Leuprolide is a synthetic analog of gonadotropin-releasing hormone, or GnRH. It has notably different functions depending on how it is administered to patients. When administered in a short pulsatile fashion, leuprolide acts as an agonist or activator of GnRH receptors and increases the production of FSH and LH. This increase in FSH and LH increases downstream sex hormone synthesis and can be used in the treatment of infertility and hypogonadism. In contrast, when leuprolide is administered in a long continuous fashion, it acts as its antagonist or blocker at GnRH receptors and decreases the production of FSH and LH.  This ultimately reduces sex hormone synthesis.

Key Points

  • Leuprolide
    • Goserelin and its related drugs (nafarelin, histrelin) also act similarly
    • Mechanism
      • Long-acting GnRH agonist
        • Synthetic GnRH analog that acts on the pituitary gland
    • Clinical Use
      • When given in a pulsatile fashion increases LH/FSH production
        • Initial administration of a continuous dose can also cause a transient rise in LH and sex hormones
        • Used for infertility
      • When given continuously decreases LH/FSH production
        • Decreases testosterone and estrogen
          • Useful for uterine fibroids, endometriosis, precocious puberty, and hormone-dependent cancers (prostate, breast)
    • Adverse Effects
      • Antiandrogen effects
        • Hot flashes, erectile dysfunction, decreased libido, hypogonadism, menstrual irregularities
      •  Nausea, vomiting