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  • Title: Chronic treatment with the gonadotropin-releasing hormone agonist D-Ser(TBU)6-EA10-LRH for contraception in women and men.
    Author: Nillius SJ, Bergquist C, Wide L.
    Journal: Int J Fertil; 1980; 25(3):239-46. PubMed ID: 6108935.
    Abstract:
    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. D-Ser(TBU)6-EA10-LHRH, the stimulatory analog of luteinizing hormone-releasing hormone (LRH) was given either subcutaneously (s.c.) or intranasally to 2 groups of persons, 10 women with amenorrhea and 44 healthy female and male volunteers, to study its contraceptive effects and side effects after chronic (over 17 weeks) treatment. The analog (LRH agonist) produced a pronounced initial release of follicle stimulating hormone (FSH) and of LH, but as treatment progressed, gonadotropin response decreased. In 7 amenorrheic women, ovulation could not be induced even with prolonged treatment. In normally ovulating women, ovulation was inhibited at daily s.c. doses of 5 mcgm or with daily intranasal doses of 400 mcgm. 4 men treated with 5 mcgm of LHRH agonist daily for more than 17 weeks showed decreased basal FSH, LH, and testosterone levels, but spermatogenesis and potency were unaffected. The paradoxical effect of the LRH agonist (intranasal administration inhibited ovulation in women) indicates this agonist may be useful for human fertility control.
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