Kisspeptin-10: FDA Counted 24 Human Studies, and Found One That Went Under the Skin
The product put to the compounding committee was for injection under the skin and into a muscle. FDA found no human study by the muscle route at all, and the whole under the skin record it identified is one arm of one 2011 study in healthy women in which no reproductive hormone moved. The committee voted 0 to 11 against.
What it is
Kisspeptin-10 is a synthetic chain of ten amino acids, molecular weight 1302 g/mol on FDA's chemistry review and at PubChem CID 25240297. The naming is the trap. The KISS1 gene makes a protein of 145 amino acids that the body cuts into shorter pieces, kisspeptin-54, -14, -13 and -10, and in FDA's words "Each isoform shares a common C-terminal decapeptide sequence, which is equivalent to kisspeptin-10." It also travels as kisspeptin 112-121, so a trial record under that name is a kisspeptin-10 record.
It switches on GPR-54, a receptor dense in the hypothalamus, the part of the brain that runs the hormonal control panel. That releases gonadotropin releasing hormone, GnRH, which makes the pituitary put out luteinising hormone, which tells the testis to make testosterone. One step upstream of anything approved for that axis.
And the signal is pulsed by design. Male rhesus monkeys on a continuous intravenous drip at 1,200 and 4,800 micrograms per kilogram per day surge for about three hours, then fall back to baseline with the drip still running. Given 2 micrograms as a one minute intravenous pulse every hour instead, juvenile males keep surging at the same size for 48 hours.
What is approved, and for what
Nothing, anywhere, on the strength of the search FDA describes: "There is no approved product in any country containing kisspeptin-10 at this time, nor is kisspeptin-10 found in the European or Japanese Pharmacopeias." I did not repeat that search of national registers, so I carry the absence as FDA's finding rather than as mine. What FDA was asked to allow was narrow: "1 mg/mL solutions for injection for subcutaneous (SC) and intramuscular (IM) administration", for one use, secondary hypogonadism in men, meaning low testosterone caused by the brain's signal failing rather than by the testis.
What the human record actually shows
FDA's Appendix 1 tabulates every human exposure it identified: 24 studies from 2011 to 2022, roughly 300 subjects, with FDA's own footnote that the figure may be an overestimate because subjects could overlap between studies. I counted the rows myself. Twenty-three of the 24 are intravenous only. Then the sentences the entry turns on: "We found no studies that administered kisspeptin-10 to humans via the IM ROA. We identified a single study that administered a single SC bolus of kisspeptin-10 to approximately 35 healthy women."
That study is Jayasena and colleagues 2011 at Imperial College London (PMC3232613): healthy women in the follicular phase, the first half of the cycle, one injection under the skin at 2, 4, 8, 16 or 32 nanomoles per kilogram, four to five per dose group, against 0.9 percent saline in the same study. "No significant changes in serum reproductive hormone levels were observed after sc bolus injection of kisspeptin-10 at any dose." Safety outcomes were not reported either.
The 35 is a pooled total. FDA's briefing prints it twice and the presenter said it aloud on the day, and FDA's own appendix does not support it: it assigns those 35 women to the intravenous bolus, the injection under the skin and the intravenous infusion sub-studies together, four to five per group. So around 20 to 25 received a dose by the nominated route. A regulator reporting a trial total as the number who got the drug does not make it so.
Everything carrying the reputation is a drip. George and colleagues 2011 infused four healthy men at 4 micrograms per kilogram per hour for 22.5 hours and saw testosterone rise from 16.6 to 24.0 nanomoles per litre, each against his own baseline, no placebo comparator reported for the infusion arms (PMID 21632807). Jayasena and colleagues 2015 compared the isoforms in ten healthy men, five per dose group, and gonadotropin release ran about three times higher on GnRH, one step downstream (PMID 26089302). FDA's briefing records the American and European guideline position that pulsatile GnRH, the pulsed form given by pump, is not currently approved in the US or Europe. FDA's conclusion: "There is insufficient evidence to make a conclusion on the effectiveness of kisspeptin-10 as a treatment option for men with secondary hypogonadism."
