Why does menopausal hormone therapy lead to irregular uterine bleeding? Changes to endometrial blood vessels

Martha Hickey, Dorota A. Doherty, Ian S. Fraser, D. M. Sloboda, Lois A. Salamonsen
In: Human Reproduction · 2008 · vol. 23(4) , pp. 912–918 · doi:10.1093/humrep/dem418 · PMID:18216041 · W2117358269
article OA: bronze CC0 ⤵ 5 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher

Abstract

BACKGROUND: Abnormal bleeding is common in hormone therapy (HT) users. We aimed to determine how HT alters endometrial blood vessels and stromal factors known to regulate vascular growth and integrity. METHODS: Prospective observational study of 165 post-menopausal women in Western Australia. The following were measured in endometrial biopsies: vascular density (vessels/mm(2)), total vessel area (total area enclosed by peripheral vascular immunostaining for perivascular pericytes in mm(2)), total luminal area (mm(2)) and vessel wall area (total vessel area minus luminal area), stromal expression of matrix metalloproteinases (MMP) -1, -3, -9 and -14, their tissue inhibitors (TIMPs) -1-4 and vascular endothelial growth factor (VEGF) by immunohistochemistry. RESULTS: Total vessel area was greater during bleeding compared with HT users with no bleeding (P = 0.028) or with a prior irregular bleeding (P = 0.039). Total vessel area was greater in non-HT users compared with HT users with no bleeding (P = 0.021). In HT users, vessel luminal area was greater during bleeding compared with HT users with no bleeding (P = 0.030) and vessel wall area was also increased (P = 0.025). During bleeding there was an increase in stromal TIMP-2 staining (P = 0.044). No significant changes in endometrial MMP or VEGF were seen. CONCLUSIONS: Abnormal bleeding in HT users is associated with changes in endometrial vessel size and in stromal expression of factors known to regulate vascular growth and integrity. These changes may contribute to abnormal bleeding.

My notes (saved in your browser only)

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (18)

Cited by (5)

Source provenance

openalex
last seen: 2026-05-11T05:53:22.067783+00:00
License: CC0 · commercial use OK