Gonadorelin alternative to hCG - Kisspeptin a peptide that is not approved for compounding

[Jason Sypolt]

Gonadorelin may sound good on paper, but will never be an alternative to HCG in the real word.

And these posts both promoting it and calling experiments with it “a success” are actually causing harm to people.

 

[Cataceous]

Gonadorelin may sound good on paper, but will never be an alternative to HCG in the real word.

And these posts both promoting it and calling experiments with it “a success” are actually causing harm to people.

Admittedly the burden of proof is on anyone claiming gonadorelin is a practical replacement for hCG. But as you have cited no evidence either, it is premature to say "never". Can you say with certainty that EOD or daily injections of gonadorelin will not produce enough of the gonadotropins to prevent testicular atrophy? I can't, and it is a question that we need to have answered.

Gonadorelin is more than good on paper. It is GnRH, the natural signaling mechanism our bodies use to produce gonadotropins. There are myriad receptors for this hormone whose functions are yet to be fully explored. It is unreasonable to assume that TRT's shutdown of all of this activity is completely benign. There is at least the possibility that GnRH replacement would be beneficial even if it fails to stimulate gonadotropin production.

I do not promote gonadorelin as a practical current treatment, but I do call my experiment with it a success. Explain how this is "actually causing harm to people."

As a reminder, hCG in men is relatively unnatural and it is more typically a marker for testicular cancer. There are lingering questions about long-term use:

Potential Dangers of Higher Dose HCG? - Peak Testosterone

HCG is widely used by women as a dietary aide - it supposedly suppresses appetite - and by men for hypogonadism (clinically low testosterone)...

www.peaktestosterone.com

 

[Jason Sypolt]

Cataceous,

I will tell you what these (your) posts are causing. They are causing people to ask for help because they feel horrible not even being able to leave the house after taking Gonadorelin and they are referencing these posts as justification for taking it. They get it from a clinic or they buy it from sites like the one that you reference in a post. They aren't sure about it so they do some searching and "the guy on Excel Male says it worked". I'm tired of seeing it happen.

There are no well-known, reputable practitioners in the academic world or otherwise who are recommending or prescribing this substance for TRT. The prescriptions are coming from clinics who have lost access to HCG and want to maintain their profits. Gonadorelin is dropped in as a replacement for HCG without even telling some people and they come here and read that it works so they take it. People are reading the headlines and jumping at it because it's human nature to hear and see what they want to. That is the reality. They do have a personal responsibility to read all information. But as someone who understands more than most, you have a responsibility to use some level of care in how you present something that can't be proven works. Because we both know that few read in entirety. My not proving that it doesn't work is not the same thing at all. I hope that you understand the difference.

While I can appreciate your relentlessness in pursuit of an alternative to HCG, I think that you have lost sight of whatever your goal was and it has been replaced by a need to be right in looking at the pattern and tone of responses that you leave when you are questioned. To be clear, my "never" comment is centered on practical use today and in the future with what is known and what we have. I could go into detail, but you are a smart guy who doesn't deserve that and frankly I'm not going to tear you apart over a peptide that you bought online. Just know that there are more than a few people who are reading and are acting without understanding what they are doing.

 

[Cataceous]

Cataceous,

I will tell you what these (your) posts are causing. They are causing people to ask for help because they feel horrible not even being able to leave the house after taking Gonadorelin and they are referencing these posts as justification for taking it. They get it from a clinic or they buy it from sites like the one that you reference in a post. They aren't sure about it so they do some searching and "the guy on Excel Male says it worked". I'm tired of seeing it happen.
...

Please share these links so we can examine them on a case-by-case basis. If there are any on Excel Male itself then I must have missed them. There are countless research papers that might also be cited for saying that gonadorelin "works". It is one of the most natural ways to treat hypogonadism, albeit also one of the most complicated. While you're at it, cite the specific things I've written that you find so troubling.

...
There are no well-known, reputable practitioners in the academic world or otherwise who are recommending or prescribing this substance for TRT. ...

And yet appropriate use of gonadorelin—with infusion pumps—probably delivers better results than traditional TRT. I've pointed out that insulin pump technology is making this form of treatment more and more practical. It may be the way of the future.

... The prescriptions are coming from clinics who have lost access to HCG and want to maintain their profits. Gonadorelin is dropped in as a replacement for HCG without even telling some people and they come here and read that it works so they take it. People are reading the headlines and jumping at it because it's human nature to hear and see what they want to. That is the reality. They do have a personal responsibility to read all information. But as someone who understands more than most, you have a responsibility to use some level of care in how you present something that can't be proven works. Because we both know that few read in entirety. My not proving that it doesn't work is not the same thing at all. I hope that you understand the difference.

