The influence of menopause on the development of hepatic fibrosis in nonobese women with nonalcoholic fatty liver disease
Abstract
We read the article by Yang et al. with great interest concerning the effect of postmenopausal status on the development of hepatic fibrosis.1 There is mounting evidence that menopause accelerates the progression and severity of nonalcoholic steatohepatitis. In their article, Yang et al. concluded that postmenopausal women are at higher risk of severe fibrosis, when compared to premenopausal women, and they concluded that this additional risk was attributable to the decrease in estrogen levels. In this study, the mean body mass index (BMI) was 44.6 and 39.2 for pre- and postmenopausal woman, respectively. These BMIs are also categorized as class III and II obesity, respectively, according to the World Health Organization. It is well known that estrogen is produced from fat cells in addition to the ovaries, which are the primary source of this hormone. This secondary source of estrogen is especially important in postmenopausal women. Indeed, postmenopausal obese women have higher estrogen levels than their nonobese postmenopausal counterparts.2 Because of these facts, reconfirmation of the results reported by Yang et al. in nonobese postmenopausal women may be needed. Therefore, we limited our target population to women with nonalcoholic fatty liver disease (NAFLD) whose BMI was less than 30 and compared the severity of hepatic fibrosis after menopause within this cohort. Utilizing the Japan Study Group of NAFLD (JSG-NAFLD) database,3 419 women with biopsy-proven NAFLD were included and comprised 90 premenopausal and 329 postmenopausal patients. As expected, even in nonobese NAFLD patients, postmenopausal women still had more severe fibrosis, when compared to the premenopausal subjects (P = 0.0266; odds ratio [OR]: 2.173), after adjusting for hepatic inflammation, ballooning hepatocytes, BMI, impaired glucose tolerance/diabetes, and hypertension. Furthermore, this OR may be higher than that found in Yang et al.'s study. Our results reconfirm that postmenopausal women are more susceptible to development of hepatic fibrosis, and this may be caused by decreased levels of estrogen. With the increased incidence of obesity and diabetes globally, Yang et al.'s findings will become of increasing importance. However, the effects of estrogen on hepatic fibrosis may also need to be put in the context of the increasing age of the subjects, because this is a known factor in the development of liver disease. In conclusion, we hope the contents of this letter are useful for validation of the influence of menopause on the development of hepatic fibrosis. Masato Yoneda, M.D., Ph.D.1 Emmanuel Thomas, M.D., Ph.D.1 Yoshio Sumida, M.D., Ph.D.2 Yuichiro Eguchi, M.D., Ph.D.3 Eugene R. Schiff, M.D.1 1Schiff Center for Liver Diseases University of Miami Miller School of Medicine Miami, FL 2Department of Gastroenterology and Hepatology Kyoto Prefectural University of Medicine Kyoto, Japan 3Liver Center Saga Medical School Saga, Japan
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The risk of severe fibrosis is elevated even in normal-weight post-menopausal women with MASLD compared to normal-weight pre-menopausal women with MASLD.
“The risk of severe fi brosis is elevated even in normal-weight post-menopausal women with MASLD compared to normal weight pre-menopausal women with MASLD.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [69]
Cites
Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis
Yang, J. D., Abdelmalek, M. F., Pang, H., Guy, C. D., Smith, A. D., Diehl, A. M., & Suzuki, A. (2014) · Hepatology · doi:10.1002/hep.26761 · Cited by 374 · see citing works
Obesity and reproductive hormone levels in the transition to menopause
Freeman, E. W., Sammel, M. D., Lin, H., & Gracia, C. R. (2010) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e3181cec85d · Cited by 260 · see citing works
Platelet count for predicting fibrosis in nonalcoholic fatty liver disease
Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD), Yoneda, M., Fujii, H., Sumida, Y., Hyogo, H., Itoh, Y., Ono, M., Eguchi, Y., Suzuki, Y., Aoki, N., et al. (2011) · Journal of Gastroenterology · doi:10.1007/s00535-011-0436-4 · Cited by 141 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease
Eslam, M., Sanyal, A. J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., Kleiner, D. E., Brunt, E., Bugianesi, E., Yki-Järvinen, H., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.312 · Cited by 3,286 · see citing works
Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210 · see citing works
Ballestri, S., Nascimbeni, F., Baldelli, E., Marrazzo, A., Romagnoli, D., & Lonardo, A. (2017) · Advances in Therapy · doi:10.1007/s12325-017-0556-1 · Cited by 546 · see citing works
(2024) · Obesity Facts · doi:10.1159/000539371 · Cited by 510 · see citing works
Hutchison, A. L., Tavaglione, F., Romeo, S., & Charlton, M. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.08.030 · Cited by 250 · see citing works
NAFLD and NASH in Postmenopausal Women: Implications for Diagnosis and Treatment
DiStefano, J. K. (2020) · Endocrinology · doi:10.1210/endocr/bqaa134 · Cited by 230 · see citing works
Klair, J. S., Yang, J. D., Abdelmalek, M. F., Guy, C. D., Gill, R. M., Yates, K. P., Ünalp–Arida, A., Lavine, J. E., Clark, J. M., Diehl, A. M., et al. (2016) · Hepatology · doi:10.1002/hep.28514 · Cited by 202 · see citing works
Reproductive Endocrinology of Nonalcoholic Fatty Liver Disease
Grossmann, M., Wierman, M. E., Angus, P., & Handelsman, D. J. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00158 · Cited by 144 · see citing works
Lonardo, A., & Suzuki, A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9051278 · Cited by 129 · see citing works
Brady, C. W. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i25.7613 · Cited by 127 · see citing works
Lee, C., Kim, J., & Jung, Y. (2019) · Cells · doi:10.3390/cells8101259 · Cited by 123 · see citing works
Torre, S. D. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.572490 · Cited by 118 · see citing works
Yang, J. D., Abdelmalek, M. F., Guy, C. D., Gill, R. M., Lavine, J. E., Yates, K. P., Klair, J. S., Terrault, N. A., Clark, J. M., Ünalp–Arida, A., et al. (2016) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2016.07.034 · Cited by 93 · see citing works
Menopause and Non-Alcoholic Fatty Liver Disease: A Review Focusing on Therapeutic Perspectives
Venetsanaki, V., & Pοlyzos, S. A. (2018) · Current Vascular Pharmacology · doi:10.2174/1570161116666180711121949 · Cited by 79 · see citing works
Non-alcoholic fatty liver disease in women – Current knowledge and emerging concepts
Eng, P. C., Forlano, R., Tan, T., Manousou, P., Dhillo, W. S., & Izzi‐Engbeaya, C. N. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100835 · Cited by 72 · see citing works
Tobari, M., Hashimoto, E., Taniai, M., 五十嵐悠一, Kodama, K., Kogiso, T., Tokushige, K., Nishino, T., & Hashimoto, N. (2018) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.14585 · Cited by 66 · see citing works
MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome.
Glintborg, D., & Andersen, M. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-0373 · Cited by 43 · see citing works
The Impact of Estrogen Deficiency on Liver Metabolism: Implications for Hormone Replacement Therapy
Dong, J., Dennis, K. M. J. H., Venkatakrishnan, R., Hodson, L., & Tomlinson, J. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnaf018 · Cited by 52 · see citing works
Gao, Y., Tian, R., Liu, H., Xue, H., Zhang, R., Han, S., Ji, L., Huang, W., Zhan, J., & You, Y. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1939265 · Cited by 43 · see citing works
Menopause and metabolic dysfunction-associated steatotic liver disease
Pοlyzos, S. A., & Goulis, D. G. (2024) · Maturitas · doi:10.1016/j.maturitas.2024.108024 · Cited by 36 · see citing works
Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones
Pafili, K., Paschou, S. Α., Armeni, E., Polyzos, S. A., Goulis, D. G., & Lambrinoudaki, I. V. (2022) · Journal of Endocrinological Investigation · doi:10.1007/s40618-022-01766-x · Cited by 31 · see citing works
Menopausal hormone therapy in women with dyslipidemia and nonalcoholic fatty liver disease
Pοlyzos, S. A., Lambrinoudaki, I. V., & Goulis, D. G. (2022) · HORMONES · doi:10.1007/s42000-022-00369-8 · Cited by 31 · see citing works
Epidemiology, Pathogenesis, and Diagnostic Strategy of Diabetic Liver Disease in Japan
Sumida, Y., Shima, T., Mitsumoto, Y., Katayama, T., Umemura, A., Yamaguchi, K., Itoh, Y., Yoneda, M., & Okanoue, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124337 · Cited by 29 · see citing works
Lin, J., Tsai, K., Chen, K., Su, F., Li, Y.-H., Lin, Y., Han, C., Lin, F., Lin, Y., Hsieh, C.-B., et al. (2018) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530319666181129163802 · Cited by 28 · see citing works