Whose evidence it is
Usually this substitution has to be inferred. This one happened out loud. The nominator did not present; compounding pharmacies spoke in the open public hearing instead, and the effectiveness case came from a speaker who introduced himself as "Jim LaValle, pharmacist, Chair of the International Peptide Society": there is "at least a randomized-controlled trial ... so up to 56 percent more than placebo".
The trial is real. Mills and colleagues, JAMA Network Open 2023: 37 men with hypoactive sexual desire disorder randomised, 32 completing, two visits in random order for "intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or ... a rate-matched placebo" (PMID 36735255).
Kisspeptin-54. Into a vein. Seventy-five minutes.
The endpoint status cuts both ways. The trial was built around brain activity on a whole brain scan, reported first and against placebo; the 56 percent tumescence figure sits under secondary analyses, though the abstract also lists tumescence as the second of its three main outcome measures. What it is not is kisspeptin-10, or the route the pharmacies were asking for.
FDA found the identical substitution in a European expert consensus statement and answered it in one line. Boehm and colleagues 2015 wrote that "although still investigational, kisspeptin seems to be emerging as useful in several therapeutic areas". FDA: "However, citations to support these statements are relevant to kisspeptin-54, not -10."
It runs the other way on safety. The nearest human answer to injecting this under the skin for weeks is kisspeptin-54 again: women with hypothalamic amenorrhoea, five randomised to 6.4 nanomoles per kilogram twice daily for two weeks and five to saline (PMID 19820030). Five women received it. The maximal luteinising hormone rise after an injection was 24.0 units per litre on day one and 2.5 on day fourteen, while they still responded to GnRH. The pathway had stopped answering, not the pituitary.
And when a company did try the sold schedule, with the analogue TAK-448 under the skin in 12 men against 5 on placebo for six weeks, placebo beat two of the three drug arms on the prespecified primary endpoint and the trial was terminated. So was a second one.
Where the circulating dose came from
FDA documented the compounded strengths, "a 100 mcg/mL injectable product and ... a 200 mcg troche", and the one adverse event report it retrieved describes exactly that schedule in use: 100 micrograms under the skin daily for six weeks, in a 17 year old male who gained weight and whose estrone, an oestrogen, rose.
I opened two dosing pages on 10 August 2026. One prints 50 to 200 micrograms under the skin, once or twice daily. The other prints tiers of 100, 200 and 500 micrograms two to three times a week for 4 to 12 weeks. Across the two, 50 to 500 micrograms, commonest at 100 to 200. Convention, reported as convention.
Neither traces it. The first says its figures "come from published research and research-use community planning", names no study for the kisspeptin-10 range, and its source list underneath is mostly kisspeptin-54 trials; the two kisspeptin-10 papers it does cite are both intravenous studies, neither of which tested the subcutaneous range the page prints. The second is blunter about itself: "There is NO peer-reviewed-validated subcutaneous '100-500mcg 3x/week' protocol for Kisspeptin-10", and what it says has been validated is "Validated human research dosing is primarily intravenous (subcutaneous is also used in research)".
FDA records the commonest intravenous bolus in the literature as 0.31 micrograms per kilogram, about 22 micrograms for a 70 kilogram adult, so 100 micrograms is roughly four and a half times it, by a route with one human study behind it. That study went as high as about 2.9 milligrams at the same weight, and nothing moved. The conversions are my arithmetic on FDA's figures.
Does the pharmacology allow the protocol
FDA gives the plasma half life, from frequent blood sampling during and after an intravenous infusion, as 3.8 minutes in healthy men and 4.1 in women. Kisspeptin-54 runs about 27.6 minutes, and the authors of the head to head draw the conclusion themselves: "kisspeptin-54 but not kisspeptin-10 can be administered subcutaneously due to its long half-life".
Ten half lives takes you to about a tenth of one percent remaining, which here is about 38 minutes. So a once daily injection leaves nothing meaningful in circulation for something like 23 hours out of 24, and a twice weekly injection for essentially the whole week. That arithmetic is mine, on FDA's number.
Which is why the specialists' schedule looks the way it does. NCT05633966 and NCT05896293 describe giving it under the skin "pulsatile, approximately every 90 minutes" and "pulsatile, every 60-240 minutes" for two weeks, with Stephanie B. Seminara, MD listed as sponsor-investigator, affiliation and study site Massachusetts General Hospital. Sixteen injections a day on the 90 minute schedule.
