The aim of this study was to present a review of the potential mechanisms involved in the occurrence of endometrial bleeding in postmenopausal women using hormone therapy. Selected literature on the incidence of bleeding in postmenopausal women using estrogen progestogen therapy was reviewed. The incidence of spotting and bleeding in women using continuous-combined hormone therapy was presented. Relevant articles related to the role of angiogenic factors and vasculogenesis in the endometrium, endometrial leukocytes, and endometrial metalloproteinases were used for the review. The cause or etiology of endometrial bleeding with hormone therapy is unknown. Several options are known to alter angiogenesis or be involved in tissue remodeling during normal menstruation. Vascular endothelial growth factor and thrombospondin-1 are proangiogenic and antiangiogenic factors that could cause dysfunction in vasculogenesis that could result in blood vessel fragility and bleeding. The role of pericytes in maintaining vessel morphology and integrity is discussed. Endometrial leukocytes and metalloproteinases are involved in normal menstruation, but their role in postmenopausal bleeding is not clear suggesting involvement of mechanisms in the bleeding. There is limited information on clinical investigation into the etiology of postmenopausal bleeding associated with hormone therapy. The major cause of hormone therapy-related bleeding is unknown. Alterations in angiogenic factors that could result in vascular dysfunction and vessel breakdown provide a working hypothesis as to the potential cause of vessel breakdown.
From The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA.
Received November 18, 2010; revised and accepted December 21, 2010.
Funding/support: None reported.
Financial disclosure/conflicts of interest: D. Archer is a consultant to Pfizer (Wyeth) and Bayer Healthcare. Grants for research were from Pfizer (Wyeth) and Bayer Healthcare.
Presented at the Premeeting Symposium: "Abnormal Uterine Bleeding: Causality, Diagnosis & Management"; October 6, 2010.
Address correspondence to: David F. Archer, MD, 601 Colley Avenue, Norfolk, VA 23507. E-mail: firstname.lastname@example.org