Key points
- Leuprolide (Lupron, Eligard) is an injection that brings male hormone (testosterone) down almost to zero and is used for advanced prostate cancer [1, 2].
- It is injected once every 1, 3, 4 or 6 months at the clinic [1, 2].
- In the first weeks the hormone rises temporarily, and symptoms of the disease may get a little worse [1].
- The most common side effect is hot flushes; other important side effects: higher blood sugar and blood fats, a risk of heart disease and weaker bones [1].
- In prostate cancer that has spread, this injection is not enough on its own; it should be combined from the start with one of the newer hormone-blocking drugs [3] (for doctors).
What is this drug and how does it work?
For physicians
Leuprolide, also called leuprorelin in some sources, is a gonadotropin-releasing hormone (GnRH) agonist. Its intramuscular depot form, Lupron Depot, was first approved in the United States in 1989, and its subcutaneous form, Eligard, in 2002 [1, 2].
The growth of most prostate cancers depends on male hormone (testosterone). Leuprolide first stimulates the pituitary gland, causing a temporary rise in LH, FSH and testosterone; continuous stimulation then desensitises the pituitary, and secretion of these hormones falls so that testosterone reaches castrate levels [1]. In the study of Lupron Depot 7.5 mg monthly, testosterone reached castrate levels within 30 days in 94% of patients [1]. This approach is called androgen deprivation therapy (ADT), and after the drug is stopped hormonal function usually returns within about three months [1].
Which cancers is it used for?
Your doctor may prescribe this drug for:
- Advanced prostate cancer [1, 2]
- Prostate cancer that has spread but still responds to hormone therapy [3, 4, 5]
- High-risk biochemical recurrence (a rising PSA after local treatment) [6]
- Prostate cancer that no longer responds to hormone therapy (CRPC) [1, 3]
Whether it suits you depends on the type and stage of your cancer and your test results. Details of each use are in the section for doctors.
For physicians
| Cancer | Setting | Key evidence |
|---|---|---|
| Advanced prostate cancer | FDA-approved use for Lupron Depot and Eligard [1, 2] | Lowering and keeping testosterone at castrate levels; in the study of the monthly form, 94% of patients reached castrate levels within 30 days [1]. |
| Metastatic hormone-sensitive prostate cancer | The backbone of treatment (ADT) with intensifying drugs | ESMO 2026 guideline: ADT plus an androgen receptor pathway inhibitor (abiraterone, apalutamide, enzalutamide or darolutamide) is strongly recommended, and ADT alone is generally not recommended [3]. In CHAARTED, adding docetaxel to ADT raised overall survival from 44.0 to 57.6 months (HR 0.61) [4]. In ARASENS, adding darolutamide to ADT and docetaxel lowered the risk of death by 32.5% (HR 0.68) [5]. |
| High-risk biochemical recurrence (a rising PSA after local treatment) | Leuprolide alone or with enzalutamide | EMBARK trial: enzalutamide with leuprolide lowered the risk of metastasis or death compared with leuprolide alone (HR 0.42); 5-year metastasis-free survival was 87.3% vs 71.4% [6]. |
| Castration-resistant prostate cancer (CRPC) | Continued treatment after castration resistance | FDA label: GnRH agonist therapy usually continues after non-metastatic and metastatic CRPC develops [1]. In high-risk nmCRPC, ESMO recommends adding apalutamide, darolutamide or enzalutamide to ADT [3]. |
This page covers only the use of leuprolide in prostate cancer. The prostate cancer forms of Lupron Depot are not approved for children, and the different doses cannot be added together because their release differs [1].
How it is taken and dosing
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- Leuprolide is always injected by healthcare staff [1, 2]. Lupron Depot is injected into a muscle (buttock, thigh or upper arm) and Eligard under the skin (usually the abdomen), and the injection site should be changed each time [1, 2].
- Depending on the product, the injection is given once every 1, 3, 4 or 6 months [1, 2]. Do not miss injection appointments; a long delay may let testosterone rise again [1].
- Treatment is usually long-term [1]. Never stop treatment without talking to your doctor.
- Your doctor regularly checks your testosterone and PSA, as well as blood sugar or HbA1c, blood fats and signs of heart disease [1].
