Reference data on estrogen metabolome in healthy pregnancy

Area of Science:

• Reproductive endocrinology
• Biochemistry
• Analytical chemistry

Background:

• Estrogen hormones and metabolites are vital for healthy pregnancy and fetal development.
• Abnormal estrogen levels are linked to pregnancy complications like preeclampsia.

Purpose of the Study:

• Develop a comprehensive method to assess the estrogen metabolome during pregnancy.
• Establish reference data for estrogen metabolites across trimesters.
• Investigate unconjugated estrogen fractions and dominant metabolic pathways.

Main Methods:

• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed.
• Samples from 183 healthy pregnant women across three trimesters were analyzed.
• Estrone, 17-beta-estradiol, estriol, and their metabolites were quantified.

Main Results:

• Estrogen levels (estrone, 17-beta-estradiol, estriol) significantly increase with gestational age.
• Levels exhibited wide ranges, complicating the definition of healthy reference ranges.
• Estrone and estriol are predominantly conjugated (<15% unconjugated), while 17-beta-estradiol is largely unconjugated.
• 4-methoxy-estradiol and 17-epiestriol were not detected.

Conclusions:

• Estrogen levels and metabolite profiles change significantly throughout pregnancy.
• The wide variability in measured levels presents challenges for clinical diagnostics.
• 17-beta-estradiol is primarily unconjugated, whereas estrone and estriol are significantly conjugated.
• Specific estrogen metabolic pathways, such as 4-methylation and 17-epimerization, appear negligible.