The effect of progestins on vascular endothelial growth factor, oestrogen receptor and progesterone receptor immunoreactivity and endothelial cell density in human endometrium

Abstract

One common side-effect of contraceptive use is that it often leads to disrupted endometrial bleeding patterns. This may be due to changes in endothelial density and vessel integrity. To investigate whether the level of endometrial immunoreactive vascular endothelial growth factor (VEGF), oestrogen receptor or progesterone receptor (PR) have any role in this, women were treated with either Mircette®, a monophasic oral contraceptive, or Implanon®, a long-acting gestagen, and immunohistochemistry performed. In addition a small number of endometria were studied from women treated with levonorgestrel released from an intrauterine coil. During the untreated normal cycle, there was a significant increase in glandular VEGF immunoreactivity and a significant decrease in PR immunoreactivity in the mid- and late secretory phases compared to the proliferative phase. There was a significant positive correlation between stromal VEGF immunoreactivity and endothelial cell density. This correlation was also apparent during treatment with Implanon, but not with Mircette. Disrupted bleeding patterns were associated with Implanon and to a lesser extent with Mircette. Both contraceptives significantly reduced glandular VEGF immunoreactivity but the intrauterine treatment with levonorgestrel resulted in strong glandular epithelial staining and intense staining of decidualized stromal cells. Implanon significantly increased glandular PR staining, but Mircette significantly reduced stromal PR staining when compared to secretory phase before-treatment biopsies. There were no changes in endothelial cell density or glandular or stromal ER during the normal cycle, or with use of either contraceptive. There was no association of the parameters measured with bleeding patterns or histological category.