Alarelin
Alarelin acetate, Dalarelin, [D-Ala6, des-Gly10]-GnRH ethylamide, des-Gly10-[D-Ala6]-LHRH ethylamide, TAP-127, AY-25205, WY-18481
Alarelin is a gonadotrophin-releasing hormone agonist: a nonapeptide analogue of GnRH with D-alanine at position 6 and an ethylamide replacing the tenth residue, the same design strategy used in leuprorelin and triptorelin. It is used clinically in China and extensively in veterinary reproduction. Despite decades of use it has generated very little peer-reviewed human trial evidence in the internationally indexed literature.
Mechanism
Alarelin binds the gonadotrophin-releasing hormone receptor, a Gq/11-coupled receptor on pituitary gonadotrophs. The two modifications to native GnRH are the standard superagonist design: substituting D-alanine at position 6 removes the site at which endopeptidases cleave the native decapeptide, and replacing glycine at position 10 with an ethylamide group blocks carboxypeptidase attack. The result is a molecule that occupies the receptor far longer than the endogenous hormone, which is normally released in discrete pulses roughly every 90 minutes. The draft quoted a dissociation constant of approximately 0.2 nanomolar; no primary source for that figure could be confirmed, so it has been removed.
That difference in kinetics produces the paradoxical clinical behaviour common to all GnRH agonists. Initially, sustained receptor occupancy causes a flare: luteinising hormone and follicle-stimulating hormone surge, and gonadal steroid output rises. Continued exposure then downregulates and desensitises the gonadotroph receptor population, uncoupling it from downstream signalling, and gonadotrophin secretion falls to castrate or menopausal levels within one to three weeks. This chemically reversible hypogonadism is the therapeutic objective in oestrogen-dependent gynaecological disease and androgen-dependent prostate cancer. In assisted reproduction the same downregulation is used to suppress a premature luteinising hormone surge so that follicular development can be controlled exogenously, while in veterinary practice the initial flare is often the point, used to induce ovulation and spermiation and to synchronise breeding. Consistent with receptor-level action, active immunisation against alarelin in ewes suppressed ovarian GnRH receptor protein while enhancing FSH and LH receptor protein and accelerating follicular development.
What the research shows
The human evidence base for alarelin, as indexed internationally, is thin for a compound in clinical use. The principal published human study compared alarelin with triptorelin in long-protocol ovulation induction for in vitro fertilisation and embryo transfer in 122 infertile patients, 78 receiving alarelin and 44 triptorelin; the authors concluded the two achieved similar pituitary downregulation and clinical outcomes, with no premature LH surge or severe ovarian hyperstimulation syndrome in either group, though the triptorelin group had significantly more cancelled cycles. A 2025 report in Frontiers in Medicine describes what the authors call the first severe hepatotoxicity linked to alarelin acetate: a 37-year-old woman in a phase I trial receiving 150 micrograms per day subcutaneously developed acute liver injury, scored as highly probable on RUCAM, with liver enzymes normalising within 18 days of stopping the drug and hepatoprotective treatment; pharmacogenomic analysis identified a homozygous NUDT15 variant and HLA risk alleles as candidate associations. Rat pharmacokinetics were characterised by liquid chromatography-tandem mass spectrometry in 2019. Beyond that, the bulk of the alarelin literature is veterinary: active immunisation studies in ewes, sustained-release microparticle delivery to induce spermiation in sturgeon, and oestrus synchronisation work in livestock.
This matters for how the compound should be read. The class pharmacology of GnRH agonists is beyond dispute - leuprorelin, triptorelin, goserelin, buserelin and nafarelin all have extensive randomised trial evidence and regulator-approved labelling for endometriosis, uterine fibroids, central precocious puberty, prostate cancer and assisted reproduction - but that evidence belongs to those molecules, not to alarelin. What can be said with confidence is that alarelin is a bona fide GnRH agonist with the expected downregulation profile. What cannot be said is that its efficacy and safety in any human indication have been characterised to the standard of its licensed siblings. Anyone encountering alarelin in a longevity or research-chemical context should also note the obvious: profound suppression of the reproductive axis is not a benign intervention, and there is no evidence in any species that it extends healthspan or lifespan.
Evidence assessment
Limited evidence
Alarelin is used clinically in China and heavily in veterinary reproduction, but the internationally indexed human evidence amounts to one comparative ovulation induction study of 122 patients in a national-language journal plus a single hepatotoxicity case report from a phase I trial. The class it belongs to has strong evidence; this specific molecule does not. That is precisely the limited tier: isolated, low-quality human data.
Tiers are applied consistently across the library and re-checked when new trials read out. Read the grading method.
Key studies
Comparison of Alarelin and Triptorelin in the long-protocol ovulation induction in in vitro fertilization and embryo transfer Preclinical only
Both agonists achieved similar pituitary downregulation and comparable clinical outcomes, with no premature LH surge, no ovulation before retrieval and no severe ovarian hyperstimulation syndrome in either group. The triptorelin group had significantly more cancelled cycles.
