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Hormone therapy and endometrial angiogenesis
Sebastian Mirkin1, Francisco Navarro, David F Archer
1The Jones Institute for Reproductive Medicine, CONRAD Clinical Research Center, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA.
Summary
Irregular endometrial bleeding in hormone therapy (HT) users may stem from altered angiogenic factors. Progestins in HT may disrupt the balance of blood vessel growth, leading to bleeding.
Area of Science:
- Reproductive Endocrinology
- Gynecology
- Vascular Biology
Background:
- Irregular endometrial bleeding affects up to 60% of hormone therapy (HT) users, causing treatment discontinuation in a third.
- Aberrant endometrial angiogenesis is a suspected cause of this abnormal bleeding.
Purpose of the Study:
- To investigate the hypothesis that altered expression of angiogenic modulators, vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1), contributes to endometrial bleeding in HT users.
Main Methods:
- In vitro study using Ishikawa cells to assess the effects of 17beta-estradiol, progesterone, and synthetic progestins on VEGF and TSP-1 expression.
- Quantification of VEGF levels and TSP-1 mRNA.
Main Results:
- 17beta-Estradiol increased VEGF expression; progesterone had no effect.
- Synthetic progestins increased VEGF more than 17beta-estradiol.
- Progesterone increased TSP-1 mRNA; 17beta-estradiol had no effect.
- Synthetic progestins had a lower effect on TSP-1 expression compared to progesterone.
Conclusions:
- Progestins in HT may disrupt the balance between pro-angiogenic and anti-angiogenic factors in the endometrium.
- This imbalance could lead to abnormal blood vessel formation (vasculogenesis) and irregular endometrial bleeding.