Gonadotropin-releasing hormone antagonist

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Overview

A gonadotropin-releasing hormone antagonist (GnRH antagonist) is a synthetic peptide that competes with the neurohormone GnRH for its receptor, thus decreasing or blocking GnRH action. As a result endogenous pituitary output of FSH and LH is shut down.

GnRH antagonists are also derivatives of the natural GnRH decapeptide with multiple amino acid substitutions. These substitutions modify the agent so that it blocks the receptor and decreases FSH and LH secretions within hours. In contrast to GnRH agonists, antagonists have no flare effect, thus their therapeutic effect is immediately apparent. However, there action is short-lived and daily injections are necessary to maintain their effect. Typically endogenous FSH and LH activity returns about 40 hours after cessation of GnRH antagonist administration, although with a higher dose the return to normal pituitary function will be postponed for longer. Unlike the GnRH agonists, long acting or depot forms of the agent are not currently available, thus GnRH antagonists are not used in the long term therapy of patients with cancer where hormone levels need to be kept low for a long time. As of 2006, Histrelin (as Supprelin-LA) is awaiting approval for use as a 12-month depot injection.

The main application of GnRH antagonists is currently short term use in the prevention of endogenous ovulation in patients who undergo exogenous stimulation with FSH in the preparation for IVF. Typically they are administered in the mid- to late follicular phase in stimulated cycles prior to the administration of hCG. Because they decrease luteal competence, patients are usually given some form of luteal support after egg retrieval.

GnRH antagonists for long term use are under investigation (i.e. abarelix), their advantage over GnRH agonist would be that they lack the initial flare stimulation and induce quickly a hypogonadal situation.

Food and Drug Administration (FDA)-approved medications are used by as injectables:

  1. Abarelix (Plenaxis®)
  2. Cetrorelix (Cetrotide®), by Serono
  3. Ganirelix (Antagon®), by Organon International.

GnRH antagonists are pregnancy category X agents.

See also

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