Kisspeptin raised LH and testosterone in men for 12 days in a 2026 placebo-controlled study (Yeung 2026). hCG is an FDA-approved prescription hormone for selected cases of hypogonadotropic hypogonadism in men (Pregnyl label). Gonadorelin, given in pulses, brought sperm sooner than gonadotropins in men with congenital hypogonadism (Wei 2021). Only hCG is approved for people in the US; kisspeptin is investigational, and human gonadorelin products are discontinued.
| Item | Kisspeptin | hCG | Gonadorelin |
|---|---|---|---|
| US FDA status | Not approved; no product in Drugs@FDA (openFDA, searched 2026-11-01) | Approved Rx biologic, e.g. Pregnyl (BLA 017692) | Human products Factrel (NDA 018123) and Lutrepulse (NDA 019687) discontinued; sold today as cattle drugs |
| Compounding | Kisspeptin-10 in Category 2 (503A) since 2023-09-29 (FDA) | A biologic since 2020-03-23; not eligible for 503A/503B compounding exemptions (FDA) | Not on FDA’s Category 2 list; no other FDA category decision found (searched 2026-11-01) |
| WADA | Prohibited in males, S2.2.1 (2026 List); no change in the 2027 advisory (USADA) | Prohibited in males, S2.2.1 (2026 List); no change for 2027 | Prohibited in males, S2.2.1 (2026 List); no change for 2027 |
| Strongest evidence | Small human RCTs (n=15 to 60) | Approved label; human RCT on testosterone (n=29) | Meta-analysis of 7 pulsatile-GnRH studies (n=420) |
| Human trials | 36 records (ClinicalTrials.gov, 2026-11-01) | 414 records (ClinicalTrials.gov) | No clean count: the registry search maps it to all GnRH drugs (ClinicalTrials.gov) |
| Next regulatory step | None announced | None announced | None announced |
| Last checked | 2026-11-01 | 2026-11-01 | 2026-11-01 |
Key points:
- All three act on the same chain: kisspeptin switches on GnRH, gonadorelin is GnRH itself, and hCG stands in for LH at the testes.
- In a 29-man trial, testosterone alone cut testicular testosterone by 94%; the middle hCG dose kept it within 7% of baseline.
- Kisspeptin kept working through 12 days of daily infusions, but after 5 days of a nonstop infusion LH was no higher than with placebo.
- No controlled study of kisspeptin or gonadorelin in men on testosterone therapy was found (PubMed, searched 2026-11-01).
- hCG labeling says it has not been shown to be effective for weight loss, and FDA says it is not approved without a prescription for any purpose.
Kisspeptin vs hCG vs gonadorelin at a glance
| Feature | Kisspeptin | hCG | Gonadorelin |
|---|---|---|---|
| What it is | Hypothalamic peptide; kisspeptin-10 and -54 studied | Two-chain placental hormone | 10-amino-acid GnRH |
| Where it acts | GnRH neurons in the brain | LH receptors in the testes | GnRH receptors in the pituitary |
| Main research focus | Hypogonadism, IVF trigger, low desire | Hypogonadism, fertility, cryptorchidism | Congenital hypogonadism (pump) |
| Human evidence | Small RCTs and pilot studies | Label; RCT; cohorts | Cohorts; one meta-analysis |
| US approval | None | Approved (Rx) | Human use discontinued |
| WADA | S2.2.1, males | S2.2.1, males | S2.2.1, males |
| Routes studied | IV, subcutaneous, nasal | Intramuscular (label) | Pulsatile pump |
| Timeline in studies | LH up within 30 minutes | Testicular testosterone kept at 3 weeks | First sperm at a median 6 months |
| Main safety concerns | Long-term effects unknown | Gynecomastia, allergy, fluid retention | Skin allergy at pump site |
What is kisspeptin?
Kisspeptin is a peptide made in the hypothalamus that switches on the brain’s GnRH neurons, which then drive LH and FSH release (George 2011). Researchers mostly test two lab-made forms: kisspeptin-10, the shortest fully active piece, and the longer kisspeptin-54. Its most promising human results are in men with low testosterone, women undergoing IVF and people with low sexual desire; the trials cited here are small and come from research groups in London and Edinburgh. Kisspeptin is not FDA approved. Its links to libido are covered in our PT-141 vs kisspeptin comparison.
What is hCG?
Human chorionic gonadotropin (hCG) is a hormone made by the placenta. Pregnyl is purified from the urine of pregnant people, and its alpha chain is essentially identical to that of LH and FSH (Pregnyl label). It is the only one of the three approved for people in the US. The label covers selected cases of hypogonadotropic hypogonadism in males, undescended testes in boys and ovulation induction in women. Use alongside testosterone therapy is not among the labeled indications.
