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

[Cips1975]

Just saw this on YouTube. Didn’t go deep at all but general observation from these guys.

 

[Cataceous]

Just saw this on YouTube. Didn’t go deep at all but general observation from these guys.

One minor correction: Gonadorelin is not just a GnRH analog; it is bioidentical GnRH. More significantly, and a more deserving target for @Jason Sypolt's ire, is that the video participants seem to be accepting without question that gonadorelin is a simple hCG replacement. One nod to a little complexity is the observation that gonadorelin won't work if the source of one's hypogonadism is in the pituitary—or testicles—rather than the hypothalamus. I have not seen statements about which scenario is more prevalent. If I had to guess I would say that a hypothalamic origin is most common, but I could be wrong.

In any case, the superficial treatment in the video means there's no mention of the fact that GnRH is normally delivered in pulses, which are typically no more than a few hours apart. Nor is there mention of the existence of negative feedback from estrogens at the pituitary, which could potentially reduce the effectiveness of exogenous GnRH. I have more background information in these two posts:

Is GnRH suppression hurting us?

Admittedly the last thing we need is some other nebulous danger to worry about that may not even exist. Read on at your peril. TL;DR: Testosterone replacement therapy suppresses the production of GnRH. Receptors for GnRH are found in places besides the pituitary. One animal model suggests GnRH...

www.excelmale.com

Pituitary restart while on TRT: promising initial results with GnRH plus enclomiphene

TL;DR: Over a period of seven weeks, treatment with GnRH and enclomiphene raised LH and FSH from around 0.1 mIU/mL to about 1.0 mIU/mL, even though TRT and hCG dosing were continued. Subjective results have been encouraging. I had written previously on the subject of GnRH suppression on TRT...

www.excelmale.com

 

[tareload]

One minor correction: Gonadorelin is not just a GnRH analog; it is bioidentical GnRH. More significantly, and a more deserving target for @Jason Sypolt's ire, is that the video participants seem to be accepting without question that gonadorelin is a simple hCG replacement. One nod to a little complexity is the observation that gonadorelin won't work if the source of one's hypogonadism is in the pituitary—or testicles—rather than the hypothalamus. I have not seen statements about which scenario is more prevalent. If I had to guess I would say that a hypothalamic origin is most common, but I could be wrong.

In any case, the superficial treatment in the video means there's no mention of the fact that GnRH is normally delivered in pulses, which are typically no more than a few hours apart. Nor is there mention of the existence of negative feedback from estrogens at the pituitary, which could potentially reduce the effectiveness of exogenous GnRH. I have more background information in these two posts:

Is GnRH suppression hurting us?

Admittedly the last thing we need is some other nebulous danger to worry about that may not even exist. Read on at your peril. TL;DR: Testosterone replacement therapy suppresses the production of GnRH. Receptors for GnRH are found in places besides the pituitary. One animal model suggests GnRH...

www.excelmale.com

Pituitary restart while on TRT: promising initial results with GnRH plus enclomiphene

TL;DR: Over a period of seven weeks, treatment with GnRH and enclomiphene raised LH and FSH from around 0.1 mIU/mL to about 1.0 mIU/mL, even though TRT and hCG dosing were continued. Subjective results have been encouraging. I had written previously on the subject of GnRH suppression on TRT...

www.excelmale.com

Excellence, as usual @Cataceous

Gonadorelin to Replace HCG

Gonadorelin cannot be used successfully by itself as a replacement for hCG for men on exogenous testosterone in the fashion I am seeing it done by guys posting on here. In addition to the excellent summary by @youthful55guy on the need to pulse a gnrh agonist 4-8 times a day, there’s also the...

forums.t-nation.com

 

[Cips1975]

Great thread guys. So I was going thru my supplies and lo and behold, I found several vials of HcG powder. Totally forgot about them. So I will be going back on. So question must be asked, do you think these clinics will continue to push the Gonadorelin? Despite the noise or we not noisy enough. I am thinking the latter as most folks on TRT are not in communities like this. So we are
Prob the minority. Ugh

 

[Cataceous]

...

