CONTRASTING EFFECTS OF COMBINED AND SEQUENTIAL ORAL CONTRACEPTIVES ON LH-RH-STIMULATED RELEASE OF LH AND FSH AS COMPARED TO MINIPILLS

Abstract

The stimulation of luteinizing hormone (LH) and follicle stimulating hormone (FSH) release from the pitutiary by LH-RH has recently been show n to be impeded in women using oral contraceptives (OCs). It remained to be shown however whether or not the steroid-induced inhibition of gonadotropin release would be influenced by type dosage and duration of application of OCs. We therefore studied the pituitary reaction to stimulation with LH-RH in 42 volunteers taking different types of OCs and in 10 women during the luteal phase of the normal cycle. The tests were performed during the last 3 days of taking the OCs. In some cases the test was repeated during the pill-free interval. In women using a normophasic sequential OC the test was carried out during the 1st and 2nd phase. The standard test dose of 100 mcg synthetic LH-RH (HOE 471) was given as rapid iv injection. In some women 100 and 500 mcg LH-RH respectively were also given as iv infusion over a 3-hour period or as iterative injection. Serum LH and FSH were measured by radioimmunoassay using a double-antibody solid-phase method. In normally cyclic women LH rose in response to the injection from a mean serum level of 1.9 + or - .9 ng/ml to a peak value of 12.9 + or -5.3 ng/ml and FSH from 2.2 + or - 1.6 ng/ml to 5.1 + or -3.8 ng/ml. In 15/18 women using combined OCs the response to LH-RH was found to be severely impeded or completely suppressed. In the remaining 3 cases normal reactions were obtained. Similar results were seen in women using a normophasic preparation. A release of LH and FSH was seen 4-6 days after taking the pill in 3/7 women but in those 3 cases normal reactions had also been obtained while taking the OC. The suppressive effect of OCs could not be overcome to an appreciable degree by iv infusion or iterative injection. In 2/5 women a slight increase in serum LH was found after 3 hours of infusion. Contrary to this a normal reaction to LH-RH was found in 8/12 volunteers using various minipills. In the remaining 4 cases the reaction was somewhat impeded. These results are interpreted as meaning that there is no difference in the suppressive effect of combined and sequential OCs and gonadotropin release seems to be affected by continuous low-dose therapy with progestagens only to a very slight degree. (FULL TEXT)