Leuprolide Peptide: Structure, Research & Science Guide

By The Peptides Codex Editorial TeamReviewed September 8, 2026

Page data last changed: 2026-10-05. Chemistry registry snapshot: 2026-10-01. Registry refreshes and identity assessments are separate from scientific content review.

Length

9 aa

Class

GnRH agonist (approved medicine)

Function

Gonadotropin-releasing hormone receptor agonist; sustained stimulation down-regulates the receptor and suppresses testosterone and oestrogen

Context

Approved for advanced prostate cancer, endometriosis, uterine fibroids and central precocious puberty (Fensolvi, FDA 2019); EMA-approved six-monthly form for prostate cancer (Camcevi, 2022)

A nine-residue GnRH analogue with a D-leucine and an ethylamide tail — the backbone of androgen-deprivation therapy for four decades.

Also known as: Leuprorelin · Lupron · Eligard · Fensolvi · Camcevi · leuprolide acetate

Part of the Foundational & therapeutic peptides cluster

Overview

Leuprolide (leuprorelin; C59H84N16O12, ≈1,209 Da) is a synthetic nine-residue analogue of gonadotropin-releasing hormone with a pyroglutamate N-terminus, a D-leucine at position 6 and a C-terminal prolyl ethylamide. Continuous GnRH-receptor stimulation down-regulates the receptor and shuts off sex-hormone production. It is approved for advanced prostate cancer, endometriosis, uterine fibroids and central precocious puberty, and is the comparator in the pivotal trials of degarelix, relugolix and enzalutamide.

Source & context

Biological / chemical source: Synthetic decapeptide analog of GnRH

Primary research or clinical context: Approved for advanced prostate cancer, endometriosis, uterine fibroids and central precocious puberty (Fensolvi, FDA 2019); EMA-approved six-monthly form for prostate cancer (Camcevi, 2022)

What leuprolide is

Leuprolide (international name leuprorelin) is a synthetic analogue of gonadotropin-releasing hormone, the ten-residue hypothalamic hormone that drives the pituitary to release LH and FSH. Leuprolide keeps nine of those residues with two engineering changes and, given continuously, does the opposite of the hormone it mimics: it drives the GnRH receptor into down-regulation, so gonadotropin secretion and sex-steroid production fall to castrate levels. Its molecular formula is C59H84N16O12 and its mass about 1,209 Da. With 519 registered studies and more than 2,300 PubMed entries it is one of the most widely used peptide medicines in oncology (Lun et al., StatPearls 2026).

Sequence and structure

The IUPHAR record gives the backbone as pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt: residue 1 is pyroglutamic acid, the leucine at position 6 is the D-enantiomer, and the C-terminal proline carries an ethylamide in place of the Gly-NH2 that ends native GnRH. The chip display shows X for the pyroglutamate. The D-Leu6 substitution and the ethylamide tail are the classic pair of modifications shared by the “superagonist” GnRH analogues; they resist enzymatic cleavage and increase receptor binding, which is why leuprolide is far more potent and longer-acting than GnRH itself.

Mechanism

Leuprolide is a GnRH receptor agonist. Sustained activation leads to down-regulation of receptor activity, decreased gonadotrophin secretion and reduced steroidogenesis (IUPHAR). The corollary is the initial flare: because it is an agonist, the first days of treatment raise LH and testosterone before suppression sets in — in the phase 3 degarelix trial, no leuprolide patient had reached castrate testosterone by day 3, versus about 96% on the antagonist (Klotz et al., BJU International 2008), and in HERO the day-4 castration rate was 0% with leuprolide versus 56% with relugolix (Shore et al., NEJM 2020). Antagonists were developed precisely to avoid this surge.

Approved uses and formulations

IUPHAR records use in advanced prostate cancer, uterine fibroids, endometriosis and precocious puberty. In May 2019 the FDA approved an injectable suspension (Fensolvi) for central precocious puberty in children aged two and over, and in 2022 the EMA approved Accord's six-monthly Camcevi for prostatic neoplasms. Leuprolide is supplied as depot formulations dosed monthly, three-monthly or six-monthly, which is why formulation-specific dosing and monitoring of metabolic, cardiovascular and bone health are emphasised in prescribing references (Lun et al., 2026). LiverTox notes a modest rate of serum-enzyme elevations without convincing links to clinically apparent liver injury.

