DOXYCYCLINE FOR BLEEDING IN PROGESTIN ONLY CONTRACEPTORS

描述(由申请人提供)：临床上，使用仅使用孕激素的避孕方法的妇女中，有很高比例经历了突破性的出血斑点，导致生活方式受损，并导致对这种避孕方法的依从性降低。 需要一种有效、低成本、易于适应的治疗方法，以减少仅使用孕激素避孕药的出血和斑点。 有突破性出血[BTB]和斑点的妇女子宫内膜的分子环境，像许多其他炎症性疾病一样，含有异常高水平的促炎细胞因子(TNF-α和IL-1β)和异常高水平的蛋白水解酶(基质金属蛋白酶[MMPs]和中性粒细胞弹性蛋白酶)，这阻碍了正常的组织修复。 强力霉素[DOX]是FDA批准的一种廉价抗生素，可抑制MMPs、TACE活性，并减少NO的合成。DOX在动物模型和牙周和溃疡性疾病的临床研究中的治疗益处是由于它对MMPs的抑制，而不是它的抗生素作用。 我们预计DOX的使用不会降低避孕效果。 我们建议对避孕药引起的BTB和斑点的DOX治疗进行临床评估，并对DOX治疗患者中发生的子宫内膜分子生物学变化进行生化表征。如果成功，DOX治疗可能成为治疗这种以及可能影响生殖道组织的其他炎症性疾病的重要辅助手段。

DESCRIPTION (provided by applicant): Clinically, a high percentage of women using progestin-only contraception experience breakthrough bleeding spotting that causes impaired lifestyle and results in decreased compliance with this contraceptive method. There is a need for an effective, low-cost, easily adapted treatment to reduce the bleeding and spotting in progestin only contraceptives. The molecular environment of the endometrium of women with breakthrough bleeding [BTB] and spotting, like many other inflammatory disorders, contains abnormally high levels of pro-inflammatory cytokines (TNF-alpha and IL-1beta)and abnormally high levels of proteases (matrix metalloproteinases [MMPs] and neutrophil elastase), which prevent normal tissue repair. Doxycycline [DOX] is an inexpensive, FDA approved antibiotic that inhibits MMPs, TACE activity, and reduces NO synthesis. The therapeutic benefit of DOX in animal models and clinical studies of periodontal and ulcerative diseases is due to its inhibition of MMPs, not to its antibiotic effect. We do not anticipate any reduction in contraceptive efficacy with the use of DOX. We propose to clinically evaluate DOX treatment of progestin-only contraceptive induced BTB and spotting, and to biochemically characterize the endometrial molecular biologic changes that occur in DOX treated patients. If successful, DOX treatment could become an important adjuvant for treatment of this and possibly other inflammatory disorders effecting reproductive tract tissues.