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M. Hickey, G. Krikun, P. Kodaman, Frederick Schatz, C. Carati, C. J. Lockwood, Long-Term Progestin-Only Contraceptives Result in Reduced Endometrial Blood Flow and Oxidative Stress, The Journal of Clinical Endocrinology & Metabolism, Volume 91, Issue 9, 1 September 2006, Pages 3633–3638, https://doi.org/10.1210/jc.2006-0724
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Abstract
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.