Leuprolide as the comparator in landmark trials

Leuprolide's second life is as the control arm. In EMBARK (Freedland et al., NEJM 2023), 1,068 men with high-risk biochemically recurrent prostate cancer were randomised to enzalutamide plus leuprolide, leuprolide alone, or enzalutamide alone: five-year metastasis-free survival was 87.3%, 71.4% and 80.0% respectively, and the 2026 update reported eight-year overall survival of 78.9% for the combination versus 69.5% for leuprolide alone (hazard ratio 0.60; Shore et al., NEJM 2026). In HERO, oral relugolix maintained castration through 48 weeks in 96.7% of men versus 88.8% with leuprolide (Shore et al., NEJM 2020), and testosterone recovered faster after relugolix (Tutrone et al., European Urology Oncology 2024). Degarelix was non-inferior to leuprolide for sustained suppression (97.2% and 98.3% vs 96.4%; Klotz et al., 2008).

Leuprolide as the control arm
Trial	Comparison	Result
Klotz 2008 (phase 3)	Degarelix vs leuprolide	Sustained castration 97.2% / 98.3% vs 96.4%; no early suppression with leuprolide at day 3
HERO 2020	Relugolix vs leuprolide	Castration maintained 48 wk: 96.7% vs 88.8%; day-4 castrate 56% vs 0%
EMBARK 2023 / 2026	Enzalutamide + leuprolide vs leuprolide alone	5-yr MFS 87.3% vs 71.4%; 8-yr OS 78.9% vs 69.5% (HR 0.60)

Side effects

Leuprolide's adverse effects are those of sex-hormone deprivation plus the initial flare. Prescribing references stress metabolic, cardiovascular and bone-health monitoring (Lun et al., 2026); a randomised study of androgen-deprivation therapy and hypertension is registered (NCT05700903); in the EMBARK age analysis, treatment-related serious adverse events were more common in men aged 70 and over across all arms but remained low overall (0.6–11.7%), with grade 3 or higher events in 36–60% (Shore et al., European Journal of Cancer 2026). A case of leuprolide-induced myopathy has been reported (Van Gerpen & McKinley, 2002). LiverTox records only modest enzyme elevations.

Leuprolide vs the antagonists

Degarelix (injectable) and relugolix (oral) are GnRH antagonists: they block the receptor directly, suppress testosterone within days and avoid the agonist flare, and relugolix showed superior sustained castration and faster recovery in HERO. Leuprolide's advantages are four decades of outcome data, six-monthly depot convenience and cost. Triptorelin, goserelin and buserelin are sibling agonists with the same D-amino-acid-at-6 design. This profile is educational; it is not guidance on obtaining or using any product and it is not medical advice.

Sequence

One-letter sequence commonly cited for Leuprolide (educational; isoforms and modifications may differ):

XHWSYLLRP

X marks a non-canonical residue — see the structure block below. (Plotted as alanine on the wheel.)

Leuprolide — Structure cardDownload SVG

Helical wheel projection

Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.

Analyze sequences in the playground →

Structure & chemistry

Molecular identity & reference confidence

Source-supported reference

The retained flag predates the current matching nine-position sequence. X is pyroglutamate, position 6 is D-Leu, and the C-terminus is Pro-NHEt. The reference mass is for leuprolide, not the acetate salt.

Molecular form: Leuprolide parent peptide (not acetate salt)
Species: Not established by this molecular identity audit
Termini (N / C): Pyroglutamate / Prolyl ethylamide

Average reference mass · Molecular identity assessment: 2026-10-05

Reference policy updated: 2026-10-05

IUPHAR/BPS source snapshot · 2026-10-01
PubChem molecular record · 2026-10-01

Molecular formula: C59H84N16O12
Average reference mass: ≈ 1,209.4
Receptors: Gonadotropin-releasing hormone receptor (GnRH-R) on pituitary gonadotrophs
Backbone: Nonapeptide analogue of the GnRH decapeptide with the C-terminal glycinamide replaced by an ethylamide
C-terminus: Prolyl ethylamide (Pro-NHEt)
Status: Approved: prostate cancer, endometriosis, uterine fibroids, central precocious puberty (Fensolvi, FDA May 2019); Camcevi (EMA 2022) for prostatic neoplasms