- Before starting: contraindicated in hypersensitivity to GnRH, GnRH agonists or product components. With vertebral metastases or urinary tract obstruction, weigh the risk of flare (about a 50% rise in testosterone in the first weeks). In congenital long QT syndrome, heart failure, recurrent electrolyte disturbances or with QT-prolonging drugs, weigh benefit and risk and correct electrolytes [1].
- First weeks: close monitoring for bone pain, neuropathy, haematuria, urinary obstruction and spinal cord compression [1].
- Dose modification: no dose reductions are defined. If a severe skin reaction (SJS/TEN, DRESS, AGEP) is suspected, interrupt the drug, and discontinue permanently if confirmed or for a grade 4 skin reaction [1].
- Kidney and liver: pharmacokinetics in renal or hepatic impairment have not been determined; the label gives no dose adjustment [2].
- Monitoring: serum testosterone (castrate levels, below 50 ng/dL, within 4 weeks in most patients) and PSA; blood glucose and/or HbA1c and serum lipids; signs of cardiovascular disease; consider periodic ECG and electrolytes [1, 2].
- Late dose: the labels give no specific instruction; schedule doses according to the product (every 4, 12, 16 or 24 weeks for Lupron Depot) [1].
For physicians
Standard dosing (FDA label; advanced prostate cancer)
Lupron Depot (leuprolide acetate depot)
Advanced prostate cancer; continued after non-metastatic and metastatic CRPC develops
Advanced prostate cancer; continued after non-metastatic and metastatic CRPC develops [1]
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Monthly | |||
| Lupron Depot | 7.5 mg | Intramuscular (buttock, anterior thigh or deltoid) | Every 4 weeks |
| 3-monthly | |||
| Lupron Depot | 22.5 mg | Intramuscular | Every 12 weeks |
| 4-monthly | |||
| Lupron Depot | 30 mg | Intramuscular | Every 16 weeks |
| 6-monthly | |||
| Lupron Depot | 45 mg | Intramuscular | Every 24 weeks |
One single injection per dose; because release differs, doses cannot be added together and partial doses or combining several products are not allowed. Inject the reconstituted suspension immediately or within 2 hours at most; change the injection site each time. Healthcare staff only [1].
Eligard (subcutaneous leuprolide acetate)
Advanced prostate cancer; continued after metastatic CRPC develops
Advanced prostate cancer; continued after metastatic CRPC develops [2]
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Monthly | |||
| Eligard | 7.5 mg | Subcutaneous (abdomen or upper buttock) | Every month |
| 3-monthly | |||
| Eligard | 22.5 mg | Subcutaneous | Every 3 months |
| 4-monthly | |||
| Eligard | 30 mg | Subcutaneous | Every 4 months |
| 6-monthly | |||
| Eligard | 45 mg | Subcutaneous | Every 6 months |
Allow it to reach room temperature before mixing; inject within 30 minutes of preparation. Rotate the injection site and avoid areas under pressure from a belt or clothing. Healthcare staff only [2].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Side effects
Common side effects
The most common side effects:
For physicians
| Adverse reaction | Frequency |
|---|---|
| Hot flushes | 58.9% |
| Upper respiratory infection or flu-like symptoms | 21.2% |
| Injection-site pain or discomfort | 19.2% |
| Fatigue | 13.2% |
| Constipation | 9.9% |
| Arthralgia | 9.3% |
| Insomnia | 8.6% |
| Headache | 7.9% |
| Hypertension | 6.6% |
Source: FDA label for Lupron Depot [1]. In studies of the 3-monthly form (22.5 mg), hot flushes or sweating were reported in 58.5% and testicular atrophy in 20.2% of patients [1]. The most common adverse reactions to Eligard are malaise and fatigue, hot flushes and sweating, and testicular atrophy [2].
Serious side effects
These are less common but serious; tell your team early if you notice any sign of them:
- A temporary flare of the disease in the first weeks: worse bone pain, difficulty passing urine, or weakness and numbness of the legs; report it straight away [1].
- Higher blood sugar and blood fats and fatty liver; check your blood sugar and blood fats regularly [1].
