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 o-Ser(TBU)6-EA10-LRH was administered subcutaneously in a dose of 10 pg 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 pg of the LRH analogue and 500 pg 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 o-Ser(TBU)6-EA10-LRH is a potent stimulatory LRH analogue with prolonged biological activity.

Reduced Gonadotropin Secretion in Postmenopausal Women During Treatment With a Stimulatory LRH Analogue

“…A single injection of the agonist has been found to result in a pattern of gonadotropin release similar to that found after continuous intravenous infusions (10). The prolonged stimulation by the analogue cannot be regarded as physiological.…”

The effect of D-Trp6-LRH upon secretion of gonadotrophin – a possible therapeutic application in anorexia nervosa

“…These ana¬ logues have found some clinical application in the treatment of hypothalamic amenorrhoea and in¬ duction of ovulation (Nillius et al 1975;Nillius & Wide 1977;Katzorke et al 1980;Bartinos et 1979; Nillius & Wide 1977Nillius et al 1978Schallyetal. 1980).…”

Intranasal LHRH Agonist Treatment for Inhibition of Ovulation in Women: Clinical Aspects

“…Potent LHRH agonists were originally developed for the stimulation of fertility (Schally et al, 1980). When daily injections of the LHRH agonist D-Ser(TBU)6-EA'o-LHRH were given to women with amenorrhoea a great initial gonadotrophin response was found (Nillius & Wide, 1977a). However, during prolonged treatment of amenorrhoeic women the gonadotrophin responsiveness decreased and follicular maturation and ovulation could not be induced by the LHRH agonist (Nillius & Wide, 1977b;Hanker et al, 1978;Skarin et al, 1980).…”

“…When daily injections of the LHRH agonist D-Ser(TBU)6-EA'o-LHRH were given to women with amenorrhoea a great initial gonadotrophin response was found (Nillius & Wide, 1977a). However, during prolonged treatment of amenorrhoeic women the gonadotrophin responsiveness decreased and follicular maturation and ovulation could not be induced by the LHRH agonist (Nillius & Wide, 1977b;Hanker et al, 1978;Skarin et al, 1980). Reduced gonadotrophin responses to daily injections of D-Ser(TBU)6-EA'o-LHRH have also been observed in regularly menstruating women (Dericks-Tan et al, 1977;Nillius et al, 1978).…”