Detirelix
A long-acting LHRH antagonist from Syntex that strongly and reversibly shut down the sex-hormone axis in men and women, but was not carried through to approval
Detirelix, coded RS-68439, is a ten-amino-acid analogue of the brain hormone that drives the reproductive system. Unlike the agonist drugs that first overstimulate and then exhaust that system, detirelix blocks it directly from the first dose. Syntex Research developed it in the 1980s as a longer-acting member of the second generation of these GnRH antagonists, and small studies in healthy men and in women showed it could lower luteinizing hormone, follicle-stimulating hormone, testosterone and estradiol for days after a single injection, with the effects wearing off cleanly afterwards. It reached early-phase human testing but was not developed to approval, and it is not a marketed medicine anywhere.
Used in human trials: 5, 10 or 20 mg, Single injection, Subcutaneous (Single doses, healthy men) Details ↓
Recommended Dosing
Used in human trials
Typical range1–20 mg · single or short-course Human studyPMID 3104388, PMID 2005218, PMID 1370507compare across peptides →
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
A small pulse generator in the base of the brain releases gonadotropin-releasing hormone (GnRH, also called LHRH) in bursts. Each burst reaches the pituitary gland and tells it to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn drive the testes to make testosterone and sperm, or the ovaries to grow follicles, make estradiol and ovulate. Two kinds of drug interrupt that signal. Agonists, like leuprolide, overdrive the receptor so hard that it shuts down after an initial flare. Antagonists block the receptor instead, so the fall in hormones is immediate and there is no flare. Detirelix is an antagonist.
It is a decapeptide, the same ten-residue backbone as natural GnRH but with several of its amino acids swapped for unnatural, mostly D-form, building blocks. Those substitutions do two things: they stop the molecule binding as a signal (so it occupies the receptor without switching it on) and they make it far harder for the body's enzymes to break down, which is why a single injection lasts for days. Syntex Research developed it as RS-68439, one of the longer-acting members of what the field called the second generation of GnRH antagonists.
The human studies were small but consistent. In nine healthy men, a single injection under the skin of 5, 10 or 20 milligrams lowered LH, FSH and testosterone within hours; testosterone fell furthest after the 20-milligram dose, and the apparent half-life measured at least 41 hours, long for a peptide. In women with normal cycles, injections on alternate days suppressed the hormones, stopped follicles maturing and blocked ovulation, and the cycle recovered within about two weeks of the last dose. In postmenopausal women, whose pituitaries run high because the ovaries have stopped, single doses of 1, 5 and 20 milligrams suppressed LH more than FSH in a dose-dependent way and confirmed that the suppression was biological, not just a change in what the assay detected.
The animal work filled in the mechanism and the pharmacology. In cynomolgus monkeys a continuous nine-week infusion produced azoospermia that reversed completely after the pump was removed, which marked the drug as a candidate for reversible male fertility control and for hormone-driven cancers. A disposition study in rats and monkeys showed that most of the drug left the body in the bile rather than the urine, that less than a tenth was excreted by the kidneys, and that a subcutaneous injection formed a depot that stretched the half-life to around a day in the monkey.
Detirelix was never approved, and its development did not continue past these early studies. The formal toxicology told part of the reason: single injections in rats and monkeys produced signs of peripheral vasodilation, including edema, facial flushing, red ears and pallor, a reaction pattern that dogged the early generations of GnRH antagonists and that limited how far they could be pushed. The human studies themselves reported only local skin reactions at the injection site and no systemic effects at the doses used. By the time the problem was solved, later antagonists such as cetrorelix, ganirelix, abarelix and degarelix had moved ahead, and detirelix was left as a studied-but-shelved compound.
Detirelix is of historical and research interest only. It is not a medicine, it is not sold as one, and nothing on this page is a dose to use. The amounts below are the quantities that volunteers were given under supervision in published trials, recorded so the science can be read, not followed.
Mechanism of Action
Detirelix competes with the body's own GnRH for the receptor on the pituitary without switching it on, so the hormones below it fall from the first dose. Its unnatural amino acids make it both an antagonist and long-lasting.
GnRH receptor on the pituitary
Detirelix occupies the gonadotropin-releasing hormone receptor on the pituitary's gonadotrope cells and blocks the natural hormone from binding, so the release of LH and FSH drops without the initial surge that an agonist causes (PMIDs 3104388, 2005220).
