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.
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.
Authors: O Guzeloglu-Kayisli; M Basar; J P Shapiro; N Semerci; J S Huang; F Schatz; C J Lockwood; U A Kayisli Journal: J Clin Endocrinol Metab Date: 2014-07-16 Impact factor: 5.958
Authors: Umit A Kayisli; Murat Basar; Ozlem Guzeloglu-Kayisli; Nihan Semerci; Helen C Atkinson; John Shapiro; Taryn Summerfield; S Joseph Huang; Katja Prelle; Frederick Schatz; Charles J Lockwood Journal: Proc Natl Acad Sci U S A Date: 2015-04-06 Impact factor: 11.205
Authors: Graciela Krikun; C J Booth; L Buchwalder; F Schatz; G Osol; Maurizio Mandala; C J Lockwood Journal: Reprod Sci Date: 2012-01-19 Impact factor: 3.060
Authors: John P Shapiro; Murat Basar; Umit A Kayisli; Ozlem Guzeloglu-Kayisli; S Joseph Huang; Adrian A Suarez; Hatice Gulcin Ozer; Frederick Schatz; Charles J Lockwood Journal: Contraception Date: 2014-11-21 Impact factor: 3.375
Authors: Ozlem Guzeloglu Kayisli; Umit A Kayisli; Murat Basar; Nihan Semerci; Frederick Schatz; Charles J Lockwood Journal: PLoS One Date: 2015-10-05 Impact factor: 3.240