Engineering changes in Leuprolide versus the native hormone
Position	Native	Analog	Purpose
Position 1	pGlu (GnRH)	pGlu	N-terminal cyclisation blocks aminopeptidases (native feature retained)
Position 6	Gly	D-Leu	Resists cleavage and increases receptor affinity
Positions 9–10	Pro-Gly-NH2	Pro-NHEt	Ethylamide replaces glycinamide; shortens to nine residues and adds stability

Identifiers

PubChem CID: 657181
IUPHAR ligand: 1175
ChEMBL: CHEMBL1201199
DrugBank: DB00007
CAS RN: 53714-56-0
UNII: EFY6W0M8TG

Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.

Clinical development snapshot

ClinicalTrials.gov lists 520 registered studies with “Leuprolide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.

Registered studies

520

Highest phase reached

Phase 4

Active in latest 100

Most recent update

2026-10-01

Most recently updated studies
NCT	Title	Phase	Status	Updated
NCT05827081	Phase IIIb Study of Ribociclib + ET in Early Breast Cancer	Phase 3	recruiting	2026-10-01
NCT07848828	Autonomic and Renal Contributions to Hypertension With ADT	Phase 4	recruiting	2026-09-30
NCT04906395	Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer	Phase 3	active not recruiting	2026-09-29
NCT01492972	Hypo-fractionated Radiation Therapy With or Without Androgen Suppression for Intermediate Risk Prostate Cancer	Phase 3	recruiting	2026-09-29
NCT05567198	Gonadotropin-releasing Hormone Agonist (GnRHa) in Ovarian Preservation in SLE Subjects Receiving Cyclophospham	—	recruiting	2026-09-28
NCT04557059	A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Pr	Phase 3	active not recruiting	2026-09-25

See all on ClinicalTrials.gov →

Concentration math

Leuprolide — reconstitution calculator

Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.

Reference form: Leuprolide parent peptide (not acetate salt)Average reference mass: 1,209.4 Da

Peptide in vial (mg)

Diluent added (mL)

Syringe graduation

Solution concentration

5 mg/mL5,000 mcg/mL

Amount to measure (optional)

mcg

Enter an amount to see the volume it corresponds to.

Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.

Open the Leuprolide calculator on its own page →

Change log

Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.

2026-10-01Trials1 registered study added on ClinicalTrials.gov (now 520).
2026-09-08EditorialProfile content reviewed and updated by the editorial team.

FAQ about Leuprolide

What is Leuprolide?+

What Canadian product status is recorded for Leuprolide?+

Canadian product status for Leuprolide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.

What is the typical length of Leuprolide?+

Leuprolide is commonly described as approximately 9 amino acids (GnRH agonist (approved medicine)).

What is leuprolide?+

A synthetic nine-residue GnRH agonist (pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt) that, given continuously, suppresses testosterone and oestrogen. Approved for prostate cancer, endometriosis, fibroids and precocious puberty.

Is leuprolide a peptide?+

Yes — a modified nonapeptide of about 1,209 Da (C59H84N16O12), marketed as the acetate salt in depot injections.

Why does leuprolide cause a testosterone flare?+

Because it is an agonist: the first days stimulate the receptor before down-regulation takes hold. In the degarelix trial no leuprolide patient was castrate at day 3; in HERO none was at day 4.

Leuprolide vs relugolix?+

Relugolix, an oral antagonist, maintained castration in 96.7% of men through 48 weeks versus 88.8% with leuprolide, with faster onset and faster testosterone recovery.

Leuprolide vs degarelix?+

Degarelix, an injectable antagonist, was non-inferior for sustained suppression and suppressed testosterone within three days, which leuprolide cannot.

What are leuprolide's side effects?+

Those of hormone deprivation — metabolic, cardiovascular and bone effects requiring monitoring — plus the initial flare. Serious treatment-related events were low overall in EMBARK.

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References & further reading

Disclaimer: Educational content only. Not medical advice. Not instructions for human use. Research peptides and unapproved products may be restricted or illegal to market for human consumption in your jurisdiction. Consult qualified professionals and applicable law.

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