LH and FSH down, then the sex steroids
With less LH and FSH, the testes make less testosterone and the ovaries less estradiol. In men testosterone fell dose-dependently to a low of 0.6 ng/mL (PMID 3104388); in cycling women LH fell 74 percent and estradiol more than halved within a day (PMID 2005220); LH was suppressed more than FSH (PMID 1370507).
D-amino acids make it last
Replacing several residues of GnRH with D-form and unnatural amino acids stops enzymes cutting the peptide; a disposition study found breakdown only at one of the two ordinary peptide bonds left, cleaving off the first four residues (PMID 3072556). A subcutaneous depot stretches the effect to days (PMIDs 3104388, 3072556).
An off-target reaction
Single injections in animals caused edema, flushing and red ears, which the toxicology report read as peripheral vasodilation (PMID 1794654). This histamine-type reaction limited the early GnRH antagonists as a class and is part of why detirelix was not taken forward.
Published Research
These are the studies of detirelix read from their PubMed abstracts on November 5, 2026. The published record is a cluster of work from the 1980s and early 1990s: four human volunteer studies (men, cycling women, women across the menstrual cycle, and postmenopausal women), a reversibility study in monkeys, a pharmacokinetic study in rats and monkeys, and the formal toxicology. Three of the human and animal titles name only 'a GnRH antagonist'; those are carded because their abstracts name detirelix or its code RS-68439.
Single doses in healthy men
Nine normal men were each given a single injection under the skin of detirelix at 5, 10 and 20 milligrams, the doses separated by at least a week. Serum FSH, LH and testosterone all fell significantly, testosterone in a dose-dependent way, from a mean of 5.1 down to nadirs of 1.3, 0.9 and 0.6 nanograms per millilitre after the three doses. Testosterone began to escape suppression 12 to 28 hours after the lower doses. The apparent half-life measured by immunoassay was at least 41 hours. The drug caused only a minor local reaction and no systemic side effects at the doses used, and the authors judged it a potent, long-acting inhibitor of the pituitary-gonadal axis in men.
Alternate-day dosing in cycling women
Six women with normal menstrual cycles were injected under the skin on alternate days for 27 days (six more women were sampled without the drug). Within 8 hours of the first injection, mean LH fell by 74 percent and FSH by 26 percent, and estradiol dropped from 165 to 70 picomoles per litre within a day. Follicular development was suppressed and none of the six women ovulated during treatment. The axis recovered quickly afterwards: every woman had an ovulatory LH surge 10 to 16 days after the last injection, followed by a normal luteal phase. The injections caused local skin reactions (redness and itch) but no systemic effects.
Across the phases of the menstrual cycle
Twelve women received detirelix at 10 milligrams under the skin on three consecutive days, timed to the mid-follicular, pre-ovulatory or early-luteal phase of the cycle (four women each). The pituitary response was the same whichever phase was treated: LH fell to about a third of baseline within 8 hours and FSH to about three-quarters. The ovarian response, by contrast, varied with timing; estradiol and progesterone fell, and the delay to the next ovulation ranged from about 6 days after pre-ovulatory treatment to about 18 days after mid-follicular treatment. The study used the antagonist as a tool to show that the ovary's dependence on gonadotropins shifts across the cycle.
Single doses in postmenopausal women
Six postmenopausal women, whose gonadotropins run high because the ovaries have stopped, each received detirelix at 1, 5 and 20 milligrams under the skin in random order a week or more apart. LH and FSH were both suppressed in a dose-dependent way, LH more than FSH: maximum LH suppression was 40, 63 and 76 percent at the three doses, against 18, 26 and 40 percent for FSH, and LH stayed below baseline for up to 72 hours after the 20-milligram dose. A mouse Leydig-cell bioassay showed the bioactive LH fell in step with the immunoassay, and testosterone fell after the 20-milligram dose, evidence that the postmenopausal ovary's androgen output still depends on gonadotropins.
Reversible suppression in monkeys
Male cynomolgus monkeys (Macaca fascicularis) were infused continuously with 2 milligrams a day of the antagonist through implanted osmotic minipumps for nine weeks. LH and testosterone fell immediately and stayed low, and within 7 to 9 weeks three of four monkeys were azoospermic and the fourth had a very low sperm count, with severe atrophy of the testicular tissue. Everything reversed after the pump was removed: the hormones returned to normal within two weeks and sperm production within 14 to 18 weeks. The authors concluded that chronic antagonist treatment reversibly shuts down pituitary and testicular function in a primate, a model for fertility control and for androgen-dependent tumours.
