Gonadorelin
updated
Gonadorelin is synthetic GnRH, the ten-amino-acid hypothalamic hormone that signals the pituitary to release LH and FSH; its US human products are discontinued, and current US Factrel is for cattle. US testosterone clinics give occasional injections as a substitute for HCG during testosterone therapy. Given by pump in repeated pulses, it produced ovulation in 91 to 96% of 109 women with hypothalamic amenorrhea, and pump therapy was followed by sperm production in GnRH-deficient men, but no controlled study tests the clinic use. Graded C for pump therapy in selected GnRH-deficient patients, not for occasional injections.
synthetic native-sequence gonadotropin-releasing hormone
- Native human GnRH sequence with ten amino acids
- Plasma half-life is about four minutes after injection
- Historical US human Factrel and Lutrepulse products are discontinued
- The current US Factrel label is for cattle only
- Ovulation, pregnancy, spermatogenesis, and live birth are separate outcomes
What exactly is gonadorelin?
Gonadorelin is synthetic native-sequence human GnRH, a ten-amino-acid hypothalamic hormone. It signals pituitary gonadotrophs to release LH and FSH and is hydrolyzed rapidly, with a labeled plasma half-life of about four minutes.
The free base, hydrochloride, and acetate name the active peptide or product salt. A salt name does not make a bolus, pump, and intermittent injection clinically equivalent.
source: UK SmPC · bolus test and four-minute half-life, Electronic Medicines Compendium. Gonadorelin 100 micrograms SmPC, revised 30 August 2022.
source: DailyMed · cattle only, not for human use, DailyMed. FACTREL gonadorelin injection, NADA 139-237, label updated 18 August 2026.
Why does the delivery pattern matter?
A single bolus briefly tests whether the pituitary can release LH. The fertility studies used a pump that repeated short pulses around the clock. Those interventions answer different questions even when the active peptide is gonadorelin.
| Delivery | Studied purpose | What the evidence answers |
|---|---|---|
| Single bolus | Pituitary stimulation test | Short-term LH response |
| Repeating pump pulses | Defined hypothalamic GnRH deficiency | Ovulation or spermatogenesis under a pump protocol |
| Occasional clinic injection | Claimed TRT support | Not established in a controlled fertility-preservation study |
source: UK SmPC · bolus test and four-minute half-life
source: 109 women · ovulation, not a live-birth report, Santoro N. American Journal of Obstetrics and Gynecology, 1990.
source: 28 men · earlier sperm, similar observed rates, Zhang L et al. American Journal of Men’s Health, 2019.
What did pulsatile gonadorelin show in women?
The 109-woman multicenter study reported ovulation in 91% of primary and 96% of secondary hypothalamic amenorrhea cases. Those are ovulation rates, not pregnancy or live-birth rates. A separate Chinese series reported two natural pregnancies among five women, but its size and uncontrolled design do not supply a dependable pregnancy estimate.
source: 109 women · ovulation, not a live-birth report
source: Chinese series · 5 women, 2 pregnancies, Liu Z et al. Zhonghua Yi Xue Za Zhi, 2015.
What did pump therapy show in men with GnRH deficiency?
In Chinese clinical cohorts with congenital or idiopathic hypogonadotropic hypogonadism, pump therapy was followed by sperm production and sometimes fertility. Comparative studies found earlier sperm appearance with a pump, while the smaller 28-man comparison did not show a significant difference in the proportion who produced sperm.
| Study | Pump group | Key result | Limit |
|---|---|---|---|
| Huang 2015 | 40 of 92 men | 20/40 produced sperm; mean 6.5 months to first sperm | Retrospective, self-selected therapy |
| Zhang 2019 | 10 of 28 men | Median 6 months; 90% produced sperm | Nonrandomized; rate difference not significant |
| Niu 2024 | 45 men | 33 produced sperm; 8 natural fertility; 3 births via assisted reproduction | Uncontrolled case series |
source: Chinese retrospective study · 40 versus 52 men, Huang B et al. Zhonghua Yi Xue Za Zhi, 2015.
source: 28 men · earlier sperm, similar observed rates
source: Chinese series · 45 men, fertility and adverse events, Niu YH et al. Zhonghua Nan Ke Xue, 2024.
Does an occasional gonadorelin injection replace HCG during TRT?
The cited human evidence does not support that substitution. HCG stimulates the testicular LH receptor directly, while gonadorelin depends on an intact, responsive pituitary and repeated timing. Positive pump results in GnRH-deficient patients do not validate sporadic injections during exogenous testosterone use.
source: Gonadorelin with TRT · fertility evidence, PubMed and ClinicalTrials.gov records for gonadorelin with testosterone therapy or fertility support.
What are the relevant side effects and safety limits of gonadorelin?
Risks depend on the use. The diagnostic label lists hypersensitivity, premature ovulation, pituitary-apoplexy concern in pituitary adenoma, drug interactions that alter gonadotropin response, and rare or frequency-unknown adverse reactions. Pump studies add line complications, injection-site allergy or induration, multiple pregnancy, and an ovarian-hyperstimulation case confounded by clomiphene.
