Leuprorelin (Leuprolide)

Leuprorelin (leuprolide) is a synthetic nonapeptide GnRH agonist featuring two key modifications from native GnRH: D-leucine substitution at position 6 and replacement of the C-terminal glycine-amide with proline-ethylamide. These changes confer dramatically enhanced receptor binding and metabolic stability.

Like other GnRH superagonists, leuprorelin produces initial pituitary stimulation followed by receptor desensitization with continuous exposure. This biphasic response results in profound suppression of LH, FSH, and downstream sex hormones, achieving medical castration levels of testosterone or estradiol.

Leuprorelin holds FDA approvals for multiple hormone-dependent conditions including advanced prostate cancer, endometriosis, uterine fibroids, and central precocious puberty. Various depot formulations provide sustained release over periods from one month to one year, enabling convenient long-term therapy.

In reproductive medicine research, leuprorelin is used to suppress endogenous gonadotropins during controlled ovarian hyperstimulation, preventing premature ovulation while exogenous gonadotropins stimulate follicular development. This GnRH agonist protocol remains widely used despite the emergence of antagonist alternatives, and research continues to optimize its application in fertility treatment.