Where the drug goes in rats and monkeys
A pharmacokinetic study in rats and monkeys. After a single injection into the vein the half-life was 1.6 hours in the rat and 7.1 hours in the monkey; after injection under the skin, monkey half-lives stretched to 18.7 and 31.6 hours, pointing to a depot forming at the injection site. The drug left the body mainly in the bile, with less than a tenth excreted by the kidneys. The main breakdown product found in rat bile was the first four amino acids of the peptide, cut at one of the only two ordinary peptide bonds the molecule's D-amino acids leave exposed, which shows how the unnatural residues protect it from enzymes.
Toxicology in rats and monkeys
Single-dose, two-week and three-month safety studies in rats and cynomolgus monkeys. A single injection into the vein produced signs of peripheral vasodilation: lethargy, edema, cyanosis, pallor and red ears in rats, and lethargy and facial flushing in monkeys. Repeated daily injections caused the expected shrinkage of the reproductive organs with blocked ovulation and sperm production, lower weight gain in males, and, at the highest rat dose, illness and deaths. The reproductive changes reversed at a rate that depended on the dose, and giving testosterone blunted them in male rats. The authors concluded the acute effects were consistent with peripheral vasodilation and the longer-term ones with suppression of the hormone axis.
Dosing Data
Detirelix has no approved label and is not a medicine. Every row below is an amount that volunteers were given under supervision in a published trial, recorded to document the science rather than to be used. All were injected under the skin. The doses span 1 to 20 milligrams depending on the study and whether a single injection or a short course was given.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Detirelix is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
An arithmetic example, not a recommendation: a 10 mg vial mixed with 3 mL of bacteriostatic water holds 3,333.3 mcg per mL, so 5 mg, the first amount in the “Single doses, healthy men” row (5, 10 or 20 mg) would be 150.0 units, more than a 1 mL U-100 syringe holds. Put your own vial's numbers into the reconstitution calculator.
Source: dose: Used in human trials, PMID 3104388 (Dosing Data below); vial and water: the calculator's default example, not a vial size we have a source for.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Detirelix, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Detirelix stays intact once mixed.
How it is taken
As it was given in human studies: Subcutaneous (Single injection; Single doses, healthy men).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of at least 41 h in men after a single subcutaneous dose (by immunoassay). After about five half-lives almost none is left.
How long the doses were given: Single doses, healthy men: One dose per level, a week apart; Short course, cycling women: 3 consecutive days; Single doses, postmenopausal women: One dose per level, a week apart.
When effects appear: unknown; no source on this page gives a time to effect for Detirelix. Results reported in the studies are under Published Research.
Source: half-life: PMID 3104388; Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Local skin reactions at the injection site, redness and itch, in cycling women (PMID 2005220); A minor local reaction and no systemic side effects at the single doses given to men (PMID 3104388); In animals, single injections caused signs of peripheral vasodilation: edema, facial flushing, red ears, pallor and lethargy (PMID 1794654); Expected hormonal effects of shutting down the axis: suppressed sex steroids, blocked ovulation and sperm production, all reversible (PMIDs 2005220, 6389185, 1794654). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Detirelix. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the published human studies and the animal toxicology”).
Interactions
Unknown: a PubMed search for human interaction studies of Detirelix (reviewed 2026-11-05) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Detirelix products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Detirelix's expected mass, 1,538.2 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Discontinued (Never approved anywhere: Drugs@FDA and the openFDA label endpoint hold no record (searched November 5, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the published human studies and the animal toxicology. The human reports are small and describe mainly local reactions; the systemic reaction pattern comes from the animal work.
Contraindications & Cautions
Detirelix has no label and no approved use. These points come from the trials and from what the drug does.
Legal Status
Detirelix is an investigational compound that was never approved in any country and is not marketed.
Frequently Asked Questions
?What is detirelix?
An experimental drug from the 1980s, coded RS-68439 by Syntex Research. It is a ten-amino-acid analogue of gonadotropin-releasing hormone (GnRH, or LHRH) that blocks the GnRH receptor and so lowers luteinizing hormone, FSH and the sex hormones below them.
?Was it ever approved or sold?
No. Detirelix reached early human testing (ChEMBL records phase 2) but was not developed further and was never approved or marketed in any country. There is no FDA application or label for it.
?Why was it not developed?
Its toxicology showed signs of peripheral vasodilation, edema, flushing and red ears, the histamine-type reaction that limited the early GnRH antagonists as a class (PMID 1794654). Later antagonists such as cetrorelix, ganirelix, abarelix and degarelix solved that problem and went forward instead.
