Leuprolide Acetate (DB00007): A Comprehensive Pharmacological and Clinical Review

Abstract

Leuprolide acetate is a potent, synthetic superagonist of the gonadotropin-releasing hormone (GnRH) receptor, classified as a small molecule peptide. Its mechanism of action is paradoxical; while it initially stimulates the pituitary-gonadal axis, its continuous, non-pulsatile administration leads to profound receptor downregulation and desensitization. This results in a sustained, reversible state of medical castration, characterized by the suppression of gonadal sex hormones—testosterone in males and estrogen in females. This unique pharmacodynamic profile has established leuprolide as a cornerstone of androgen deprivation therapy (ADT) for the palliative treatment of advanced, hormone-sensitive prostate cancer. Its utility extends into gynecology, where it is a key therapeutic agent for managing endometriosis and uterine fibroids by inducing a hypoestrogenic state. Furthermore, specific pediatric formulations are indicated for the treatment of central precocious puberty, effectively halting premature sexual development. The clinical application of leuprolide has been revolutionized by the development of long-acting depot formulations, which provide sustained drug release over one to six months, enhancing patient compliance and therapeutic consistency. Its safety profile is largely defined by the expected consequences of hormone deprivation, including hot flashes, decreased bone mineral density, and metabolic and cardiovascular risks. Leuprolide is also subject to extensive and often controversial off-label use, including for ovarian suppression in breast cancer, in vitro fertilization protocols, and as a puberty blocker in gender dysphoria. Ongoing research focuses on its role in combination therapies, the development of more convenient formulations, and a deeper understanding of its long-term safety profile, ensuring its continued relevance in modern medici