I have to question if you've even read my posts. I have expressed a great deal of skepticism about this use of gonadorelin.

"On the minus side, it's unclear if such infrequent pulses can activate the pituitary to begin with. It will be interesting to see. Also on the minus side, these doses are supraphysiological by a factor of 100 or so. Might there be side effects due to this?"[R]​

​

"As monotherapy it is effective if delivered every couple hours or so with an infusion pump. As an adjunct to TRT it works if taken six times a day along with a SERM. Less rigorous protocols are questionable, particularly the ones saying to inject it only once a week."[R]​

​

"I'd first ask the clinic to provide references demonstrating that gonadorelin (GnRH) would be effective in your situation. If you're on TRT then it is questionable that you'd get acceptable results unless you inject multiple times daily and also use a SERM."[R]​

​

"More practically, the TRT community needs to know whether or not less frequent GnRH injections can provide benefits beyond the production of gonadotropins. ... Anybody wanting to experiment should of course do it under a doctor's supervision."[R]​

​

"...I don't want to create excessive expectations. The outcome of any particular protocol can be quite dependent on the individual, and all too often just when you think you've figured something out, things change."[R]​

​

Earlier in the current thread even!

"Gonadorelin may work with TRT—producing endogenous LH and FSH—if you add a SERM. But it's not clear if even daily injections would be enough."[R]​

​

"It's true that for most men on TRT these hormones are not practical replacements for hCG..."[R]​

While I can appreciate your relentlessness in pursuit of an alternative to HCG, I think that you have lost sight of whatever your goal was ...

One of those goals is to feel better, and though complicated, my current protocol accomplishes this beyond my expectations. Another goal is to learn more and share that knowledge. These goals are front and center, not lost from sight.

 

[Cataceous]

... People are reading the headlines and jumping at it because it's human nature to hear and see what they want to. That is the reality. ...

Let's examine this criticism more closely. I have authored exactly one thread on actual use of gonadorelin. It is titled "Pituitary restart while on TRT: promising initial results with GnRH plus enclomiphene". You're telling me that guys are reading this "headline" and jumping on random doses of gonadorelin as a result? How many guys even know that gonadorelin is GnRH? So they must be including the enclomiphene too, right? The title says nothing about hCG; you'd actually have to read the article to see that one of the questions is if the protocol might be an hCG replacement. But the conclusion that it's possible is many posts down.

Is this really what's setting you off?

One other thing: You mention posts that are "promoting" gonadorelin. Do cite some examples so we can discuss.

 

[kassad]

Hollandale is lying. Gonadorelin isn't an FDA approved product for compounding, so it violates the 503A Bulks List, the same way Kisspeptin does. They will eventually be stopped.

We should be advocating for access to low cost hCG, a product that can be used 2-3 times per week instead of a product that needs to be injected several times a day with high cost.

I agree with @Nelson Vergel that gonadorelin and multiple daily injections don't seem to be the way to go as a viable alternative to HCG.

From the gnrh analogues buserelin acetate in a nasal spray seems most promising. Thanks to the delivery method, a 3 times a day application is not a problem. The spray is readily available from overseas pharmacies. It is also very cheap.

Case study from Japan for it's use in hypogonadism containing detailed description on how to use it and has multiple links: https://www.fertstert.org/article/S0015-0282(09)01228-X/pdf

 

[Cataceous]

I agree with @Nelson Vergel that gonadorelin and multiple daily injections don't seem to be the way to go as a viable alternative to HCG.
...

I'm not aware of anyone arguing that this manual method of multiple daily injections is a practical treatment for most. However, the minimum number of injections needed has not been established. It's not impossible that daily or EOD injections would create some LH and FSH. And regardless, there is a subset of men who do not get acceptable results with conventional TRT, and for them the latest insulin pump technology is to the point where treatment with gonadorelin is practical, and there are already products available, albeit rather costly.

...
From the gnrh analogues buserelin acetate in a nasal spray seems most promising. ...

Interesting case study. Are there reasons why actual GnRH would not be a better option?

 

[kassad]

Interesting case study. Are there reasons why actual GnRH would not be a better option?

I would say cost, availability and shelf-life. Also actual GnRH might need more than 3 times a day application, while buserelin also works with once a day administration at 20mcg/day according to another study if I remember correctly.

 

[Cataceous]

I would say cost, availability and shelf-life. Also actual GnRH might need more than 3 times a day application, while buserelin also works with once a day administration at 20mcg/day according to another study if I remember correctly.

