Gonadorelin
Also known as Gonadorelin, GnRH, LHRH, Factrel, Lutrelef
Synthetic and identical to endogenous GnRH; registered for diagnostics of the pituitary-gonadal axis.
At a glance
- Category
- Hormonal & sexual
- Status
- approved drug
- Route
- intravenous or subcutaneous; pulsatile via infusion pump for therapeutic use
- Half-life
- about 4 minutes; gonadorelin is rapidly hydrolysed in plasma and excreted in urine 1
- Onset
- LH peak approximately 15-30 minutes after administration
- Molecular weight
- 1182.3 g/mol
- Sequence
- pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2
Registered as a diagnostic agent (among others as Factrel in the US and as gonadorelin 100 microgram powder for injection in the United Kingdom) to evaluate anterior pituitary gonadotroph function and responsiveness, including suspected gonadotropin deficiency and residual pituitary function after tumour removal or irradiation 1. Pulsatile gonadorelin via a portable pump is registered in a few countries for the treatment of hypogonadotropic hypogonadism and anovulation. The drug is poorly available in many countries, partly because long-acting GnRH analogues have displaced it.
Doping status: Prohibited in men (WADA S2, gonadotrophins and their releasing factors)
Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.
Mechanism of action
Gonadorelin is a decapeptide with exactly the same structure as endogenous gonadotropin-releasing hormone. It binds to GnRH receptors on the gonadotroph cells of the anterior pituitary and there initiates the release of LH and FSH.
The clinically decisive point is the pattern of administration. Pulsatile administration — a short pulse every 60 to 120 minutes — mimics physiology and maintains gonadotrophin release. Continuous or prolonged exposure does the opposite: the receptors desensitise and the axis is suppressed. That latter principle is precisely what long-acting GnRH agonists such as leuprorelin rely on, which is why they are used in prostate carcinoma and endometriosis.
The very short half-life of a few minutes is functional 1: it makes a pulse sharply bounded, but makes single injections unsuitable for achieving a lasting hormonal effect.
What the research shows
The evidence for the registered applications is solid and goes back on decades of clinical use: the GnRH stimulation test is a validated endocrinological investigation, and pulsatile gonadorelin is a recognised treatment for hypogonadotropic hypogonadism. For the popular off-label use alongside testosterone replacement, by contrast, the evidence is virtually absent.
Research in humans
Extensive clinical experience with the stimulation test in delayed puberty, precocious puberty and hypogonadotropic hypogonadism 1. Pulsatile administration via pump induces ovulation and spermatogenesis respectively in both women and men with an intact pituitary; this is described in treatment series and is included in guidelines. There are no controlled studies demonstrating that single subcutaneous injections of gonadorelin preserve testicular function during testosterone therapy — that is an extrapolation from hCG research.
Animal and lab research
Widely used in veterinary medicine to induce ovulation in cattle. This application confirms the mechanism but does not contribute to the evidence base in humans.
Caveats. The main limitation is the pharmacokinetics: the effect of a single injection is over within an hour. Protocols in which gonadorelin is injected twice a day or a few times a week do not approximate the physiological pulse pattern and have never been prospectively studied for the intended purpose. Moreover, part of the product on the market is not pharmaceutically prepared.
What it is used for
- Diagnostic GnRH stimulation test of anterior pituitary gonadotroph function and responsiveness 1
- Pulsatile treatment of hypogonadotropic hypogonadism and of anovulatory infertility (via pump)
- Evaluation of delayed or precocious puberty
- Off-label use alongside testosterone therapy to counter testicular atrophy — often as a substitute for hCG, but without clinical support
Dosing
- In the diagnostic test, 100 micrograms is given subcutaneously or intravenously after baseline samples at -15 minutes and immediately before injection, with further samples at 15, 30, 45, 60 and 120 minutes 1. This is done under medical supervision.
- In women the LH response depends strongly on the phase of the cycle; where the phase can be established the test should be performed in the early follicular phase, days 1-7 1.
- Doses circulating in user protocols (for example 100-200 micrograms subcutaneously, twice a day) do not come from clinical studies. Given the half-life of minutes, it is unlikely that this mimics a physiological pulse pattern.
- Repeated administration without a pulse interval may suppress rather than stimulate the pituitary — the opposite of the intended effect.
- The off-label pattern used alongside testosterone replacement is set out as a circulating protocol below. The label directs a single supervised diagnostic dose 1; users instead self-inject repeatedly as an hCG substitute, with no clinical support and a real risk of suppressing the very axis they mean to protect. It is recorded because readers encounter it, not because it is validated.
These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.