What is gonadorelin?
Gonadorelin is synthetic GnRH, with the same 10-amino-acid sequence as the hormone the hypothalamus makes (Factrel veterinary label). The two US human products, Factrel and Lutrepulse, are listed as discontinued in FDA’s database. The products listed today are veterinary: Factrel is labeled for ovarian cysts in cattle and carries the line “Not for human use.” In people, its best evidence comes from small pumps that deliver it in pulses to men born without working GnRH signaling.
How they work differently
- Kisspeptin: acts highest up the chain, on GnRH neurons. A kisspeptin-10 bolus raised LH from 4.1 to 12.4 IU/L within 30 minutes in six healthy men [Human, n=6] (George 2011).
- Gonadorelin: skips the brain and acts on the pituitary. Timing matters: in monkeys, hourly GnRH pulses restored LH and FSH release, while a constant infusion did not and could shut it down [Animal] (Belchetz 1978).
- hCG: skips both brain and pituitary and acts like LH on the testes. It keeps the testes making testosterone even when LH is shut off [Human RCT, n=29] (Coviello 2005).
- Kisspeptin: it also needs breaks. Daily 8-hour infusions kept LH up for 12 days, but after 5 days of a nonstop infusion LH and FSH were similar to placebo [Human RCT, n=15] (Yeung 2026).
The practical difference: kisspeptin and gonadorelin only work if the pituitary still responds, while hCG works on the testes directly. That is why the testosterone-therapy question splits them.
Evidence head-to-head
No study has compared all three in one trial (PubMed, searched 2026-11-01). The rows below draw on separate studies, so any comparison between columns is cross-trial.
| Outcome | Kisspeptin | hCG | Gonadorelin |
|---|---|---|---|
| Testosterone in men with low levels | Human pilot, n=4: 8.5 to 11.4 nmol/L during an 11-hour infusion (George 2013) | Approved label for male hypogonadotropic hypogonadism (Pregnyl) | Cohort, n=202: lower testosterone than hCG/HMG, 8.3 vs 16.2 nmol/L (Mao 2017) |
| Testes while on testosterone | No study found (searched 2026-11-01) | Human RCT, n=29: testicular testosterone near baseline vs 94% drop without (Coviello 2005) | No study found (searched 2026-11-01) |
| Sperm in congenital hypogonadism | No fertility outcome found (PubMed, searched 2026-11-01); trials registered (ClinicalTrials.gov) | Cohort, n=18 on hCG/HMG: sperm in 83.3% (Zhang 2019) | Cohort, n=10: sperm in 90%, at a median 6 months (Zhang 2019) |
| Sperm recovery after testosterone use | No study found (searched 2026-11-01) | Retrospective, n=66: 70% reached the target count with hCG plus a SERM (Kohn 2017) | No study found (searched 2026-11-01) |
| IVF egg-maturation trigger | Phase 2 RCT, n=60: maturation in 95%, no moderate or severe OHSS (Abbara 2015) | Approved label for ovulation induction (Pregnyl) | Not studied in the sources reviewed |
| Sexual desire | Crossover RCT, n=32 completers: tumescence up to 56% above placebo (Mills 2023) | Not studied in the sources reviewed | Not studied in the sources reviewed |
Which fits which goal?
hCG has more evidence for keeping the testes working during testosterone therapy. In a randomized trial, testosterone alone cut testicular testosterone by 94%, while the middle hCG arm kept it within 7% of baseline after three weeks (Coviello 2005). The trial measured testicular hormone levels, not sperm counts or pregnancies. hCG is also the only one of the three with cohort data on sperm recovery after testosterone use: 74% of 77 men improved on hCG with FSH (Stocks 2025).
Gonadorelin has more evidence for starting sperm production in men born with GnRH deficiency. A meta-analysis of seven studies and 420 men found sperm appeared about 5.3 months sooner with pulsatile GnRH than with gonadotropins, though sperm rates and pregnancy rates did not differ (Wei 2021). The authors call for high-quality randomized trials, and the GnRH was given in frequent pulses, not as occasional injections.
Kisspeptin’s most distinctive evidence is in IVF triggering for women at high risk of ovarian hyperstimulation and in sexual-desire research, with early evidence for raising testosterone. Its most promising result for men: it raised testosterone in men with type 2 diabetes and low levels (George 2013). But the longest human course in the studies reviewed here lasted 12 days, and none of them reported safety over longer use. A 2026 review found that direct evidence that peptide-based approaches such as kisspeptin or GnRH restore sperm or fertility after testosterone therapy “remains limited” (Cretu 2026).