Cost for research grade of either substance is presumably low. Triptorelin seems more common than buserelin at the better known research chemical vendors. Name brand medicine of either seems likely to be frightfully expensive. Availability of pharma-grade buserelin is questionable, but at least gonadorelin is available from Hallandale. Shelf life? There's a veterinary version of gonadorelin that says it can be stored unrefrigerated for two months. I've found that when refrigerated in bacteriostatic water gonadorelin is fine for two months. I've also found that in bacteriostatic water it can be frozen for months and thawed and then retain potency in the refrigerator for at least another month. This site says that buserelin nasal spray should be used within five weeks.

The much greater potency of buserelin is interesting: "... with potency for induction of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion of about 20 to 170 times that of GnRH itself."[R] But this fact also emphasizes that less is known about long-term use of buserelin for this purpose, and dosing is a balancing act between HPTA stimulation and suppression. Personally I'm more comfortable with the bioidentical nature of gonadorelin.

 

[ghce]

I agree with @Nelson Vergel that gonadorelin and multiple daily injections don't seem to be the way to go as a viable alternative to HCG.

From the gnrh analogues buserelin acetate in a nasal spray seems most promising. Thanks to the delivery method, a 3 times a day application is not a problem. The spray is readily available from overseas pharmacies. It is also very cheap.

Case study from Japan for it's use in hypogonadism containing detailed description on how to use it and has multiple links: https://www.fertstert.org/article/S0015-0282(09)01228-X/pdf

Lots of really good stuff in this thread, can not but admire Cats determination to push the envelope to see whats possible, more tools in the tool box can only be a good thing.

Buserelin acetate in a nasal spray sure looks like a very practical way forward for many men that are difficult to treat with the current range of cookie cutter treatments that get dispatched from GP's and specialist clinics alike.

 

[kassad]

Name brand medicine of either seems likely to be frightfully expensive.

I could source brand Sanofi and brand Nativa for ~$50 and ~100$. One is available locally with prescription and the other one is from asia incl. shipping. Both products last 10 months for this price at the dosage used in the study (90mcg/day=3 times 1-1 puff of 15mcg in each nostril).

Now if you wish to compare that regarding price with gonadorelin from a research company than one should factor in that using it as a nasal spray (to compare apples to apples) gonadorelin requires a lot higher dose to be used than buserelin: if I remember correctly the study dose for hypogonadism is 400 mcg three times a day for gonadorelin via nasal spray. That means a 10 000 mcg of research gonadorelin lasts 8 days for the cost of ~$50 plus $15 shipping ending up costing ~$200 per month or ~$2000 per 10 months.

That is obviously a massive cost difference let alone the fact that you are getting pharma grade with buserelin and research grade with gonadorelin. If I am wrong on the gonadorelin nasal dose or you wish to compare using nasal buserelin to injecting gonadorelin than the numbers are obviously different and the same amount of research gonadorelin may last you 3 months or more depending on the protocol.

This site says that buserelin nasal spray should be used within five weeks.

This site says: Shelf-life: 3 years. 5 weeks after first opening. If I am honest however, I would personally care much less for advertised shelf life if I used something as a nasal spray than as an injectable, but that is just me, I am no way advocating others to do so...

The much greater potency of buserelin is interesting: "... with potency for induction of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion of about 20 to 170 times that of GnRH itself."[R] But this fact also emphasizes that less is known about long-term use of buserelin for this purpose, and dosing is a balancing act between HPTA stimulation and suppression. Personally I'm more comfortable with the bioidentical nature of gonadorelin.

The data from the study I have linked above is only 1 year long. I have no data further out. I obviously respect your opinion for preferring gonadorelin for its bioidentical nature. I would also believe that there are people out there who found buserelin costing ~$50 or ~$100 for nearly a year's supply (then spending ~$2k on gonadorelin) the more attractive option in spite of this.

 

[Cataceous]

I could source brand Sanofi and brand Nativa for ~$50 and ~100$. One is available locally with prescription and the other one is from asia incl. shipping. Both products last 10 months for this price at the dosage used in the study (90mcg/day=3 times 1-1 puff of 15mcg in each nostril).
...

Apparently this is moot for guys in the U.S., as buserelin is not legally available here.

 

[kassad]

Apparently this is moot for guys in the U.S., as buserelin is not legally available here.

'...the other one is from asia incl. shipping. '

 

[Cataceous]

'...the other one is from asia incl. shipping. '

Right, but in the eyes of our government it's presumably just a research chemical, not legal for human use. The more adventurous won't mind this, but without the involvement of doctors here the use of buserelin will remain very limited. Given what happened with Androxal it seems unlikely that any companies will want to spend millions to get FDA approval.