Gonadorelin to Replace HCG

Gonadorelin cannot be used successfully by itself as a replacement for hCG for men on exogenous testosterone in the fashion I am seeing it done by guys posting on here. In addition to the excellent summary by @youthful55guy on the need to pulse a gnrh agonist 4-8 times a day, there’s also the...

forums.t-nation.com

Thanks for the link. It reminds me that I really need to update the pituitary restart thread with the latest information. One item of interest is that I tried a period without the SERM and with a minimal TRT dose—26 mg pure T/week. After 3.5 weeks the gonadotropins were down 30% from their previous values. Subjective results generally weren't too bad, except that testicular discomfort was becoming downright intrusive, and that led me to resume the SERM. So unfortunately I don't know whether or not the gonadotropins would have continued to decline.

 

[tareload]

Thanks for the link. It reminds me that I really need to update the pituitary restart thread with the latest information. One item of interest is that I tried a period without the SERM and with a minimal TRT dose—26 mg pure T/week. After 3.5 weeks the gonadotropins were down 30% from their previous values. Subjective results generally weren't too bad, except that testicular discomfort was becoming downright intrusive, and that led me to resume the SERM. So unfortunately I don't know whether or not the gonadotropins would have continued to decline.

Thanks for the data point. Trend supports the hypothesis that SERM is needed for gonaotopin use combined with TRT. I look forward to your updates and thank you for taking the time to post them.

 

[platypus5007]

@Cataceous @Nelson Vergel Have you guys seen this? This clinic is offering Gonadorelin in place of hCG and posting labs showing that it indeed maintains LH. They don't mention frequency but I called and they are doing 2 (0.5ml) self-administered subcutaneous injections per week.

Legit to bogus?

Gonadorelin vs hCG - Royal Medical Center

Our new replacement to hCG, Gonadorelin, works more effectively for patients. Gonadorelin will actually raise LH levels during testosterone therapy.

www.royalmedicalcenters.com

 

[Nelson Vergel]

I doubt this is true with a twice per week program, but there is only one way to find out. Get on it and send us results a month later. Also, ask them if they can guarantee those types of LH increases.

What is the cost per month for their product?

 

[platypus5007]

I doubt this is true with a twice per week program, but there is only one way to find out. Get on it and send us results a month later. Also, ask them if they can guarantee those types of LH increases.

What is the cost per month for their product?

Meds (T, AI and Gonadorelin), plus all standard labs and doc tele visits for $200/mo. They used to rx hCG, but say they've successfully used Gonadorelin since the change forced them to switch.

 

[Cataceous]

Interesting. If they have "hundreds" of measurements from their "clinical trials" then why can't they report the average LH level seen with the treatment? How do we know that the one example isn't an extreme outlier?

... They don't mention frequency but I called and they are doing 2 (0.5ml) self-administered subcutaneous injections per week.
...

How many micrograms of gonadorelin is that?

If it's working as claimed then the AI dose must be fairly high to allow pituitary activation without a SERM. The example somewhat suggests this, with estradiol on the low side relative to testosterone.

 

[platypus5007]

How many micrograms of gonadorelin is that?

Good question. 100 IUs a week, 50 at each injection. Not sure how much water is mixed with the powder.

 

[Cataceous]

I called Royal Medical Center myself to see if I could wring out any more information. It seems likely the protocol is 50 or 100 mcg of gonadorelin twice a week. The gentleman I talked with wasn't completely sure, but said he thinks the concentration is 0.2 mg/mL, and the dose size is 0.5 mL. Unfortunately he had no information on the clinical trials. When pressed he said he thought almost all of their patients are on aromatase inhibitors. He said they target a total testosterone level of ~800+ ng/dL. It sounds like they try to adjust estradiol to be in the reference range, while being mindful of the subjective results.

