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Hormonal

Leuprolide

Also known as Leuprorelin · Leuprolide acetate · Lupron Depot · Lupron Depot-PED · Eligard · Camcevi

FDA-approvedAHuman trial evidenceWhat this means

Leuprolide (leuprorelin) is a synthetic GnRH agonist nonapeptide, FDA-approved in depot and injectable forms (Lupron Depot, Eligard, Camcevi, Fensolvi and generics) for advanced prostate cancer, endometriosis, fibroid-related anemia and central precocious puberty.

US status
FDA-approved
Evidence
Grade A
Half-life
Elimination half-life approximately 3 hours based on a two-compartment model; depot formulations release drug over 1 to 6 months 1,2.
Class
Gonadotropin-releasing hormone (GnRH) agonist
Studied in: Hormonal & endocrine research · Class: Kisspeptin & GnRH axis
More
Log a sample
Dosing referenceCycle-length evidence
Unbranded reference vial illustrating Leuprolide; not an actual product
Research reference, not advice. Label quotes, not a recommendation. Amiravo sells nothing; some links are referrals.Read the full notice

Key takeaways

  • Leuprolide is a GnRH agonist approved in multiple depot and injectable formulations for advanced prostate cancer, endometriosis, fibroid-related anemia and central precocious puberty 1,2,3,4.
  • Continuous exposure suppresses LH and FSH after an initial surge, lowering testosterone to castrate levels in men within 2 to 4 weeks 1.
  • The initial testosterone rise can cause tumor flare in prostate cancer, including bone pain, urinary obstruction and spinal cord compression 1.
  • Labeled risks include metabolic changes, cardiovascular disease in men, QT prolongation, convulsions, severe cutaneous reactions and, in women, bone mineral density loss 1,2.
  • WADA's 2026 list names leuprorelin among GnRH agonist analogues prohibited at all times in males under S2.2.1 8.

Development stage

Where Leuprolide sits between laboratory work and regulatory approval.

  1. Preclinical
  2. Phase 1
  3. Phase 2
  4. Phase 3
  5. Approved (current)

Stage comes from the regulatory record and ClinicalTrials.gov studies naming the compound (for compounds approved nowhere, only completed trials or trials with posted results count) (checked 2026-10-24). A registered trial is not a result.

Mechanism of action

Leuprolide acetate is a GnRH agonist that acts as an inhibitor of gonadotropin secretion when given continuously 1.

Biphasic effect

  • Initial stimulation: administration produces an initial increase in LH and FSH and a transient rise in testosterone and dihydrotestosterone in men, or estrone and estradiol in premenopausal women 1.
  • Suppression: continuous administration decreases LH and FSH; testosterone falls to castrate concentrations in men and estrogens to postmenopausal concentrations in premenopausal women within 2 to 4 weeks 1.

Animal findings

In animals, continuous administration suppressed ovarian and testicular steroidogenesis, reversibly on discontinuation, and inhibited growth of certain hormone-dependent tumors 1. Leuprolide is not active orally 1.

Molecular structure

PubChem CID 657181 ↗
2D chemical structure of Leuprolide

2D depiction generated from the PubChem record. Depictions are schematic and do not show salt form, counter-ions or conformation.

Formula
C59H84N16O12
Molecular weight
1209.4 g/mol
CAS
53714-56-0
InChIKey
GFIJNRVAKGFPGQ-LIJARHBVSA-N

Research overview

Human research

Approval rests on clinical studies in men with advanced prostate cancer (testosterone suppression and tumor response), women with endometriosis or fibroids, and children with central precocious puberty 1,2,3,4. A 1984 randomized trial compared leuprolide with diethylstilbestrol 6, and HERO used leuprolide as the comparator to oral relugolix 7.

Animal research

In rats, leuprolide inhibited growth of hormone-dependent tumors (prostatic tumors in Noble and Dunning rats, DMBA-induced mammary tumors) and caused reproductive organ atrophy; embryo-fetal toxicity was seen in animal studies 1.

In-vitro research

No in vitro findings are summarized in the sources reviewed beyond its action as a GnRH receptor agonist 1.

Key studies

  1. Leuprolide Study Group, N Engl J Med (1984)
    Randomized comparison with diethylstilbestrol, cross-over at progression
    Model: Humans (199 men with stage D2 prostate cancer)

    Comparable testosterone suppression and objective response (86% versus 85%); 1-year survival 87% versus 78% (not significant); fewer gynecomastia, edema and thromboembolic events, more hot flashes 6.

  2. Lupron Depot prescribing information, Section 14.1 (2026)
    Open-label, non-comparative, multicenter study
    Model: Humans (56 men with stage D2 prostatic adenocarcinoma)

    Testosterone suppressed to castrate range within 30 days in 94% and within 66 days in all 54 evaluable patients; 'no progression' in 84% at week 24 1.

  3. Shore et al., N Engl J Med (HERO) (2020)
    Randomized phase 3 trial, oral relugolix versus leuprolide, 48 weeks
    Model: Humans (930 men with advanced prostate cancer)

    Sustained castration 88.8% with leuprolide versus 96.7% with relugolix; castrate testosterone on day 4 in 0% versus 56%; MACE 6.2% versus 2.9% 7.

