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Dose-response study with a new LH-RH analogue, D-Ser (TBU)6 LH-RH 1-9 (EA)10 during the follicular phase of the menstrual cycle.

D-Ser (TBU)6 LH-RH 1-9 (EA)10 (HOE 766) a highly active LH-RH analogue, was studied with regard to its effects on the release of follicle stimulating hormone (FSH), luteinizing hormone (LH) and oestradiol-17beta (Oe2) during the follicular phase of the menstrual cycle. Forty-two regularly menstruating women were allowed to five different treatment groups with different doses (1.25 microgram; 2.5 microgram; 5.0 microgram; 10.0 microgram; 20.0 microgram) of HOE 766 given as intravenous bolus injections and the plasma concentrations of FSH, LH and Oe2 were measured up to 24 h after injection using specific radioimmunoassays. In the majority of cases, peak values of both FSH and LH occurred 4 h after injection being significantly different from pre-injection levels (P less than 0.02 in the 1.25 microgram treatment group, P less than 0.005 for the other treatment groups). Statistical analysis of maximum values as well as the absolute and relative increase in the different treatment groups revealed a dose-dependent effect of HOE 766. Maximum values of Oe2 occurred 8 h after injection and were found to be significantly different from pre-injection levels (P less than 0.005). However, no dose dependent effect was observed. It was concluded that HOE 766 is a potent and long-acting stimulator of FSH, LH and OE2 release in women. The effect of HOE 766 is dose dependent for FSH and LH but not for Oe2.