A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatment of hormone-sensitive cancers such as prostate cancer and breast cancer, certain gynecological disorders like heavy periods and endometriosis, high testosterone levels in women, early puberty in children, as a part of transgender hormone therapy, and to delay puberty in transgender youth among other uses. It is also used in the suppression of spontaneous ovulation as part of controlled ovarian hyperstimulation, an essential component in IVF. GnRH agonists are given by injections into fat, as implants placed into fat, and as nasal sprays. Side effects of GnRH agonists are related to sex hormone deficiency and include symptoms of low testosterone levels and low estrogen levels such as hot flashes, sexual dysfunction, vaginal atrophy, penile atrophy, osteoporosis, infertility, and diminished sex-specific physical characteristics. They are agonists of the GnRH receptor and work by increasing or decreasing the release of gonadotropins and the production of sex hormones by the gonads. When used to suppress gonadotropin release, GnRH agonists can lower sex hormone levels by 95% in both sexes. GnRH was discovered in 1971, and GnRH analogues were introduced for medical use in the 1980s. Their nonproprietary names usually end in -relin. The most well-known and widely used GnRH analogues are leuprorelin (brand name Lupron) and triptorelin (brand name Decapeptyl). GnRH analogues are available as generic medications. Despite this, they continue to be very expensive.
Medical uses GnRH agonists are used medically to manage hormone-related conditions such as uterine fibroids and endometriosis, precocious puberty, and hormone-sensitive cancers like prostate and breast cancer, as well as in fertility treatments to control the timing of ovulation. GnRH agonists that have been marketed and are available for medical use include buserelin, gonadorelin, goserelin, histrelin, leuprorelin, nafarelin, and triptorelin. GnRH agonists that are used mostly or exclusively in veterinary medicine include deslorelin and fertirelin. GnRH agonists can be administered by injection, by implant, or intranasally as a nasal spray. Injectables have been formulated for daily, monthly, and quarterly use, and implants are available that can last from one month to a year. With the exception of gonadorelin, which is used as a progonadotropin, all approved GnRH agonists are used as antigonadotropins. The clinically used desensitizing GnRH agonists are available in the following pharmaceutical formulations:
Short-acting injection (once per day): buserelin, histrelin, leuprorelin, triptorelin Long-acting depot injection or injected pellet (once every one to six months): leuprorelin, triptorelin Injected implant (once every one to three months): buserelin, goserelin, leuprorelin Surgically implanted pellet (once per year): histrelin, leuprorelin Nasal spray (two to three times per day): buserelin, nafarelin
Cancer Treatment of cancers that are hormonally sensitive and where a hypogonadal state decreases the chances of a recurrence. Thus they are commonly employed in the medical management of prostate cancer and have been used in patients with breast cancer.
Puberty GnRH agonists are used in puberty treatment primarily to manage precocious puberty (early onset of puberty) by suppressing the release of sex hormones, to slow pubertal progression until an appropriate age. They are also used in gender-affirming care to delay puberty in transgender and non-binary youth, providing time to explore gender identity before irreversible physical changes occur.
Estrogen disorders Management of female disorders that are dependent on estrogen production. Women with menorrhagia, endometriosis, adenomyosis, or uterine fibroids may receive GnRH agonists to suppress ovarian activity and induce a hypoestrogenic state.
Sex hormone treatment Suppressing sex hormone levels in transgender people, especially transgender women. Severe cases of hyperandrogenism, such as in congenital adrenal hyperplasia. As part of the pharmacologic treatment of paraphilic disorders in sexual offenders or men with a high risk of sexual offending.
Fertility treatments A common use of GnRHa is in fertility treatment and assisted reproduction technology. These medications are often used to moderate or reduce increases in luteinizing hormone when a person is preparing for an oocyte retrieval for in vitro fertilization. GNRHa's act as a suppressor of spontaneous ovulation as part of controlled ovarian hyperstimulation, which is an essential component in in vitro fertilisation (IVF). Typically, after GnRH agonists have induced a state of hypoestrogenism, exogenous FSH is given to stimulate ovarian follicle, followed by human chorionic gonadotropins (hCG) to trigger oocyte release. GnRH agonists routinely used for this purpose are: buserelin, leuprorelin, nafarelin, and triptorelin. In addition, GnRHa medications may be used to assist with final maturation induction after having performed controlled ovarian hyperstimulation. Usage of GnRH agonist for this purpose necessitates using a GnRH antagonist instead of a GnRH agonist for suppression of spontaneous ovulation, because using GnRH agonist for that purpose as well inactivates the axis for which it is intended to work for final maturation induction. 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.
Summary of available forms
Contraindications GnRH agonists are pregnancy category X drugs.
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