GnRH agonists

The development of GnRH agonists has had a major impact on the practice of gynecology and reproductive endocrinology. The clinical usefulness of GnRH agonists will increase as modes of administration are improved and indications become better defined. GnRH agonists and, potentially, antagonists will provide a prompt, effective, and reversible method of suppressing ovarian function. GnRH agonists may soon become a treatment of choice for many of the noncontraceptive uses of oral contraceptives. Current indications for GnRH agonist administration are best divided into two groups: short-term (less than 6 months) and long-term (greater than 6 months) suppression. Short-term administration of GnRH agonist include most of the current usage of GnRH agonists. Short-term administration avoids most of the side effects of GnRH agonist and offers the most potential for development of GnRH antagonists. Short-term therapy has been shown to be particularly effective in the preoperative treatment of fibroids, suppression of ovarian function before ovulation induction, for short-term suppression of endometriosis, and for diagnostic purposes to determine whether a medical illness is related to ovarian function. Chronic administration of GnRH agonist has produced varying degrees of success. The treatment of precocious puberty is probably the perfect indication for GnRH agonist suppression. The disease is completely reversed with a remarkable absence of side effects. Long-term administration for metastatic breast or prostatic cancer has been shown to be as efficacious as other forms of gonadal suppression and the potential benefits of suppression outweigh the potential side effects of long-term suppression. The risk-benefit ratio must be carefully analyzed for the other indications for long-term suppression. Long-term suppression could be used for medical illnesses exacerbated by the menstrual cycle, painful symptoms related to endometriosis, contraception, and suppression of hyperandrogynism. Although initial studies show the agonist to be quite effective in treating all of these disorders, long-term suppression also may result in potential serious side effects related to hypoestrogenism including hot flashes and osteoporosis. Long-term administration of GnRH agonist may become feasible by lowering the dose and degree of suppression or by combining GnRH agonist with estrogen or progestin replacement, or both.