?How is it different from drugs like leuprolide?
Leuprolide is a GnRH agonist: it overstimulates the receptor, causing a hormone flare before the system shuts down. Detirelix is an antagonist: it blocks the receptor, so hormones fall from the first dose with no flare.
?How long did a dose last?
Long for a peptide. In men a single subcutaneous injection had an apparent half-life of at least 41 hours (PMID 3104388), and in monkeys a subcutaneous dose formed a depot with a half-life around a day (PMID 3072556), because its unnatural amino acids resist breakdown.
?Is it available to buy?
No. Detirelix is not a medicine and is not sold as one. Grey Peptides lists no sellers and recommends no source; this page is a record of the published science.
References
- [clinical-trial] Pavlou SN, et al. "Suppression of pituitary-gonadal function by a potent new luteinizing hormone-releasing hormone antagonist in normal men." J Clin Endocrinol Metab, 1987;64(5):931-6. PMID: 3104388.
- [clinical-trial] Marshall LA, et al. "Inhibition of follicular development by a potent antagonistic analog of gonadotropin-releasing hormone (detirelix)." J Clin Endocrinol Metab, 1991;72(4):927-33. PMID: 2005220.
- [clinical-trial] Fluker MR, et al. "Variable ovarian response to gonadotropin-releasing hormone antagonist-induced gonadotropin deprivation during different phases of the menstrual cycle." J Clin Endocrinol Metab, 1991;72(4):912-9. PMID: 2005218.
- [clinical-trial] Andreyko JL, et al. "Concordant suppression of serum immunoreactive luteinizing hormone (LH), follicle-stimulating hormone, alpha subunit, bioactive LH, and testosterone in postmenopausal women by a potent gonadotropin releasing hormone antagonist (detirelix)." J Clin Endocrinol Metab, 1992;74(2):399-405. PMID: 1370507.
- [animal] Weinbauer GF, et al. "Reversible inhibition of testicular function by a gonadotropin hormone-releasing hormone antagonist in monkeys (Macaca fascicularis)." Fertil Steril, 1984;42(6):906-14. PMID: 6389185.
- [animal] Chan RL, et al. "Disposition of detirelix, a potent luteinizing hormone-releasing hormone antagonist, in rats and monkeys." Pharm Res, 1988;5(6):335-40. PMID: 3072556.
- [animal] Chester AE, et al. "Acute and subchronic toxicity studies with detirelix, a luteinizing hormone-releasing hormone antagonist, in the rat and monkey." Fundam Appl Toxicol, 1991;17(3):505-18. PMID: 1794654.
- [other] FDA Global Substance Registration System, Detirelix, UNII 05ME7P8ZBJ (acetate V81F7B15KR; protein; INN 6000, CAS 89662-30-6, NCI Thesaurus C132693, PubChem 16129698; code RS-68439), read November 5, 2026: a synthetic decapeptide analogue of gonadotropin-releasing hormone, N-acetyl-3-(2-naphthyl)-D-alanyl-4-chloro-D-phenylalanyl-D-tryptophyl-L-seryl-L-tyrosyl-N,N-diethyl-D-homoarginyl-L-leucyl-L-arginyl-L-prolyl-D-alaninamide (C78H105ClN18O13, 1538.24 g/mol). https://gsrs.ncats.nih.gov/ginas/app/beta/substances/05ME7P8ZBJ
- [other] ChEMBL molecule CHEMBL2106408 (DETIRELIX ACETATE), read November 5, 2026: molecule type Protein; synonym RS-68439 (research code); highest clinical phase recorded 2. https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2106408/
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 5, 2026: no application and no label record for detirelix. It has an FDA substance record (UNII 05ME7P8ZBJ) and a 1987 USAN, which name a molecule and do not approve it.
- [registry] ClinicalTrials.gov API v2, searched November 5, 2026: 0 records for detirelix or RS-68439. The registry began in 2000, after the drug's 1980s-90s trials, so the absence is expected and is not evidence of later study. https://clinicaltrials.gov/search?term=detirelix
Sources & Citations
The seven studies carded above were read from their PubMed records on November 5, 2026. Structure, codes and identifiers come from the FDA Global Substance Registration System (UNII 05ME7P8ZBJ) and ChEMBL (CHEMBL2106408); the absence of approval from Drugs@FDA and openFDA, and the absence of registered trials from ClinicalTrials.gov, all checked the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.