Leuprolide
GnRH receptor agonist
Status
Approved
FDA-approved since 1985, now mainly as long-acting depots for advanced prostate cancer, endometriosis, fibroid-related anaemia and central precocious puberty, and authorised in the EU both centrally (Camcevi, 2022) and through national licences; it is prohibited for male athletes.
Evidence
Strong
Randomized trials since the 1980s and decades of use show reliable suppression of testosterone and oestrogen for its approved indications.
In sport
WADAProhibited (WADA)
Leuprolide is a long-acting synthetic version of gonadotrophin-releasing hormone. After a brief initial surge, it shuts down the body's production of testosterone and oestrogen, and is used for prostate cancer, endometriosis, fibroids and early puberty in children.
Structure
9 residuesPoint at a bead, or focus the chain and use the arrow keys, to name it. Pick a chemistry to highlight it.
D-form (mirror image), shown in lower case
Sequence as text
pGlu-H-W-S-Y-D-Leu-L-R-P-NHEt
What it is used for
- Advanced and hormone-dependent prostate cancer (approved)
- Endometriosis pain and lesions (approved)
- Anaemia from uterine fibroids before surgery, with iron (approved)
- Central precocious puberty in children (approved)
How it works
Leuprolide binds pituitary GnRH receptors more potently than natural GnRH. At first this causes a surge in LH and FSH and a brief rise in testosterone or oestrogen (the 'flare'). Because it is present continuously rather than in pulses, the receptors then become desensitised, LH and FSH fall, and testosterone drops to castrate levels in men and oestrogen to postmenopausal levels in women. The effect reverses after treatment stops.
How strong the evidence is
Strong
In a randomized trial of 199 men with untreated metastatic prostate cancer, daily leuprolide suppressed testosterone as effectively as the oestrogen diethylstilbestrol, with similar objective response rates (86% versus 85%) and less painful breast enlargement, nausea, oedema and blood clots, though more hot flushes (Leuprolide Study Group 1984, NEJM). Depot formulations were approved on the basis of studies showing testosterone held at castrate levels (50 ng/dL or less) between injections (Lupron Depot label). Separate trials supported approvals for endometriosis, fibroid-related anaemia and central precocious puberty.
Risks and side effects
- Initial hormone flare that can temporarily worsen prostate cancer symptoms, including bone pain or spinal cord compression
- Hot flushes, loss of libido and loss of bone mineral density
- Metabolic changes (high blood sugar, diabetes, raised lipids) and increased cardiovascular risk
- Possible QT prolongation on the ECG and, rarely, convulsions
- Can harm a fetus; severe skin reactions and hypersensitivity reported
- Prohibited for male athletes at all times (WADA S2)
Label dosing
Label (Lupron Depot, advanced prostate cancer): one intramuscular 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.
Regulatory status
| Region | Year | Approved for |
|---|---|---|
| USFDA | 1985 | Advanced prostate cancer |
| USFDA | 1990 | Endometriosis (fibroid-related anaemia added later) |
| USFDA | 1993 | Central precocious puberty |
| EUEMA | 2022 | Hormone-dependent advanced prostate cancer, and high-risk localised or locally advanced disease with radiotherapy |
Status by country
| Jurisdiction | Status | Source |
|---|---|---|
| USUnited States | Authorised medicine | Source 4 |
| EUEuropean Union | Authorised medicine | Source 5 |
| UKUnited Kingdom | Authorised medicine | Source 9 |
| AUAustralia | Authorised medicine | Source 10 |
| CACanada | Authorised medicine | Source 11 |
Trials of Leuprolide to watch
OVELIA(opens the source in a new tab)
Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer
Adjuvant leuprorelin after prostatectomy(opens the source in a new tab)
Evaluation of Adjuvant Hormonal Treatment for 24 Months After Radical Prostatectomy in High Risk of Recurrence Patients.
ADOPT(opens the source in a new tab)
Androgen Deprivation Therapy for Oligo-recurrent Prostate Cancer in Addition to radioTherapy
Leuprolide mesylate in early puberty(opens the source in a new tab)
Efficacy, Safety, and Pharmacokinetics of Leuprolide Mesylate in Subjects With Central Precocious Puberty
Timeline
2027
2026
2025
2022
- Approved, EU (EMA)Hormone-dependent advanced prostate cancer, and high-risk localised or locally advanced disease with radiotherapy
1993
- Approved, US (FDA)Central precocious puberty
1990
- Approved, US (FDA)Endometriosis (fibroid-related anaemia added later)
1985
- Approved, US (FDA)Advanced prostate cancer
Sources
- 01LUPRON DEPOT (leuprolide acetate for depot suspension) for prostate cancer: label(opens the source in a new tab)
- 02LUPRON DEPOT 3.75 mg (endometriosis and fibroids): label(opens the source in a new tab)
- 03LUPRON (leuprolide acetate) NDA 019010: approval history(opens the source in a new tab)
- 04LUPRON DEPOT-PED NDA 020263: approval history(opens the source in a new tab)
- 05Camcevi (leuprorelin): EPAR(opens the source in a new tab)
- 06Leuprolide versus diethylstilbestrol for metastatic prostate cancer(opens the source in a new tab)
- 07Leuprolide (CID 657181)(opens the source in a new tab)
- 08World Anti-Doping Code International Standard: Prohibited List 2026(opens the source in a new tab)
- 09Prostap SR DCS 3.75 mg Powder and Solvent for Prolonged-release Suspension for Injection in Pre-filled Syringe: Summary of Product Characteristics(opens the source in a new tab)
- 10LUCRIN DEPOT leuprorelin acetate 7.5mg powder for injection prefilled dual-chamber syringe (114302)(opens the source in a new tab)
- 11Drug Product Database: Lupron Depot (DIN 02239834)(opens the source in a new tab)
Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.