TY - JOUR
T1 - Long-Term Progestin-Only Contraceptives Result in Reduced Endometrial Blood Flow and Oxidative Stress
AU - Hickey, Martha
AU - Krikun, G.
AU - Kodaman, P.
AU - Frederick, S.
AU - Carati, C.
AU - Lockwood, C.J.
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
U2 - 10.1210/jc.2006-0724
DO - 10.1210/jc.2006-0724
M3 - Article
SN - 0021-972X
VL - 91
SP - 3633
EP - 3638
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 9
ER -