Endothelial cell dysfunction following prolonged activation of progesterone receptor

J. C. Rodríguez-Manzaneque, M. Graubert, M. L. Iruela-Arispe

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Progestin-only contraceptives are associated with breakthrough bleeding in up to 50% of users. The causes of blood vessel rupture are not well understood. Here we report that both normal and Norplant®-exposed endothelium express progesterone receptor. Experiments performed in vitro on endothelial cells isolated from human endometrium revealed that long-term progesterone exposure leads to suppression of endothelial cell proliferation, inhibition of migration and alteration in the profile of extra-cellular matrix proteins secreted by human endometrial endothelial cells. In addition, we detected increased levels of matrix metalloproteinase-9 in endothelial cultures treated with progesterone. The effect of progesterone on the cell cycle, along with the increased amounts of matrix-degrading enzymes, could account for breakdown of basement membrane components, vascular fragility and consequent vessel rupture leading to breakthrough endometrial bleeding.

Original languageEnglish (US)
Pages (from-to)39-47
Number of pages9
JournalHuman Reproduction
StatePublished - 2000


  • Angiogenesis
  • Endothelial cell
  • Migration
  • Progesterone
  • Proliferation

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine


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