DOXYCYCLINE FOR BLEEDING IN PROGESTIN ONLY CONTRACEPTORS

描述（由申请人提供）：临床上，使用仅孕激素避孕的女性中有很高比例发生突破性出血，导致生活方式受损，并导致对该避孕方法的依从性降低。 需要一种有效的、低成本的、易于适应的治疗方法来减少单用避孕药的出血和点滴出血。 与许多其他炎症性疾病一样，具有突破性出血[BTB]和斑点的女性子宫内膜的分子环境含有异常高水平的促炎细胞因子（TNF-α和IL-1 β）和异常高水平的蛋白酶（基质金属蛋白酶[MMPs]和中性粒细胞弹性蛋白酶），其阻止正常组织修复。 多西环素[DOX]是一种廉价的，FDA批准的抗生素，抑制MMP，TACE活性，并减少NO的合成。DOX在牙周和溃疡性疾病的动物模型和临床研究中的治疗益处是由于其对MMPs的抑制，而不是其抗生素作用。 我们预计使用DOX不会降低避孕效果。 我们建议临床评价DOX治疗孕激素避孕药诱导的BTB和斑点，并生化表征DOX治疗患者中发生的子宫内膜分子生物学变化。如果成功，DOX治疗可能成为治疗这种和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.