Results of three-times-per-week long-term administration of a luteinizing hormone-releasing hormone (LHRH) analog, d-Ser-(TBU)6-LHRH-(EA)10 in primary amenorrhea

The effectiveness of a luteinizing hormone (LH) -releasing hormone (LHRH) analog, d-Ser-(TBU)6-LHRH-(EA)10 (Hoe 766), applied intranasally in a 3 days-per-week regimen, was assessed in four patients with hypogonadotropic or normogonadotropic primary amenorrhea by measuring LH, follicle-stimulating hormone (FSH), and estradiol (E2) levels before and 4 hours after its application and by observing the clinical effects of these hormones on the genital tract. The LH response increased progressively over the first 21 days (nine applications) in three of the four patients; it was subsequently reduced but never abolished throughout the study, which was terminated with the 25th application on the 59th day. Basal values of E2 increased until the 12th to 14th day (fifth or sixth application) and then showed a definite decline despite the continuing increase in LH response. FSH release attained a maximum by the second to fourth application and its magnitude of response remained remarkably stable thereafter. The clinical response did not correspond to the serum levels of E2. It is postulated that the development of LH unresponsiveness is due to densensitization of the receptors by the analog. The poor response of the genital tissues to the normal levels of E2 and the subsequent decrease in E2 levels, which occurred despite increasing LH responsiveness, are attributed to an inhibitory action of the analog on E2 biosynthesis in the ovary and on E2 receptors in the genital organs.