Supplied ready in solution

Hormonal & Reproductive

At a glance

Ten answers, each one line. Open any row for the detail behind it.

What it does The definitive demonstration that dosing pattern determines direction.

The definitive demonstration that dosing pattern determines direction. Leuprolide is a more potent GnRH agonist than the natural hormone — and because it is given continuously rather than in pulses, it shuts the reproductive axis down instead of switching it on.

How it works in detail

Half-life ~3 hours (depot formulations release over months) — Documented

~3 hours (depot formulations release over months)

Typical studied dose Set on the approved label, which states the starting dose, how it is… — On the label

Set on the approved label, which states the starting dose, how it is increased and the maximum. Read it there rather than anywhere else — including here.

Read the prescribing information

How often it is used The label schedule is monthly. Dosing intervals follow the half-life… — On the label

The label schedule is monthly. Dosing intervals follow the half-life above, and the prescribing information is what sets them.

How it is taken Subcutaneous or intramuscular depot (monthly to 6-monthly) — Documented

Subcutaneous or intramuscular depot (monthly to 6-monthly)

Main side effects Testosterone flare in the first two weeks · Bone mineral density loss · Cardiometabolic effects — Carries serious risk

Testosterone flare in the first two weeks — The initial agonist surge can worsen prostate cancer symptoms, causing spinal cord compression or urinary obstruction. Anti-androgen cover is required in patients at risk.

Bone mineral density loss — Sustained hypogonadism causes progressive bone loss and osteoporotic fracture risk with long-term use.

Cardiometabolic effects — Androgen deprivation is associated with insulin resistance, dyslipidaemia and increased cardiovascular risk.

All benefits and risks, weighed

Storage before mixing Supplied already in solution and kept refrigerated, not frozen. Freezing…

Supplied already in solution and kept refrigerated, not frozen. Freezing a protein solution can aggregate it, which is not always visible.

Shelf life after mixing Nothing to mix — it is not supplied as a powder. The relevant date is…

Nothing to mix — it is not supplied as a powder. The relevant date is the one printed on the product.

Evidence level 5/5 · Very strong — Documented

Multiple phase 3 randomized trials plus regulatory approval in a major market.

How we rate evidence · What the studies found

Regulatory status FDA Approved — Documented

FDA-approved for advanced prostate cancer, endometriosis, uterine fibroids and central precocious puberty. Prescription drug.

Read the prescribing information · The full legal position

Overview

FDA ApprovedFDA-approved for advanced prostate cancer, endometriosis, uterine fibroids and central precocious puberty.

At a glance

Regulatory status	FDA-approved for advanced prostate cancer, endometriosis, uterine fibroids and central precocious puberty.
Drug class	GnRH receptor superagonist — nonapeptide analog of gonadotropin-releasing hormone
Route	Subcutaneous or intramuscular depot (monthly to 6-monthly)
Half-life	~3 hours (depot formulations release over months)
Evidence rating	5/5 Very strong Evidence rating 5 out of 5: Very strong Multiple phase 3 randomized trials plus regulatory approval in a major market.
Studied in	Decades of randomized trials in prostate cancer, endometriosis, uterine fibroids and central precocious puberty.

Leuprolide sequence & structure

Leuprolide is a 9-residue linear peptide with a free C-terminal acid, carrying D-amino acid substitutions; molecular weight 1,209.42 Da.

Amino acid sequence (N-terminus → C-terminus)

pGlu-[pGlu]HWSYlLRP-OH

lowercase = D-amino acid[bracketed] = non-standard residue

Three-letter	`pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt`
Length	9 amino acid residues
Modifications	N-terminal pyroglutamate — N-terminal 5-oxo-L-proline (pGlu1), as in native GnRH D-amino acid substitution — D-Leu at position 6 replaces Gly6 of GnRH Other modification — C-terminal N-ethyl secondary amide on Pro9 (Pro-NHEt) replaces Gly10-NH2 of GnRH
Molecular formula	C₅₉H₈₄N₁₆O₁₂
Molecular weight	1,209.42 Da (average, free base)
SMILES	`CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1`
Identifiers	CAS 53714-56-0 · PubChem CID 657181 · DrugBank DB00007
Which molecule	Leuprolide (USAN) and leuprorelin (INN) are the same molecule; Lupron, Lupron Depot, Eligard and Enantone are formulations of leuprolide acetate. This record describes the free-base nonapeptide.
Sources	ChEBI CHEBI:6427 (leuprolide: sequence, formula, MW, CAS)PubChem CID 657181 (formula, MW, IUPAC name, SMILES)KEGG DRUG D08113 (leuprorelin: formula, MW, CAS)Wikidata Q907160 (DrugBank, CAS, PubChem, ChEBI, ChEMBL cross-references)

Formula, MW and CAS 53714-56-0 refer to the free base; marketed products are the acetate salt, which has a different CAS and MW. Position numbering follows GnRH (pGlu1 ... Pro9), so leuprolide is a [D-Leu6, Pro9-NHEt] GnRH analogue with the native Gly10 amide deleted; the ethylamide is written as cTerm other/-NHEt rather than -NH2 because it is a secondary amide.

