Reviewed & approved by Dr. Nova Reyes · Last checked 2026-10-25. ← Back to Evidence Library

title: "Leuprolide: What the evidence says" slug: leuprolide status: Draft (v1), pending review by Dr. Nova Reyes (Batch F #68) last_checked: 2026-10-25 evidence_verdict: "Labeled uses: Strong · Gray-market/off-label endocrine use: No human data" card_verdict: "Strong (prostate cancer, endometriosis, early puberty) · Gray-market: No human data · Banned in male athletes" related: [gonadorelin, kisspeptin-54, hcg]

Draft (v1), pending review. Not public. · ← Library · DRAFT · not published · last checked 2026-10-25

Leuprolide: what the evidence says

At a glance

What it is: a 9-amino-acid GnRH agonist (leuprorelin) that, after a first surge, shuts down the body's sex-hormone production. Sold as Lupron Depot, Eligard, Fensolvi, Camcevi and generics for advanced prostate cancer, endometriosis, fibroid-related anemia and central precocious puberty. ^{R1, R2}

What the evidence says: it is a standard way to lower testosterone in advanced prostate cancer; in a 603-man trial, adding flutamide to leuprolide extended survival (35.6 vs 28.3 months). ^R3 In a 52-woman endometriosis trial it relieved pain better than placebo. ^R4

Biggest risks: a testosterone "flare" (about 50% above baseline) in the first weeks that can worsen bone pain or urinary blockage; metabolic changes including diabetes; heart attack, sudden cardiac death and stroke reported in men; QT prolongation; and bone loss. ^R1

Rating


Human Human evidence	Strong for labeled uses (prostate cancer, endometriosis, central precocious puberty) ^{R1, R3, R4}; No human data on gray-market products
Animal Animal / lab evidence	Not reviewed for this page
Regulatory	FDA-approved (Lupron Depot NDAs 019732, 020011, 020517, 020708; Lupron Depot-PED NDA 020263; Eligard; Fensolvi; Camcevi; generics) ^R2 · WADA: prohibited at all times in males (S2.2.1, "leuprorelin") ^R5
Established human dose	For labeled uses: on the FDA labels ^R1. Study details lists what trials used

Evidence verdict: Labeled uses: Strong · Gray-market/off-label endocrine use: No human data Card verdict: Strong (prostate cancer, endometriosis, early puberty) · Gray-market: No human data · Banned in male athletes Card note: Lowers testosterone after an initial surge, see page.

This page reports what studies used. It is not dosing advice.

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

About the evidence: the prostate cancer trial was a National Cancer Institute / Southwest Oncology Group (SWOG) intergroup randomized trial ^R3; the endometriosis trial was a manufacturer study group (TAP Pharmaceuticals product). ^R4

What is it?

Leuprolide overstimulates the pituitary's GnRH receptors; after an initial rise in LH, FSH and testosterone or estrogen, the receptors shut down and sex hormones fall to castrate or menopausal levels. ^R1 Related pages: Gonadorelin, Kisspeptin-54, hCG.

Does it work?

Human Advanced prostate cancer: 603 men; leuprolide plus flutamide vs leuprolide plus placebo: progression-free 16.5 vs 13.9 months, survival 35.6 vs 28.3 months. The authors note leuprolide alone often causes a painful early flare. ^R3
Human Endometriosis: 52 women: pain, cramping and tenderness improved vs placebo; estradiol fell to menopausal levels. ^R4

Is it safe?

Human Tumor flare: testosterone rises about 50% in the first weeks. ^R1
Human Metabolic and heart risks: hyperglycemia/diabetes, hyperlipidemia; MI, sudden cardiac death and stroke reported with GnRH agonists in men; QT prolongation. ^R1
Human Endometriosis trial: hot flashes (vasodilatation) most common. ^R4

Gray-market "research use only" Leuprolide: extra risks

Not the approved product. Gray-market leuprolide has unknown identity and strength. Unknown Because continuous leuprolide first raises and then suppresses sex hormones, continuous use lowers rather than boosts endogenous testosterone ^R1, and no clinical studies evaluate gray-market leuprolide.

What we don't know

Unknown Outcomes of off-label or gray-market endocrine use
Unknown Quality of gray-market products

Is it legal?

US: FDA-approved under several brand NDAs and generic ANDAs for advanced prostate cancer, endometriosis, uterine fibroid anemia (with iron) and central precocious puberty (label-specific). ^{R1, R2} EU, UK and others: UNVERIFIED. WADA: prohibited at all times in males under S2.2.1 (GnRH agonist analogues, named "leuprorelin"). ^R5

Study details

These are amounts researchers used, not recommendations. ### R3 Human RCT: leuprolide ± flutamide (Crawford 1989) | Study | People / model | Route | Amount used | Follow-up | Reported | Side effects / limitations | Citation | |---|---|---|---|---|---|---|---| | Crawford 1989 | 603 men with stage D2 prostate cancer | Subcutaneous + oral flutamide/placebo | 1 mg daily SC leuprolide + flutamide 250 mg TID or placebo | Until progression | Survival 35.6 vs 28.3 months with added flutamide | Compares add-on, not leuprolide vs placebo | [PMID 2503724](https://pubmed.ncbi.nlm.nih.gov/2503724/) | ### R4 Human RCT: endometriosis (Dlugi 1990) | Study | People / model | Route | Amount used | Follow-up | Reported | Side effects / limitations | Citation | |---|---|---|---|---|---|---|---| | Dlugi 1990 | 52 women with endometriosis | Intramuscular depot | 3.75 mg depot | Not in abstract | Pain relief vs placebo | Small; vasodilatation | [PMID 2118858](https://pubmed.ncbi.nlm.nih.gov/2118858/) |

Full reference list (PubMed, ClinicalTrials.gov, openFDA and DailyMed entries checked Oct 25, 2026)

^R1 DailyMed. LUPRON DEPOT (leuprolide acetate) prostate cancer label, AbbVie, effective Mar 15, 2026. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=cbc8f94e-7330-4465-05ad-16d64493a5dd
^R2 FDA. Drugs@FDA data (openFDA drugsfda), leuprolide: NDA 019732, 020011, 020517, 020708 (Lupron Depot), 020263 (Lupron Depot-PED), 021343/021379/021488/021731 (Eligard), 213150 (Fensolvi), 211488 (Camcevi), plus generic ANDAs; checked Oct 25, 2026. https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:leuprolide
^R3 Crawford ED, et al. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989. PMID 2503724
^R4 Dlugi AM, et al. Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Fertil Steril. 1990. PMID 2118858
^R5 WADA. The 2026 Prohibited List (in force 1 January 2026). https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf

Disclaimer

This page is for education and harm reduction, not medical advice or a recommendation to use Leuprolide. Talk to a clinician you trust before using any drug, and report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).

Approved for Adam Greene by Dr. Nova Reyes, 2026-10-25.