No. My work was done decades ago when synthetic GnRG first became commercially available.
I don’t think you have much else for options beside HCG. There are some that believe that Clomid can do this but I am skeptical and have yet to see any hard data to back up their theories. I don’t see GnRG analogs as an answer either, simply because of the pulsatile nature of the hormone. Perhaps there may be some protocols and delivery systems (e.g., nasal sprays) that may pan out but we need to see some real data.
If you are willing to use and wear an infusion pump all day, yes. There are several relatively recent papers published on the subject. However, it takes a lot of dedication and I don’t see it as a long-term solution as an adjunct to TRT therapy.
The reason I ask, is because a small percent of men on TRT feel terrible when taking hCG; I am one of them.
I’ve been taking 100 mcg of kisspeptin-10, 3 times per day and that has yielded marked improvement and has halted atrophy, but progress has stalled and while no additional atrophy has occurred, improvement has halted as well. It seems this is a better alternative for myself than hcg, but it would be nice to have my boys back to even 75%. I’d say they’re at 50% right now.
3X per day sounds like a reasonable approach and 50% maintenance seems like a reasonable response… However, for me, 3X per day is just not sustainable. Then again, I have no issues with using HCG, even at my standard 1050 IU/week dose which is higher than most. Bottom line is that you need to do what’s right for you. Hope it continues for you.
BTW, I would be interested in knowing your dosage per injection and the overall cost of the program. I’ve considered trialing something like that as an adjunct to HCG for a better response. HCG has some FSH activity but not nearly to the extent that it has LH activity. I read somewhere that the spermatogenic tissues of the testicles make up 75% of the volume. If that is true, then one would expect an additional response if i were to layer in some FSH from the pituitary. However, HMG is just way too expensive for me to consider trialing.
Kisspeptin-10 - $90/month for below:
100 mcg - 3x per day
One 5,000 mcg Vial with 10 mL BAC water added = 5,000 mcg/10mL or 500 mcg/ml
1 U100 Insulin Syringe = 1 mL w/ 50 tick marks – 1 tick mark = 0.02 mL
500 mcg/syringe – 500 mcg/50 tick marks = 10 mcg/tick mark = 100 mcg = 10 iu’s
10 iu’s = 100 mcg dose – So 10 iu’s 3 times per day
Cost: 300 mcg/day x 30 days = 9,000 mcg/month ~ $90/month (2 x 5mg vial ($45/5mg vial)).
I wrote a long ass reply on reddit before I deleted my account. I follow the work of Dr. Seminara at MGH very closely and have spoken to a few people pushing the edge of Kisspeptin-10 research.
There is 0 point in taking Kisspeptin without an infusion pump to micro-dose you with micrograms every 2 hours. Anything else will just cause shut-down of the HPTA via desensitization of the GnRH receptors.
I’m already shut down and even though this is n=1, I have seen improvements and I can’t tolerate hCG. I’ve read a few studies that seem to indicate that there is no shutdown with kisspeptin-10 because it’s not a GnRG. It stimulates the pituitary to release GnRG.
You don’t believe 100 mcg’s 3 times per day would be better than nothing if hCG wasn’t an option? I’d be curious to know your thoughts on how to best utilize kisspeptin-10 or anything other than hCG that’s not cost prohibitive (like HMG).
Too much kisspeptin-10 or 54 can cause excessive GnRH production which will eventually lead to GnRH receptor desensitization. I’ve spoken to the physicians directly that publish these papers and they all concur an infusion pump is the only real way as it stands now to deliver it in 2 hour boluses to match physiological production. No real work has been done to determine “minimum injection frequency/amount” before downregulation occurs. So, any amounts/injections currently doctors are putting patients on as an hCG replacement are speculative from what I’ve seen. Of course, the fact that one is on testosterone would mask any HPTA shutdown that occurs via Kiss-10 suppression, so doctors may not care or fully understand the potency of the compound they’re dealing with.
I’ve been looking into re-purposing micro-needle patches or other drug delivery devices for Kiss-10 as I’m trying to start a company with one of the physicians to bring Kiss-10 to market. I discussed a paper from the UK with one of the doctors that showed every 3 day injections (in women) didn’t seem to lead to downregulation of the axis, but they hypothesized in that experiment the SQ injection was creating a depot allowing for extended release, and it also only ran for 2-3 weeks, perhaps not long enough to see desensitization.
The truth appears to be, doctors know how to mimic Kiss-10/54 pulses with infusion pumps, but not what amount/frequency is minimally viable outside of an infusion pump.
