Rhythmic Fluctuations in Levels of Liver Enzymes During Menstrual Cycles of Healthy Women and Effects of Body Weight

Chunwei Walter Lai; Sneha Jadhav; Basile Njei; Aijun Ye; Jean Wactawski-Wende; Sunni L Mumford; Enrique F Schisterman; Yaron Rotman

doi:10.1016/j.cgh.2019.11.047

Rhythmic Fluctuations in Levels of Liver Enzymes During Menstrual Cycles of Healthy Women and Effects of Body Weight

Clin Gastroenterol Hepatol. 2020 Aug;18(9):2055-2063.e2. doi: 10.1016/j.cgh.2019.11.047. Epub 2019 Dec 4.

Authors

Chunwei Walter Lai¹, Sneha Jadhav¹, Basile Njei², Aijun Ye³, Jean Wactawski-Wende⁴, Sunni L Mumford³, Enrique F Schisterman³, Yaron Rotman⁵

Affiliations

¹ Liver and Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
² Liver and Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut.
³ Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, Maryland.
⁴ Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York.
⁵ Liver and Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. Electronic address: rotmany@niddk.nih.gov.

Abstract

Background & aims: Female sex hormones affect several non-reproductive organs, but little is known about their effects on the liver during a normal menstrual cycle. We aimed to investigate the association between sex hormones and liver enzymes in healthy menstruating women.

Methods: We performed a post-hoc analysis of data from the BioCycle study, a longitudinal cohort study designed to determine the association of sex hormones with markers of oxidative stress during the menstrual cycle. We analyzed data collected from 259 menstruating women, over 1-2 menstrual cycles, who had as many as 16 separate office visits, timed by fertility monitors. Levels of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase (ALKP), bilirubin, and lipids were measured by laboratory assays.

Results: We found a natural cyclic pattern for liver enzymes, with transaminases and ALKP peaking in the mid-follicular phase and reaching a trough in the late luteal phase; the peak to trough differences were 4.0 ± 4.9 U/L for ALT and 8.8 ± 4.0 U/L for ALKP. Levels of ALT were significantly and negatively associated with levels of progesterone on the preceding visit (P = 5x10^-4), whereas level of ALKP was negatively associated with level of estrogen (P = .007) and progesterone (P = 1x10^-11). Food and alcohol intake did not modify the association. The amplitude of ALT fluctuation was greater in African Americans and decreased with age. Fluctuations in levels of ALT were smaller in women with body mass indices >30 kg/m² (P = .03). During menstrual fluctuation, 49% of participants had ALT values both above and below the normal cut-off value (19 U/L).

Conclusions: Levels of liver enzymes fluctuate during the normal menstrual cycle, possibly mediated by progesterone, and the fluctuation varies with age and body mass index. These findings indicate the importance of accounting for phase of menstrual cycle when interpreting liver enzyme measurements in menstruating women.

Keywords: AST; BMI; Estrogen Receptor; Rhythm.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Body Weight
Estradiol*
Female
Humans
Liver
Longitudinal Studies
Menstrual Cycle*

Substances

Estradiol

Abstract

Publication types

MeSH terms

Substances

Grants and funding