Pharmacogenomic analysis of alarelin acetate-induced hepatotoxicity: a case report and literature review Preclinical only
A 37-year-old woman in a phase I trial receiving 150 micrograms per day subcutaneously developed acute liver injury, assessed as highly probable on RUCAM and reported by the authors as the first severe hepatotoxicity linked to alarelin acetate. Liver enzymes normalised within 18 days of drug cessation and hepatoprotective treatment. A homozygous NUDT15 variant and specific HLA risk alleles were identified as candidate associations requiring confirmation.
Liquid chromatography tandem mass spectrometry with triple stage fragmentation for highly selective analysis and pharmacokinetics of alarelin in rat plasma Preclinical only
A triple-stage fragmentation LC-MS/MS method linear over 0.3-10 ng/ml enabled highly selective analysis of alarelin and characterised its pharmacokinetics in rats; the approach was proposed as transferable to other peptide drugs.
Alarelin active immunization influences expression levels of GnRHR, FSHR and LHR proteins in the ovary and enhances follicular development in ewes Preclinical only
Immunisation raised GnRH antibody titres, suppressed ovarian GnRH receptor protein expression and enhanced FSH receptor and LH receptor protein levels, accelerating ovarian development and follicular maturation relative to controls.
Induction of Spermiation in Sterlet Acipenser ruthenus by PLGA Microparticle Delivery with Sustained Alarelin Release Preclinical only
Carp pituitary extract gave maximum sperm production at 24 hours, but spermatozoon motility was significantly higher with alarelin at 35 micrograms/kg than at 200 micrograms/kg, and the lower alarelin dose in microparticles gave the best overall outcome for inducing spermiation.
Safety
Adverse effects follow directly from induced hypogonadism and are well characterised for the GnRH agonist class: hot flushes, night sweats, vaginal dryness, reduced libido, mood disturbance and headache. Bone mineral density falls with exposure beyond about six months, which is why licensed agonists in benign gynaecological indications carry duration limits and add-back hormone strategies. The initial flare can transiently worsen symptoms, and in advanced prostate cancer it can precipitate spinal cord compression or urinary obstruction. Alarelin specifically has one published human case of severe hepatotoxicity, scored highly probable on RUCAM and accompanied by pharmacogenomic analysis; that is a genuine, if isolated, signal rather than a theoretical one, and it was reversible on withdrawal. GnRH agonists are contraindicated in pregnancy and breastfeeding, and unexplained vaginal bleeding must be investigated before use. Injection site reactions are common across the class. None of this class safety information has been formally established for alarelin to licensed-drug standard outside China, and material sold outside regulated pharmaceutical channels has unverified identity and purity.
Regulatory status
| Jurisdiction | Status |
|---|---|
| United Kingdom | No UK marketing authorisation for human or veterinary use. Licensed GnRH agonists available in the UK include leuprorelin, triptorelin, goserelin, buserelin and nafarelin for human use, and deslorelin and buserelin in veterinary medicine. Supplying alarelin for human use would constitute supply of an unlicensed medicinal product under the Human Medicines Regulations 2012. |
| United States | No FDA approval for any human or veterinary indication in the United States could be identified. Several other GnRH agonists including leuprorelin, triptorelin, goserelin, nafarelin and histrelin hold FDA approvals for the indications alarelin is used for elsewhere, and deslorelin holds US veterinary approval. |
| WADA (sport) | Prohibited in males only, at all times. Gonadotrophin-releasing hormone agonists sit under section S2.2.1 of the WADA Prohibited List (chorionic gonadotrophin and luteinising hormone and their releasing factors, in males), which restricts the prohibition to male athletes. Alarelin is not itself named among the listed examples - those are buserelin, deslorelin, gonadorelin, goserelin, leuprorelin, nafarelin and triptorelin - but it is captured by the list's catch-all for substances of similar chemical structure or biological effect. The draft cited section S2.2 without the subsection and stated alarelin was covered as a named substance; both have been corrected. |
Questions
In China it is used clinically in humans, and published Chinese studies and a documented adverse drug reaction case from a phase I trial confirm that. It holds no marketing authorisation in the United States or the United Kingdom, where leuprorelin, triptorelin, goserelin, buserelin and nafarelin fill the same therapeutic roles with far more extensive trial evidence.
Natural GnRH arrives in pulses roughly every 90 minutes, and the pituitary receptor is built for that rhythm. A long-acting agonist occupies the receptor continuously. The first response is a surge of luteinising and follicle-stimulating hormone, the flare. Within one to three weeks the receptors downregulate and uncouple from signalling, and gonadotrophin output collapses to castrate levels.
Overwhelmingly veterinary reproduction: inducing ovulation, synchronising oestrus and inducing spermiation across livestock and farmed fish. Human clinical use is largely confined to China, where it has been applied in assisted reproduction and hormone-dependent gynaecological conditions.
One. A 2025 case report describes severe but reversible drug-induced liver injury in a woman receiving alarelin acetate in a phase I trial, assessed as highly probable by RUCAM. That is a single case and cannot establish incidence, but it is a real signal rather than a theoretical one, and it sits on top of the ordinary hypogonadal effects of the class.
No. There is no evidence in any species that alarelin extends lifespan or healthspan. Suppressing the reproductive axis in humans causes bone mineral density loss, vasomotor symptoms and mood disturbance, which is why licensed agonists carry duration limits in benign indications.