Record confidence: high — two independent authoritative sources agree on the sequence and modifications. Every sequence on the site is listed with its sources on the peptide sequences index.

How it works

Continuous GnRH receptor occupancy causes receptor downregulation and pituitary desensitisation after an initial surge. LH and FSH fall, and gonadal steroid production drops to castrate levels within 2–4 weeks. Pulsatile GnRH, by contrast, stimulates the axis — which is why gonadorelin and leuprolide have opposite clinical effects.

Evidence base

Rated 5 of 5 — Very strong. Multiple phase 3 randomized trials plus regulatory approval in a major market.

Decades of randomized trials across four distinct approved indications.

Benefits and risks, weighed against the evidence

Every entry below carries the strength of the evidence behind it — three bars for strong human data, two for moderate, one for preliminary or preclinical work. The two columns are not equal by design: where a compound has more documented risk than demonstrated benefit, the lists say so.

Reported benefits

4 entries · 4 on strong human evidence

Effective androgen deprivation in prostate cancer

Achieves castrate testosterone levels reliably, a cornerstone of advanced prostate cancer treatment.
Evidence: Strong evidence
Halts central precocious puberty

Arrests premature pubertal progression and preserves adult height potential, with the effect reversing on discontinuation.
Evidence: Strong evidence
Reduces endometriosis pain and fibroid volume

Randomized evidence in both indications.
Evidence: Strong evidence
Long-acting depot formulations

Dosing intervals from one to six months substantially improve adherence.
Evidence: Strong evidence

Risks and cautions

7 entries · 4 serious or common

Testosterone flare in the first two weeks

The initial agonist surge can worsen prostate cancer symptoms, causing spinal cord compression or urinary obstruction. Anti-androgen cover is required in patients at risk.
Evidence: Serious
Bone mineral density loss

Sustained hypogonadism causes progressive bone loss and osteoporotic fracture risk with long-term use.
Evidence: Serious
Cardiometabolic effects

Androgen deprivation is associated with insulin resistance, dyslipidaemia and increased cardiovascular risk.
Evidence: Serious
Vasomotor and sexual side effects

Hot flushes, loss of libido and erectile dysfunction are near-universal in men.
Evidence: Moderate evidence
Mood effects

Depression and emotional lability are commonly reported, and specifically flagged in pediatric use.
Evidence: Moderate evidence
Fetal harm

Contraindicated in pregnancy.
Evidence: Serious
Add-back therapy usually required

For endometriosis and fibroids, hormonal add-back is standard to limit bone loss, which complicates the regimen.
Evidence: Moderate evidence

Counts are not a score. A single serious risk can outweigh several well-supported benefits, and a long benefit list built on preclinical work outweighs nothing at all.

Opinion — what people actually report

6 themes · 4 reported problems

This is the weakest tier on this site. These are themes drawn from public discussion — forums, subreddits and patient threads — not from trials. There is no control group, no denominator, and no way to confirm that what someone injected matched its label. People post when a result is dramatic and when something goes wrong, and rarely when nothing happens, so treat everything below as a description of the conversation rather than of the compound. The bars count how often a thing is said, not how well it is supported.

The flare reaction at the start Reported problem. Dominant theme: Comes up in most discussions of this compound.

A well-known and much-discussed initial worsening as hormones surge before they fall, distressing when patients are not warned about it in advance.
Hot flushes, mood and cognitive fog Reported problem. Dominant theme: Comes up in most discussions of this compound.

The dominant symptom cluster across every indication. Frequently described as harder than expected and as under-acknowledged in consultations.
Bone density loss with prolonged use Reported problem. Dominant theme: Comes up in most discussions of this compound.

The concern that dominates long-term discussion, particularly in endometriosis communities where patients are often young.
Add-back therapy is central to the endometriosis conversation Practical note. Dominant theme: Comes up in most discussions of this compound.

Widely discussed as the thing that makes extended treatment tolerable, and as something patients often had to ask for.
Reports of symptoms persisting after stopping Reported problem. Recurring: Raised regularly, though not by everyone.

