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

Abstract

The agonistic analogue of luteinizing hormone-releasing hormone (LRH) D-Ser-(TBU)⁶-EA¹⁰-LRH was given subcutaneously or intranasally to 21 women with longstanding secondary amenorrhoea in an attempt to induce follicular maturation and ovulation. Seven women were given daily subcutaneous injections of 10 /ug of the LRH analogue for 21 days. The pituitary and ovarian responses were monitored by follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol (E₂) and progesterone (P) in serum. A significant increase of the E₂ levels in blood was seen during the first three days of treatment but the E₂ elevations were not sustained. No signs of follicular maturation were detected during the treatment. Intranasal treatment with the LRH agonist was instituted in 14 women. Repeated daily low intranasal spray doses (1–10 /ug) were given. The treatment was continued for 2–4 weeks. Intranasal doses of 5 /ug and below were ineffective in increasing gonadotrophin and gonadal steroid secretion. An initial gonadotrophin release was observed after intranasal doses of 10 /ug and there was a slight increase of the E₂ concentrations in serum during the first 2–3 days. The pituitary responsiveness to the agonist then decreased markedly during the treatment. None of the 14 women showed signs of follicular maturation during or after the treatment. The pituitary desensitization caused by this potent agonistic LRH analogue seems to limit its therapeutic use for treatment of anovulatory infertility.