Long-Term Progestin-Only Contraceptives Result in Reduced Endometrial Blood Flow and Oxidative Stress

Martha Hickey, G. Krikun, P. Kodaman, S. Frederick, C. Carati, C.J. Lockwood

    Research output: Contribution to journalArticlepeer-review

    40 Citations (Scopus)


    Context: Because of their safety and efficacy, long-term progestin-only contraceptives (LTPOCs) are well-suited for women with restricted access to health care. However, abnormal uterine bleeding (AUB) causes half of all users to discontinue therapy within 12 months. Endometria of LTPOC-treated patients display aberrant angiogenesis with abnormally enlarged, thin-walled, fragile blood vessels, inflammation, and focal hemorrhage. In this study, similar effects were observed with a new third-generation implantable LTPOC.Objective: We hypothesized that LTPOC reduces uterine and endometrial blood flow, leading to hypoxia/reperfusion, which triggers the generation of reactive oxygen species. The latter induce aberrant angiogenesis, causing AUB.Design: Endometrial perfusion was measured by laser-Doppler fluxmetry in women requesting LTPOCs. Endometrial biopsies were obtained for in vivo and in vitro experiments.Setting: The study was conducted in the Yale University School of Medicine and Family-Planning Center in Western Australia.Patients: Seven women 18 yr or older requesting implantable LTPOCs were recruited in Western Australia.Intervention: Women received etonorgestrel implants.Main Outcome: LTPOC treatment resulted in reduced endometrial perfusion and increased endometrial oxidative damage.Conclusions: We propose that LTPOCs result in hypoxia reperfusion, which leads to aberrant angiogenesis resulting in AUB.
    Original languageEnglish
    Pages (from-to)3633-3638
    JournalThe Journal of clinical endocrinology and metabolism
    Issue number9
    Publication statusPublished - 2006


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