Original Article
Pancreas, Biliary Tract, and Liver
Rhythmic Fluctuations in Levels of Liver Enzymes During Menstrual Cycles of Healthy Women and Effects of Body Weight

https://doi.org/10.1016/j.cgh.2019.11.047Get rights and content

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.

Section snippets

BioCycle Study

This is a post hoc analysis of data from the BioCycle study, a prospective longitudinal cohort study designed to determine the association of sex hormones with markers of oxidative stress during the menstrual cycle.7 Briefly, 259 healthy premenopausal women, aged 18–44 years, with a regular menstrual cycle were recruited. Exclusion criteria included the use of hormonal contraceptives, pregnancy or breastfeeding, body mass index (BMI) >35 kg/m2, chronic use of medications, alcohol or substance

Participant Characteristics

Two hundred fifty-nine women participated in the BioCycle study. Four participants were excluded from the analysis, one because of persistently elevated liver enzymes consistent with chronic hepatitis and three for transient elevations >100 U/L, consistent with an episode of acute hepatitis. The characteristics of the remaining 255 participants are detailed in Table 1. As expected, women with a higher BMI had significantly higher ALT, ALKP, and triglycerides, as well as a trend for higher

Discussion

Reproductive hormones have been shown to influence organs beyond the reproductive system.8,19, 20, 21, 22 Using data from BioCycle, the largest prospective study investigating multiple biochemical measurements in healthy menstruating women,7 we identified a rhythmic fluctuation of liver enzyme levels during the menstrual cycle that is tightly associated with the fluctuations in sex hormone levels.

We found that ALT and AST peak at the mid-follicular phase and reach a nadir just before

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    Conflicts of interest The authors disclose no conflicts.

    Funding This work and E.F.S. and S.L.M. were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (contract number: HHSN275200403394C, HHSN275201100002I, Task 1 HHSN27500001). C.W.L., S.J., B.N., and Y.R. were supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases.

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    Authors share co-first authorship.

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