Inversion of angiogenesis with ethinyl estradiol/dienogest or estradiol valerate/dienogest

В. А. Бурлев, N. A. Ilyasova
In: Problemy reproduktsii · 2022 · vol. 28(4) , pp. 8 · doi:10.17116/repro2022280418 · W4294050819
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⚙ AI-generated summary by claude@2026-06+body, 2026-06-07 ⓘ

This study assessed the inversion of angiogenesis with ethinyl estradiol/dienogest or estradiol valerate/dienogest, focusing on dienogest's antiangiogenic properties.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This paper examined whether combined oral contraceptives containing ethinyl estradiol plus dienogest (Jarin) or dienogest plus estradiol valerate (Klayra) produce “inversion” of angiogenesis by assessing local endometrial microvasculature and systemic circulating angiogenic factors. In a cohort of 130 women (18–49) undergoing contraceptive selection, endometrial tissue and blood were collected before treatment and after 3, 6, and 9 months; investigators used immunohistochemistry for CD31 (microvessel density) and VEGF-A expression, and measured serum VEGF-A and VEGFR1, with additional assessments including uterine/leg Doppler. The authors report that both COCs were acceptable and showed high contraceptive efficacy, with intermenstrual bleeding more common in the groups receiving ethinyl estradiol/dienogest or dienogest/estradiol valerate in specific subgroups, and that microvessel density decreased after 9 months under ethinyl estradiol plus dienogest, with differences also associated with presence vs absence of intermenstrual bleeding. A key limitation is that the study largely focused on women with “eutopic” endometrium without pathological changes and does not provide the randomized, mechanistic clinical proof of causality beyond measured biomarkers. This paper is centrally about endometriosis — it builds its rationale on dienogest’s established antiangiogenic/antiproliferative effects and discusses dienogest’s EU approval for endometriosis, using hormonal contraceptive exposure to evaluate angiogenesis inversion relevant to endometriosis biology.

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