These are evidence statements, not recommendations. A clinician, ideally an endocrinologist or reproductive urologist, is the person to decide whether any of the three fits a particular situation.
Can they be combined?
Combinations of hCG with FSH or HMG are standard in the fertility studies above (Zhang 2019). No controlled human study of kisspeptin combined with hCG, or of gonadorelin combined with either, in men was found on PubMed or ClinicalTrials.gov (searched 2026-11-01). Because kisspeptin and gonadorelin both depend on the pituitary responding, and hCG bypasses it, what a combination would add is unknown.
Safety and regulatory status
hCG. The label lists allergic reactions including anaphylaxis, headache, irritability, depression, fatigue, edema and injection-site reactions; in men, high doses can cause water and sodium retention, and gynecomastia occurs sporadically (Pregnyl label). It is contraindicated in men with breast or prostate tumors. In women it carries warnings for ovarian hyperstimulation and blood clots. The Pregnyl label states hCG “has not been demonstrated to be effective” for obesity, and FDA says it “is not approved without a prescription for any purpose” (FDA). Since March 2020 it is regulated as a biologic and outside the compounding exemptions (FDA notice).
Gonadorelin. In pump studies, skin allergy at the pump site was the common side effect, while hCG-based therapy brought more acne and breast tenderness (Zhang 2019). The Wei meta-analysis found the same pattern (Wei 2021). With no current US human product, gonadorelin sold online is not an FDA-approved human drug; the approved veterinary versions are labeled not for human use.
Kisspeptin. The intranasal study reported no side effects or adverse events (Mills 2025), but the longest course in the studies reviewed here lasted 12 days. FDA placed kisspeptin-10 in Category 2, citing possible immunogenicity, impurity concerns and little safety information for the proposed routes (FDA).
Athletes. All three are named under S2.2.1 of the 2026 Prohibited List as testosterone-stimulating peptides prohibited in males (WADA). USADA’s summary of the 2027 List, in force from 2027-01-01, describes no change for them (USADA). For more on how anti-doping rules treat peptides, see peptides vs steroids vs SARMs, and for the wider safety picture, are peptides safe?
Anyone who suspects a side effect from kisspeptin, hCG, gonadorelin or any other drug or product can report it to the FDA through MedWatch.
How long do effects take in studies?
- Kisspeptin: LH rose within 30 minutes of a bolus (George 2011); daily infusions still raised LH on day 12 (Yeung 2026).
- hCG: testicular testosterone was measured after 3 weeks (Coviello 2005); sperm recovery after testosterone use was judged at 6 and 12 months, and older men and longer testosterone use recovered more slowly (Kohn 2017).
- Gonadorelin: first sperm at a median 6 months on a pump, against 18 months on hCG/HMG in one cohort (Mao 2017).
What users report
What follows are unverified self-reports from people who usually bought unregulated products, not evidence. People who post about these three on testosterone-therapy and bodybuilding forums most often discuss them as ways to keep the testes from shrinking while on testosterone. A common thread is that hCG gets credit for visible effects on testicular size and fullness, while reports on gonadorelin are split: some say they noticed nothing, and others argue it was used the wrong way. Kisspeptin posts are fewer and newer, and many describe it as an experiment after hearing about it on podcasts or social media. Recurring complaints include nipple sensitivity or water retention blamed on hCG, injection-site irritation, and doubts about whether a product was what the label said. Many posters say they relied on blood tests to judge any effect, and arguments often turn on whether gonadorelin can work at all outside a pump. Sexual-desire changes are mentioned for kisspeptin, but reports conflict.
Frequently asked questions
Is kisspeptin better than hCG for testosterone?
Not on current evidence. hCG is FDA approved for male hypogonadotropic hypogonadism and, in a 29-man RCT, kept testicular testosterone near baseline during testosterone therapy. Kisspeptin’s best result is a small RCT where daily infusions kept LH up for 12 days (Yeung 2026). The two were never compared directly, so this is a cross-trial comparison.
What is the difference between gonadorelin and hCG?
Gonadorelin is GnRH and acts on the pituitary; hCG acts like LH on the testes. In one cohort of 28 men, sperm appeared at a median 6 months on a gonadorelin pump versus 14 months on hCG/HMG, with similar final rates (Zhang 2019). That study was not randomized, and only hCG is currently approved for people.
Is kisspeptin the same as gonadorelin?
No. Kisspeptin acts one step higher, telling the brain to release GnRH, while gonadorelin is GnRH. Kisspeptin-10 raised LH threefold within 30 minutes in six men (George 2011); gonadorelin’s best data are pulsatile-GnRH studies pooled in a 420-man meta-analysis. They come from separate studies, so the figures are cross-trial, and neither is available as an FDA-approved human product today.