Example, this paper shows twice daily, Twice-Daily Subcutaneous Injection of Kisspeptin-54 Does Not Abolish Menstrual Cyclicity in Healthy Female Volunteers - PMC
Very interesting! Thanks for sharing. Short of infusion pumps or the device you’re looking to create, what’s your best guess for best utilization of kisspeptin-10 for those of us on TRT and are already shut down?
Do you think kisspeptin is the best alternative aside from hCG and HMG currently?
My interest in Kiss-10 is first and foremost as a diagnostic for delayed puberty / normosmic congenital hypogonadotropic hypogonadism/Kallmann syndrome. There is no diagnosis currently for people that show signs during puberty of delayed puberty. Like me, a “late bloomer” turns into T lvls of 171 ng/dL at 26 and a life that is ruined via not progressing physically/mentally/emotionally through the phases of life. A doctor won’t risk starting unnecessary hormone treatment early because it can obviously have consequences.
The condition ends up being a diagnosis of exclusion, which is a shit way to find out if you have a condition.
So, as a diagnostic it has great potential.
Second, I am very interested in alternative treatments that allow for endogenous production of testosterone. Shots have not been a walk in the park for me, and Clomid made me want to cry.
I really wish enclomiphene citrate passed Phase 3, the company set dumbass endpoints.
Can’t live in the past.
Both GnRH and Kiss-10 have potential for endogenous production. GnRH works with people with Kallmann/ncHH but Kiss-10 does not, because it’s issues with the GnRH neurons (not the pituitary) that causes these conditions.
For “normal” men with secondary hypogonadism, and a functioning hypothalamus/pituitary that is suppressed for unknown reasons, Kiss-10 could be the replacement master-cascade switch to start the Kiss–GnRH–LH/FSH–Testosterone cascade.
The issue is it’s very sensitive, pulsing ~120 minutes in adults…so how is that mimicked? Slow release? Infusion pump? An electronic patch that micro-needles a dose every 2 hours? These are the things we are thinking about.
The compound is very stable, very safe (it’s a naturally occurring compound), but it’s the delivery that needs work…either the best way to mimic 2 hour pulse delivery, or finding the maximum injection frequency that still leads to therapeutic / intended effect.
I do not think Kisspeptin is the best alternative to hCG because if HPTA shutdown occurs due to GnRH receptor desensitization, it’s masked by testosterone shots, and you’re simply wasting money / fucking with your HPTA for no reason.
Kiss-10 as a monotherapy may make sense, but honestly anyone who uses it as a monotherapy would indeed be a lab-rat for injection frequency. Kiss-10 needs to be delivered the same way as GnRH, infusion pumps, so they face the same issue with delivery, not with effectiveness. We know they work, their delivery needs make them not ideal at all as compared to methods of testosterone replacement currently.
Thanks for the detailed reply. When did you discover your condition and how old are you now? That sounds terrible and I can understand your focus and motivation.
I also didn’t like Clomid. What problems have you had with injections?
Can you elaborate on the below: how do gnhr receptors become desensitized and how it’s masked by trt shots?
“I do not think Kisspeptin is the best alternative to hCG because if HPTA shutdown occurs due to GnRH receptor desensitization, it’s masked by testosterone shots, and you’re simply wasting money / fucking with your HPTA for no reason.”
Diagnosed at 26. Went on TRT for ~1.5 years had a mental breakdown and quit. Injections cause a lot of issues with libido/ED for me (and accentuated mania/psychosis). It’s very hard to figure out. Alcohol was not helpful.
When I was 26 I was on 150mg/week a drinking almost daily and had a trough of 550ng/dL and INSANE libido and erections. Now at 33 I’m on 140mg/week and my trough is 770 ng/dL and I have 0 libido/0 erection quality, and feel anhedonia.
Was drinking causing excessive estradiol production, was it calming me down a little allowing me to relax? Was it removing testosterone/estrogen from my body faster with more liver clearance? I’m 2 years sober now and don’t really want to pick up drinking to have a normal existence.
Injections have just put me all over the place in terms of mood and drive and I can’t key in on it, especially if my doctor stopped testing estradiol because he doesn’t believe in it.
I don’t know if I should drop my dose or increase it. I have really low SHBG and I think my free levels are just too high. A lower dose may be better for me.
----Kiss-10 forces release of GnRH, if too much GnRH is being sent to the pituitary, receptors will desensitize, and LH/FSH will stop being produced. The end result of LH is testosterone, so if you’re on exogenous testosterone, you won’t feel any difference.