 

[kassad]

Understanding where you are getting at, I am still convinced that for the 'subset of men who do not get acceptable results with conventional TRT' that are from the US, a government approved, doctor involved, pricey insulin pump incorporating, gonadorelin available only from Hallandale who-are-not-shipping-to-every-state using solution that MIGHT become developed in the future doesn't seem to be the greatest thing to hope for.

I'm also not saying they should all jump on google and order buserelin acetate spray from asia right now either, just because I have linked a study on an internet forum. Just that I find it the most promising GNrH analog solution for now as I wrote in my first post in this thread.

 

[Cataceous]

Gonadorelin treatment has been around for a while. It's the improved technology that makes it more practical.

LUTREPULSE® / LUTRELEF® (gonadorelin acetate) is used in replacement therapy of endogenous GnRH-deficiency, for the treatment of infertility in women and men. This can induce sexual development, follicle maturation and ovulation in women whose normal secretion of GnRH (and therefore of FSH and LH) is affected. It can also be used in men to induce sperm production.​

​

LUTREPULSE® / LUTRELEF® is administered automatically using an injection device (Pod). The Pod comes together with the Manager, a remote control used to set up the Pod and monitor its function.[R]​

Home | Insulet

www.omnipoddelivery.com

ClinicalTrials.gov

clinicaltrials.gov

The Pulsatile Gonadorelin Pump Induces Earlier Spermatogenesis Than Cyclical Gonadotropin Therapy in Congenital Hypogonadotropic Hypogonadism Men - PubMed

The objective of this study was to compare the effect of pulsatile gonadorelin pump (PGP) and cyclical gonadotropin (human chorionic gonadotropin [HCG]/human menopausal gonadotropin [HMG]) therapy (CGT) on spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) men. Twenty-eight...

pubmed.ncbi.nlm.nih.gov

Optimal treatment for spermatogenesis in male patients with ... : Medicine

ogenesis. Methods: In total, 220 idiopathic/isolated HH patients were divided into the GnRH pulse therapy and HCG/HMG combined treatment groups (n = 103 and n = 117, respectively). The luteinizing hormone and follicle-stimulating hormone levels were monitored in the groups for the 1st week and...

journals.lww.com

 

[Jason Sypolt]

Practicality... People are not going to wear insulin / infusion pumps. It isn’t a popular option now even though it is available such as for diabetics unless it is life-sustaining/saving and the patient has no choice. Patients won’t wear their CPAPs. People won’t wear face masks that are free. Does anyone seriously think that TRT patients are going to wear an infusion pump all day, every day so that their testicles may not shrink as much? Even if the devices didn’t cost hundreds of dollars? Outside of armchair academics or replacing or replicating natural processes in the real world, that is why almost every person wants HCG. Parts of practicality are availability and acceptance, and that isn’t going to happen on a scale of general use such as being a prescribed option to a TRT protocol that most would consider as “practical”.

There are reasons why so few pharmacies are making gonadorelin, and also why it isn’t being prescribed en masse by urologists or docs in most TRT clinics. It is designed for short-term fertility treatments. The docs who understand what gonadorelin is laugh at using it in place of HCG. They would never do such a thing to their patients. Some of the larger pharmacies have staff who have spent their days researching these and other substances. And they say it won’t work - so they don’t make it.

And that isn’t even getting into all of the possible substances that have zero chance of being approved for human use by the FDA. There is interest here in making sure that TRT does not harm and that natural processes are restored to try to avoid any unwanted/unintended long-term issues. Absolutely no one knows what they are doing to themselves using these things to mimic or replace or restore LH, even for a short time. This isn’t Magellan charting the unknown. The conclusion was already made by the real physicians and researchers and that is why you probably have to buy it from a peptide site who makes it in a Tupperware bowl, then promises that it is 99% pure. The clinics and pharmacies selling this stuff are looking to recoup lost HCG profits either as a result of indifference or ignorance. It is a waste of time and money as Nelson said, and you don’t know what you are doing to yourself.

 

[Cataceous]

... Does anyone seriously think that TRT patients are going to wear an infusion pump all day, every day so that their testicles may not shrink as much? Even if the devices didn’t cost hundreds of dollars? Outside of armchair academics or replacing or replicating natural processes in the real world, that is why almost every person wants HCG. Parts of practicality are availability and acceptance, and that isn’t going to happen on a scale of general use such as being a prescribed option to a TRT protocol that most would consider as “practical”.
...

I see you're doubling down on your previous straw man argument. Who proposed that an infusion pump should be used solely to prevent testicular shrinkage? Who said that gonadorelin is a practical replacement for hCG? Clearly there is at least one clinic in this latter category, but I've yet to see a single post on ExcelMale saying that it works as a drop-in replacement.

