Reference data on estrogen metabolome in healthy pregnancy.

INTRODUCTION: Estrogen hormones and their metabolites are implicated in the maintenance of healthy pregnancy and adequate fetal development. Abnormal levels were related to increased risk of pregnancy complications, particularly preeclampsia. Our aims were (1) to develop a methodological platform for the comprehensive assessment of estrogen metabolome in pregnancy; (2) to collect healthy reference data for relevant elements of estrogen metabolome in each trimester; (3) to assess unconjugated fractions of the estrogen metabolome, (4) to assess the dominant metabolic pathways of estrogen compounds. METHODS: We enrolled healthy pregnant mothers between gestational week 5-15 (on the confirmation of pregnancy; 79 samples), gestational weeks 19-27 (70 samples), and gestational week 34-39 (54 samples). A method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to assess estrone, 17-beta-estradiol, estriol levels, and their metabolites as conjugated and unconjugated forms. Descriptive statistics were used to characterize the level of compounds in each trimester. RESULTS: Estrone, 17-beta-estradiol and estriol levels are dramatically increasing with the advancement of pregnancy. Measured levels were in a very wide range. 17-beta-estradiol is neither glucuronated nor sulphated. To the contrary, estriol and estrone are significantly conjugated; unconjugated fraction is <15% of total hormone levels in any trimester. Regarding metabolism, 4-methoxy-estradiol and 17-epiestriol were not detected. CONCLUSION: We concluded that (1) the levels of estrogen compounds and metabolites increase with advancing gestational age; (2) the wide ranges of levels challenge the establishment of a healthy reference range for clinical purposes; (3) 17-beta-estradiol is not conjugated significantly; (4) 4-methylation and 17-epimerization pathways of estrogens are negligible with our LC-MS/MS method.

Interrelationship of hemoglobin A1c level lipid profile, uric acid, C-reactive protein levels and age in a large hospital database.

INTRODUCTION: Hemoglobin A1c (HbA1c) is used to monitor glucose homeostasis and to identify risk for diabetes. As diabetic patients are frequently present with dyslipidaemia, low-grade inflammation and hyperuricemia, we tested whether HbA1c levels can be estimated having the information about lipid profile, uric acid (UA) and C-reactive protein (CRP) levels. We developed formulas to describe the association of these parameters with HbA1c levels. METHODS: Data of 9599 male and 10,817 female patients, measured between 2008 and 2018, were analysed. Patients represented a general hospital patient population with overrepresentation of those with elevated HbA1c over 5.6%. The impact of gender, age, CRP, lipid profile and UA levels on HbA1c % on HbA1c levels was tested with multiple linear regression model. The magnitude of effects of individual factors was used to develop formulas to describe the association between HbA1c and other cardiometabolic parameters. With these formulas we estimated median HbA1c values in each age in both gender and compared them to measured HbA1c levels. RESULTS: The developed formulas are as follow: HbA1c (estimated) in women = 0.752 + 0.237*log10(HDL/cholesterol) + 0.156*log10 (cholesterol) + 0.077*log10 (triglyceride) + 0.025*log10(CRP) +0.001*log10 (age) -0.026*log10(HDL/LDL) -0.063*log10 (uric acid)-0.075*log10 (LDL)-0.199*log10(HDL); HbA1c (estimated) in men = 1.146 + 0.08*log10 (triglyceride) + 0.046*log10(CRP) + 0.01*log10 (cholesterol) + 0.001*log10 (age) -0.014*log10(HDL)-0.018*log10(HDL/LDL)-0.025*log10(HDL/cholesterol) -0.068*log10 (LDL)-0.159*log10 (uric acid) Between 20 and 70 years of age, estimated HbA1c matched perfectly to measured HbA1c in. CONCLUSION: At population level, HbA1c levels can be estimated almost exactly based on lipid profile, CRP and uric acid levels in female patients between 20 and 70 years.

Vitamin D Deficiency has no Impact on PSA Reference Ranges in a General University Hospital - A Retrospective Analysis.

BACKGROUND: Vitamin D deficiency has been linked to a higher risk of prostate cancer. We tested the hypothesis that vitamin D levels would have an impact on prostate specific antigen (PSA) levels. METHODS: From our laboratory database we selected 5136 male patients with simultaneously determined vitamin D and PSA levels. Subgroups of several age cohorts with different vitamin D levels were created and PSA 95 percentile values were assessed. The independent effect of vitamin D levels and age on PSA levels was determined with logistic regression. RESULTS: PSA levels increased with age, while no difference was identified in PSA levels in different vitamin D subgroups. CONCLUSION: Vitamin D levels do not have an effect on PSA. Hence, there is no need to adjust PSA reference ranges and threshold values to vitamin D levels during the process of decision making.