Chronic treatment with the gonadotropin-releasing hormone agonist D-Ser(TBU)6-EA10-LRH for contraception in women and men.
The stimulatory analogue of luteinizing hormone-releasing hormone (LRH) D-Ser(TBU)6-EA10-LRH was administered subcutaneously (sc) or intranasally to 10 women with amenorrhea and to 44 healthy female and male volunteers. The LRH agonist evoked a pronounced initial release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but the gonadotropin response decreased during the course of the chronic treatment. Ovulation could not be induced in seven amenorrheic women who were given prolonged treatment with the analogue. In normally ovulating women, ovulation was inhibited during chronic treatment with a daily sc dose of 5 microgram or a daily intranasal dose of 400 microgram. In four healthy men treated with 5 microgram of the LRH agonist daily over 17 weeks basal FSH, LH, and testosterone levels decreased but spermatogenesis and potency were unaffected. The negative effects on testosterone secretion may limit the use of the LRH agonist for male contraception. Chronic intranasal administration of the stimulatory LRH analogue paradoxically inhibited ovulation and proved to be a safe and effective new approach to contraception in women.
D000281:Administration, Intranasal; D000328:Adult; D000568:Amenorrhea / Q000188:drug therapy*; D002064:Buserelin; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D003272:Contraceptive Agents, Male / Q000008:administration & dosage*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D010060:Ovulation / Q000187:drug effects; D010062:Ovulation Induction; D011374:Progesterone / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D003271:Contraceptive Agents, Female; D003272:Contraceptive Agents, Male; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002064:Buserelin