GnRH Analogs

Gonadotropin releasing hormone (GnRH) is a hormone that is released from the hypothalamus and promotes production and release of the gonadotropins (LH and FSH) from the pituitary gland. A number of “analogs” have been produced that share some properties of the native GnRH, but have a prolonged time of action. There are two types of analogs, agonists and antagonists. Antagonists directly block the action of GnRH. There are several of these under development, but none currently marketed in the U.S. Their side effects have been troublesome. Agonists first stimulate the release (called a flare) of GnRH, then block. There are three agonists used in the United States, Lupron, Zoladex and Synarel. Their action is identical, but they differ in route of administration; monthly to tri-monthly injection, implant, or daily nasal spray. By blocking GnRH and subsequently LH release, follicle growth is inhibited and estrogen, an androgen, production is markedly reduced. The side effects are those of menopause, including hot flushes and reversible reduction in bone density. Adrenal androgen production is unaffected. While quite a good therapy for suppression of the ovary and its abnormal hormonal production of PCOS, the high cost and undesirable side-effects limit GnRH use. The side effects can be reduced when estrogen and progestins, either separately, or in combination as an oral contraceptive, are given in addition to the analog. This “add back” therapy offers additional advantages of increasing SHBG, reducing the risk of osteoporosis and symptoms of menopause. A great disadvantage remains in the high cost of this regimen.

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