In a comparison of pulsatile GnRH (gonadorelin) and gonadotropin (hCG/hMG) therapy in men with idiopathic hypothalamic hypogonadism, both restored testosterone and induced spermatogenesis.
men with idiopathic hypothalamic hypogonadism
Gonadorelin
Not currently offered
Vitality
Gonadorelin
A synthetic copy of the hormone GnRH
Not currently offered by RiptideRxOverview.
No FDA-approved gonadorelin product is marketed in the US. Gonadorelin is the synthetic form of native gonadotropin-releasing hormone (GnRH/LHRH), a hypothalamic decapeptide that stimulates the pituitary to release LH and FSH. It was FDA-approved in the 1980s as Factrel (diagnostic pituitary testing) and Lutrepulse (pulsatile-pump therapy for hypothalamic anovulatory infertility); both were discontinued. It is now available only as a compounded product and is used off-label alongside testosterone replacement therapy, as an alternative to hCG, with the aim of preserving testicular size and fertility, but there are no controlled trials of the intermittent injections used with TRT. Evidence for fertility effects comes from pulsatile pump delivery in hypogonadotropic hypogonadism, and continuous or non-pulsatile exposure can suppress rather than stimulate LH and FSH.
Also known as Factrel · Lutrepulse · Lutrepulse Kit · GnRH
The molecule, decoded.
- Sequence
-
pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2
- Length
- 10 residues
- Molecular weight
- 1,182.3 g/mol
- Formula
- C55H75N17O13
- CAS number
- 33515-09-2
- Half-life
- Not established
- Routes studied
- intravenous bolus (diagnostic single-dose use), subcutaneous or intravenous pulsatile infusion via pump (therapeutic use)
- Modifications
- N-terminal pyroglutamate (cyclized N-terminal residue); C-terminal glycinamide (amidated Gly10); sequence is identical to native mammalian GnRH/LHRH with no synthetic amino-acid substitutions - distinguishing it from longer-acting GnRH agonist analogs such as leuprolide, triptorelin, or buserelin, which carry substitutions at positions 6 and/or 10
How it works.
Binds the pituitary gonadotrope GnRH receptor (a Gq-coupled GPCR); pulsatile exposure (mimicking endogenous hypothalamic secretion) stimulates synthesis and release of LH and FSH, which in men drives Leydig-cell testosterone production and spermatogenesis and in women drives follicular development and ovulation. Unlike hCG, which acts directly on the testicular/ovarian LH receptor and bypasses the pituitary, gonadorelin acts one step upstream and therefore requires an intact, responsive pituitary gonadotrope population to be effective; continuous (non-pulsatile) exposure instead desensitizes/down-regulates the receptor, which is the basis for the opposite (suppressive) effect exploited by longer-acting GnRH agonist analogs (e.g. leuprolide).
Evidence · Previously FDA-approved brand, now discontinued · limited data for current uses
What the research shows
Among 28 men with congenital hypogonadotropic hypogonadism who had a poor sperm-production response to at least 6 months of combined hCG/hMG therapy, switching to pulsatile GnRH (gonadorelin) achieved spermatogenesis in 17 of 28 (60.7%), and testicular volume increased further than under the prior hCG/hMG therapy (to 8.45 mL, P<0.001).
28 men with congenital hypogonadotropic hypogonadism, hCG/hMG poor-responders
What to know first.
Based on: clinical studies of pulsatile pump therapy; no controlled trials of use alongside testosterone therapy.
Reported side effects
- No reliable human data.
Cautions
- Hypersensitivity to GnRH or its analogs
- Off-label use alongside testosterone replacement therapy (as an hCG alternative) is not FDA-approved and is not covered by any current label, and no standardized regimen exists
Checked 2026-09
Where it stands.
Not currently offered by RiptideRx. No FDA-approved Gonadorelin product is marketed in the US, and its eligibility for pharmacy compounding hasn’t been confirmed, so RiptideRx doesn’t offer it.
- FDA
- No FDA-approved gonadorelin product is currently marketed in the US. Two branded products were approved and later discontinued: Factrel (gonadorelin hydrochloride injection; NDA 018123; original sponsor Wyeth, application now held by Hikma; original approval 1982-09-30) for diagnostic evaluation of anterior pituitary gonadotropin-releasing function, and Lutrepulse Kit (gonadorelin acetate, for pulsatile-pump delivery; NDA 019687; sponsor Ferring; original approval 1989-10-10) for induction of ovulation in women with primary hypothalamic amenorrhea/anovulatory infertility. Drugs@FDA lists every strength of both as discontinued (Sep 2026).
- Approved products
- Factrel (FDA, 1982): Diagnostic evaluation of anterior pituitary gonadotropic function (GnRH/LHRH stimulation test)
- Lutrepulse Kit (FDA, 1989): Induction of ovulation in women with primary hypothalamic amenorrhea (anovulatory infertility of hypothalamic origin), via pulsatile subcutaneous/intravenous pump
- Compounding
- Gonadorelin is not in FDA's 503A nomination categories (list updated May 14, 2026), which cover substances that are neither USP-monograph subjects nor components of FDA-approved drugs; FDA does not place substances nominated on or after Jan 7, 2025 into those categories. Because gonadorelin was the active ingredient of two FDA-approved (now discontinued) drugs (Factrel, Lutrepulse), it may qualify for 503A compounding as a component of an approved drug (FDCA 503A(b)(1)(A)(i)), although FDA has not said so explicitly. On the 503B side, 'Gonadorelin Acetate**' is in Category 1 (bulk drug substances under evaluation; the ** marks components of FDA-approved drugs) of FDA's 503B categories list (updated Mar 21, 2025), so outsourcing facilities may compound it under FDA's interim policy. In practice, gonadorelin is available in the US only as a compounded product (503A pharmacies or 503B outsourcing facilities).
- Sport (WADA)
- Prohibited at all times (in and out of competition) for male athletes: WADA 2026 Prohibited List S2.2.1 (testosterone-stimulating peptides in males) names 'gonadotrophin-releasing hormone (GnRH, gonadorelin) and its agonist analogues' alongside chorionic gonadotrophin, LH and kisspeptin; non-Specified Substance. Unchanged in the 2027 List. (GnRH analogues in females under 18 are on the Monitoring Program only.)