Abstract
Effects of short and long term administrations of an oral contraceptive preparation on the pituitary responses to the synthetic LH-RH were compared in the present experiment.
Five normal cycling women were used as controls in the late proliferative phase. Five healthy volunteers taking an oral contraceptive agent (1.0 mg norethindrone with 0.05 mg mestranol) for less than 10 cycles were served as short term group and other 4 women taking the same preparation for more than 40 cycles were studied as long term group. Volunteers in each group were kept fasting overnight and 5 ml of blood was drawn at 9 to 10 am on the day of experiment. Ten minutes after drawing blood, 200 μg synthetic LH-RH was injected subcutaneously in the late proliferative phase in the normal cycling women. According to the same procedure, women taking pills were administered LH-RH on the 7th to 12th day after the beginning of taking the first tablet in each cycle. Three ml of blood was taken at 15, 30, 60,120 minutes and 24 hours, and serum LH and FSH were determined by the double antibody radioimmunoassay. The 2nd IRP-HMG was used as the standard materials and expressed as mIU/ml of serum.
Mean baseline serum LH and FSH concentrations were not suppressed in a short term administration of norethindrone-mestranol combination. Fifteen minutes after the subcutaneous injection of LH-RH, mean LH level was significantly elevated, and thereafter the level was not significantly changed as compared with that seen in the late proliferative phase of the cycle. Concerning the FSH response to LH-RH, a short term administration did not induce a significant rise. On the other hand, mean baseline serum LH and FSH concentrations were inhibited in long term use of the agent, and mean LH and FSH levels were always markedly suppressed after the administration of LH-RH. In a short term treatment the mean net increase of LH above the baseline was significantly greater than that of the control at 15 minutes after the injection of LH-RH, but at all other points the mean net increases of LH and FSH following LH-RH were not markedly changed. Moreover, the maximum FSH increase occurred earier than that seen in the late proliferative phase of the cycle. In a long term treatment, the net increases of LH and FSH were significantly lowered as compared with the control.
In terms of percent changes from baseline level, the initial LH release within the first 30 minutes after LH-RH was distinguishable from that in the control group, but thereafter the percent chages in both treated groups and in women in the late proliferative phase were not distinguishable. However, the percent increase over the baseline level of serum FSH after the injection of LH-RH was not significant at all points.
From these results, it was suggested that norethindrone-mestranol combination exerted a direct action on pituitary gonadotropin response to LH-RH. An enhansement of pituitary response to LH-RH may be due to an effect of estrogen or estrogenic activity of norethindrone-mestranol combination. In women treated in a long term, the de-creased response of both LH and FSH was most likely a reflection of an decreased pituitary gonadotropin storage, al least redily releasable component. However, the increment of the percent changes after LH-RH administration was seemed to suggest that a concomitant increase in the sensitivity of the gonadotropin producing cell (especially LH gonadotroph) to LH-RH also existed.