I suspect the lab work was done within an hour of a gonadorelin injection, and that LH pretty rapidly goes back to low levels. If so it's surprising that two big pulses a week can prevent testicular atrophy and provide decent subjective results. Natural men have on the order of 100 pulses a week.

The video below reports a few more individual lab results, ranging from small LH increases—0.5 mIU/mL—to gigantic ones—46.5 mIU/mL. These are around the 8:00 mark. Kind of annoying to have ads in a video that is essentially an ad itself.

 

[gerardo]

I called Royal Medical Center myself to see if I could wring out any more information. It seems likely the protocol is 50 or 100 mcg of gonadorelin twice a week. The gentleman I talked with wasn't completely sure, but said he thinks the concentration is 0.2 mg/mL, and the dose size is 0.5 mL. Unfortunately he had no information on the clinical trials. When pressed he said he thought almost all of their patients are on aromatase inhibitors. He said they target a total testosterone level of ~800+ ng/dL. It sounds like they try to adjust estradiol to be in the reference range, while being mindful of the subjective results.

I suspect the lab work was done within an hour of a gonadorelin injection, and that LH pretty rapidly goes back to low levels. If so it's surprising that two big pulses a week can prevent testicular atrophy and provide decent subjective results. Natural men have on the order of 100 pulses a week.

The video below reports a few more individual lab results, ranging from small LH increases—0.5 mIU/mL—to gigantic ones—46.5 mIU/mL. These are around the 8:00 mark. Kind of annoying to have ads in a video that is essentially an ad itself.

I believe that this doubt of Gonadorelin twice or 3 times a week is enough to maintain the size of the testicles and consequently the amount of sperm. It will be great to know how far it goes. A more economical and viable alternative.

 

[platypus5007]

I believe that this doubt of Gonadorelin twice or 3 times a week is enough to maintain the size of the testicles and consequently the amount of sperm. It will be great to know how far it goes. A more economical and viable alternative.

Yea, it is perhaps reasonable to guess that high enough doses could theoretically provide coverage between the peaks and valleys. I wonder though if long-term exogenous GNRH agonists use has negative effects.

The below studies suggest that Gonadorelin (at higher doses) will suppress testosterone and LH production long term due to altered production of LH that doesn't activate the receptors but is detectable on labs.

Mechanisms of gonadotropin-releasing hormone agonist action in the human male - PubMed

Agonist analogs of GnRH are being increasingly utilized to induce medical castration for treatment of a variety of hormonally responsive clinical disorders. However, the mechanism/s of their paradoxical antigonadal action in the human male remain poorly understood. Basal and integrated...

pubmed.ncbi.nlm.nih.gov

Influence of continuous gonadotropin-releasing hormone (GnRH) agonist treatment on luteinizing hormone and testosterone secretion, the response to GnRH, and the testicular response to human chorionic gonadotropin in male rhesus monkeys - PubMed

Five adult male rhesus monkeys were continuously infused for 56 days with 25 micrograms/day of GnRH agonist (Wy-40972; Ag) using an implanted osmotic pump. Bioassayable serum levels of LH were elevated 8-fold on the second day of Ag treatment and then declined precipitously to below pretreatment...

pubmed.ncbi.nlm.nih.gov

 

[platypus5007]

Ok, got off a call with Royal. They say that the blood tests showing LH is maintained is due to exactly what @Cataceous presumed: Royal is running labs within 1-2 hours of injecting Gonadorelin. So of course it drops precipitously after that timeframe until the next injection in a couple days. The head doc commented that this is on purpose because constant stimulation actually leads to lower LH (possibly based on the studies above), whereas a pulse can provide symptom relief.

From the study on monkeys: "GnRH administration (50 micrograms) induced a 13- to 20-fold rise in serum LH and a 3- to 7-fold increase in serum T in control monkeys. After 4 weeks of Ag administration, none of the animals responded to GnRH."

