2-methoxyestradiol plasma levels are associated with clinical severity indices and biomarkers of preeclampsia

Abstract

We investigated whether clinical severity indices and biomarkers for preeclampsia (PE) are associated with low plasmatic 2-methoxyestradiol (2ME) in the third trimester of gestation. Blood was collected from 53 women with PE and 73 control pregnant women before parturition. The concentration of 2ME was significantly higher in controls than in patients with PE (2906.43 ± 200.69 pg/mL vs 1818.41 ± 189.25 pg/mL). The risk of PE decreased as 2ME levels increased. The 2ME values were negatively correlated with systolic peak arterial pressure and proteinuria in PE. Additionally, those women with PE with lower 2ME had a more serious clinical situation and needed a more aggressive therapy. Finally, 2ME levels (in patients with PE and total population) were significantly correlated with concentrations of soluble fms-like tyrosine kinase 1 and placental growth factor . Summarizing, patients with PE had lower 2ME levels that were correlated with different clinical indices and biomarkers of severity, indicating that 2ME could be taken into account for the clinical management of this syndrome.

Keywords: PlGF; catechol-O-methyltransferase; estrogen; pregnancy; sFlt-1.

Figure 1.

Levels of 2-methoxyestradiol in maternal plasma.The graph shows the mean and 95% confidence interval of 2-methoxyestradiol in maternal plasma in the population with preeclampsia and control population samples. ^# p < .001.

Figure 2.

Frequency distribution of 2-methoxyestradiol. Each bar represents the percentage of the total population in each quartile of 2ME. *P < .05 compared to control pregnancies. **P < .01 compared to control pregnancies.

Figure 3.

Correlation of 2-methoxyestradiol with blood pressure and proteinuria. A, Negative correlation in the preeclamptic population sample between maternal 2ME levels and systolic peak blood pressure (BP; n = 50; r = −.283; P = .047). B, Negative correlation in the population with preeclampsia sample between maternal 2ME levels and proteinuria (n = 34; r = −.212; P = .229).

Figure 4.

Values of 2-methoxyestradiol according to hypertension treatment. The graph shows the mean and 95% confidence interval of 2-methoxyestradiol levels in different groups of hypertension treatment in women with PE. *Significant difference between groups “no treatment” and “oral treatment” compared with “intravenous treatment” (P = .016 and P = .013, respectively).

Figure 5.

Correlation of 2-methoxyestradiol with angiogenic and antiangiogenic factors. A, The positive correlation between maternal plasmatic 2ME levels and maternal serum levels of placental growth factor (PlGF) in the population with preeclampsia sample (n = 50; r = .402; P = .004). B, The negative correlation between maternal plasmatic 2ME levels and maternal serum levels of soluble fms-like tyrosine kinase 1 (sFlt1) in the population with preeclampsia sample (n = 50; r = −.325; P = .021). C and D, The same correlations in the total population sample (n = 116; r = .436; P < .001 and r = −.344; P < .001, respectively).