GONADOTROPIN-RELEASING-HORMONE AGONIST SUPPRESSIVE TREATMENT OF OVARIAN-FUNCTION DECREASES SERUM LH-BETA AND BIOACTIVE LH BUT MAINTAINS ELEVATED LEVELS OF LH-ALPHA

Ten patients with endometriosis were treated by a continuous subcutaneous infusion of the GnRH agonist buserelin for 6 months. Although serum oestradiol decreased into the menopausal range within 2 weeks after starting treatment, serum LH levels as measured by immunoassay remained elevated at least fivefold over baseline during the entire treatment. However, the bioactivity of LH as determined of mouse Leydig cell assay was rapidly lost, changing the mean +/- SEM bioactivity/immunoassay ratio from 2.4 +/- 0.5 before treatment to 0.4 +/- 0.01 after only 1 week of medication. When LH-alpha and LH-Beta immunoreactivities were assessed by specific antibodies, the serum LH-alpha profile was parallel to immunoreactive LH whereas the LH-Beta profile corresponded to the pattern of bioactive LH. LH-alpha was elevated at least tenfold over baseline whereas LH-Beta decreased to less than 35% of pretreatment level. The alpha/Beta ratio shifted from 1.3 +/- 0.2 before treatment to 0.04 +/- 0.06 after 2 weeks of buserelin infusion. Thus in response to continuous buserelin exposure, the gonadotrophin releases excessive amounts of LH having predominant LH-alpha immunoreactivity. The effective loss of LH bioactivity would be related to decreased LH-Beta subunits. The significance of high levels of LH-alpha or possibly modified LH molecules remains to be evaluated during GnRH agonist treatment using well characterized assays.