Marbaix E, Vekemans M, Galant C, Rigot V, Lemoine P, Dubois D, Picquet C, Henriet P, Twagirayezu P, Sufi S, Eeckhout Y, Courtoy P J
Christian de Duve Institute of Cellular Pathology, Department of Pathology, Medical School of the Université catholique de Louvain, Bruxelles, Belgium.
Hum Reprod. 2000 Aug;15 Suppl 3:120-34. doi: 10.1093/humrep/15.suppl_3.120.
Unpredictable endometrial bleeding is the major side-effect of levonorgestrel-releasing s.c. implants (Norplant), otherwise a method of choice for long-term contraception. The mechanisms responsible for bleeding are still unknown and no reliable treatment is available. Several matrix metalloproteinases (MMP) are expressed and activated in human endometrium only at menstruation and specific synthetic inhibitors of MMP fully prevent the tissue breakdown that occurs in menstrual-like endometrial explants. To investigate whether MMP are inappropriately expressed and activated in Norplant-treated endometria during bleeding episodes, volunteers were recruited to provide blood and endometrial biopsies at the start of bleeding episodes and during non-bleeding intervals. Whereas serum concentrations of levonorgestrel and sex hormones showed no change at bleeding, except for a slight decrease of oestradiol concentration, the expression and activation of stromelysin-1 released by explants cultured for 1 day were consistently increased at the start of bleeding episodes. Furthermore, stromelysin-1 was immunolocalized in stromal cells within breakdown areas of several bleeding endometria, but not in non-bleeding endometria. These observations suggest that the expression and activation of stromelysin-1 participate in the initiation of bleeding episodes upon Norplant contraception. New strategies in the prevention and treatment of abnormal bleeding based on MMP control should be envisaged.
不可预测的子宫内膜出血是皮下植入左炔诺孕酮（Norplant）的主要副作用，而皮下植入左炔诺孕酮是长期避孕的一种首选方法。出血的机制尚不清楚，且没有可靠的治疗方法。几种基质金属蛋白酶（MMP）仅在月经期间于人类子宫内膜中表达并被激活，MMP的特异性合成抑制剂可完全阻止类月经子宫内膜外植体中发生的组织分解。为了研究在出血发作期间，MMP在接受Norplant治疗的子宫内膜中是否表达和激活异常，招募了志愿者，在出血发作开始时和非出血间隔期间采集血液和子宫内膜活检样本。尽管在出血时左炔诺孕酮和性激素的血清浓度没有变化，除了雌二醇浓度略有下降外，但培养1天的外植体释放的基质溶素-1在出血发作开始时的表达和激活持续增加。此外，基质溶素-1在几个出血子宫内膜的分解区域内的基质细胞中免疫定位，但在非出血子宫内膜中没有。这些观察结果表明，基质溶素-1的表达和激活参与了Norplant避孕时出血发作的起始过程。应该设想基于控制MMP的预防和治疗异常出血的新策略。