- Heart attack or stroke: chest pain, weakness on one side of the body or trouble speaking [1].
- Weaker bones and fractures with long-term treatment [1, 7].
- Heart rhythm changes, seizures, severe skin reactions and suicidal thoughts (rare) [1].
For physicians
Leuprolide has no boxed warning, but the important warnings and precautions in the drug label are [1]:
- Tumour flare: in the first weeks testosterone rises about 50% above baseline, and bone pain, neurological symptoms, haematuria or urinary obstruction may worsen. Spinal cord compression may lead to paralysis (sometimes fatal) [1].
- Metabolic changes: hyperglycaemia, diabetes or worsening of existing diabetes, raised blood lipids and non-alcoholic fatty liver disease (including cirrhosis) [1].
- Cardiovascular disease: an increased risk of myocardial infarction, sudden cardiac death and stroke has been reported in men [1].
- QT prolongation: especially in people with congenital long QT syndrome, heart failure, recurrent electrolyte disturbances or QT-prolonging drugs [1].
- Decreased bone density: long-term medical castration affects bone density [1]. In a large study, 19.4% of men who had ADT had a fracture within 5 years, vs 12.6% of men who did not [7].
- Seizures, even in people with no previous history [1].
- Severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS and AGEP [1].
- Rare cases: pituitary apoplexy (usually within the first 2 weeks and in people with a pituitary adenoma), suicidal thoughts or attempts, serious liver injury and anaphylactic reactions [1].
When should I call my doctor?
Call your doctor or go to the emergency department straight away if you have [1]:
- In the first weeks of treatment: severe or worsening bone pain, weakness, numbness or tingling of the legs, difficulty walking, blood in the urine or being unable to pass urine
- Chest pain, shortness of breath, or signs of a stroke such as sudden weakness of one side of the body or trouble speaking
- A seizure
- Fever, flu-like symptoms, mouth sores or a spreading rash
- A sudden severe headache, vomiting or vision problems (especially in the first two weeks after the first injection)
- Severe depression or thoughts of harming yourself
- Pain, hardness, an abscess or a sore at the injection site
Interactions, pregnancy and precautions
- Bone health: long-term treatment lowers bone density [1]. In men receiving ADT for non-metastatic prostate cancer, denosumab injections strengthened the lower spine and more than halved new spinal fractures [8]. Talk to your doctor about a bone density scan.
- Exercise: the ESMO guideline recommends combined aerobic and resistance exercise for all patients receiving ADT; at least 12 weeks supervised and then on your own [3].
- QT-prolonging drugs: if you take medicines that prolong the QT interval, tell your doctor; your ECG and electrolytes may be monitored [1].
- Hormone tests: results of pituitary and gonadal function tests may be affected by the drug during treatment and for up to 3 months afterwards [1].
- Fertility: leuprolide may cause infertility; talk to your doctor about family planning and contraception [1].
Frequently asked questions
What is “tumour flare” and why does it happen in the first weeks?
How often are the injections given?
Are hot flushes and sexual problems normal?
Is leuprolide on its own enough for metastatic prostate cancer?
In metastatic hormone-sensitive prostate cancer, the ESMO 2026 guideline generally does not recommend androgen deprivation therapy alone and suggests combining it with drugs such as abiraterone, apalutamide, enzalutamide or darolutamide (and docetaxel in some patients) [3]. Leuprolide is usually the “backbone” of these combinations.
If the disease stops responding to hormone therapy, are the injections stopped?
Usually not. According to the drug label, GnRH agonist treatment often continues with other drugs after the cancer becomes castration-resistant (CRPC) [1].
Scientific evidence
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Key studies
5 itemsAdvanced and metastatic prostate cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design
Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer
Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer
Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer
Related cancer types
References
8 referencesShow all references, 6 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1LUPRON DEPOT (leuprolide acetate for depot suspension) 7.5 mg, 22.5 mg, 30 mg, 45 mg — Prescribing Information
- 2
- 3
- 4Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer
- 5Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer
- 6Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer
- 7Risk of Fracture after Androgen Deprivation for Prostate Cancer
- 8Denosumab in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer
This page is based on reputable scientific sources and was last updated on 27 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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