So the sold schedule sits in the gap between the two things the pharmacology permits. Not the frequent pulsing that keeps the pulse generator answering, and not the long infusion that moved testosterone in four men.
What the regulators have on file
Kisspeptin-10 has sat since 29 September 2023 in category 2 of FDA's nominated bulk substances, the group flagged as possibly presenting significant safety risks, because the agency "has no, or only limited, safety-related information for the proposed routes of administration". Not a finding that it is harmful. A finding that FDA does not know, and the reason is the route.
On 29 October 2024 the Pharmacy Compounding Advisory Committee took kisspeptin-10 as topic 4 of five. Zero yeses, 11 noes, zero abstentions. The chair, from the floor: "the committee has unanimously voted against adding this to the list, and the reasons so far stated have been a lack of convincing safety and efficacy data." Before FDA presented, the same chair had said: "I would like to state into the record that we do not have a nominator presentation for the kisspeptin-10 topic." The nomination sits on the docket at FDA-2015-N-3534-0289, clarified at FDA-2015-N-3534-0377, and whoever filed it did not turn up to argue it.
A vote is a recommendation rather than the end of it, but kisspeptin-10 was not among the seven peptides the committee took up again on 23 and 24 July 2026. The 2026 World Anti-Doping Agency list names "kisspeptin and its agonist analogues" under testosterone-stimulating peptides in males, prohibited at all times.
What could go wrong
FDA's evaluation states that "No serious adverse events were reported in these studies", then qualifies it in the same breath: short studies, small samples, and "No published clinical trials were found that assessed the safety of kisspeptin-10 when administered chronically or on a fixed schedule for over one day." Fourteen of the 24 appendix rows record safety findings as "Not reported", and two more say "None reported", which is a different statement. I counted the rows myself, twice.
Immunogenicity is FDA's stated first concern, with a sting specific to a molecule identical to one you already make: antibodies raised against the injection "may cross-react with and may cross-neutralize endogenous kisspeptin-10". FDA adds that injection under the skin is generally more immunogenic than into a vein, and that no immunogenicity study was submitted or identified.
The unresolved animal signal is cardiovascular. In ApoE knockout mice, bred to clog their arteries, kisspeptin-10 delivered continuously by an implanted pump at 5 or 12.5 micrograms per kilogram per hour for four weeks accelerated aortic plaque, with no dose free of the effect (PMID 28411243). FDA's verdict is that clinical relevance "remains unclear", and it identified no genotoxicity, reproductive or carcinogenicity studies at all.
What nobody knows
Whether it does anything by the route people use. No man has been given kisspeptin-10 under the skin in any published study I located, and FDA reports finding no human study by the intramuscular route at all.
What the finished trials found. NCT05633966 with 13 enrolled and NCT04648969 with 18, both completed on 31 August 2025, had posted no results when I queried the registry on 10 August 2026.
Whether the fade applies here. It is demonstrated for kisspeptin-54 under the skin in five women, and for kisspeptin-10 held continuously in monkeys, and not, so far as I found, for kisspeptin-10 once daily under the skin in a person.
Whether a hormone rise is worth anything. Testosterone rose in two studies, both intravenous infusions of 11 and 22.5 hours, four men in each, both against the men's own baseline. FDA's own question: "even if kisspeptin-10 induces an LH response in men, it is unclear if there are corresponding increases in testosterone levels."
What the selling rests on
Take the pieces apart and each belongs to something else. The testosterone number belongs to four men on a drip for the better part of a day. The sexual desire number belongs to a different molecule on a 75 minute infusion. The demonstration that a kisspeptin can go under the skin and keep working belongs to kisspeptin-54, whose half life is about seven times longer. What belongs to kisspeptin-10 under the skin is a 2011 study in healthy women in which nothing measurable happened.
FDA did not have to reason its way to that. It found the same substitution in a European consensus statement and wrote one sentence under it: the citations are relevant to kisspeptin-54, not -10.
None of which makes kisspeptin-10 fake. It makes the case for it borrowed, and the borrowed parts come from routes and molecules nobody is selling you.
If you check one thing, open FDA's briefing document at https://www.fda.gov/media/182089/download and go to Appendix 1. Read the route column and nothing else.
