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Hum. Reprod. Advance Access published online on August 5, 2005
Human Reproduction, doi:10.1093/humrep/dei239
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Received November 2, 2004
Revised June 30, 2005
Accepted July 4, 2005

Article

Influence of different hormonal regimens on endometrial microvascular density and VEGF expression in women suffering from breakthrough bleeding

P.A.W. Rogers 1*, F. Martinez 2, J.E. Girling 1, F. Lederman 1, L. Cann 1, E. Farrell 3, F. Tresserra 2, and N. Patel 4

1 Centre for Women’s Health Research, Monash University Department of Obstetrics & Gynaecology, Monash Medical Centre, Clayton, Victoria 3168, Australia
2 Menopause Clinic, Monash University Department of Obstetrics & Gynaecology, Monash Medical Centre, Clayton, Victoria 3168, Australia
3 Service of Reproductive Medicine, Department of Obstetrics and Gynaecology, Institut Universitari Dexeus, 08017 Barcelona, Spain
4 Genentech, South San Francisco, CA 94080, USA

* To whom correspondence should be addressed.
P.A.W. Rogers, E-mail: peter.rogers{at}med.monash.edu.au


  Abstract

BACKGROUND: The aim of this study was to quantify blood vessel density (BVD) and immunoreactive vascular endothelial growth factor (VEGF) levels in endometrial biopsies taken from women suffering breakthrough bleeding (BTB) under different exogenous hormonal regimes. METHODS: Endometrial biopsies from women in Melbourne with BTB were divided into four groups: combined--continuous hormone therapy (HT) (estrogen and progestin taken daily), cyclical HT (daily estrogen with progestin for 14 days each cycle), progestin-only, or no HT. Subjects from Barcelona were using the Mirena intrauterine levonorgestrel-releasing system for contraceptive purposes, with menstrual diaries for classification into four groups (amenorrhea, infrequent, regular and prolonged). Control biopsies from Melbourne were included in the study. Endometrial samples were immunostained for VEGF and blood vessel localization using an antibody to CD34. RESULTS: Results showed that BVD was significantly reduced in the progestin-only treated group compared with the other three treatment groups (P = 0.028). In addition, all four Mirena BTB groups had significantly reduced BVD compared with controls. Considerable heterogeneity was observed in VEGF immunostaining within and between individual samples with no major differences between HT or Mirena. CONCLUSION: These results provide strong evidence that unopposed progestins reduce endometrial BVD and that there is no link between VEGF immunostaining and BVD or BTB.

Keywords: breakthrough bleeding/endometrium/microvascular density/progestin/VEGF.
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