Roles of estrogen and progesterone in endometrial hemodynamics and vascular endothelial growth factor production.

BACKGROUND The endometrium becomes receptive to the embryo after sequential actions of estrogen and progesterone. The purpose of this study was to examine the effects of estrogen and progesterone on endometrial hemodynamics and on secretion of vascular endothelial growth factor (VEGF) from endometrial epithelial cells (EEC). METHODS Six early postmenopausal women taking sequential estrogen and progestin [days 1-11: estradiol valerate (estrogen) 2 mg daily; days 12-21: estradiol valerate 2 mg plus norethisterone acetate (progestin) 1 mg daily] were recruited. Three-dimensional power Doppler angiography (3D-PDA) was performed before hormone treatment (phase 0), on days 10-11 of hormone treatment (phase E), and on days 18-20 of hormone treatment (phase E + P). Ishikawa EEC were treated with or without 17-beta-estradiol and progesterone for 24 hours, followed by determination of VEGF concentrations in the supernatants. RESULTS The endometrial volume was significantly increased in phase E and phase E + P as compared with that in phase 0. The vascularization index, flow index, and vascularization flow index in the subendometrial region, as measured by 3D-PDA, were significantly higher in phase E + P than in phase 0, but there were no significant differences in these indices between phase 0 and phase E. While treatment of EEC with 17-beta-estradiol had little enhancing effect on VEGF production, progesterone alone or in combination with 17-beta-estradiol significantly increased VEGF secretion from EEC. CONCLUSION Our data suggested that progesterone could stimulate VEGF secretion from EEC and subsequently increase subendometrial vascularity and blood flow.