Rogers P A
Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
Hum Reprod. 1996 Oct;11 Suppl 2:45-50. doi: 10.1093/humrep/11.suppl_2.45.
Disrupted, prolonged and irregular endometrial bleeding are major unwanted side-effects of progestin-only contraceptives. The aim of this paper is to review current information on steroid control of the microvasculature, microvascular heterogeneity and microvascular fragility, with emphasis on the relevance of these issues to the endometrial microvasculature in women receiving Norplant implant contraception. Subjects were either Indonesian women with between 3 and 12 months exposure to Norplant (n = 191) or Caucasian controls recruited in Melbourne, Australia. Norplant endometrium was always thinner than control endometrium, with a varied histology that usually included a basalis-type appearance, signs of haemorrhage and some dilated and congested subepithelial vessels. Thin-walled vessels were seen which could have been either blood vascular or lymphatics. Steroid control of the vasculature can operate through numerous direct and indirect mechanisms, with up to 30 genes relevant to vascular function having consensus oestrogen response elements in their promoter regions. The vasoactive effects of progesterone are less well documented. However, experimental data for direct effects on the endometrial vasculature are mounting. Progestin-induced endometrial breakthrough bleeding is often focal, suggesting that microvascular heterogeneity may be an important factor in understanding this phenomenon. Increased susceptibility to bleeding may result from increased microvascular fragility, possibly as a consequence of progestins altering the balance of angiogenic promoters and inhibitors in the endometrium, thus leaving the vessels in a permanently weakened state.
月经紊乱、经期延长和不规则阴道出血是仅含孕激素避孕药的主要不良副作用。本文旨在综述有关类固醇对微血管的调控、微血管异质性和微血管脆性的现有信息，重点关注这些问题与接受Norplant皮下埋植避孕的女性子宫内膜微血管的相关性。研究对象为暴露于Norplant皮下埋植剂3至12个月的印度尼西亚女性（n = 191）或在澳大利亚墨尔本招募的白人对照者。Norplant皮下埋植剂使用者的子宫内膜总是比对照组薄，组织学表现多样，通常包括基底型外观、出血迹象以及一些扩张和充血的上皮下血管。可见薄壁血管，可能是血管或淋巴管。类固醇对血管系统的调控可通过多种直接和间接机制发挥作用，多达30个与血管功能相关的基因在其启动子区域具有一致的雌激素反应元件。孕酮的血管活性作用记录较少。然而，关于其对子宫内膜血管系统直接作用的实验数据正在增加。孕激素诱导的子宫内膜突破性出血往往是局灶性的，这表明微血管异质性可能是理解这一现象的重要因素。出血易感性增加可能是由于微血管脆性增加，这可能是孕激素改变子宫内膜中血管生成促进因子和抑制因子平衡的结果，从而使血管处于永久脆弱状态。
