Leuprolide (Lupron Depot, Eligard)

Summary

Leuprolide is a nine amino acid GnRH agonist, a lab-made version of the brain hormone that controls sex hormone production, that after an initial surge desensitizes the pituitary and drops testosterone or estrogen to castrate levels (as low as after surgical removal of the testes or ovaries) within 2 to 4 weeks. It has been FDA approved since 1985 and is a standard treatment for advanced prostate cancer, endometriosis, uterine fibroids (noncancerous growths in the womb), and central precocious puberty (puberty that starts too early). In the 1984 pivotal trial it matched diethylstilbestrol, an older estrogen drug, for prostate cancer response with fewer cardiovascular side effects, and adding flutamide extended median survival from 28.3 to 35.6 months in a 603 patient trial. It is prescription only and available as daily injections and 1 to 6 month depots (slow release injections).

What is Leuprolide?

Leuprolide is a synthetic nonapeptide GnRH (LHRH) agonist analog. It is also known as Lupron, Lupron Depot, Eligard, Fensolvi, Camcevi, Leuprorelin, Leuprolide acetate.

How does it work?

Leuprolide is a potent GnRH receptor agonist. Continuous exposure first stimulates then downregulates pituitary GnRH receptors, so LH and FSH secretion falls and gonadal production of testosterone or estradiol drops to castrate or postmenopausal levels after an initial 1 to 2 week flare. Hormone sensitive tissues such as prostate cancer, endometriosis implants, and fibroids regress. The effect reverses after treatment stops.

FDA-approved uses of Leuprolide

Yes. Leuprolide products are FDA approved for advanced prostate cancer (Lupron Depot 7.5 to 45 mg, Eligard, Camcevi), for endometriosis and for anemia from uterine fibroids (noncancerous growths in the womb) before surgery (Lupron Depot 3.75 mg and 11.25 mg), and for central precocious puberty, puberty that starts too early, in children (Lupron Depot-Ped, Fensolvi). All are prescription only and given by a healthcare provider. [4] [6] [7] [8] [9] [10]

What does the evidence say about Leuprolide?

Randomized trials across four decades. The Leuprolide Study Group 1984 trial (n = 199) found leuprolide equivalent to diethylstilbestrol for objective response in metastatic prostate cancer with less gynecomastia, nausea, and thromboembolism. Crawford 1989 (n = 603) found leuprolide plus flutamide extended median survival versus leuprolide alone (35.6 versus 28.3 months). Klotz 2008 (n = 610) used leuprolide 7.5 mg monthly as the comparator for degarelix and documented testosterone suppression below 0.5 ng/mL in 96.4% of patients from day 28 to day 364.

Human evidence

Leuprolide Study Group 1984: 199 men with previously untreated stage D2 prostate cancer randomized to leuprolide 1 mg subcutaneously daily or diethylstilbestrol 3 mg daily; objective response and 1 year survival were similar, with fewer cardiovascular and breast side effects on leuprolide. Crawford 1989: 603 men with stage D2 prostate cancer randomized to leuprolide plus flutamide or leuprolide plus placebo; median progression free survival 16.5 versus 13.9 months and median survival 35.6 versus 28.3 months. Klotz 2008: leuprolide 7.5 mg monthly comparator arm achieved sustained castration in 96.4% but with a testosterone surge in the first week and microsurges on reinjection. Endometriosis, fibroid, and pediatric indications rest on smaller controlled trials summarized in the labels.

Animal evidence

Preclinical rodent studies established GnRH receptor downregulation and reversible gonadal suppression. Rat carcinogenicity studies showed benign pituitary adenomas at high doses, a species specific finding not reproduced in humans over decades of use.

Key studies

Conditions studied

Is Leuprolide legal in the United States?

FDA and compounding status

FDA approved as Lupron injection in April 1985 for advanced prostate cancer, with Lupron Depot (1989), Lupron Depot-Ped (1993), Eligard (2002), Fensolvi (2020), and Camcevi (2021) following for prostate cancer, endometriosis, fibroids, and central precocious puberty. Generic leuprolide injection is available. Compounding is limited to patient specific needs because approved products exist.

WADA status

WADA prohibited. Athletes subject to anti-doping testing should treat this as prohibited at all times unless the current prohibited list says otherwise.

Regulatory timeline

No regulatory events recorded.

Full tracker for Leuprolide or the category-wide tracker.

Leuprolide dose on the FDA label

Doses below are quoted from the FDA label for its approved uses, plus the doses used in the pivotal trials where noted. The prescriber sets the dose; PeptideAgent does not recommend doses or protocols.

FDA labels (DailyMed). Advanced prostate cancer: Lupron Depot 7.5 mg intramuscularly every 4 weeks, 22.5 mg every 12 weeks, 30 mg every 16 weeks, or 45 mg every 24 weeks; Eligard 7.5 mg subcutaneously every month, 22.5 mg every 3 months, 30 mg every 4 months, or 45 mg every 6 months; Camcevi 42 mg subcutaneously every 6 months. Endometriosis: Lupron Depot 3.75 mg intramuscularly monthly for up to 6 injections, or 11.25 mg every 3 months for up to 2 injections, alone or with daily 5 mg norethindrone acetate add back, and no more than 12 months in total with add back. Uterine fibroids with anemia: Lupron Depot 3.75 mg or 11.25 mg with iron therapy before surgery, when 3 months of hormonal suppression is needed. Central precocious puberty: Lupron Depot-Ped 7.5, 11.25, or 15 mg monthly by weight, 11.25 or 30 mg every 3 months, or 45 mg every 6 months, intramuscularly; Fensolvi 45 mg subcutaneously every 6 months from age 2. Depot strengths have different release profiles and are not interchangeable or additive.

Routes reported

What are the side effects and interactions of Leuprolide?

Side effects

Interactions

Contraindications

How do people access Leuprolide legally?

Typical cost: Lupron Depot 7.5 mg lists at roughly 2,000 to 2,500 USD per monthly injection and about 6,000 to 7,000 USD for the 3 month 22.5 mg depot; Eligard and generic leuprolide are lower. Insurance and Medicare Part B routinely cover it for cancer and other approved indications.

• Rules by state
• Verified provider directory

Compare Leuprolide

• Leuprolide vs degarelix

Frequently asked questions

Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.

Sources

Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.