Is there a peptide that works like hCG?
Neither kisspeptin nor gonadorelin does what hCG does, because hCG acts on the testes directly. Kisspeptin and gonadorelin instead prompt the body to make its own LH, so they need a working pituitary. FDA says hCG itself “is not approved without a prescription for any purpose” (FDA), and products sold as hCG without one are unapproved.
How long does it take for kisspeptin to kick in?
In studies, kisspeptin raised LH within 30 minutes of an injection into a vein, and a nasal spray raised it quickly in healthy men, by a mean 3.1 IU/L more than placebo (Mills 2025). Lasting changes in testosterone, sperm or symptoms over months were not measured in these studies.
References
- Yeung AC, Phylactou M, Koysombat K, et al. 2026. Chronic subcutaneous kisspeptin-10 stimulates gonadotropin secretion for 12 days in healthy men. Eur J Endocrinol. PubMed 42549827
- George JT, Veldhuis JD, Roseweir AK, et al. 2011. Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. J Clin Endocrinol Metab. PubMed 21632807
- George JT, Veldhuis JD, Tena-Sempere M, et al. 2013. Kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism. Clin Endocrinol (Oxf). PubMed 23153270
- Abbara A, Jayasena CN, Christopoulos G, et al. 2015. Efficacy of kisspeptin-54 to trigger oocyte maturation in women at high risk of OHSS during IVF therapy. J Clin Endocrinol Metab. PubMed 26192876
- Mills EG, Ertl N, Wall MB, et al. 2023. Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder. JAMA Netw Open. PubMed 36735255
- Mills EG, et al. 2025. Intranasal kisspeptin administration rapidly stimulates gonadotropin release in humans. EBioMedicine. PubMed 40215751
- Coviello AD, Matsumoto AM, Bremner WJ, et al. 2005. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J Clin Endocrinol Metab. PubMed 15713727
- Kohn TP, et al. 2017. Age and duration of testosterone therapy predict time to return of sperm count after human chorionic gonadotropin therapy. Fertil Steril. PubMed 27855957
- Stocks BT, et al. 2025. Optimal restoration of spermatogenesis after testosterone therapy using human chorionic gonadotropin and follicle-stimulating hormone. Fertil Steril. PubMed 39442683
- Zhang L, Cai K, Wang Y, et al. 2019. The pulsatile gonadorelin pump induces earlier spermatogenesis than cyclical gonadotropin therapy in congenital hypogonadotropic hypogonadism men. Am J Mens Health. PubMed 30569789
- Mao JF, Liu ZX, Nie M, et al. 2017. Pulsatile gonadotropin-releasing hormone therapy is associated with earlier spermatogenesis compared to combined gonadotropin therapy in patients with congenital hypogonadotropic hypogonadism. Asian J Androl. PubMed 28051040
- Wei C, et al. 2021. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile GnRH therapy versus gonadotropin therapy: a systematic review and meta-analysis. World J Mens Health. PubMed 32777865
- Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E. 1978. Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone. Science. PubMed 100883
- Cretu AM, Kamar AAM, Ciobica A, et al. 2026. Emerging peptide and neuroendocrine strategies for TRT-induced reproductive suppression and functional male hypogonadism: a narrative review. Front Reprod Health. PubMed 42666625
- Organon. Pregnyl (chorionic gonadotropin) prescribing information, revised 03/2025. DailyMed. DailyMed
- US FDA. Drugs@FDA: Pregnyl, BLA 017692. Drugs@FDA
- US FDA. Drugs@FDA: Factrel (gonadorelin hydrochloride), NDA 018123. Drugs@FDA
- US FDA. Drugs@FDA: Lutrepulse (gonadorelin acetate), NDA 019687. Drugs@FDA
- Zoetis. Factrel (gonadorelin hydrochloride) injection, veterinary label, NADA 139-237. DailyMed. DailyMed
- US FDA. Certain bulk drug substances for use in compounding that may present significant safety risks (Category 2), content current as of 2026-04-22. FDA
- US FDA. Notice to compounders: changes that affect compounding as of March 23, 2020. FDA
- US FDA. Avoid dangerous hCG diet products. Consumer update, 2020. FDA
- World Anti-Doping Agency. 2026 Prohibited List. WADA
- USADA. Athlete advisory: what’s new on the 2027 WADA Prohibited List. USADA
- ClinicalTrials.gov. Intervention searches for kisspeptin, chorionic gonadotropin and gonadorelin, 2026-11-01. kisspeptin; chorionic gonadotropin; gonadorelin
Change log
2026-11-01: first published after review by the editorial team.