Gonadotropin-releasing hormone agonist

Gonadotropin-releasing hormone agonist
Drug class
Leuprorelin (leuprolide), one of the most widely used GnRH agonists.
Class identifiers
Synonyms	GnRH blockers; GnRH inhibitors; Antigonadotropins
Use	Infertility; Prostate cancer; Precocious puberty; Breast cancer; Endometriosis; Uterine fibroids; Transgender people
Biological target	GnRH receptor
Chemical class	Peptides

A gonadotropin-releasing hormone agonist (GnRH agonist, GnRH–A) 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. However, after the initial "flare" response, continued stimulation with GnRH agonists desensitizes the pituitary gland (by causing GnRH receptor downregulation) to GnRH. Pituitary desensitization reduces the secretion of LH and FSH and thus induces a state of hypogonadotropic hypogonadal anovulation, sometimes referred to as “pseudomenopause” or “medical oophorectomy.”

GnRH agonists are pregnancy category X drugs.

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 of the GnRH agonists are signs and symptoms of hypoestrogenism, including hot flushes, 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%.

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"). Levels of LH may increase by up to 10-fold. However, after about 10 to 20 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.