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  • Title: Ovulation inhibition by daily i.m. administration of a highly active LH-RH analog (d-ser(TBU)6-LH-RH-(1-9)-nonapeptide-ethylamide).
    Author: Baumann R, Kuhl H, Taubert HD, Sandow J.
    Journal: Contraception; 1980 Feb; 21(2):191-7. PubMed ID: 6768492.
    Abstract:
    A highly active LH-RH-analog (D-Ser(TBU)6-LH-RH-(1-9)-nonapeptide-ethylamide = HOE 766) was administered to normally cyclic and ovulatory women in a double-blind study. Each woman received from day 1 through day 14 of the cycle according to a randomization plan either 10 microgram HOE 766 i.m. or a placebo. Ovulation was inhibited for at least two weeks in all subjects receiving HOE 766. The initially very marked release of LH measured 4 hourse after the injection decreased within 3 days by approximately 50%, and remained at this level for the remainder of the experiment while the initially high FSH response was abolished during further treatment. In 3 out of 5 women receiving the analog, serum estradiol was severely suppressed, in the remaining 2 slightly. Within 5 days after the discontinuation of treatment, the pituitary had regained the capacity to respond normally to LH-RH. It is postulated that follicular maturation is disturbed by the unphysiologic pattern of gonadotropin secretion during administration of HOE 766. A LH-RH analog (luteinizing hormone-releasing hormone) was studied in a double-blind trial to test its effectiveness as an ovulation inhibitor. It was administered to 10 healthy female volunteers, aged 22-34 years, with regular, ovulatory cycles. Each volunteer received from Day 1-14 of cycle an intramuscular injection of a coded ampoule by a randomized plan. 3 consecutive cycles were covered in the study; blood samples were drawn for hormone determinations, and basal body temperature data were used to determine ovulation along with the hormonal profiles. HOE 766 (D-Ser(TBU)-LH-RH-(1-9)-nonapeptide-ethylamide) inhibited ovulation for at least 2 weeks in all subjects receiving the agent in the injection (i.e., 5 of 10). Starting at 4 hours postinjection, a marked release of LH (luteinizing hormone) was recorded which decreased within 3 days by approximately 50% and then remained at this level for the remainder of the experiment. FSH (follicle stimulating hormone), however, though initially very high after treatment, was completely abolished for the remainder of the study. Estradiol was severely depressed in 3 of 5 women in the study; 2 women showed slightly depressed estradiol levels. Pituitary capacity returned within 5 days of cessation of intramuscular injections of the LH-RH analog. The mechanism of action is thought to be disruption of follicular maturation caused by the unphysiological pattern of secretion which occurs under HOE 776 therapy.
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