Quick summary
Leuprolide (Lupron) is one of the most widely used GnRH agonists globally, FDA-approved for prostate cancer, endometriosis, uterine fibroids, and central precocious puberty. Long-acting depot formulations provide 1 to 6 months of sex steroid suppression per injection.
Overview
Leuprolide (leuprorelin) is a synthetic GnRH agonist nonapeptide approved by the FDA under the brand name Lupron for advanced prostate cancer, endometriosis, uterine fibroids, and central precocious puberty. It is one of the most widely used GnRH analogs globally. Available as daily subcutaneous injection or long-acting depot formulations releasing drug over 1, 3, 4, or 6 months, it achieves profound sex steroid suppression through pituitary desensitization.
Mechanism of action
Leuprolide is a potent GnRH receptor agonist with roughly 100 times the receptor affinity of endogenous GnRH. Initial administration stimulates pituitary gonadotrophs, causing an LH and FSH surge ('flare') lasting 1–2 weeks. With continuous administration, persistent non-pulsatile receptor stimulation causes GnRH receptor downregulation and pituitary desensitization. LH and FSH secretion falls to castrate levels within 2–4 weeks, reducing testosterone in men to <50 ng/dL and estradiol in women to postmenopausal levels. This medical castration effect is fully reversible upon discontinuation. In prostate cancer, testosterone suppression removes the androgen stimulus that drives tumor proliferation, inducing cancer cell apoptosis.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| Advanced prostate cancer — ADT | intramuscular | 7.5–22.5 mg | every 1–3 months (depot) | 7.5 mg monthly, 22.5 mg every 3 months, 30 mg every 4 months, or 45 mg every 6 months. Add antiandrogen for first 4 weeks to prevent flare. |
| Endometriosis or uterine fibroids | intramuscular | 3.75–11.25 mg | monthly or every 3 months (depot) | 3.75 mg monthly or 11.25 mg every 3 months. Maximum 6 months. Often combined with norethindrone acetate 5 mg/day to limit bone loss. |
| Daily subcutaneous injection (non-depot) | subcutaneous | 1–1 mg | once daily | Used in specific clinical scenarios; depot formulations preferred for adherence. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Decades of trials establish leuprolide depot as the standard androgen deprivation therapy (ADT) for advanced and metastatic prostate cancer, achieving castrate testosterone levels in >97% of patients. For endometriosis, 6-month courses reduce lesion volume and pelvic pain scores significantly versus placebo. The central precocious puberty indication is supported by long-term data demonstrating restoration of normal pubertal timing and final adult height. The depot formulations achieve equivalent clinical outcomes to daily injection with improved adherence. Long-term ADT is associated with metabolic side effects including bone loss, sarcopenia, and cardiovascular risk.[1][2][3][4][5]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Leuprolide for synergistic effects.
Legal status
FDA-approved for: palliative treatment of advanced prostate cancer; endometriosis; uterine leiomyomata (preoperative); and central precocious puberty. Multiple NDA approvals spanning 1985–2019. Prescription-only. Generic versions available since patent expiration.
Sourcing & access
Prescription required
Leuprolide is an FDA-approved prescription medication available through licensed healthcare providers, telehealth platforms, and 503A/503B compounding pharmacies.
Frequently asked questions
Leuprolide, sold as Lupron, Lupron Depot, Eligard, and Fensolvi, is a synthetic GnRH agonist nonapeptide FDA-approved for palliative treatment of advanced prostate cancer, endometriosis, uterine leiomyomata before surgery, and central precocious puberty. It suppresses luteinizing hormone and follicle-stimulating hormone to castrate levels through sustained pituitary desensitization with fully reversible effects.
Leuprolide is a GnRH agonist roughly 100 times more potent than endogenous GnRH. Initial administration causes an LH/FSH flare lasting 1-2 weeks, then continuous non-pulsatile receptor stimulation causes pituitary desensitization, suppressing sex steroids within 2-4 weeks.
The initial 1-2 week hormone surge (flare) can temporarily worsen disease symptoms before suppression occurs. In prostate cancer, an antiandrogen is added for the first 4 weeks to block the flare. This effect is inherent to GnRH agonist mechanisms.
Lupron Depot is available as 7.5 mg monthly, 22.5 mg every 3 months, 30 mg every 4 months, or 45 mg every 6 months. For endometriosis, treatment is limited to 6 months.
Long-term androgen deprivation causes hot flashes, bone mineral density loss, sarcopenia, sexual dysfunction, mood changes, fatigue, and metabolic syndrome. These are consequences of sustained sex steroid suppression and are generally reversible upon discontinuation.
Research references
- Leuprolide: a gonadotropin-releasing hormone analog for the palliative treatment of prostatic cancerPubMed
- Clinical effects of gonadotropin-releasing hormone analogue in metastatic carcinoma of prostatePubMed
- Six-month leuprorelin acetate depot formulations in advanced prostate cancer: a clinical evaluationPubMed
- Development of GnRH antagonists for prostate cancer: new approaches to treatmentPubMed
- Coronary Plaque Progression After Androgen Deprivation Therapy in Men With Prostate Cancer: A Randomized Clinical TrialPubMed