Abnormal Uterine Bleeding (AUB)

Pathogenesis: Abnormal Uterine Bleeding (AUB)


Key Points

  • 
  • Abnormal uterine bleeding, particularly heavy menstrual bleeding (HMB), is commonly associated with leiomyomas.
  • Submucous leiomyomas located adjacent to the endometrium can impact endometrial hemostasis mechanisms, particularly following the initiation of menses.
  • Leiomyomas secrete vasoactive growth factors that contribute to abnormal hemostasis mechanisms.
  • Abnormal expression of growth factors such as bFGF, EGF, VEGF, PDGF, IGF-1, TGF-β, PTHrP, and prolactin in leiomyomas leads to the proliferation and growth of new blood vessels in the endometrium.
  • Leiomyomas affect the coagulation cascade and thrombolytic factors in the endometrium, resulting in decreased expression of hemostatic factors like PAI-1 and TM.
  • TGF-β3, which is generally overexpressed in leiomyomas, influences smooth muscle proliferation, extracellular matrix deposition, and the hemostatic pathway.
  • Altered regulation of coagulation/anticoagulation mechanisms due to increased endometrial TGF-β3 may contribute to HMB in women with leiomyomas.
  • There may be other mechanisms including localized bleeding from perimyoma vessels


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I. Introduction

A. Prevalence and significance of leiomyomas in patients with abnormal uterine bleeding (AUB)


II. Role of Vasoactive Growth Factors

A. Secretion of vasoactive growth factors by leiomyomas

B. Abnormal expression of growth factors (bFGF, EGF, VEGF, PDGF, IGF-1, TGF-β, PTHrP, prolactin) in leiomyomas

C. Induction of angiogenesis and vasculogenesis in the endometrium

D. Impact on blood vessel proliferation and abnormal hemostasis mechanisms


III. Coagulation Cascade and Thrombolytic Factors

A. Decreased expression of hemostatic factors (PAI-1, TM) in the endometrium

B. Role of TGF-β3 in influencing coagulation/anticoagulation mechanisms

C. Implications for leiomyoma-associated abnormal bleeding


IV. Proximity to the Endometrium

A. Distortion of the endometrial cavity caused by leiomyoma location

B. Hypothesis for leiomyomas contributing to AUB based on proximity to the endometrium

C. Impact of submucous leiomyomas on endometrial hemostasis


V. Therapeutic Implications

A. Importance of understanding the underlying mechanisms for developing targeted treatments

B. Potential therapeutic targets based on the pathogenesis of abnormal uterine bleeding



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