Dosing as stated on the FDA label

Quoted from the prescribing information for reference. Prescribing decisions belong to a licensed clinician; this is not a recommendation or instruction for use.

Full dosing reference, study durations and vial arithmetic →
  • Advanced prostate cancer (Lupron Depot): one injection of 7.5 mg every 4 weeks, 22.5 mg every 12 weeks, 30 mg every 16 weeks, or 45 mg every 24 weeks, administered by a healthcare provider 1.
  • Advanced prostate cancer (Eligard, subcutaneous): 7.5 mg monthly, 22.5 mg every 3 months, 30 mg every 4 months or 45 mg every 6 months 4.
  • Endometriosis (Lupron Depot 3.75 mg): 3.75 mg IM monthly for 1 to 6 doses initially, with or without norethindrone acetate 5 mg daily; retreatment requires norethindrone add-back; total treatment should not exceed 12 months. Fibroids: one 3.75 mg injection monthly for up to 3 months 2.
  • Central precocious puberty (Lupron Depot-PED 1-month): starting dose by body weight (7.5 mg up to 25 kg, 11.25 mg above 25 to 37.5 kg, 15 mg above 37.5 kg) monthly, adjusted based on hormonal and clinical suppression 3.
  • Formulations have different release characteristics; labels state not to substitute or combine fractional doses. Preparation and administration instructions are in the labels and are not reproduced here 1,2.

Published adverse-event data

Reported in the cited trials or product labels. Frequencies apply to the stated population and do not transfer to other settings.

Label warnings

  • Contraindicated with known hypersensitivity to GnRH agonists or excipients; gynecologic labels also contraindicate undiagnosed abnormal uterine bleeding and pregnancy 1,2. 1
  • Tumor flare: testosterone rises to about 50% above baseline in the first weeks; worsening bone pain, neuropathy, hematuria, bladder outlet obstruction or spinal cord compression may occur 1. 1
  • Metabolic changes (hyperglycemia, diabetes, hyperlipidemia; NAFLD postmarketing), increased risk of myocardial infarction, sudden cardiac death and stroke in men, and QT/QTc prolongation with androgen deprivation 1. 1
  • Convulsions and severe cutaneous adverse reactions (SJS/TEN, DRESS, AGEP) have been reported 1. 1
  • In women, Lupron Depot 3.75 mg induces a hypoestrogenic state with bone mineral density loss that may not be fully reversible; endometriosis treatment with add-back therapy should not exceed 12 months total 2. 2
  • In children with CPP, warnings include the initial rise in gonadotropins and sex steroids, psychiatric events, convulsions, severe cutaneous reactions and pseudotumor cerebri 3. 3
  • Hot flashes/sweats
    57.1% (32/56)
    Men with prostate cancer, Lupron Depot 7.5 mg, 24 weeks 1 · Expected physiologic effect of decreased testosterone
  • General pain
    23.2%
    Same study 1 · Not graded
  • GI disorders
    14.3%
    Same study 1 · Not graded
  • Edema
    14.3%
    Same study 1 · Not graded
  • Urinary disorder
    12.5%
    Same study 1 · Not graded
  • Decreased libido, impotence, testicular atrophy
    5.4% each
    Same study 1 · Expected physiologic effects of decreased testosterone

Emerging safety signals

  • In HERO, major adverse cardiovascular events occurred in 6.2% of men on leuprolide versus 2.9% on relugolix (HR 0.46 favoring relugolix) 7. 7 (2020)

What is not known: Intact leuprolide and an inactive major metabolite could not be distinguished by the assay used in early depot PK studies 1. The size of cardiovascular risk with GnRH agonists in men is described as appearing low based on reported odds ratios but not precisely quantified in the label 1. Bone mineral density loss in women may not be fully reversible 2.

Background viewing

We haven't found a clinician video focused on Leuprolide yet. Meanwhile, this widely watched talk covers the science of aging in general. It does not discuss Leuprolide.

David Sinclair, PhD (Harvard Medical School) on the biology of aging
The Diary Of A CEO · 6.9M views · 2026

These creators are not affiliated with Amiravo and do not endorse Amiravo or any product linked on this site. Nothing here is medical advice. Video views counted on YouTube as of Oct 24, 2026.

Regulatory status

Status
FDA-approved (Lupron Depot initial U.S. approval 1989; Lupron Depot-PED label lists 1985). As of 2026-10-24, Drugs@FDA lists Lupron Depot, Lupron Depot-PED, Eligard, Camcevi, Fensolvi and multiple generic leuprolide acetate products with prescription marketing status; some older products (Lupron injection, Viadur, Lupaneta Pack) are discontinued 1,3,5.
United States (FDA)
FDA-approved in multiple formulations; Drugs@FDA lists Lupron Depot (several NDAs), Lupron Depot-PED, Eligard, Camcevi, Fensolvi and generic leuprolide acetate products with prescription marketing status as of 2026-10-24 1,2,3,4,5.
Sport (WADA)
The WADA 2026 Prohibited List names leuprorelin among GnRH agonist analogues under S2.2.1 (testosterone-stimulating peptides in males); S2 is prohibited at all times 8.

