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

Overview

Journal Clin Gastroenterol Hepatol

Specialty Gastroenterology

Date 2019 Dec 8

PMID 31811951

Citations 1

Authors

Chunwei Walter Lai

Sneha Jadhav

Basile Njei

Aijun Ye

Jean Wactawski-Wende

Sunni L Mumford

Enrique F Schisterman

Yaron Rotman

Affiliations

Soon will be listed here.

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), whereas level of ALKP was negatively associated with level of estrogen (P = .007) and progesterone (P = 1x10). 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/m (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.

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References

Lipson S, Ellison P . Normative study of age variation in salivary progesterone profiles. J Biosoc Sci. 1992; 24(2):233-44. DOI: 10.1017/s0021932000019751. View

Zlotnik A, Gruenbaum B, Mohar B, Kuts R, Gruenbaum S, Ohayon S . The effects of estrogen and progesterone on blood glutamate levels: evidence from changes of blood glutamate levels during the menstrual cycle in women. Biol Reprod. 2010; 84(3):581-6. DOI: 10.1095/biolreprod.110.088120. View

Mumford S, Steiner A, Pollack A, Perkins N, Filiberto A, Albert P . The utility of menstrual cycle length as an indicator of cumulative hormonal exposure. J Clin Endocrinol Metab. 2012; 97(10):E1871-9. PMC: 3674299. DOI: 10.1210/jc.2012-1350. View

Kelley C, Brown A, Diehl A, Setji T . Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. World J Gastroenterol. 2014; 20(39):14172-84. PMC: 4202347. DOI: 10.3748/wjg.v20.i39.14172. View

Yeung E, Zhang C, Albert P, Mumford S, Ye A, Perkins N . Adiposity and sex hormones across the menstrual cycle: the BioCycle Study. Int J Obes (Lond). 2012; 37(2):237-43. PMC: 3361001. DOI: 10.1038/ijo.2012.9. View

Davyduke T, Tandon P, Al-Karaghouli M, Abraldes J, Ma M . Impact of Implementing a "FIB-4 First" Strategy on a Pathway for Patients With NAFLD Referred From Primary Care. Hepatol Commun. 2019; 3(10):1322-1333. PMC: 6771169. DOI: 10.1002/hep4.1411. View

Gaskins A, Wilchesky M, Mumford S, Whitcomb B, Browne R, Wactawski-Wende J . Endogenous reproductive hormones and C-reactive protein across the menstrual cycle: the BioCycle Study. Am J Epidemiol. 2012; 175(5):423-31. PMC: 3282877. DOI: 10.1093/aje/kwr343. View

Ostberg J, Thomas E, Hamilton G, Attar M, Bell J, Conway G . Excess visceral and hepatic adipose tissue in Turner syndrome determined by magnetic resonance imaging: estrogen deficiency associated with hepatic adipose content. J Clin Endocrinol Metab. 2005; 90(5):2631-5. DOI: 10.1210/jc.2004-1939. View

Mumford S, Schisterman E, Gaskins A, Pollack A, Perkins N, Whitcomb B . Realignment and multiple imputation of longitudinal data: an application to menstrual cycle data. Paediatr Perinat Epidemiol. 2011; 25(5):448-59. PMC: 4059763. DOI: 10.1111/j.1365-3016.2011.01204.x. View

10.

Scarpin K, Graham J, Mote P, Clarke C . Progesterone action in human tissues: regulation by progesterone receptor (PR) isoform expression, nuclear positioning and coregulator expression. Nucl Recept Signal. 2010; 7:e009. PMC: 2807635. DOI: 10.1621/nrs.07009. View

11.

Gorczyca A, Sjaarda L, Mitchell E, Perkins N, Schliep K, Wactawski-Wende J . Changes in macronutrient, micronutrient, and food group intakes throughout the menstrual cycle in healthy, premenopausal women. Eur J Nutr. 2015; 55(3):1181-8. PMC: 6257992. DOI: 10.1007/s00394-015-0931-0. View

12.

Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E . Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002; 137(1):1-10. DOI: 10.7326/0003-4819-137-1-200207020-00006. View

13.

Petersen S, Intlekofer K, Moura-Conlon P, Brewer D, Del Pino Sans J, Lopez J . Novel progesterone receptors: neural localization and possible functions. Front Neurosci. 2013; 7:164. PMC: 3776953. DOI: 10.3389/fnins.2013.00164. View

14.

Mumford S, Browne R, Schliep K, Schmelzer J, Plowden T, Michels K . Serum Antioxidants Are Associated with Serum Reproductive Hormones and Ovulation among Healthy Women. J Nutr. 2015; 146(1):98-106. PMC: 4700980. DOI: 10.3945/jn.115.217620. View

15.

Kempe P, Eklund D, Hallin A, Hammar M, Olsson T, Brynhildsen J . Immune profile in relation to sex steroid cyclicity in healthy women and women with multiple sclerosis. J Reprod Immunol. 2018; 126:53-59. DOI: 10.1016/j.jri.2018.02.006. View

16.

Mumford S, Schisterman E, Siega-Riz A, Browne R, Gaskins A, Trevisan M . A longitudinal study of serum lipoproteins in relation to endogenous reproductive hormones during the menstrual cycle: findings from the BioCycle study. J Clin Endocrinol Metab. 2010; 95(9):E80-5. PMC: 2936053. DOI: 10.1210/jc.2010-0109. View

17.

Della Torre S, Mitro N, Fontana R, Gomaraschi M, Favari E, Recordati C . An Essential Role for Liver ERα in Coupling Hepatic Metabolism to the Reproductive Cycle. Cell Rep. 2016; 15(2):360-71. PMC: 4835581. DOI: 10.1016/j.celrep.2016.03.019. View

18.

Rabinowich L, Shibolet O . Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease. Biomed Res Int. 2015; 2015:168905. PMC: 4529891. DOI: 10.1155/2015/168905. View

19.

Bouman A, Heineman M, Faas M . Sex hormones and the immune response in humans. Hum Reprod Update. 2005; 11(4):411-23. DOI: 10.1093/humupd/dmi008. View

20.

Yeung E, Zhang C, Mumford S, Ye A, Trevisan M, Chen L . Longitudinal study of insulin resistance and sex hormones over the menstrual cycle: the BioCycle Study. J Clin Endocrinol Metab. 2010; 95(12):5435-42. PMC: 2999972. DOI: 10.1210/jc.2010-0702. View