A contentious and emotive strand, particularly in patient advocacy groups, and disputed in its interpretation.
Very different conversations by indication Practical note. Recurring: Raised regularly, though not by everyone.

Prostate cancer, endometriosis, precocious puberty and gender-affirming care communities discuss this drug in almost entirely separate terms.

Where the reports and the evidence part ways

The flare, the hypoestrogenic or hypogonadal symptoms and the bone density loss are all well documented and match patient reports closely; so does the effectiveness of add-back therapy. The genuinely unresolved area is the persistent-symptoms strand: reports of lasting cognitive, musculoskeletal or mood effects after discontinuation are numerous and taken seriously by patient groups, but the controlled evidence needed to establish incidence or causation largely does not exist. That is an absence of study rather than evidence of absence, and it is one of the few places on this site where the community is describing something the literature has not adequately investigated.

Questions & answers

Readers on Leuprolide

Questions and answers from readers, under generated names. Nothing here has been checked or reviewed by the site and none of it is medical advice. It is the least verified thing on this page — and it is here because people ask each other these things anyway, and most of the other places they can ask are run by sellers.

0 questions · 0 answers

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No questions yet. Ask the first one above — it takes one box and an email address.

How names work, and the house rules

Names. Every verified address is given one generated name — two ordinary words — and keeps it. Nobody chooses a name and nobody can take another's. Posts marked desk were written by the site's own editorial desk, usually to open a thread; they carry a generated name like everyone else's and are held to the site's rules, which means they never state an amount.

What is not allowed. Selling, sourcing, vendor names, coupon codes and "message me" — posts that read that way are held and usually removed. Personal medical details you would not want public. Abuse. Instructions framed as what someone else should do.

What this is not. A reader's report of what happened to them is a report, not a finding, and an answer here is one person's view. Nothing in this section changes the evidence rating above it. If something you read here would change what you take, take it to a pharmacist or physician first.

Your data. Delete any post of yours at any time, or remove everything you have written together with your name. Details in the privacy notice.

Who should avoid it

Pregnancy and breastfeeding
Undiagnosed abnormal vaginal bleeding
Known hypersensitivity to GnRH analogs
Caution with pre-existing osteoporosis

If used under medical supervision, monitor

Testosterone and PSA in prostate cancer
Bone mineral density with therapy beyond 6 months
Glucose, HbA1c and lipids
Growth velocity and bone age in pediatric use
Mood assessment

Interactions

Not exhaustive. Always have a pharmacist or physician review your full medication list — including supplements.

Drugs that prolong QT — androgen deprivation adds risk
Antihyperglycemic agents — requirements often increase

Commonly confused with

These mix-ups cause real harm — two products sold under one name, or two molecules whose effects run in opposite directions.

Gonadorelin Limited Approval Evidence 3/5

Same receptor, opposite outcome. Gonadorelin given in pulses stimulates the axis and is used to preserve testicular function. Leuprolide given continuously suppresses it to castrate levels. The dosing pattern, not the molecule, decides the direction.

Compare side by side

Regulatory & legal status

Prescription drug.

Infographic

Leuprolide — benefits & risks at a glance Download SVG

Where to read further

We link to live literature searches rather than a frozen citation list, so you always see current results — including anything published after our last review.

prostate cancerendometriosisGnRHprecocious pubertyapproved

Related peptides in Hormonal & Reproductive

Terms used on this page

Hypothalamic-Pituitary-Gonadal (HPG) Axis: The hypothalamic-pituitary-gonadal axis is the GnRH to gonadotropin to gonadal steroid loop that governs puberty, fertility and sex steroid production in both sexes.
GnRH Agonist vs Antagonist: GnRH agonists suppress gonadotropins only after an initial hormonal flare and receptor downregulation, while GnRH antagonists block the receptor immediately and produce no flare.
Potency vs Efficacy: Potency is the concentration a drug needs to produce a given effect, while efficacy is the largest effect it can produce at any concentration; the two are independent properties.
Receptor Downregulation: Receptor downregulation is a sustained reduction in the number of receptors a cell presents, produced by prolonged agonist exposure and reversed only by resynthesis over hours to days.
Receptor Occupancy: Receptor occupancy is the fraction of a receptor population bound by a ligand at a given concentration, set by affinity through the relation occupancy equals concentration divided by concentration plus Kd.
Receptor Desensitisation: Receptor desensitisation is the rapid, reversible loss of responsiveness that occurs during continued agonist exposure, as the activated receptor is uncoupled from its signalling machinery.

This page is educational information, not medical advice. It cannot account for your medical history, medications, or risk factors. Do not start, stop or change any treatment based on it. Speak to a qualified healthcare professional who knows your case.