Status varies by country and changes over time. How we describe regulatory status.

Quality and testing notes

A certificate of analysis for leuprolide acetate material would be expected to show HPLC purity, identity by mass spectrometry against the free-base molecular weight (PubChem 1209.4 g/mol), D-Leu6 stereochemistry and C-terminal ethylamide, acetate and net peptide content, and endotoxin level [1, 9]. Approved depot products are microsphere or polymer formulations whose release characteristics differ and are not interchangeable [1, 2].

How purity testing works · Reading a certificate of analysis

Check a Leuprolide certificate of analysis against its expected mass (1,209.4 Da)

Storage and handling

Lupron Depot prostate formulations are stored at controlled room temperature (20-25°C) per the label; other formulations differ, so follow the specific product label [1].

Frequently asked questions

What is leuprolide?
A synthetic nonapeptide GnRH agonist, also called leuprorelin 1,9.
What is it approved for?
Advanced prostate cancer, endometriosis, preoperative treatment of fibroid-related anemia, and central precocious puberty, depending on formulation 1,2,3,4.
Why does testosterone rise at first?
GnRH agonists first stimulate LH and FSH release; continued exposure then suppresses them, lowering testosterone within 2 to 4 weeks 1.
What is tumor flare?
Worsening of prostate cancer symptoms in the first weeks due to the initial testosterone surge, such as bone pain or urinary obstruction 1.
Are the depot products interchangeable?
No. Labels state formulations have different release characteristics and should not be substituted or given as fractional or combined doses 1,2.
Does it affect bone?
In women, the hypoestrogenic state causes bone mineral density loss, which limits treatment duration 2.
Is it banned in sport?
WADA's 2026 list names leuprorelin under S2.2.1 for males, prohibited at all times 8.

Latest indexed research

Search all studies on Leuprolide (PubMed, Europe PMC, ClinicalTrials.gov)

Listed by publication type from the index record. Inclusion is not an endorsement; open the source to read the findings.

Revision history

Meaningful changes to this entry, with dates and sources. Last reviewed Oct 24, 2026. Typo and layout fixes are not listed.

  • New section· entryOct 24, 2026

    New research reference added: Leuprolide.

References

  1. LUPRON DEPOT 7.5 mg, 22.5 mg, 30 mg, 45 mg (leuprolide acetate for depot suspension) prescribing information, advanced prostate cancer (effective 03/2026) FDA label (DailyMed). 2026
  2. LUPRON DEPOT 3.75 mg (leuprolide acetate for depot suspension) prescribing information, endometriosis and fibroids (effective 09/2025) FDA label (DailyMed). 2025
  3. LUPRON DEPOT-PED (leuprolide acetate for depot suspension) prescribing information, central precocious puberty (effective 11/2025) FDA label (DailyMed). 2025
  4. ELIGARD (leuprolide acetate) for injectable suspension prescribing information (effective 04/2026) FDA label (DailyMed). 2026
  5. Drugs@FDA (openFDA) application records for leuprolide U.S. FDA. 2026
  6. Leuprolide versus diethylstilbestrol for metastatic prostate cancer N Engl J Med. 1984
  7. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer (HERO) N Engl J Med. 2020
  8. World Anti-Doping Agency Prohibited List 2026 (online version) WADA. 2026
  9. PubChem compound record for leuprolide PubChem. 2026

Last reviewed October 24, 2026 by the Amiravo editorial team.

Read our editorial policy · Report an error on this page

Need the math?

Laboratory arithmetic with every formula shown.

For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page is educational and is not medical advice.

Unbranded reference vial illustrating Leuprolide; not an actual product

Unbranded reference image. Amiravo does not produce, supply or sell this compound.

Specifications

Molecular formula
C59H84N16O12
Molecular weight
1,209.4 g/mol
CAS number
53714-56-0
PubChem CID
657181
FDA UNII
EFY6W0M8TG
ChEMBL
CHEMBL1201199
DrugBank
DB00007
Sequence
pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt
Type
Single compound

Identifiers from PubChem. Verify against the supplier’s documentation for your lot.

Research stats

How much has been published, not how good it is.

PubMed records
2,984
Indexed as human research
2,183
Animal-only research
312
Randomized controlled trials
443
Registered trials
521
Trials with posted results
173
FDA adverse-event reports (FAERS)
11,143
NIH-funded projects naming it
402
2006: 782007: 782008: 712009: 782010: 852011: 732012: 882013: 902014: 1032015: 982016: 822017: 752018: 772019: 1022020: 1002021: 1252022: 1012023: 1002024: 1062025: 1362026: 11120062026
PubMed records per year (current year is partial).

Counts from title/abstract searches of PubMed, ClinicalTrials.gov, openFDA and NIH RePORTER, checked 2026-10-24. Names shared with other substances can inflate counts. FAERS reports are spontaneous and do not establish cause. Funding shows interest, not evidence. Method

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