Zhang, X., Mou, Y., Aribas, E., Amiri, M., Nano, J., Bramer, W. M., Kavousi, M., de Knegt, R. J., Asllanaj, E., & Ghanbari, M. (2022) · Genes · doi:10.3390/genes13060966 · Cited by 24 · see citing works
Ntikoudi, A., Spyrou, A., Evangelou, E., Dokoutsidou, E., & Mastorakos, G. P. (2024) · Healthcare · doi:10.3390/healthcare12111081 · Cited by 21 · see citing works
Pummoung, S., Werawatganon, D., Chayanupatkul, M., Klaikeaw, N., & Siriviriyakul, P. (2020) · Antioxidants · doi:10.3390/antiox10010024 · Cited by 21 · see citing works
Hypogonadism and nonalcoholic fatty liver disease
Papadimitriou, K., Mousiolis, A. C., Mintziori, G., Tarenidou, C., Pοlyzos, S. A., & Goulis, D. G. (2024) · Endocrine · doi:10.1007/s12020-024-03878-1 · Cited by 17 · see citing works
DiStefano, J. K. (2023) · Nutrients · doi:10.3390/nu15122670 · Cited by 15 · see citing works
Non-alcoholic fatty liver disease and women's health
Livzan, M. A., Syrovenko, M. I., & Сергеевна, К. Т. (2023) · Russian Medical Inquiry · doi:10.32364/2587-6821-2023-7-5-9 · Cited by 13 · see citing works
Raverdy, V., Chatelain, E., Lassailly, G., Caiazzo, R. J., Vandel, J., Verkindt, H., Marciniak, C., Legendre, B. L., Bauvin, P., Daoud, N. O., et al. (2023) · Obesity · doi:10.1002/oby.23904 · Cited by 12 · see citing works
Yang, C., Chen, S., Feng, B., Lu, Y., Wang, Y., Liao, W., Wu, S., & Wang, L. (2024) · Maturitas · doi:10.1016/j.maturitas.2024.108148 · Cited by 8 · see citing works
Phytoestrogens and NAFLD: Possible Mechanisms of Action
Li, H., Jia, E., Hong, Y. A., Chen, Y., & Jiao, J. (2020) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557520666200103114123 · Cited by 6 · see citing works
Phytoestrogens in NAFLD: Potential Mechanisms of Action
Li, H., Jia, E., & Jiao, J. (2020) · Hormone and Metabolic Research · doi:10.1055/a-1089-7710 · Cited by 5 · see citing works
Stokar, J., & Dresner–Pollak, R. (2026) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.70121 · Cited by 4 · see citing works
The importance of sex dimorphism in liver metabolism and progressive liver diseases
Kočar, E., Cokan, K. B., Kreft, T., Režen, T., & Rozman, D. (2025) · Biology of Sex Differences · doi:10.1186/s13293-025-00811-7 · Cited by 6 · see citing works
Tajiri, K., & Shimizu, Y. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804274-8.00026-6 · Cited by 2 · see citing works
Metabolic dysfunction-associated steatotic liver disease in women across the life course
Okigbo, C. C., Springel, E. H., Blaney, H. L., & Sanyal, A. J. (2026) · The Lancet Obstetrics Gynaecology & Women s Health · doi:10.1016/s3050-5038(26)00177-9 · Cited by 1 · see citing works
Bulatova, I. A., & Shevlyukova, T. P. (2024) · Meditsinskiy sovet = Medical Council · doi:10.21518/ms2024-112 · Cited by 1 · see citing works
Bellentani, S., & Rosso, N. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737860439.793575991
Pummoung, S., Werawatganon, D., & Siriviriyakul, P. (2017) · doi:10.58837/chula.the.2017.368
Hormone replacement therapy for steatotic liver management after surgical menopause
Kobayashi, Y., Yamashita, Y., Kimura, T., Iwadare, T., Okumura, T., Wakabayashi, S., Kobayashi, H., Sugiura, A., Joshita, S., & Umemura, T. (2025) · Clinical Journal of Gastroenterology · doi:10.1007/s12328-024-02090-y
Influence du sexe dans la susceptibilité aux hépatopathies métaboliques
Smati, S. (2019) · theses.fr (ABES) · doi:10.70675/01997f55za990z41e6z96baz8221de2a6281
Menopause Transition: Accelerating Cardiometabolic Risk
Qi, M., & Khoudary, S. R. E. (2026) · Springer eBooks · doi:10.1007/978-3-032-18203-6_7
- Authors
- Yoneda, M., Thomas, E., Sumida, Y., Eguchi, Y., & Schiff, E. R.
- Affiliations
- University of Miami (US)
- Kyoto Prefectural University of Medicine (JP)
- Saga Medical School Hospital (JP)
- Venue
- Hepatology
- Published
- 2014-11
- Volume
- 60
- Issue
- 5
- Pages
- 1792
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2106186648
- Cited by
- 45
- References
- 3
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 3 · 2021: 1 · 2020: 9 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 1
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- menopause, liver fibrosis, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, estrogen, postmenopausal women, non-obese women, body mass index, liver inflammation, diabetes mellitus, impaired glucose tolerance, hypertension, liver biopsy, fibrosis severity
- MeSH terms
- Fatty Liver, Female, Humans, Liver Cirrhosis, Male, Menopause, Severity of Illness Index, Sex Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review