Short diagnostic exposure does not establish the safety of months of pump therapy. Neither diagnostic-bolus nor pump studies establish long-term safety for intermittent clinic formulations of uncertain provenance.
source: UK SmPC · bolus test and four-minute half-life
source: 109 women · ovulation, not a live-birth report
source: 28 men · earlier sperm, similar observed rates
source: Chinese series · 45 men, fertility and adverse events
Which Factrel and Lutrepulse products are human products?
US human Factrel and Lutrepulse applications are historical, and all listed strengths are discontinued. Current US Factrel is an FDA-labeled intramuscular cattle product. In Canada, Lutrepulse 0.8 mg is cancelled post-market and 3.2 mg is dormant.
source: Drugs@FDA · all human Factrel strengths discontinued, US Food and Drug Administration. FACTREL, NDA 018123.
source: Drugs@FDA · both pump-kit strengths discontinued, US Food and Drug Administration. LUTREPULSE KIT, NDA 019687.
source: DailyMed · cattle only, not for human use
source: Health Canada · 0.8 mg cancelled, 3.2 mg dormant, Health Canada Drug Product Database search for the brand name LUTREPULSE, run on 9 September 2026: drug codes 16274 and 16273.
Which studies define the diagnostic and pump-therapy results?
Regulated records cover diagnostic use, while historical and current pump studies concern pulsatile treatment of GnRH deficiency. Chinese clinical reports and the cited TRT evidence do not establish intermittent gonadorelin as a substitute for HCG during testosterone use.
source: UK SmPC · bolus test and four-minute half-life
source: Drugs@FDA · all human Factrel strengths discontinued
source: Drugs@FDA · both pump-kit strengths discontinued
source: DailyMed · cattle only, not for human use
source: Health Canada · 0.8 mg cancelled, 3.2 mg dormant
source: 109 women · ovulation, not a live-birth report
source: Chinese series · 5 women, 2 pregnancies
source: Chinese retrospective study · 40 versus 52 men
source: 28 men · earlier sperm, similar observed rates
source: Chinese series · 45 men, fertility and adverse events
Studies and sources
UK SmPC · bolus test and four-minute half-life
Regulated product information
Electronic Medicines Compendium. Gonadorelin 100 micrograms SmPC, revised 30 August 2022.
The product is a single subcutaneous or intravenous bolus used to test pituitary gonadotroph response. The label says that this test does not determine the cause of a subnormal response or measure reserve, and reports rapid plasma hydrolysis with a half-life of about four minutes.
- Pregnancy and hypersensitivity are contraindications.
- The label warns about premature ovulation, pituitary apoplexy in patients with pituitary adenoma, and effects of drugs that alter pituitary gonadotropin secretion.
- Participants / model
- People undergoing assessment of anterior-pituitary gonadotroph function
- Treatment
- Single 100 microgram subcutaneous or intravenous bolus
- Study design
- Current regulated product information for a diagnostic use
Drugs@FDA · all human Factrel strengths discontinued
FDA application record
US Food and Drug Administration. FACTREL, NDA 018123.
The application record identifies gonadorelin hydrochloride injectable Factrel as a human new drug approved in 1982. All three listed strengths have a marketing status of Discontinued.
- Study design
- FDA application and product-status record
Drugs@FDA · both pump-kit strengths discontinued
FDA application record
US Food and Drug Administration. LUTREPULSE KIT, NDA 019687.
The application record identifies gonadorelin acetate Lutrepulse kits at 0.8 mg and 3.2 mg. Both products have a marketing status of Discontinued.
- Study design
- FDA application and product-status record
DailyMed · cattle only, not for human use
FDA animal-drug label
DailyMed. FACTREL gonadorelin injection, NADA 139-237, label updated 18 August 2026.
The current Factrel product is a prescription animal drug containing 50 micrograms per mL gonadorelin for intramuscular use in cattle. Its label explicitly says cattle only and not for human use.
- Participants / model
- Cattle
- Treatment
- Veterinary intramuscular gonadorelin under NADA 139-237
- Study design
- Current animal-drug label
The shared brand name does not make this a human product.
Read the original sourceHealth Canada · 0.8 mg cancelled, 3.2 mg dormant
Health Canada product-status database
Health Canada Drug Product Database search for the brand name LUTREPULSE, run on 9 September 2026: drug codes 16274 and 16273.
The 0.8 mg gonadorelin acetate product, code 16274, is Cancelled Post Market as of 24 December 2024. The 3.2 mg product is drug code 16273 and remains Dormant.
- Study design
- Federal drug product and status database
109 women · ovulation, not a live-birth report
Multicenter clinical trial
Santoro N. American Journal of Obstetrics and Gynecology, 1990.
