Gonadorelin receptor antagonists

GnRH-like substances that bind to GnRH receptors and lead to an immediate inhibition of GnRH secretion.

The production of sex hormones is subject to a three-stage control loop, which is regulated by negative feedback, among other things. The gonadorelin (gonadotropin-releasing hormone, GnRH; also LHRH or gonadoliberin) formed in the hypothalamus stimulates the formation and secretion of the follicle-stimulating hormone (FSH) and the luteinising hormone (LH) in the anterior pituitary gland. These stimulate the production of testosterone, estrogens and progestins in the testes and ovaries.

Gonadorelin receptor blockers such as the synthetic decapeptides Abarelix and Degarelix offer a new possibility of chemical castration. They competitively block the gonadorelin receptors, causing the rapid reduction of serum levels of LH and FSH, thus lowering testosterone levels to castration levels within a week. In contrast to the gonadorelin agonists, there is no initial testosterone flooding, so a combination with antiandrogens is not necessary.

As the receptors are not changed during treatment, testosterone levels normalise quickly after discontinuation of therapy. As a result, the accompanying symptoms caused by the hormone therapy, such as hot flushes, also subside quickly.

• Abarelix
• Degarelix

• Cetorelix

• Ganirelix

The first gonadorelin antagonist for the treatment of prostate cancer was Abarelix, which was launched in February 2008. Degarelix is a newer active ingredient in the same class of substances. Like Abarelix, Degarelix is indicated for initiating hormonal castration in advanced or metastatic hormone-dependent prostate cancer when androgen suppression is required. Both substances lower serum testosterone levels to castration levels (<50ng/dl) within one week.