Acute Effects of a New Stimulatory Luteinizing Hormone-releasing Hormone Analogue D-Ser(TBU)6-EA10-LRH on the Gonadotrophin and Gonadal Steroid Secretion in Women with Amenorrhoea

Abstract

A new stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)⁶-EA¹⁰-LRH was administered subcutaneously in a dose of 10 μg into 10 women with amenorrhoea. The injection resulted in a 20-fold increase of the LH level in blood and a 5-fold increase of the FSH level with maxima at 4 and 6 h after the administration, respectively. There was an evident biphasic pattern of LH release similar to that described after extended pituitary stimulation by constant infusions of LRH with early and late peaks of LH combined with a gradual, progressive FSH release. The duration of the effect on LH and FSH was at least 12 and 24 h, respectively. All the women responded with evident oestradiol increases in blood during the last 18 h of the 24 h study period. A comparison between the effects of a single subcutaneous injection of 10 μg of the LRH analogue and 500 μg of LRH showed that the initial FSH and LH release was similar. However, the FSH and LH release during the remainder of the study period was significantly greater after administration of the analogue and so was the oestradiol increase. Thus, this study in women confirms previous studies in men that D-Ser(TBU)⁶-EA¹⁰-LRH is a potent stimulatory LRH analogue with prolonged biological activity.