Among 109 women with primary or secondary hypothalamic amenorrhea, intravenous pulsatile gonadorelin produced ovulation in 91% and 96% of the two groups. The abstract reports a mean 7% rate of intravenous-line complications, 12% multiple pregnancy, and one ovarian-hyperstimulation case in a woman also given clomiphene. It does not give subgroup denominators, total pregnancy count, or live births.
- Participants / model
- 109 women with primary or secondary hypothalamic amenorrhea
- Treatment
- Intravenous pulsatile gonadorelin acetate through the Lutrepulse system
- Follow-up
- Through ovulation induction; follow-up duration not stated in the abstract
- Study design
- Multicenter clinical trial; randomization and comparator allocation are not described in the abstract
The large percentages are ovulation endpoints. Pregnancy and live birth cannot be inferred from them.
Read the original sourceChinese series · 5 women, 2 pregnancies
Retrospective case series in Chinese
Liu Z et al. Zhonghua Yi Xue Za Zhi, 2015.
Five women with idiopathic hypogonadotropic hypogonadism received pump pulses for at least 12 weeks. Four had menstrual bleeding after 35 to 55 days and two natural pregnancies were reported. With five uncontrolled patients, this adds a downstream pregnancy observation but cannot estimate a dependable pregnancy or live-birth rate.
- Participants / model
- 5 women with idiopathic hypogonadotropic hypogonadism
- Treatment
- Pulsatile gonadorelin by pump, 10 micrograms every 90 minutes
- Follow-up
- At least 12 weeks
- Study design
- Retrospective uncontrolled case series; Chinese-language article with English abstract
The abstract reports no live-birth outcome.
Read the original sourceChinese retrospective study · 40 versus 52 men
Retrospective comparative study in Chinese
Huang B et al. Zhonghua Yi Xue Za Zhi, 2015.
Ninety-two men self-selected treatment: 40 received pulsatile GnRH and 52 received HCG/HMG. Sperm appeared in 20 of 40 versus 15 of 52, and mean time to first sperm was 6.5 versus 10.8 months. The voluntary treatment choice, retrospective design, and unequal follow-up leave confounding.
- Participants / model
- 92 male outpatients with idiopathic hypogonadotropic hypogonadism
- Treatment
- Pulsatile GnRH infusion or HCG/HMG
- Follow-up
- Median follow-up 8.2 versus 9.2 months
- Study design
- Retrospective nonrandomized comparison; Chinese-language article with English abstract
Treatment was self-selected, so the between-group difference is not a randomized effect estimate.
Read the original source28 men · earlier sperm, similar observed rates
Nonrandomized comparative study
Zhang L et al. American Journal of Men’s Health, 2019.
Ten azoospermic men received a pulsatile gonadorelin pump and 18 received cyclical HCG/HMG for up to 24 months. Median time to sperm was 6 versus 14 months. Sperm appeared in 90% versus 83.3%, a difference that was not statistically significant. Pump users commonly had allergic erythema or induration.
- Participants / model
- 28 azoospermic men with congenital hypogonadotropic hypogonadism
- Treatment
- Pulsatile gonadorelin pump or cyclical HCG/HMG
- Follow-up
- Up to 24 months
- Study design
- Nonrandomized comparative study
The small, unrandomized groups do not prove that the pump gives a higher eventual spermatogenesis rate.
Read the original sourceChinese series · 45 men, fertility and adverse events
Retrospective case series in Chinese
Niu YH et al. Zhonghua Nan Ke Xue, 2024.
In 45 men treated with pump pulses for a mean 19.1 months, sperm was observed in 33, eight achieved natural fertility, and three achieved childbirth through assisted reproduction. Gynecomastia occurred in eight, subcutaneous induration in six, and allergic reaction in three. There was no untreated or active comparator.
- Participants / model
- 45 men with congenital hypogonadotropic hypogonadism
- Treatment
- Gonadorelin pump, 7 to 15 micrograms every 90 minutes
- Follow-up
- Mean 19.1 months
- Study design
- Retrospective uncontrolled case series; Chinese-language article with English abstract
Observed outcomes in a selected endocrine disorder do not establish results for men whose GnRH axis is being suppressed by exogenous testosterone.
Read the original sourceGonadorelin with TRT · fertility evidence
PubMed and ClinicalTrials.gov records
PubMed and ClinicalTrials.gov records for gonadorelin with testosterone therapy or fertility support.
The cited records include one Chinese CHH follow-up cohort in which participants selected among pump, gonadotropin, or testosterone treatments. It did not test intermittent gonadorelin added to TRT, and the cited registry records include no controlled trial of occasional clinic injections as an HCG substitute.
Read the original sourceWhy is Gonadorelin in C tier?
C reflects human efficacy for pulsatile pump therapy in selected GnRH-deficient populations. Diagnostic boluses, intermittent TRT-clinic injections, and the veterinary Factrel product use different regimens and evidence.
how tiers are graded: methodology · every cited source · about reptides.
Research reference, not medical advice. Entries distinguish product labels, study doses and reported protocols. Check the linked source for the product, route and population.