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Leuprolide

Leuprolide

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GnRH agonist decapeptide used for androgen deprivation therapy via pituitary desensitization; FDA-approved for prostate cancer, endometriosis, uterine fibroids, central precocious puberty, and breast cancer.

Quick Facts

Property Value
Also Known As Leuprorelin, Lupron, Lupron Depot, Eligard, Viadur, Fensolvi
Category GnRH Agonist / Sexual Health / Reproductive
Sequence pyroGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt
Molecular Weight ~1209 Da
Molecular Formula C59H84N16O12
PubChem CID 5311191
Administration SubQ / IM depot (monthly, 3-month, 4-month, 6-month formulations)
Typical Dose Range 3.75 mg monthly / 7.5 mg monthly / 11.25 mg q3mo / 22.5 mg q3mo / 30 mg q4mo / 45 mg q6mo (depot)
Half-Life ~3 hours (free peptide); depot formulations provide sustained release over weeks to months
Storage Depot formulations at room temperature or refrigerated per manufacturer; reconstitute immediately before injection
FDA Status Approved (1985) — Lupron/Lupron Depot for prostate cancer, endometriosis, uterine fibroids, central precocious puberty; Eligard for prostate cancer; Fensolvi for central precocious puberty
WADA Status Not prohibited (FDA-approved medication)

Mechanism of Action

Leuprolide is a synthetic GnRH agonist that is approximately 80-fold more potent than native GnRH (gonadorelin). It acts on the anterior pituitary GnRH receptors (GnRHR) to produce an initial stimulatory phase ("flare") followed by sustained pituitary desensitization and downregulation of GnRH receptors.

Upon initial administration, leuprolide stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary, causing a transient increase in gonadal steroid production (testosterone in males, estradiol in females). This "flare" effect typically lasts 1-3 weeks. With continuous administration, the sustained agonist exposure causes internalization and downregulation of GnRH receptors on pituitary gonadotroph cells, leading to a dramatic decline in LH and FSH secretion.

The resulting hypogonadal state achieves castrate levels of testosterone (<50 ng/dL) in men within 2-4 weeks and suppresses estradiol to postmenopausal levels in women. The D-Leu6 substitution confers resistance to enzymatic degradation, and the ethylamide C-terminal modification enhances receptor binding affinity. Depot formulations use biodegradable polymer microspheres or in situ gelling systems to provide sustained drug release over 1-6 months (PMID: 10744594).

Key Research Areas

  1. Prostate cancer androgen deprivation — Established as equivalent to bilateral orchiectomy for advanced prostate cancer in multiple RCTs and meta-analyses, with equivalent survival outcomes (PMID: 10744594)
  2. Endometriosis pain management — Reduces endometriosis-associated pelvic pain by inducing a hypoestrogenic state; comparable efficacy to continuous oral contraceptives in RCTs (PMID: 21300339)
  3. Uterine fibroids — Preoperative shrinkage of fibroids and symptomatic relief via estrogen suppression
  4. Central precocious puberty — Delays puberty progression by suppressing the HPG axis in children with premature activation
  5. Breast cancer — Ovarian suppression in premenopausal hormone receptor-positive breast cancer (typically combined with tamoxifen or aromatase inhibitors)
  6. Comparative GnRH agonist equivalence — Systematic reviews confirm no significant efficacy differences among leuprolide, goserelin, and triptorelin for prostate cancer (PMID: 29438592)

Evidence Level Summary

Evidence Type Count Notes
Systematic reviews 2 Meta-analysis of LHRH agonists; GnRH agonist equivalence review
Human RCTs 1 Leuprolide vs oral contraceptives for endometriosis
Human observational 0 —
Animal in vivo 0 —
In vitro 0 —

Clinical Applications

  • Cancer Adjunct Therapy — First-line androgen deprivation therapy for advanced prostate cancer; ovarian suppression for premenopausal breast cancer
  • Sexual Health — Suppression of gonadal hormones for hormone-dependent conditions
  • Endometriosis — Pain management via estrogen suppression (typically limited to 6-12 months due to bone loss)
  • Fertility — Ovarian stimulation protocols in assisted reproduction (short-term agonist use for flare protocols)

Protocols Using This Peptide

  • No current vault protocols use leuprolide (FDA-approved prescription medication, not a research peptide)

Ageless Peps Products

  • Not sold by Ageless Peps. Leuprolide is an FDA-approved prescription medication available only through licensed pharmacies.

Dosing Reference

FDA-Approved Dosing

Indication Dose Route Frequency Duration Source
Prostate cancer 7.5 mg or 22.5 mg or 45 mg IM/SubQ depot Monthly / q3mo / q6mo Ongoing FDA label
Endometriosis 3.75 mg or 11.25 mg IM depot Monthly / q3mo 6 months max (without add-back) FDA label
Uterine fibroids 3.75 mg or 11.25 mg IM depot Monthly / q3mo 3-6 months preoperatively FDA label
Central precocious puberty 7.5-15 mg IM depot Monthly Until appropriate age for puberty FDA label

Cycling

Not applicable in the traditional peptide cycling sense. Leuprolide is used continuously for cancer indications. For endometriosis, treatment is typically limited to 6 months (or up to 12 months with norethindrone add-back therapy) due to bone mineral density loss. Intermittent ADT strategies with planned treatment breaks are used in some prostate cancer protocols.

Contraindications & Safety

  • Contraindications: Pregnancy (Category X — causes fetal harm), undiagnosed vaginal bleeding, hypersensitivity to GnRH or GnRH agonists
  • Common side effects: Hot flashes (>50%), injection site reactions, headache, decreased libido, erectile dysfunction (males), vaginal dryness (females), mood changes, fatigue
  • Serious adverse effects: Bone mineral density loss (with prolonged use), testosterone flare (first 1-3 weeks — can worsen symptoms in prostate cancer), cardiovascular events, QTc prolongation (rare), pituitary apoplexy (very rare in patients with pituitary adenomas)
  • Drug interactions: May reduce efficacy of drugs dependent on gonadal hormones; avoid concurrent use with QTc-prolonging medications
  • Pregnancy/nursing: Contraindicated (Category X); contraception required during treatment
  • Special populations: Monitor bone mineral density with use >6 months; add-back therapy (norethindrone 5 mg daily) recommended for endometriosis treatment beyond 6 months; use with caution in patients with cardiovascular disease

Synergistic Combinations

  • Goserelin — Same drug class; not used in combination but provides alternative GnRH agonist option
  • Degarelix — GnRH antagonist alternative; switching from leuprolide to degarelix avoids need for anti-androgen flare protection
  • Relugolix — Oral GnRH antagonist alternative with potentially improved cardiovascular profile

Related Research

PMID Title Year Study Type
10744594 Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis 2000 Systematic Review
21300339 Randomized trial of leuprolide versus continuous oral contraceptives for endometriosis-associated pelvic pain 2011 RCT
29438592 Are all GnRH agonists equivalent for prostate cancer? A systematic review 2018 Systematic Review

References

Related

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