Leuprolide (leuprorelin): what the evidence shows

What the human research shows

One of the most-used peptide medicines in the world, on evidence that is old, large and settled. The interesting rows are the side effects — the price of switching a hormone axis off — and the fact that the same family of molecules, pulsed instead of continuous, does the reverse.

Evidence profile0–5

Metabolic & weight—0.0
Cardiovascular—0.0
Muscle & growth—0.0
Healing & repair—0.0
Neuro & sleep—0.0
Immune & inflammation—0.0
Sexual & hormonalA5.0
Skin & appearance—0.0
Ageing & longevity—0.0

Each score is confidence × effect size, taken from the best-evidenced benefit in that domain: the grade (A–D) sets the confidence, the measured effect sets the size. Hover a domain to see the outcomes behind it. Adverse effects are excluded and listed separately below.

Outcome	Grade	Effect size	Human studies	Where the evidence comes from
Metastatic prostate cancer (hormone suppression)	AEstablished	Large	RCT vs DES (n=199) + 40 years of trials	Objective response in 86% against 85% on diethylstilbestrol, with equivalent testosterone suppression and fewer serious side effects — the trial that made GnRH agonists the standard of care.1
Testosterone suppression to castrate levels	AEstablished	Large	Approval-grade	Reliable suppression to castrate range within weeks, after an initial surge — the pharmacology every indication rests on.1 2
Central precocious puberty	AEstablished	Large	Approval-grade programmes	Halts pubertal progression in children with early central puberty; a licensed indication in every major market.2
Endometriosis and uterine fibroids	AEstablished	Moderate	Multiple RCTs	Reduces pain and lesion or fibroid volume by inducing a reversible low-oestrogen state; use is limited by bone loss and menopausal symptoms, usually to six months with add-back therapy.2
Adverse effectsadverse	AEstablished	Large	Same trials + surveillance	The consequences of hormone deprivation: hot flushes, loss of libido and bone density, muscle loss, fatigue, and in men a cardiovascular and metabolic risk signal with long-term use. The initial hormone surge can worsen symptoms in the first weeks.1 2

AMultiple good human trials, consistentBSome human trials, mostly consistentCFew or weak human studiesDAnimal or anecdotal onlyeffect size · red = adverse

Literature searched to 10 September 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.

Registered trials

ClinicalTrials.gov lists 143+ interventional studies naming Leuprolide (leuprorelin) as an intervention — 64 completed, 13 recruiting, and 49 with results posted to the registry.

A registration is not a result. Anyone can register a study, and many never report — so this list shows what has been attempted, not what has been shown. The graded evidence above is the answer to whether something works.

Study	Phase	Status	Participants	Sponsor	Results
A Study to Assess the Safety and Efficacy of Leuprorelin in Central Precocious Puberty in Chinese ParticipantsNCT02427958 · started Aug 2015	Phase 4	Completed	307	Takeda	Posted
Menopur® Versus Follistim® in Polycystic Ovarian Syndrome (PCOS)NCT00805935 · started Jan 2009	Phase 4	Completed	110	Ferring Pharmaceuticals	Posted
A Study of Leuprolide Acetate Depot in Children With Central Precocious PubertyNCT05341115 · started Mar 2023	Phase 4	Completed	79	Takeda	Posted
Evaluate Recovery of Testosterone for Patients Using EligardNCT01136226 · started Oct 2003	Phase 4	Completed	42	Chesapeake Urology Research Associates	Posted
Polycystic Ovary Syndrome (PCOS) and Sleep ApneaNCT00203996 · started Sept 2003	Phase 4	Terminated	37	University of Chicago	Posted
Endometrial Markers and Response of Endometriosis Patients to Prolonged GnRH Agonist Prior to IVFNCT00621179 · started Mar 2003	Phase 4	Completed	37	Colorado Center for Reproductive Medicine	Posted
Study of Dual Trigger Ovulation in Oocyte DonorsNCT01443546 · started Jan 2013	Phase 4	Terminated	26	Weill Medical College of Cornell University	Posted
Maximal Stimulation and Delayed Fertilization for Diminished Ovarian Reserve: a Randomized Pilot StudyNCT01921166 · started Jan 2011	Phase 4	Completed	23	Wake Forest University Health Sciences	Posted

135 further studies are registered. Participant counts marked * are the sponsor's estimate, not a final enrolment. Source: ClinicalTrials.gov, read directly from the registry and refreshed weekly.

