Angiogenesis in abnormal uterine bleeding: a narrative review

Area of Science:

• Reproductive Medicine
• Gynecology
• Vascular Biology

Background:

• Abnormal uterine bleeding (AUB) significantly impacts quality of life and current treatments lack etiological targeting.
• Endometrial-AUB (AUB-E) and iatrogenic-AUB (AUB-I) may stem from abnormal endometrial vascularization, specifically altered angiogenesis and vascular maturation.

Purpose of the Study:

• To investigate the role of angiogenesis and vascular maturation in patients with AUB.
• To hypothesize that aberrant endometrial angiogenesis is a key factor in the etiology of AUB-E and AUB-I.

Main Methods:

• A systematic literature search was conducted across major databases (PubMed, Embase, Web of Science, Cochrane Library) until September 2021.
• Included studies focused on angiogenesis in the endometrium of premenopausal women with AUB-E or AUB-I.
• Study quality was assessed using the Cochrane tool and Newcastle-Ottawa Scale.

Main Results:

• In AUB-E, increased vascular endothelial growth factor A, angiopoietin-1:angiopoietin-2 ratio, and Tie-1 were observed, alongside differential expression of other angiogenic factors.
• Endometrial microvessel density (MVD) was comparable between AUB-E patients and controls.
• AUB-I patients exhibited higher MVD and proangiogenic factor expression, particularly after short-term hormone exposure, with altered vessel maturation noted in both short- and long-term exposures.

Conclusions:

• Aberrant endometrial angiogenesis and impaired vessel maturation are strongly associated with both AUB-E and AUB-I.
• These findings support the hypothesis that altered angiogenesis leads to fragile, permeable vessels, contributing to AUB pathophysiology.
• Targeting angiogenesis alterations presents a potential therapeutic strategy for AUB.