DOXYCYCLINE FOR BLEEDING IN PROGESTIN ONLY CONTRACEPTORS

强力霉素治疗仅使用孕激素的避孕者的出血

• 批准号: 6560253
• 负责人: DAVID Fitzgerald ARCHER
• 金额: $ 24.47万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-27 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6560253
• 关键词: angiogenesis factor; chemoprevention; clinical research; clinical trials; cytokine; drug adverse effect; drug delivery systems; endometrium; enzyme linked immunosorbent assay; female; female antifertility drug; genetic polymorphism; genetic susceptibility; hemorrhage; human therapy evaluation; levonorgestrel; medroxyprogesterone; metalloendopeptidases; microarray technology; patient oriented research; pharmacogenetics; progestins; reproductive system pharmacology; tetracyclines; tissue /cell culture; women's health

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.

描述（由申请人提供）：临床上，使用纯孕激素避孕药的女性中有很高比例会出现突破性点状出血，这会导致生活方式受损，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、易于适应的治疗来减少仅含孕激素的避孕药中的出血和点滴出血。 与许多其他炎症性疾病一样，患有突破性出血 [BTB] 和点滴出血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-1β）和异常高水平的蛋白酶（基质金属蛋白酶） [MMP] 和中性粒细胞弹性蛋白酶），它们会阻止正常组织修复。 多西环素 [DOX] 是一种廉价的、经 FDA 批准的抗生素，可抑制 MMP、TACE 活性并减少 NO 合成。 DOX 在牙周病和溃疡病的动物模型和临床研究中的治疗益处是由于其对 MMP 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。 我们建议对纯孕激素避孕药引起的 BTB 和点滴出血进行 DOX 治疗的临床评估，并对 DOX 治疗患者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疾病以及可能影响生殖道组织的其他炎症性疾病的重要辅助剂。