THE EFFECTS OF PROLONGED ADMINISTRATION OF D‐SER(TBU) 6‐LH‐RH‐EA10 (HOE 766) IN SUBJECTS WITH HYPOGONADOTROPHIC HYPOGONADISM

Publisher Website
Google Scholar
Abstract
SUMMARY: Nine patients with hypogonadotrophic hypogonadism (five due to isolated gonadotrophin deficiency and four due to craniopharyngioma) were treated with daily subcutaneous injections of a long acting LHRH analogue, Hoe 766. Therapy was continued for between 27 and 38 weeks and doses varied between 1–25 and 5 μg per day. At monthly intervals patients were assessed by their LH and FSH response to 100 μg of LHRH and by second hourly sampling for LH, FSH and testosterone for the 24 hours after their Hoe 766 dose. Regardless of the diagnosis or the dose of Hoe 766 the LH response to Hoe 766 and to LHRH deteriorated with increasing duration of therapy. Plasma FSH values became low after only 1 week of therapy and failed to improve. Peak plasma testosterone during therapy correlated with peak plasma LH regardless of the duration of treatment (r = 0±43, P < 0±05, n = 22). Peak plasma LH on LHRH stimulation tests correlated with peak plasma LH on Hoe 766 24 hour studies independently of the length of treatment or the dose of Hoe 766 (r=0±62, P < 0±01, n = 18). In this group of patients peak plasma LH on LHRH stimulation tests did not correlate with basal plasma LH. Throughout the study in all patients testosterone was subnormal at 08.00 h. If testosterone rose after Hoe 766 it did so within the first 12 hours following the injection and had returned to baseline levels by 08.00 h the following day. It is concluded that prolonged daily administration of Hoe 766 within the dose range studied leads to loss of pituitary LH and FSH responses to both Hoe 766 and LHRH. Our results suggest that the loss of LH responsiveness is not due to testosterone feedback inhibition or selective resistance to Hoe 766, but may be explained by depletion of gonadotrophin stores in the pituitary gland.