{"id":"leuprolide","name":"Leuprolide (leuprorelin)","aliases":["Lupron","leuprorelin","Eligard","Prostap","GnRH agonist","LHRH agonist"],"url":"https://lyoresearch.com/compounds/leuprolide","class":{"id":"reproductive-hormones","name":"Reproductive and neuroendocrine hormones","url":"https://lyoresearch.com/classes/reproductive-hormones"},"summary":"Leuprolide is a modified version of GnRH that, given continuously, does the opposite of the natural pulsed hormone: after a brief surge it exhausts the pituitary and shuts down testosterone or oestrogen production almost completely. That makes it a mainstay of advanced prostate cancer, where the 1984 trial that launched it matched the standard oestrogen treatment with far fewer side effects; it is also used for endometriosis, fibroids, central precocious puberty and IVF cycle control. It is a prescription medicine everywhere and prohibited for male athletes.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"Randomised trials since 1984; decades of use","regulatory_status":"Approved (Rx)","molecule":{"formula":"C59H84N16O12","molecular_weight":"1209.4","cas":"53714-56-0","pubchem_cid":657181,"note":null},"pharmacokinetics":{"basis":"label","route":"Intramuscular depot injection, every 1, 3, 4 or 6 months","half_life":"About 3 hours (the peptide itself, intravenous)","licensed_regimen":"7.5 mg IM every 4 weeks, 22.5 mg every 12 weeks, 30 mg every 16 weeks, or 45 mg every 24 weeks (advanced prostate cancer)","product":"Lupron Depot","source":{"title":"Lupron Depot prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cbc8f94e-7330-4465-05ad-16d64493a5dd"}},"outcomes":[{"outcome":"Metastatic prostate cancer (hormone suppression)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"RCT vs DES (n=199) + 40 years of trials","evidence":"Objective response in 86% against 85% on diethylstilbestrol, with equivalent testosterone suppression and fewer serious side effects — the trial that made GnRH agonists the standard of care.","references":[{"citation":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","where":"N Engl J Med, 1984","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/"}],"verbatim":{"text":"Overall, 86 per cent of the leuprolide group had an objective response (complete response, 1 per cent; partial response, 37 per cent; stable disease, 48 per cent), as compared with 85 per cent of the DES group (complete, 2 per cent; partial, 44 per cent; stable, 39 per cent).","citation":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/"}},{"outcome":"Testosterone suppression to castrate levels","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Approval-grade","evidence":"Reliable suppression to castrate range within weeks, after an initial surge — the pharmacology every indication rests on.","references":[{"citation":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","where":"N Engl J Med, 1984","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/"},{"citation":"Leuprolide acetate (Lupron Depot) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Central precocious puberty","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Approval-grade programmes","evidence":"Halts pubertal progression in children with early central puberty; a licensed indication in every major market.","references":[{"citation":"Leuprolide acetate (Lupron Depot) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Endometriosis and uterine fibroids","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Multiple RCTs","evidence":"Reduces pain and lesion or fibroid volume by inducing a reversible low-oestrogen state; use is limited by bone loss and menopausal symptoms, usually to six months with add-back therapy.","references":[{"citation":"Leuprolide acetate (Lupron Depot) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"Same trials + surveillance","evidence":"The consequences of hormone deprivation: hot flushes, loss of libido and bone density, muscle loss, fatigue, and in men a cardiovascular and metabolic risk signal with long-term use. The initial hormone surge can worsen symptoms in the first weeks.","references":[{"citation":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","where":"N Engl J Med, 1984","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/"},{"citation":"Leuprolide acetate (Lupron Depot) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}],"verbatim":{"text":"The leuprolide group reported more \"hot flashes\" (P = 0.00001).","citation":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Authorised in every member state for prostate cancer, endometriosis, fibroids and precocious puberty."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved since 1985 (Lupron); multiple depot products."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Licensed (Prostap and others)."},{"region":"Australia","status":"Registered, prescription-only","note":"On the ARTG (Lucrin, Eligard)."},{"region":"Canada","status":"Authorised, prescription-only","note":"Health Canada-authorised."},{"region":"Sport (WADA)","status":"Prohibited at all times (males)","note":"Leuprorelin is named on the Prohibited List among gonadotrophin-releasing factors, prohibited in males."}],"faq":[{"q":"Does leuprolide raise or lower testosterone?","a":"Both, in order: a surge for one to two weeks, then suppression to castrate levels for as long as it is given. The surge is why prostate-cancer patients are often covered with an anti-androgen at the start."},{"q":"Is leuprolide the same as gonadorelin?","a":"No — opposite effects from the same receptor. Gonadorelin is the natural hormone and needs pulsing to work; leuprolide is a long-acting analogue whose continuous presence shuts the axis down."},{"q":"Is it reversible?","a":"Yes. Hormone production resumes after the depot wears off, over weeks to months depending on the formulation and duration of use."}],"references":[{"cite":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","where":"N Engl J Med, 1984","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/","note":"199 men; the trial that established GnRH agonists in prostate cancer."},{"cite":"Leuprolide acetate (Lupron Depot) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/","note":"Licensed indications."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade A across licensed indications."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}