GnRH agonist: Wikis


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A gonadotropin-releasing hormone agonist (GnRH agonist) is a synthetic peptide modeled after the hypothalamic neurohormone GnRH that interacts with the gonadotropin-releasing hormone receptor to elicit its biologic response, the release of the pituitary hormones FSH and LH.

GnRH agonists are pregnancy category X drugs.

Contents

Flare effect and downregulation

Agonists do not quickly dissociate from the GnRH receptor. As a result initially there is an increase in FSH and LH secretion (so-called "flare effect").

However after about ten days a profound hypogonadal effect (i.e. decrease in FSH and LH) is achieved through receptor downregulation by internalization of receptors. Generally this induced and reversible hypogonadism is the therapeutic goal.

Agonists with double and single substitutions

GnRH agonists are synthetically modeled after the natural GnRH decapeptide with specific amino acid substitutions typically in position 6 and 10. These substitutions inhibit rapid degradation. Agonists with 2 substitutions include:

  1. leuprolide (Lupron, Eligard)
  2. buserelin (Suprefact, Suprecor)
  3. nafarelin (Synarel)
  4. histrelin (Supprelin)
  5. goserelin (Zoladex)
  6. deslorelin (Suprelorin, Ovuplant)

Triptorelin is an agonist with only a single substitution at position 6.

Administration

These medications can be administered intranasally, by injection, or by implant. Injectables have been formulated for daily, monthly, and quarterly use; and implants can last from 1 to 12 months.

Uses

GnRH agonists are useful in:

Women of reproductive age who undergo cytotoxic chemotherapy have been pretreated with GnRH agonists to reduce the risk of oocyte loss during such therapy and preserve ovarian function. Further studies are necessary to prove that this approach is useful.

Side effects

Side effects of the GnRH agonists are signs and symptoms of hypoestrogenism, including hot flashes, headaches, and osteoporosis. In patients under long-term therapy, small amounts of estrogens could be given back (“add-back regimen”) to combat such side effects and to prevent bone wastage. Generally, long-term patients, both male and female, tend to undergo annual DEXA scans to appraise bone density.

There is also a report that GnRH agonists used in the treatment of advanced prostate cancer may increase the risk of heart problems by 30%[1].

See also

External links

References

  1. ^ http://www.genengnews.com/news/bnitem.aspx?name=63455946&source=genwire "Researchers Suggest Hormone Therapy for Prostate Cancer Can Cause Serious Heart Problems and Death"







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