What it is
Leuprolide is a nine-amino-acid copy of GnRH, the hormone the hypothalamus uses to tell the pituitary to drive the testes and ovaries. Natural GnRH has ten amino acids and survives only minutes. Leuprolide changes two things:
| Position | Natural GnRH | Leuprolide |
|---|---|---|
| 6 | Glycine | D-leucine (a mirror-image amino acid) |
| 10 | Glycinamide | Removed; proline 9 capped with an ethylamide |
The label's chemical name — ending "D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide" — records both changes. They make the peptide resistant to the enzymes that clear GnRH and make it bind the receptor more strongly.
The paradox: on, then off
The pituitary listens to GnRH only in pulses. That is the whole trick behind leuprolide, and the reason a hormone "copy" is used to remove hormones.
- First days — the flare. A strong, steady GnRH signal makes the pituitary release more LH and FSH, and testosterone or oestrogen rise.
- Then — the shutdown. Faced with a signal that never pauses, the pituitary stops responding. LH and FSH fall, and sex-hormone production falls with them.
- After stopping — recovery. The Lupron Depot label describes the effect as reversible, with normal function usually restored within three months.
The flare is why prostate-cancer labels warn of worsening bone pain or urinary obstruction in the first weeks, and why the paediatric labels warn that signs of puberty may briefly increase.
Gonadorelin is natural GnRH itself; triptorelin is a closely related analogue with the same on-then-off action.
What it is approved for
| Condition | Products | Source |
|---|---|---|
| Advanced prostate cancer | Eligard, Camcevi, Lupron Depot (7.5 mg and up) | Eligard and Camcevi labels |
| Endometriosis (pain and lesions) | Lupron Depot 3.75 mg / 11.25 mg | Lupron Depot label |
| Anaemia from fibroids, before surgery | Lupron Depot 3.75 mg / 11.25 mg, with iron | Lupron Depot label |
| Central precocious puberty | Lupron Depot-Ped; Fensolvi (age 2+) | Fensolvi label |
Forms and timing
Leuprolide is not active when swallowed, per the Lupron Depot label. Injected into a vein its terminal half-life is about 3 hours, so nearly every product is a depot: microspheres or a polymer gel that release the peptide steadily for one, three, four or six months. After a Lupron Depot 3.75 mg injection, the label reports a peak at four hours and then a plateau of about 0.30 ng/mL lasting four to five weeks.
The label is emphatic that the depots are not interchangeable: a 3-month 11.25 mg injection is not equivalent to three 1-month 3.75 mg injections, and neither may be split or multiplied to imitate the other.
Safety
From the Lupron Depot 3.75 mg label: loss of bone mineral density — the reason endometriosis treatment with add-back hormone therapy is capped at 12 months — plus severe skin reactions, hypersensitivity, convulsions and clinical depression. Its commonest effects (over 10%) are hot flashes and sweats, headache, vaginitis, mood changes, pain, weight change, nausea and decreased libido. The prostate-cancer labels (Eligard, Camcevi) add tumour flare, raised blood sugar and diabetes, and an increased risk of heart attack, sudden cardiac death and stroke in men on GnRH agonists.
Where it stands
FDA application data list 21 leuprolide applications on 2026-09-27: 12 brand applications and 9 generic daily injections (14 mg in 2.8 mL), the first approved in 1998. ClinicalTrials.gov holds 519 records with leuprolide as an intervention; Europe PMC's MEDLINE index holds 2,294 records naming it in the title or abstract, 346 tagged as randomised controlled trials.
Related reading
The GnRH axis in this library: gonadorelin is the natural hormone, triptorelin the closest related drug, and kisspeptin the signal one step further up that tells the hypothalamus to release GnRH in the first place. hCG acts at the other end of the chain, directly on the testes and ovaries.