they do, especially in the long term. We would need to examine the exact mechanism of the androgens and estrogen on their pituitary receptors and the effects on the LH and FSH secretory cells.
You sure brought up a good one here !

I've got some new information that will put one of these points to rest: the issue of pituitary suppression. The following is from the second edition (2005) of Endocrinololgy: Basic and clinical principles by Shlomo Melmed and P. Michael Conn (Chapter 13: Anterior Pituitary Hormones, Section 6.3 Regulation and secretion of LH and FSH):

"GnRH is the major regulator of gonadotropin secretion from pituitary cells. The frequency and amplitude of GnRH pulses are critical for stimulating LH and FSH output. Estrogens can exert both stimulatory and inhibitory effects on gonadotropin secretion, depending on the dose, duration, and other physiological factors. Testosterone inhibits in vivo serum FSH levels, but its direct effects on FSH release at the pituitary level are stimulatory. Another regulator of FSH secretion is inhibin, a gonadal peptide produced by Sertoli cells that inhibits FSH release and, under some conditions, may also regulate LH output."

From this paragraph, we get the following information:

• GnRH is the major regulator.
• Estrogen, not testosterone, inhibits gonadotropin secretion at the pituitary.

How does testosterone limit gonadotropins then? Because Testosterone inhibits GnRH at the hypothalamus:

"The latter provides a GnRH pulse into the hypophyseal-portal vessels at approx 90 intervals, which can be slowed down or accelerated by gonadal hormones. Testosterone and progesterone in physiologic concentratons and hyperprolactinemia slow the discharge rate of the generator, whereas estrogens have no effect on the frequency of the GnRH pulses. Females of all species respond to estrogens with an acute increase in LH and, to a lesser degree, FSH, a phenomenon that explains the "ovulatory LH surge" via positive estrogen feedback on the pituitary."

Here, it is made clear that the hypothalamus doesn't pay any attention to estrogen, but instead is affected by testosterone.

Does anyone have information to contradict this? It seems to support the idea that if you keep your E2 in check, Kryptocur will in fact keep the pituitary producing gonadotropins.

 

[Michael Scally MD]

Hint: Keep it to MALES!!!
Hint: Are T & E2 the only factors in the HPTA?
Hint: Keep it to MALES!!! [E2 DOES AFFECT THE HYPOTHALAMUS.]

 

[Michael Scally MD]

http://www.youtube.com/watch?v=UPw-3e_pzqU

Thats a classic allrite. Is there a hidden relevant meaning?

Hint: Keep it to MALES!!!
Hint: Are T & E2 the only factors in the HPTA?
Hint: Keep it to MALES!!! [E2 DOES AFFECT THE HYPOTHALAMUS.]

Not very hidden!!! Just trying' to keep the facts straight.

 

[Structure]

Hint: Keep it to MALES!!!
Hint: Are T & E2 the only factors in the HPTA?
Hint: Keep it to MALES!!! [E2 DOES AFFECT THE HYPOTHALAMUS.]

Scally, if you've got something to say, then just say it.