If you’re on 20ug every 2 hours, you’ll probably see LH surges and testosterone production. If you’re on giant injections, at anything other than 2 hour windows, no one actually knows how it will work. There’s probably data out there on short-term kisspeptin treatment, but is that translatable to a life-time therapy?
My main point is - there is not an established protocol for Kisspeptin OUTSIDE OF (as in the case of GnRH also) infusion pumps every 2 hours. You are going into uncharted territory.
Would 100ug once a week work? Who knows. Would 50ug twice a day SQ work? Who knows. Would 100ug once a day work? Who knows. No one knows.
If your doctor prescribes it to you, and you do his injection suggestions - you’ll need to test for presence of LH in a few months, that will be proof it 1. works, and 2. didn’t cause HPTA shutdown. If you’re on Kisspeptin for 3 months, and you still have no LH, it’s caused HPTA shutdown and it’s a waste of money.
It’s so hard to tease out individual variables over time. I’ve gone through that as well. I’m sure that alcohol was changing your physiology. There was a time I was crushing my estrogen with an AI and drinking actually made me feel substantially better. I believe it had a multitude of affects, but it probably most had to do with stressing my liver and actually helped reduce the AI and kept my estrogen from completely bottoming out/crashing too low.
It’s also been my experience that libido is a very fickle bitch. It seems to be a complex weave of not only hormones but also neurotransmitters. It’s not as simple as a ratio of estrogen to testosterone and I wish that it were; dopamine, ACTH, serotonin, etc all seem to come into play as well.
What are you thoughts on this below?
Based on what I’ve read as far as kisspeptin-10 goes, it looks like with current limited delivery methods (not having access to a pump) 1 mcg/kg of bodyweight seems to be most effective for bolus injections with a spike after 90 minutes. There seems to be diminishing returns past that dose of 1 mcg/kg. There seem to be a decent response from doses as low as 0.1mcg/kg as well. I’m around 100 kg’s, so that bolus dose for me would be 100 mcgs or ug’s.
I think with the limited delivery system right now, someone would need to literally dose 1 mcg/kg every 2 hours to mimic pulsatile patterns. I’m not willing to do that.
If I wanted to get crazy, on days I have the time and ability, it may be optimal to inject 100mcg’s kisspeptin every 2 hours, 6-8 times per day.
On “normal” days for me, that’s why I settled on 100 mcg/s three times per day due to cost and time.
I agree with you, I should get my LH/FSH tested acutely after a 100 mcg injection and also a few months down the road to see if I’m shut down.
I’d venture to guess someone on TRT would not get gnhr desensitization since gnhr should only be stimulated during kisspeptin injections by someone on TRT - It should nnever naturally be stimulated since my hpta axis should be shut down - so there wouldnt/shouldnt be constant overstimulation.
What do you think?
Sounds like a reasonable hypothesis, but the answer is I don’t know. You’d in effect be running a clinical trial on yourself. Hopefully with a TRT doctor.
You’re right that the HPTA axis is already shutdown, and that means the Kisspeptin pathway is shutdown, as is the GnRH pathway. Who knows if the GnRH response will be immediate (as it is with a non-suppressed HPTA) or it could take days/weeks/months to come back online, even via exposure to exogenous kisspeptin. Even once that starts your testicles need to respond to the LH as well.
Short bursts of kisspeptin will cause a near instantaneous rise in LH, how much more endogenous testosterone production that translates to, who knows. GnRH desensitization is reversible. Long term affects of Kisspeptin on endogenous kisspeptin signaling appears to be unknown. Neukinin B also seems to play a roll.
It’s not even really understood what controls the “clock” that starts all these different surges, from mini puberty, to going dormant in middle childhood, to surging again, then reaching a steady state. This is uncharted territory.
If the FDA recommended GnRH to replace hCG, there has to be standard dosing protocols available, as I’ve read from a people now that their TRT clinics are replacing hCG with GnRH, and so, these doctors are doing this for a reason with a protocol in mind.
Thanks for your thoughts. Let us know if you get your device that allows for continuous microdelivery via needles/a patch in the market!
Hello Everyone, I’m new here to share news about my personal experience with Gonadorelin actate so far.
1st injection was Tuesday (nothing)
2nd injection was Saturday morning ( up and down erections and libido.
Note: I stopped taking hcg about 3 weeks before I started taking Gonadorelin felt horrible.
Are you still taking the gonadorelin? Results?
Yes, I’m still taking it but having issues with low e2 so it’s hard to tell.
There are moments of terrible and irritable libido spikes.
My e2 was at 6.4 a couple weeks ago so gotta get that taken care of, nothing works for me when my e2 is low.
Any follow up on that?