I will tell you what these (your) posts are causing. They are causing people to ask for help because they feel horrible not even being able to leave the house after taking Gonadorelin and they are referencing these posts as justification for taking it. ...

I trust you would not frivolously level such a serious accusation, but you have yet to provide a single piece of evidence. Will you document the circumstances and the offending posts?

...
And that isn’t even getting into all of the possible substances that have zero chance of being approved for human use by the FDA. There is interest here in making sure that TRT does not harm and that natural processes are restored to try to avoid any unwanted/unintended long-term issues. Absolutely no one knows what they are doing to themselves using these things to mimic or replace or restore LH, even for a short time. ...

Saying that typical TRT is restoring natural processes is like saying that a baby pounding on a piano is making music.

So because of fear of harm we should stop looking into ways to improve HRT? We already know the drill. Kisspeptin can't be patented, so who is going to spend the money to prove it's a viable treatment? Some company may create a patented analog that seems to work, but then what will be known about its long-term safety?

Speaking of long-term safety, what if we find out that long-term suppression of GnRH by TRT leads to more rapid cognitive decline later in life? It is not a totally outlandish proposition, given that GnRH appears to have a role in neurogenesis.

 

[Jason Sypolt]

I see you're doubling down on your previous straw man argument. Who proposed that an infusion pump should be used solely to prevent testicular shrinkage? Who said that gonadorelin is a practical replacement for hCG?

You are inserting words in your defensiveness that no one has used. No one said a pump is the sole answer. But you do suggest them as a solution virtually every time the topic arises.

I didn't have to look far..

Gonadorelin treatment has been around for a while. It's the improved technology that makes it more practical.

Clearly there is at least one clinic in this latter category, but I've yet to see a single post on ExcelMale saying that it works as a drop-in replacement.

The world is a lot bigger than ExcelMale, and PeakT for that matter.

I trust you would not frivolously level such a serious accusation, but you have yet to provide a single piece of evidence. Will you document the circumstances and the offending posts?

It is ridiculous and out of touch with reality to request, let alone expect a list of people to analyze or contact or whatever you think you need to do.

Speaking of long-term safety, what if we find out that long-term suppression of GnRH by TRT leads to more rapid cognitive decline later in life? It is not a totally outlandish proposition, given that GnRH appears to have a role in neurogenesis.

Is that what this is about? The data that we do in fact have today after many decades of men using testosterone indicates that testosterone leads to cognitive improvement and may slow the progression of decline. There is nothing natural about taking any medication. I would go so far as to say that the 2 things are mutually exclusive. My comment was intended as a nod to going to such extreme lengths out of concern to solve a problem that isn't known to be a problem. That sounds a lot more like fear to me. All of that for an LH of 1 or 2? There is nothing remotely scientifically reproducible about it either because you have no way to validate that what you are buying online 1) is what you think it is, and 2) is the strength that you think it is, and 3) is not contaminated with another substance. The patterns of literals and absolutes in your replies along with the dismissive and argumentative tone to any member when you are questioned indicate that your reality is only centered around what you want to believe and what you think is right. And that makes it borderline impossible to take you seriously.

 

[Cataceous]

You are inserting words in your defensiveness that no one has used. No one said a pump is the sole answer. But you do suggest them as a solution virtually every time the topic arises. ...

Don't dodge the question and mischaracterize the exchange:
You: "Does anyone seriously think that TRT patients are going to wear an infusion pump all day, every day so that their testicles may not shrink as much?"
Me: "Who proposed that an infusion pump should be used solely to prevent testicular shrinkage?"

I didn't have to look far..

"Gonadorelin treatment has been around for a while. It's the improved technology that makes it more practical."
"Clearly there is at least one clinic in this latter category, but I've yet to see a single post on ExcelMale saying that it works as a drop-in replacement."

Are you serious? You think statements like these are encouraging guys to hurt themselves, rather than the opposite? Did you even read/understand that second quote?

...
It is ridiculous and out of touch with reality to request, let alone expect a list of people to analyze or contact or whatever you think you need to do. ...

Sorry, I'm not willing to take your word on it. The lack of evidence hurts your credibility. If you actually believe I'm a menace to society then you would help me change my ways.

The patterns of literals and absolutes in your replies along with the dismissive and argumentative tone to any member when you are questioned indicate that your reality is only centered around what you want to believe and what you think is right. ...

Once again it's as if you've never read a word I've written, as amply illustrated above. Keep building those straw men. They are a lot easier to push down.