Gonadotropin-releasing hormone analogues

Gonadotropin-releasing hormone analogues

Gonadotropin-releasing hormone analogues are used for treat-ment of advanced prostate cancer. They include:

·                 goserelin

·                 leuprolide

·                 triptorelin.

Pharmacokinetics

Goserelin is absorbed slowly for the first 8 days of therapy and rapidly and continuously thereafter. After subcutaneous injection, leuprolide is well absorbed. Neither drug’s distribution, metabo-lism, or excretion is defined clearly.

Pharmacodynamics

Goserelin and leuprolide act on the male’s pituitary gland to increase luteinizing hormone (LH) secre-tion, which stimulates testosterone production. The peak testosterone level is reached about 72 hours after daily administration.

Running the reverse

With long-term administration, however, goserelin and leuprolide inhibit LH release from the pituitary and subsequently inhibit tes-ticular release of testosterone. Because prostate tumor cells are stimulated by testosterone, the reduced testosterone level inhibits tumor growth.

Then there’s triptorelin

Triptorelin is a potent inhibitor of gonadotropin secretion. After the first dose, levels of LH, follicle-stimulating hormone (FSH), testosterone, and estradiol surge transiently. After long-term con-tinuous administration, LH and FSH secretion steadily declines and testicular and ovarian steroid production decreases. In men, testosterone declines to a level typically seen in surgically castrat-ed men. As a result, tissues and functions that depend on these hormones become inactive.

Pharmacotherapeutics

Goserelin, leuprolide, and triptorelin are used for the palliative treatment of metastatic prostate cancer. The drugs lower the testosterone level without the adverse psychological effects of castration or the adverse cardiovascular effects of diethylstilbe-strol.

Drug interactions

No drug interactions have been identified with goserelin, leupro-lide, or triptorelin. (See Adverse reactions to gonadotropin-releasing hormone analogues.)