Charnock-Jones D S, Macpherson A M, Archer D F, Leslie S, Makkink W K, Sharkey A M, Smith S K
Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, UK.
Hum Reprod. 2000 Aug;15 Suppl 3:85-95. doi: 10.1093/humrep/15.suppl_3.85.
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 midand 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.
使用避孕药的一个常见副作用是它常常导致子宫内膜出血模式紊乱。这可能是由于内皮细胞密度和血管完整性的变化所致。为了研究子宫内膜免疫反应性血管内皮生长因子（VEGF）、雌激素受体或孕激素受体（PR）水平是否在此过程中起作用，对妇女分别给予单相口服避孕药米非司酮或长效孕激素依托孕烯进行治疗，并进行免疫组织化学检测。此外，还研究了少量使用宫内节育器释放左炔诺孕酮治疗的妇女的子宫内膜。在未治疗的正常周期中，与增殖期相比，分泌中期和晚期腺VEGF免疫反应性显著增加，PR免疫反应性显著降低。基质VEGF免疫反应性与内皮细胞密度之间存在显著正相关。这种相关性在使用依托孕烯治疗期间也很明显，但在使用米非司酮治疗期间则不明显。出血模式紊乱与依托孕烯有关，与米非司酮的相关性较小。两种避孕药均显著降低腺VEGF免疫反应性，但宫内给予左炔诺孕酮治疗导致腺上皮细胞强烈染色和蜕膜化基质细胞强烈染色。与治疗前分泌期活检相比，依托孕烯显著增加腺PR染色，但米非司酮显著降低基质PR染色。在正常周期或使用任何一种避孕药期间，内皮细胞密度或腺或基质ER均无变化。所测参数与出血模式或组织学类别之间无关联。