I'm skeptical that the infrequent pulse is enough to prevent shrinkage, let alone maintain fertility. In fact, I think if maintaining fertility is a concern, you should be extremely skeptical and hesitant to jump on Gonadorelin as an alternative to hCG. Look at the negative effects on sperm on Gonadorelin and even many months post-treatment:

"The quality of semen samples taken from oligospermic monkeys was greatly reduced. The percentage of motile and percentage of live sperm per ejaculate, the net negative surface charge on sperm, and the scores of sperm in the hamster oocyte penetration test were subnormal." Influence of simultaneous gonadotropin-releasing hormone agonist and testosterone treatment on spermatogenesis and potential fertilizing capacity in male monkeys - PubMed

I think, but don't want to accuse, that Royal is performing a sleight of hand by testing right after injection without disclosing that. If infrequent pulsing is the answer, we need more research and case studies following people undergoing treatment.

 

[JA Battle]

Frequent pulses are needed. Not infrequent pulses. 90-120 minutes roughly 15 micrograms I believe. The answer is infusion pump. Only problem is that if the pumps fail and deliver too much too consistently then you can desensitize gnrh receptors on pituitary and be unable of LH secretion. This may take a long time to correct itself if that happens.

Also this would work better for primary hypogonadal patients injecting testosterone and just creating LH for the sake of upstream hormone replacement. Secondary patients will benefit but it get tricky because if pump fails they will have low testosterone quickly without realizing it if they are using it as a sole testosterone replacement source. If pairing it with testosterone injection, then they will likely have too high a level of testosterone because they will be creating it endogenously and be administering it exogenously. Also it would require a enclomifene to be co administered to overcome negative feedback at the pituitary from exogenous testosterone. Possibly in primary patients dosed properly with testosterone or patients keeping e2 low enough one can omit the serm and still produce LH with GNRH pulsatile infusion.

we need to get a pump that works and pulses accurately and consistently and there are very few products in the world right now and I’ve tried to access them for 6 months but no luck.
we need to test this.

 

[platypus5007]

Frequent pulses are needed.

Frequent pulses is what the research studies use, yes. But is that what we need?

This guy thinks differently. Does Gonadorelin need to be pulsed?

@JA Battle what do you think of his reasoning? Is it possible that infrequent pulses are all that's needed to preserve minimum testicular function?

 

[platypus5007]

 

[Cataceous]

...Royal is running labs within 1-2 hours of injecting Gonadorelin. So of course it drops precipitously after that timeframe until the next injection in a couple days. The head doc commented that this is on purpose because constant stimulation actually leads to lower LH (possibly based on the studies above), whereas a pulse can provide symptom relief.
...

It's true that if you have a way to constantly infuse GnRH then it does in time shut everything down; the pituitary becomes insensitive to it. In fact this is how most of the GnRH analogs work—intentionally: they have much longer half-lives than GnRH, which results in overexposure of the pituitary.

As @JA Battle says, normal HPTA operation requires frequent GnRH pulses. I did encounter some research showing that if there is a longer delay between pulses, e.g. one day, then the corresponding LH pulse is considerably larger. I don't believe this research was designed to see if single daily pulses would work indefinitely. The Royal trials are perhaps suggesting they do.

...
This guy thinks differently. Does Gonadorelin need to be pulsed?

@JA Battle what do you think of his reasoning? Is it possible that infrequent pulses are all that's needed to preserve minimum testicular function?

I'd like to see some hard data on this. Basically he's imputing a very long half-life to whatever abstract process he's sketching on his timeline. I'd like to know if testicular volume would actually have this pattern—that is, be above the "active" line even with infrequent pulses. What about endogenous testosterone production?

 

[JA Battle]

Frequent pulses is what the research studies use, yes. But is that what we need?

This guy thinks differently. Does Gonadorelin need to be pulsed?

@JA Battle what do you think of his reasoning? Is it possible that infrequent pulses are all that's needed to preserve minimum testicular function?

The monkey study you linked used continuous infusion. Not frequent pulses. I don’t have time to watch at moment but if I get a chance I will comment.