Peptides›Sexual / hormonal›Leuprolide

Leuprolide

/ Synthetic GnRH (gonadotropin-releasing hormone) superagonist — nonapeptide-amide

TIER 1 · ClinicalN = 0 · TESTING PENDINGMW 1209.42 g·mol⁻¹

ALIAS · Lupron (trade) · Lupron Depot (trade) · Leuprorelin · GnRH analog (decapeptide superagonist)

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequencepyroGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt

MW · 1209.42CLASS · Synthetic GnRH (gonadotropin-releasing hormone) superagonist — nonapeptide-amideCATEGORY · Sexual / hormonal

FDA-approved 1985 (Lupron); decades of Phase 3 RCTs across prostate cancer, endometriosis, central precocious puberty, and uterine fibroids. Multiple FDA-approved indications.

§ B · Mechanism of action

Leuprolide is a synthetic decapeptide GnRH receptor superagonist. Continuous (rather than pulsatile) receptor occupancy produces an initial flare of LH and FSH followed by receptor downregulation and chemical castration of the hypothalamic-pituitary-gonadal axis. Sex-steroid (testosterone in males; estradiol in females) suppression begins within 2–4 weeks of depot administration.

In central precocious puberty, the same suppression halts premature gonadarche; in endometriosis and uterine fibroids, estrogen-deprivation regresses lesions and shrinks fibroid volume; in metastatic hormone-sensitive prostate cancer, androgen deprivation slows disease progression. Used in IVF cycles as the long agonist protocol to prevent premature LH surge.

§ C · Human clinical evidence

Tier 1. Multiple Phase 3 RCTs in advanced prostate cancer (Leuprolide Study Group 1984, SWOG 9346 / Hussain 2014), endometriosis (Cochrane reviews), central precocious puberty (Carel 2009 consensus), and uterine fibroids (preoperative regimens). FDA-approved formulations include daily SC, monthly depot, and 3-, 4-, and 6-month long-acting depot forms.

§ D · Primary literature

PubMed6436700Leuprolide Study Group et al. — Leuprolide versus diethylstilbestrol for metastatic prostate cancer · New England Journal of Medicine · human-phase-3-rctLeuprolide produced equivalent objective tumour response and survival to DES with significantly fewer thromboembolic and gynecomastia adverse events; pivotal trial supporting US approval of GnRH agonists in advanced prostate cancer.Limitations: Open-label; pre-PSA era endpoints; DES dose (3 mg/day) chosen for efficacy parity rather than tolerability.1984

PubMed19332438Carel JC et al. — Consensus statement on the use of gonadotropin-releasing hormone analogs in children · Pediatrics · reviewInternational consensus on GnRH analog use for central precocious puberty: efficacy in restoring adult height when started before age 6, no consistent long-term effect on BMI or BMD.Limitations: Consensus statement, not a meta-analysis; long-term cardiovascular and bone outcomes still under-characterised at time of publication.2009

PubMed23550669Hussain M et al. — Intermittent versus continuous androgen deprivation in prostate cancer (SWOG 9346) · New England Journal of Medicine · human-phase-3-rctIntermittent androgen deprivation with leuprolide-based regimens was non-inferior on overall survival in metastatic hormone-sensitive prostate cancer with a quality-of-life benefit, but not statistically established as equivalent.Limitations: Long enrolment window; PSA-driven cycling thresholds may not generalise to modern imaging.2013

§ F · Safety signal

Well-characterised class effects: hot flashes, fatigue, decreased libido, erectile dysfunction, bone-mineral-density loss with prolonged use, transient symptom flare in the first 1–2 weeks of treatment from initial gonadotropin surge (clinically managed with antiandrogen pre-treatment in prostate cancer). FDA boxed warning added 2010 for risk of cardiovascular disease and diabetes in men receiving androgen deprivation therapy.

In central precocious puberty, long-term outcome studies show no consistent effect on adult body composition or fertility once treatment is discontinued. In endometriosis, BMD loss is generally reversible within 12–24 months post-treatment; add-back norethindrone or low-dose estrogen is standard for treatment courses beyond 6 months.

§ H · Regulatory status

Regulatory status

FDA status:: FDA-approved
Compounding:: Not eligible for compounding (approved, not in shortage)

§ I · Notable gaps and controversies

Use in adolescents for gender-affirming care is the subject of active regulatory and medical-society debate; as of 2026, several jurisdictions have restricted off-label use in this population while others maintain endorsement under endocrine-society guidelines. Open Assay reports the regulatory status, not a clinical position.

Long-term cardiovascular outcomes from continuous androgen deprivation in prostate cancer remain an active research question — randomised data favour intermittent dosing on quality-of-life grounds, though survival non-inferiority is statistically borderline (SWOG 9346).