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Updated: Aug 8, 2026

An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Long-term progestin-only contraceptives result in reduced endometrial blood flow and oxidative stress
M Hickey1, G Krikun, P Kodaman
1Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06520-8063, USA.
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.
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