# Leuprolide

> The long-acting GnRH agonist — a nonapeptide that first flares, then shuts the reproductive axis down; the workhorse of hormone-suppression medicine.

- Also known as: Leuprorelin, Lupron, Eligard, Leuprolide acetate
- Class: Reproductive, Peptide Hormones
- FDA approved: Yes
- Canonical page: https://americanpeptide.com/catalog/leuprolide

## Overview

Leuprolide (Lupron) is a synthetic GnRH agonist and the most widely used member of its class. Two changes to the native decapeptide — a D-leucine at position 6 and a C-terminal ethylamide replacing the terminal glycinamide — make it far more potent and degradation-resistant than gonadorelin. Given continuously as depot injections or implants, it exploits GnRH’s central paradox: sustained receptor stimulation first causes a transient hormone flare, then desensitizes the pituitary and suppresses LH, FSH, and the downstream sex steroids.

Leuprolide is the drug that made GnRH’s paradox therapeutically useful. Native GnRH must be pulsed to stimulate the pituitary; delivered continuously it does the opposite, and leuprolide is engineered to deliver exactly that steady, high-affinity signal. A D-leucine at position 6 blocks the enzymatic cleavage that clears native GnRH in minutes, and the C-terminal ethylamide raises receptor affinity — together extending its action from minutes to weeks or months in depot form.

The result is controlled, reversible chemical castration. After a brief initial flare of LH and testosterone (or estrogen), the pituitary receptor desensitizes and sex-steroid output collapses. That single effect underlies a broad set of uses: advanced prostate cancer, endometriosis and uterine fibroids, central precocious puberty, IVF protocols, and gender-affirming hormone suppression.

Leuprolide is the long-acting counterpart to gonadorelin already in this catalog: the native hormone shows the axis can be switched on or off by rhythm, while leuprolide is the manufactured, degradation-resistant analog built to hold it off. It is delivered almost entirely as sustained-release depots and implants, since its purpose depends on continuous exposure.

## Mechanism

GnRH-receptor agonism. Continuous (non-pulsatile) exposure downregulates the receptor after an initial flare, suppressing LH / FSH and the gonadal steroids they drive.

## Chemistry

| Property | Value |
| --- | --- |
| Molecular formula | C59H84N16O12 |
| Molecular weight | 1209.4 Da |
| CAS number | 53714-56-0 |
| PubChem CID | [657181](https://pubchem.ncbi.nlm.nih.gov/compound/657181) |
| UniProt | [P01148](https://www.uniprot.org/uniprotkb/P01148) |

## Sequence

```
pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt
```

## Research areas

Studied in: Prostate cancer, Endometriosis, Central precocious puberty, Fertility (IVF), Gender-affirming care.

Guides on this site:

- [Sexual & Reproductive Health](https://americanpeptide.com/research-areas/sexual-reproductive): Peptides studied across the HPG axis and CNS sexual-response pathways.

## Key research

- GnRH-agonist workhorse — a D-Leu6, C-terminal-ethylamide nonapeptide analog of GnRH, far more potent and stable than the native hormone.
- Flare-then-suppress — continuous exposure causes a transient hormone flare, then desensitizes the pituitary and suppresses LH, FSH, and sex steroids.
- Broad approved uses — prostate cancer, endometriosis, uterine fibroids, central precocious puberty, IVF, and gender-affirming care.
- Depot delivery — formulated as long-acting injections and implants because the therapeutic effect requires sustained, non-pulsatile signaling.
- Contrast with gonadorelin — same receptor, opposite intent: gonadorelin (pulsatile) switches the axis on; leuprolide (continuous) shuts it down.

## Storage, handling & synthesis

**Synthesis.** Leuprolide is a GnRH nonapeptide analog: an N-terminal pyroglutamate, a D-leucine at position 6, and a C-terminal ethylamide in place of the native glycinamide. Solid-phase assembly is short and routine; the D-residue and the ethylamide cap are the features that must be installed correctly, and Trp/Ser byproduct control sets the purity.

## FAQs

### What is leuprolide?

Leuprolide (Lupron, Eligard) is a synthetic, long-acting GnRH agonist used to suppress the reproductive hormone axis — a nonapeptide analog of GnRH with a D-leucine and a C-terminal ethylamide.

### Why does it suppress hormones if it is an agonist?

Because the GnRH receptor responds to rhythm. Continuous stimulation, after a brief initial flare, desensitizes the receptor, so LH, FSH, and sex steroids fall — the opposite of the pulsatile signal that stimulates them.

### How is it different from gonadorelin?

Gonadorelin is native GnRH, cleared in minutes and used in pulses to stimulate the axis. Leuprolide is a degradation-resistant analog given continuously (as depots) to shut it down.

### Is leuprolide FDA-approved?

Yes — it is approved for several conditions including prostate cancer, endometriosis, and central precocious puberty. This page is a research and educational reference, not medical advice.

## Latest research

Recent trials and publications mentioning Leuprolide, pulled automatically from ClinicalTrials.gov and PubMed (unfiltered search results, refreshed daily).

### Recent trials

- [Phase IIIb Study of Ribociclib + ET in Early Breast Cancer](https://clinicaltrials.gov/study/NCT05827081) — RECRUITING · PHASE3 · NCT05827081
- [Evaluating Hormone Therapy to Achieve Optimal Doses in Metastatic Prostate Cancer](https://clinicaltrials.gov/study/NCT07751133) — RECRUITING · PHASE3 · NCT07751133
- [Neoadjuvant Endocrine Therapy Combined With Chemotherapy in ER-positive, HER2-negative Stage I-III Breast Cancer](https://clinicaltrials.gov/study/NCT07801898) — NOT_YET_RECRUITING · PHASE2 · NCT07801898
- [Short Course ADT for High Risk Low/Intermediate Risk ARTERA Prostate Cancer](https://clinicaltrials.gov/study/NCT07801664) — RECRUITING · PHASE2 · NCT07801664
- [Contributions to Hypertension With Androgen Deprivation Therapy](https://clinicaltrials.gov/study/NCT05700903) — TERMINATED · PHASE4 · NCT05700903
- [Phase Ia Trial of HHK001 Compared With Enantone in Patients With Endometriosis](https://clinicaltrials.gov/study/NCT07755956) — RECRUITING · PHASE1 · NCT07755956

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Source: AmericanPeptide.com — https://americanpeptide.com/catalog/leuprolide
Data license: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Attribution: AmericanPeptide.com.
Research reference only — computational and educational content, not medical advice.