What it is

Leuprolide is GnRH with two substitutions that make it far more potent and longer-lasting, developed by Takeda and Abbott and approved in 1985 as Lupron. Depot formulations lasting one to six months followed, and it is sold under many names — Eligard, Prostap, Lucrin — with generics.

Its family — goserelin, triptorelin, buserelin — share the mechanism. Gonadorelin, the natural hormone, sits on the other side of the same axis and is covered separately.

How it is thought to work

Timing decides everything. GnRH pulsed every hour or two keeps the pituitary releasing LH and FSH; GnRH present continuously desensitises the receptor and stops them. Leuprolide is engineered to be present continuously, so after a surge lasting one to two weeks the axis shuts down and testosterone or oestrogen falls to near zero. Stop the drug and it recovers.

What is still unknown

Long-term cardiovascular and cognitive effects of androgen deprivation in prostate cancer, still being quantified.
Long-term outcomes of puberty suppression outside precocious puberty, where evidence remains limited and contested.

The molecule and how long it lasts

Identity

Formula: C59H84N16O12
Molecular weight: 1209.4 g/mol
CAS number: 53714-56-0
PubChem: CID 657181

PubChem record, read 23 September 2026.

Pharmacokinetics

Route: Intramuscular depot injection, every 1, 3, 4 or 6 months
Half-life: About 3 hours (the peptide itself, intravenous)
Licensed regimen (Lupron Depot): 7.5 mg IM every 4 weeks, 22.5 mg every 12 weeks, 30 mg every 16 weeks, or 45 mg every 24 weeks (advanced prostate cancer)

From the approved product's prescribing information: Lupron Depot prescribing information (DailyMed) The regimen is the label's own wording, reproduced as a regulatory fact.

Regulatory status

European Union

Approved, prescription-only

Authorised in every member state for prostate cancer, endometriosis, fibroids and precocious puberty.

United States

Approved, prescription-only

FDA-approved since 1985 (Lupron); multiple depot products.

United Kingdom

Licensed, prescription-only

Licensed (Prostap and others).

Australia

Registered, prescription-only

On the ARTG (Lucrin, Eligard).

Canada

Authorised, prescription-only

Health Canada-authorised.

Sport (WADA)

Prohibited at all times (males)

Leuprorelin is named on the Prohibited List among gonadotrophin-releasing factors, prohibited in males.

Questions people actually ask

Does leuprolide raise or lower testosterone?

Both, in order: a surge for one to two weeks, then suppression to castrate levels for as long as it is given. The surge is why prostate-cancer patients are often covered with an anti-androgen at the start.

Is leuprolide the same as gonadorelin?

No — opposite effects from the same receptor. Gonadorelin is the natural hormone and needs pulsing to work; leuprolide is a long-acting analogue whose continuous presence shuts the axis down.

Is it reversible?

Yes. Hormone production resumes after the depot wears off, over weeks to months depending on the formulation and duration of use.

One page per claimed effect

ADoes Leuprolide (leuprorelin) help with metastatic prostate cancer?RCT vs DES (n=199) + 40 years of trials
ADoes Leuprolide (leuprorelin) help with testosterone suppression to castrate levels?Approval-grade
ADoes Leuprolide (leuprorelin) help with central precocious puberty?Approval-grade programmes
ADoes Leuprolide (leuprorelin) help with endometriosis and uterine fibroids?Multiple RCTs
AHow common is adverse effects with Leuprolide (leuprorelin)?Same trials + surveillance

References

1
The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.N Engl J Med, 1984199 men; the trial that established GnRH agonists in prostate cancer.
2
Leuprolide acetate (Lupron Depot) prescribing information and approved indications.FDA / EMA product informationLicensed indications.

Change log

2026-09-10Initial publication. Grade A across licensed indications.