Overview
Leuprolide is a synthetic nonapeptide analog of gonadotropin-releasing hormone (GnRH) with approximately 80-fold greater potency than the natural hormone. Paradoxically, continuous (non-pulsatile) administration causes GnRH receptor downregulation, leading to profound suppression of LH, FSH, and downstream sex hormones. This mechanism is exploited therapeutically for prostate cancer, endometriosis, uterine fibroids, precocious puberty, and as part of gender-affirming hormone therapy protocols.
Mechanism of Action
Leuprolide initially stimulates GnRH receptors on pituitary gonadotrophs (flare effect), transiently increasing LH and FSH. With continuous exposure, receptor desensitization and downregulation occur within 2-4 weeks, causing sustained suppression of gonadotropin secretion. Testosterone and estradiol fall to castrate levels. The flare effect can be clinically significant in prostate cancer (tumor flare) and is managed with antiandrogen co-administration.
Potential Benefits
- Medical castration for androgen-sensitive prostate cancer
- Endometriosis and uterine fibroid symptom control
- Treatment of central precocious puberty
- Component of gender-affirming protocols
- Fertility treatment (controlled ovarian stimulation protocols)
Research Dosage Notes
The following reflects doses used in published research studies. This is not medical advice.
Depot injection: 3.75 mg/month, 11.25 mg/3 months, or 22.5 mg/6 months formulations. Dose varies by indication.
Amino Acid Sequence
pyroGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt
Side Effects & Safety
- Hot flashes
- Sexual dysfunction (low libido, erectile dysfunction)
- Bone density loss with long-term use
- Initial tumor flare in prostate cancer
- Mood changes, depression
Synergistic Compounds
The following compounds have been studied alongside Leuprolide for potential complementary or synergistic effects:
Learn More
References & Further Reading
- [object Object]
- [object Object]