2-Methoxyestradiol deficiency is strongly related to hypertension in early onset severe pre-eclampsia

Abstract

2-Methoxyestradiol (2ME) deficiency leading to placental insufficiency has been related to pre-eclampsia (PE). Here we investigate whether 2ME is related to clinical profiles and vasoactive factors in early onset severe PE patients. 28 severe PE patients and 20 uncomplicated normal pregnant women, with gestational weeks between 24 and 32weeks, were recruited. All cases and controls had singleton pregnancies and were matched for maternal age, parity, body mass index, and gestational weeks. Plasma levels of 2ME, estradiol (E2), soluble Fms-like tyrosine kinase-1 (sFLT-1), endothelin-1 (ET-1), nitric oxide (NO) were determined. PE patients had significant lower 2ME [906(422-1768) vs. 2032(1400-2910)pg/mL, P=0.002], higher sFLT-1 [5.55(3.24-11.22) vs. 3.13(2.17-5.36)ng/mL, P=0.015] and higher NO [122.40(72.92-168.23) vs. 45.83(25.52-61.46)μmol/L, P=0.0008] levels in their plasma than the controls. In the PE group, plasma 2ME level correlated negatively with systolic pressure (r=-0.48, P=0.012), diastolic pressure (r=-0.52, P=0.007) and mean arterial pressure (r=-0.54, P=0.005) even after controlling for maternal age; 2ME level did not correlate with proteinuria, plasma levels of E2, sFLT-1, ET-1 or NO. In the control group, plasma 2ME level did not correlate with any of the above clinical profiles or laboratory measurements. 2ME levels were markedly lower in early onset severe PE and they correlated inversely with blood pressure only in women with PE. Although we cannot tell whether lower 2ME level is the causation or the result of PE, our study provides clinical evidences that 2ME deficiency is strongly related to hypertension in early onset severe PE patients.