GnRH agonist that first spikes, then shuts down, sex hormones; FDA-approved for prostate cancer, endometriosis, fibroids and early puberty.
Also called Leuprorelin, Leuprolide acetate, Lupron, Lupron Depot, Lupron Depot-Ped, Eligard, Fensolvi, Camcevi, Lutrate Depot, Viadur
When Leuprolide's status or evidence changes, it's in the next morning's email.
Leuprolide is a 9-amino-acid copy of GnRH, the brain hormone that tells the pituitary to release LH and FSH. It is far stronger than the natural hormone. The first doses cause a surge: testosterone rose about 50% above baseline in the first week in prostate cancer trials. With constant exposure the pituitary stops responding, and LH, FSH, testosterone and estrogen fall to castrate or prepubertal levels, usually within 2 to 4 weeks. That shutdown is the point of the drug.
FDA first approved leuprolide in 1985 as a daily injection for advanced prostate cancer. Today it is mostly given as slow-release depots that last 1 to 6 months: Lupron Depot and Eligard for prostate cancer, Lupron Depot 3.75 mg and 11.25 mg for endometriosis and for anemia from fibroids before surgery, and Lupron Depot-Ped and Fensolvi for central precocious puberty. In IVF, clinics use leuprolide off-label to keep the body from ovulating too early, or as a single trigger shot instead of hCG to lower the risk of ovarian hyperstimulation.
The side effects come from low sex hormones: hot flashes in most patients, bone loss, lower libido, mood changes and, in men, a link to diabetes and heart disease. In endometriosis, women on leuprolide alone lost 6.3% of spine bone density in a year, which is why treatment is capped at 12 months and paired with norethindrone add-back. WADA bans GnRH agonists, naming leuprorelin, in male athletes.
What it binds to, and what happens inside the body after that, step by step.
Leuprolide binds GnRH receptors on the pituitary. A single dose acts like a strong burst of GnRH and releases LH and FSH, which briefly raises testosterone or estrogen. Continuous exposure from a daily injection or depot desensitizes the receptors, so LH and FSH fall and the testes or ovaries stop making sex hormones. The effect reverses after the drug is stopped, usually within about 3 months according to the Lupron Depot label, though it can take longer after long-acting depots.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
Leuprolide is an approved drug with decades of trial data. It reliably drives testosterone to castrate levels in prostate cancer, relieves endometriosis pain as well as danazol, and halts early puberty in most children. Its IVF uses are off-label but backed by large Cochrane reviews of GnRH agonist protocols and agonist triggers, which show a lower OHSS risk with the trigger but fewer live births in fresh transfers.
199 men with metastatic prostate cancer
Leuprolide 1 mg daily matched DES 3 mg daily for testosterone suppression and response (86% vs 85% objective response), with less gynecomastia, nausea, edema and clotting but more hot flashes.
Read the study930 men with advanced prostate cancer (622 relugolix, 308 leuprolide), 48 weeks
88.8% on leuprolide kept castrate testosterone through 48 weeks vs 96.7% on relugolix; major cardiovascular events were 6.2% vs 2.9%.
Read the study17 RCTs, 1,847 women in IVF/ICSI
An agonist trigger cut OHSS (odds ratio 0.15) but lowered live birth in fresh transfers (odds ratio 0.47), so it suits egg freezing, donors and freeze-all cycles.
Read the study73 RCTs, 12,212 women comparing antagonist with long GnRH agonist protocols
Live birth was similar (odds ratio 1.02), but the long agonist protocol carried more OHSS (antagonist odds ratio 0.61).
Read the study66 women under 40 at high risk of OHSS
No OHSS with an agonist trigger vs 31% (10 of 32) with an hCG trigger, with similar ongoing pregnancy rates (53% vs 48%).
Read the studyNo preclinical studies are listed as key studies here. The human data above carries the evidence.
When a new Leuprolide study in people is published, the daily email covers it.
These are questions the published research has not answered.
IVF use (pituitary suppression in the long protocol, or a single GnRH agonist trigger) is off-label in the US; no US leuprolide label lists infertility. The Lupron Depot 3.75 mg and 11.25 mg labels cap endometriosis treatment plus add-back at 12 months because of bone loss, and the prostate cancer labels warn about diabetes, heart attack, stroke, QT prolongation and seizures. WADA's 2026 list names leuprorelin under S2.2.1, testosterone-stimulating peptides prohibited in males at all times.
When the FDA or WADA changes Leuprolide's status, it's in the next morning's email.
How much of Leuprolide is left after a single dose
Simple first-order model from the published half-life. Real clearance varies with dose, route, kidney and liver function and formulation. This is not a dosing schedule.
This table records the doses that trials and approved labels used, with the source for each row. It is a record of research, not a recommendation, and it is open to free members.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
Tap a claim to see what the studies found.
Only at the start. Testosterone rises about 50% in the first week, then falls to castrate levels within about 4 weeks with continued dosing. Long-term use lowers it.
Hormone suppression usually reverses within about 3 months of stopping, per the label, but recovery after long depots can be slow: in the HERO trial mean testosterone was 58.6 ng/dL 90 days after leuprolide stopped. Part of the bone loss may not reverse.
A Cochrane review of 17 RCTs found an agonist trigger nearly removes OHSS risk but lowers live birth in fresh embryo transfers. It fits egg freezing, donor cycles and freeze-all cycles better.
The label limits treatment with add-back therapy to 12 months total because women on leuprolide alone lost 6.3% of spine bone density in a year.
These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.
Norethindrone acetate 5 mg daily is added to monthly Lupron Depot to reduce bone loss and hot flashes during endometriosis treatment.
EvidenceLabel-backed: in a controlled study, spine bone density fell 1.0% at a year with add-back vs 6.3% on leuprolide alone.
An antagonist prevents early ovulation during IVF stimulation, then a single agonist dose replaces hCG to trigger egg maturation with less OHSS risk.
EvidenceCochrane review of 17 RCTs: much less OHSS, but fewer live births in fresh transfers. Off-label in the US.
Lupron Depot and Lupron Depot-Ped kits: 20 to 25°C (68 to 77°F). Eligard: refrigerated at 2 to 8°C, or up to 8 weeks at room temperature in its packaging before mixing. Leuprolide acetate injection vials: below 25°C, protected from light, not frozen.
Depots are mixed right before injection by a healthcare provider. Eligard and Fensolvi must be injected within 30 minutes of mixing.
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