{"id":"gonadorelin","name":"Gonadorelin (GnRH)","aliases":["gonadotropin-releasing hormone","GnRH","LHRH","Factrel","Lutrelef"],"url":"https://lyoresearch.com/compounds/gonadorelin","class":{"id":"reproductive-hormones","name":"Reproductive and neuroendocrine hormones","url":"https://lyoresearch.com/classes/reproductive-hormones"},"summary":"Gonadorelin is synthetic gonadotropin-releasing hormone, the ten-amino-acid signal the hypothalamus sends to make the pituitary release LH and FSH. Given in pulses by pump it restores fertility in men and women whose own signal is missing; given once it is a licensed test of pituitary function. Neither is what it is mostly sold for today: clinics add it to testosterone replacement to 'keep the testes working', a use that has never been tested in a trial. It is prohibited for male athletes.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"Decades of pulsatile-therapy studies; meta-analysis of 420 men; no trial of the TRT use","regulatory_status":"Licensed (diagnostic / pulsatile); TRT use unstudied","molecule":{"formula":"C55H75N17O13","molecular_weight":"1182.3","cas":"33515-09-2","pubchem_cid":638793,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous or intravenous injection, single diagnostic dose; pulsatile pump for fertility","half_life":"About 4 minutes","licensed_regimen":"100 micrograms SC or IV as a single diagnostic dose","product":"Gonadorelin 100 micrograms powder for solution for injection (UK)","source":{"title":"Gonadorelin 100 micrograms SmPC (UK eMC)","url":"https://www.medicines.org.uk/emc/product/4853/smpc"}},"outcomes":[{"outcome":"LH and FSH release (diagnostic)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Approval-grade","evidence":"A single injection reliably provokes an LH and FSH response, which is the basis of its licence as a pituitary-function test. Not in dispute.","references":[{"citation":"Gonadorelin 100 micrograms powder for solution for injection — Summary of Product Characteristics.","where":"MHRA / emc, UK","url":"https://www.medicines.org.uk/emc/search?q=gonadorelin"}]},{"outcome":"Fertility in hypogonadotropic hypogonadism (pulsatile pump)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"7 comparative studies, 420 men (meta-analysis); many small series","evidence":"In men whose hypothalamus does not produce GnRH, pulsatile gonadorelin by pump induces puberty and sperm production. Against gonadotropin injections it produced larger testes and earlier sperm, but no significant difference in the share who produced sperm, sperm counts or pregnancies; the studies are small and mostly not randomised.","references":[{"citation":"Wei C, Long G, Zhang Y, et al. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile gonadotropin-releasing hormone therapy versus gonadotropin therapy: a systematic review and meta-analysis.","where":"World J Mens Health, 2021;39(4):654–665","url":"https://pubmed.ncbi.nlm.nih.gov/32777865/"}],"verbatim":{"text":"GnRH therapy was related to a larger testicular volume (standardized mean difference=-1.43; p=0.01) and earlier spermatogenesis (WMD=-5.30 months; p=0.004) compared to GT.","citation":"Wei C, Long G, Zhang Y, et al. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile gonadotropin-releasing hormone therapy versus gonadotropin therapy: a systematic review and meta-analysis.","url":"https://pubmed.ncbi.nlm.nih.gov/32777865/"}},{"outcome":"Preserving testicular function on testosterone therapy","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"The use it is most often sold for. A search of the trial literature finds no controlled study of gonadorelin added to testosterone replacement for testicular size, fertility or hormone recovery. The physiological rationale is that intermittent GnRH could keep the pituitary signalling; continuous GnRH does the opposite and shuts it down, which is how the same molecule's analogues treat prostate cancer.","references":[{"citation":"Wei C, Long G, Zhang Y, et al. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile gonadotropin-releasing hormone therapy versus gonadotropin therapy: a systematic review and meta-analysis.","where":"World J Mens Health, 2021;39(4):654–665","url":"https://pubmed.ncbi.nlm.nih.gov/32777865/"},{"citation":"Searches of PubMed and trial registries for gonadorelin added to testosterone replacement therapy.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=gonadorelin+testosterone+replacement+therapy"}]},{"outcome":"Adverse effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Pulsatile-therapy series","evidence":"Allergic reactions at the infusion site are the characteristic problem of pulsatile therapy; the comparison meta-analysis found fewer oestrogen-related effects (gynaecomastia, acne) than with gonadotropin injections.","references":[{"citation":"Wei C, Long G, Zhang Y, et al. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile gonadotropin-releasing hormone therapy versus gonadotropin therapy: a systematic review and meta-analysis.","where":"World J Mens Health, 2021;39(4):654–665","url":"https://pubmed.ncbi.nlm.nih.gov/32777865/"}]}],"regions":[{"region":"European Union","status":"Authorised in several member states","note":"National authorisations exist as a diagnostic and, in pump form, for hypothalamic infertility; there is no central authorisation. Use alongside testosterone replacement is off-label."},{"region":"United States","status":"Approved products discontinued; compounded","note":"Factrel (diagnostic) and Lutrepulse (pulsatile) were FDA-approved and later withdrawn from the market for commercial reasons. It is now supplied by compounding pharmacies on prescription, which is how TRT clinics use it."},{"region":"United Kingdom","status":"Licensed, prescription-only (diagnostic)","note":"A 100 microgram injection is licensed for assessing pituitary function. Use on testosterone therapy is off-label."},{"region":"Australia","status":"Prescription-only","note":"Schedule 4. LYO did not verify a current ARTG product at review; supply is on prescription or by compounding."},{"region":"Canada","status":"Prescription-only","note":"LYO did not verify a current authorised product at review."},{"region":"Sport (WADA)","status":"Prohibited at all times (males)","note":"Gonadorelin is named on the Prohibited List among gonadotrophin-releasing factors, prohibited in males in and out of competition."}],"faq":[{"q":"Does gonadorelin keep your testicles from shrinking on TRT?","a":"There is no trial. The idea is that pulses of GnRH keep the pituitary signalling to the testes while testosterone suppresses it; the same molecule given continuously shuts the axis down. Whether a few injections a week does the first or the second has not been studied. hCG, which acts directly on the testes, is the better-documented option for that purpose."},{"q":"Is gonadorelin the same as hCG?","a":"No. Gonadorelin acts on the pituitary and needs pulsing; hCG acts directly on the testes as an LH substitute. They sit at different points in the same axis."},{"q":"Is gonadorelin legal?","a":"It is a licensed medicine in several countries for diagnosis and fertility, compounded on prescription in the US, and prohibited in sport for men. Use alongside testosterone therapy is off-label everywhere."}],"references":[{"cite":"Wei C, Long G, Zhang Y, et al. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile gonadotropin-releasing hormone therapy versus gonadotropin therapy: a systematic review and meta-analysis.","where":"World J Mens Health, 2021;39(4):654–665","url":"https://pubmed.ncbi.nlm.nih.gov/32777865/","note":"7 studies, 420 men; mostly non-randomised."},{"cite":"Searches of PubMed and trial registries for gonadorelin added to testosterone replacement therapy.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=gonadorelin+testosterone+replacement+therapy","note":"No controlled trial of the TRT use identified."},{"cite":"Gonadorelin 100 micrograms powder for solution for injection — Summary of Product Characteristics.","where":"MHRA / emc, UK","url":"https://www.medicines.org.uk/emc/search?q=gonadorelin","note":"Licensed diagnostic use."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. A for the diagnostic response, B for pulsatile fertility therapy, D for the TRT use on absence of any trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}