Gonadotrophin releasing hormone analogues

Close to 700 analogs of luteinizing hormone-releasing hormone (LH-RH) have been made since its sequence was described in 1971. Since all peptide hormones have very transient effects after injection, analog studies have attempted to find compounds which have increased and prolonged activities. Analog studies described here have produced several potent analogs which have been tested in humans. These include (D-Ala6, desGly-NH210)-LH-RH ethylamide, (D-Leu6, desGly-NH210)-LH-RH ethylamide, and (D-Trp6)-LH-RH, all of which promote massive release of gonadotropins, the levels of which can remain elevated for 24 hours in men and women after subcutaneous injection. These powerful compounds have use for inducing ovulation in amenorrheic women and treating oligospermia in men. Though LH-RH is an ideal candidate for developing antagonists since they could represent a relatively safe method of disrupting the reproductive cycle, no inhibitory analogs exist which are powerful enough for extensive clinical use. Several of the most potent inhibitory peptides successfully blocked gonadotropin release and/or ovulation in a number of animal species other than rats. More importantly, 1 inhibitory analog is capable of blocking LH release in normal men after injection of LH-RH. Some branched-chain analogs which block rat ovulation at a single dose of less than .5 mg/kg provide excellent possibilities for further increases in inhibitory activity.