Frequently asked
Is kisspeptin-10 approved for anything?
Not according to FDA's search. Its October 2024 briefing document states that there is no approved product in any country containing kisspeptin-10, and that the substance appears in neither the European nor the Japanese pharmacopoeia. FDA also reports no monograph for it in either of those pharmacopoeias, meaning no official quality specification a laboratory can test a batch against. FDA reached that by searching global EDGE and the two pharmacopoeias; I did not repeat that search of national registers myself, so I carry the absence as FDA's finding rather than as my own.
How much human research is there on kisspeptin-10?
More than most compounds covered here, and almost all of it by a route that is not the one the sellers I read offer. FDA's appendix tabulates 24 published human studies from 2011 to 2022 and roughly 300 subjects, with FDA's own footnote that the total may be an overestimate because subjects could overlap between studies. Twenty-three of those 24 rows are intravenous only. FDA reports finding no study giving kisspeptin-10 to humans into a muscle, and one study giving it under the skin, a single injection in healthy women in which no reproductive hormone changed at any dose tested.
Does kisspeptin-10 raise testosterone?
The two testosterone rises I found were both drips. George and colleagues 2011 infused it into a vein at 4 micrograms per kilogram per hour for 22.5 hours in four healthy men and reported a rise from 16.6 to 24.0 nanomoles per litre, measured against each man's own baseline rather than against a placebo. A second study infused it for 11 hours into four men with type 2 diabetes, again against their own baseline. FDA's conclusion on the whole file is that there is insufficient evidence to reach a conclusion on effectiveness in men with secondary hypogonadism, and its own open question is whether a luteinising hormone response in men is followed by any rise in testosterone at all.
What was the randomised trial showing 56 percent more than placebo?
That figure was read to the FDA committee, and it belongs to a different molecule given a different way. Mills and colleagues 2023 randomised 37 men with hypoactive sexual desire disorder, meaning persistently low sexual desire that distresses them, of whom 32 completed. Each man attended two visits at least a week apart, in random order, receiving a 75 minute intravenous infusion of kisspeptin-54 at 1 nanomole per kilogram per hour at one and a rate-matched dummy infusion at the other, so every man was his own comparison. The trial was built around brain activity on a whole brain scan, which is the result reported first; the 56 percent penile tumescence figure appears under secondary analyses, though the abstract also lists tumescence among its three main outcome measures. It is not kisspeptin-10, and it is not injection under the skin.
What doses circulate, and where did the numbers come from?
Reported here as circulating convention and not as a recommendation: across the two dosing pages I read on 10 August 2026, the range runs 50 to 500 micrograms under the skin, with 100 to 200 micrograms the commonest tier, given daily on one page and two to three times a week on the other. Neither page traces the figures to a study. One says its ranges come from published research and community planning, then names no study for the kisspeptin-10 range; the other states in its own words that there is no peer-reviewed-validated protocol under the skin at those amounts, and that validated human research dosing is primarily intravenous, with subcutaneous also used in research. For comparison, FDA records the commonest studied intravenous bolus dose as 0.31 micrograms per kilogram, roughly 22 micrograms for a 70 kilogram adult.
Is kisspeptin-10 safe?
The published trial record is short and unremarkable, and both halves of that matter. FDA's evaluation states that no serious adverse events were reported in the studies it identified, then qualifies it in the same breath: the studies were short, the samples small, they often carried no adverse event information, and FDA found no published trial assessing safety of kisspeptin-10 given on a fixed schedule for longer than one day. Fourteen of the 24 rows in its appendix record safety findings as not reported. FDA's stated first concern is immunogenicity, because antibodies raised against the injected peptide could cross-neutralise the kisspeptin-10 the body makes itself, and it notes that injection under the skin is generally more immunogenic than injection into a vein. Its surveillance database held one report, a 17 year old male on 100 micrograms daily under the skin for six weeks who gained weight and whose estrone, an oestrogen, rose.
This content is for educational and informational purposes only and is not medical advice. Peptides discussed are research compounds and may not be approved for human use. Nothing here should be used to diagnose, treat, cure, or prevent any disease. Always consult a qualified healthcare professional before starting any peptide, supplement, or protocol. Individual responses vary. Do not self-administer compounds without proper medical supervision.
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