Protocols
Gonadorelin 100 mcg pituitary function test (diagnostic)
approved product informationSource: Gonadorelin 100 micrograms powder for solution for injection, SmPC (electronic Medicines Compendium)
| Baseline | LH and FSH sampled immediately before the injection |
|---|---|
| Time zero | 100 micrograms as a single intravenous or subcutaneous dose |
| After the dose | further LH and FSH samples at the fixed time points the test protocol specifies |
A diagnostic procedure performed under medical supervision, not a course of treatment - the result is the hormone curve, not an effect on the patient. In women the LH response varies strongly with the phase of the cycle, so the test is preferably done in the early follicular phase. Pulsatile therapeutic use requires a programmable pump delivering a dose every 60-120 minutes; repeated fixed injections do not reproduce that and suppress the pituitary instead.
Off-label alongside testosterone replacement (circulating)
user protocol — not validatedSource: TRT and bodybuilding forums, telehealth-clinic 'protocols' and compounding-pharmacy labelling
This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.
| Most commonly reported | roughly 100 micrograms subcutaneously two or three times a week, taken as an hCG substitute to limit testicular atrophy during testosterone replacement |
|---|---|
| Also reported | 100-200 micrograms once or twice daily, and 'a dose before each testosterone injection' — the reported frequency varies far more than the amount |
| Reported purpose | preserving testicular size, fertility or intratesticular testosterone while exogenous testosterone suppresses the axis |
The label use is a single supervised diagnostic dose of 100 micrograms 1; what circulates is repeated self-injection to prop up the testes during testosterone replacement, standing in for hCG. No controlled study supports it — it is an extrapolation from hCG research, not a finding about gonadorelin. The pharmacology argues against it: gonadorelin's half-life is only a few minutes 1, so a twice-weekly or even twice-daily injection cannot reproduce the roughly 60-to-120-minute pulse the axis needs, and poorly spaced continuous exposure can desensitise the pituitary and suppress the axis rather than stimulate it — the opposite of the intended effect. The reported schedules diverge widely, from twice weekly to twice daily, which reflects the absence of any validated regimen. Much of the material sold for this purpose is compounded or grey-market rather than the registered diagnostic product, and its identity and purity are not assured.
Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.
Reconstitution
- Vial sizes
- 100 micrograms, 500 micrograms, 2 mg (grey market), 10 mg (grey market)
- Solvent
- Registered product: the supplied solvent or sterile water for injection. Powders from the grey market: bacteriostatic water (0.9% benzyl alcohol)
- Storage
- Powder cool and dry, protected from light; the registered product is used immediately after dissolution. Reconstituted at 2-8 °C, shelf life limited — gonadorelin is not very stable in solution.
Worked example
2 mg vial + 2 ml bacteriostatic water = 1 mg/ml. 100 micrograms corresponds to 0.1 ml, that is 10 units on a U100 insulin syringe.
Do not shake. The limited stability in solution is a real practical problem: with longer storage in liquid form the content declines.
Work it out for Gonadorelin
Safety
Side effects
- Headache 1
- Nausea and abdominal discomfort 1
- Flushing and hot flushes 1
- Induration, redness, swelling or pain at the injection site 1
- Hypersensitivity reactions including bronchospasm and urticaria 1; anaphylaxis is rare
- With pulsatile therapy: risk of ovarian hyperstimulation and multiple pregnancy
- With repeated non-pulsatile administration: suppression rather than stimulation of the gonadal axis, with a fall in testosterone or oestradiol
Do not use if
- Hypersensitivity to gonadorelin or to any of the excipients 1, and to GnRH analogues
- Hormone-sensitive tumours, including prostate carcinoma and hormone receptor-positive breast carcinoma
- Known or suspected pregnancy 1
- Ovarian cysts or unexplained vaginal bleeding
- Concurrent use of GnRH agonists or antagonists
- Pulsatile therapy should take place under endocrinological supervision, with monitoring of hormone values and ultrasound
Interactions
Oral contraceptives and digoxin suppress gonadotropin levels and spironolactone transiently raises them, so all three can distort the result of the diagnostic test 1; levodopa is also cited as an interferent. Dopamine antagonists and phenothiazines blunt the response by raising prolactin 1. Concurrent use of GnRH agonists or antagonists abolishes the effect. Exogenous testosterone or oestrogen administration suppresses the axis via negative feedback.
Sources
- Gonadorelin 100 micrograms powder for solution for injection — Summary of Product Characteristicselectronic Medicines Compendium (emc), United Kingdom
- Factrel (gonadorelin) — product information, indications, dosing and side effectsRxList