Endometrial angiogenic response in Norplant users

Abstract

The levonorgestrel-releasing subdermal contraceptive implant Norplant is well accepted among Indonesian users, despite the problems with irregular and prolonged menstrual bleeding. Bleeding can be the major reason for women discontinuing their use of Norplant. The causes of endometrial bleeding may include disturbances in endometrial regeneration and angiogenesis. The aim of this study was to investigate endometrial angiogenic activity in Norplant users and to compare it to that in the normal menstrual cycle. The study also aimed to determine the correlation between endometrial angiogenic activity and plasma concentrations of oestradiol, progesterone, sex hormone binding globulin and levonorgestrel, as well as the free levonorgestrel index. The subjects for this study were selected from Norplant users with an exposure of between 3 and 12 months. Endometrial angiogenic response was assayed using an endothelial cell migration assay. Six blood samples to monitor oestradiol and progesterone concentrations were taken during the 2 weeks prior to endometrial biopsy. Samples for the analysis of sex hormone binding globulin and levonorgestrel were taken on the day of biopsy. The results showed that the median score of endometrial angiogenic activity in the 30 women used as controls were significantly higher than the 40 Norplant acceptors (z = -3.80, one tail, P < 0.001). There was no significant correlation between the endothelial migration score and peripheral hormonal concentrations or the free levonorgestrel index in Norplant users. There was no difference in the endometrial angiogenic activity in endometrium with and without bleeding problems. However, it is interesting to note that four Norplant acceptors who had an endothelial cell migration score > or = 1.0 had the lowest free levonorgestrel index.

PIP: A study of 40 Norplant acceptors and 30 controls from Jakarta, Indonesia, demonstrated that use of this contraceptive method reduces angiogenic activity in the endometrium. The endothelial cell migratory activity toward endometrial explants from controls was significantly higher than explants from Norplant users (p 0.001). There was no significant association between the endothelial migration score and peripheral hormonal concentrations or the free levonorgestrel index in Norplant users. Plasma estradiol concentrations in Norplant users fluctuated from 20.00 to 453.54 pg/ml, and there was a nonsignificant trend for lower estradiol concentrations to be associated with amenorrhea. The plasma concentration of levonorgestrel was 0.81 +or- 0.07 nmol/l at 6.20 +or- 0.33 months' duration of Norplant use. There was no difference in the endometrial angiogenic activity in the endometrium on the basis of the presence of prolonged or irregular bleeding/spotting. Of interest was the finding that the 4 Norplant acceptors with an endothelial cell migration score of 1.0 or above had the lowest free levonorgestrel index. This suggests the possibility that the free levonorgestrel index could be used to predict a better endometrial angiogenic response in Norplant users.