Shi Y, Zhang Y, Zhou AD, Zou HY, Wang MM, Xu F, Cai MY. Association between circulating sex hormone levels and diabetic kidney disease in men and postmenopausal women with type 2 diabetes mellitus. World J Diabetes 2025; 16(11): 111366 [DOI: 10.4239/wjd.v16.i11.111366]
Corresponding Author of This Article
Meng-Yin Cai, PhD, Chief Physician, Department of Endocrinology and Metabolism, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou 510630, Guangdong Province, China. caimengyin@mail.sysu.edu.cn
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Endocrinology & Metabolism
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Retrospective Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Nov 15, 2025 (publication date) through Nov 14, 2025
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World Journal of Diabetes
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1948-9358
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Shi Y, Zhang Y, Zhou AD, Zou HY, Wang MM, Xu F, Cai MY. Association between circulating sex hormone levels and diabetic kidney disease in men and postmenopausal women with type 2 diabetes mellitus. World J Diabetes 2025; 16(11): 111366 [DOI: 10.4239/wjd.v16.i11.111366]
World J Diabetes. Nov 15, 2025; 16(11): 111366 Published online Nov 15, 2025. doi: 10.4239/wjd.v16.i11.111366
Association between circulating sex hormone levels and diabetic kidney disease in men and postmenopausal women with type 2 diabetes mellitus
Yi Shi, Yao Zhang, An-Dong Zhou, Hui-Yu Zou, Man-Man Wang, Fen Xu, Meng-Yin Cai
Yi Shi, An-Dong Zhou, Hui-Yu Zou, Man-Man Wang, Fen Xu, Meng-Yin Cai, Department of Endocrinology and Metabolism, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Yao Zhang, Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Zhaoqing Hospital, Zhaoqing 510630, Guangdong Province, China
Co-first authors: Yi Shi and Yao Zhang.
Co-corresponding authors: Fen Xu and Meng-Yin Cai.
Author contributions: Shi Y and Zhang Y contributed to the data analysis and interpretation, and manuscript drafting; they contributed equally to this manuscript and are co-first authors. Shi Y, Zhang Y, Zhou AD, and Zou HY contributed to the data collection; Shi Y, Zhang Y, and Wang MM contributed to the conception and design of the study; Xu F and Cai MY participated in the manuscript revision and editing; they contributed equally to this manuscript and are co-corresponding authors. All authors reviewed and approved the final version of the manuscript. Shi Y and Zhang Y contributed equally to this manuscript and are co-first authors. Xu F and Cai MY contributed equally to this manuscript and are co-corresponding authors.
Supported by the National Natural Science Foundation of China, No. 82270942.
Institutional review board statement: This study was approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University, No. II2024-056-01 Guangzhou, China.
Informed consent statement: Written informed consent was obtained from all participants prior to their involvement in the study.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Meng-Yin Cai, PhD, Chief Physician, Department of Endocrinology and Metabolism, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou 510630, Guangdong Province, China. caimengyin@mail.sysu.edu.cn
Received: July 7, 2025 Revised: August 22, 2025 Accepted: October 22, 2025 Published online: November 15, 2025 Processing time: 132 Days and 11.8 Hours
Abstract
BACKGROUND
Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease. The disease characteristics, morbidity, and renal function progression rate of patients with DKD are all related to sex. This suggests that sex hormones may play an important role in changing renal function in patients with diabetes. There have been only a few studies on the correlation between sex hormones and DKD, which have contradictory conclusions.
AIM
To investigate the relationship between circulating sex hormone levels and DKD in men and postmenopausal women with type 2 diabetes mellitus (T2DM).
METHODS
This retrospective cross-sectional study included 356 patients with T2DM. Pearson or Spearman rank correlation analyses assessed the relationships between sex hormone levels and renal function indices. By adjusting for age, body mass index, systolic blood pressure, diastolic blood pressure, duration of diabetes, use of sodium-glucose cotrasporter-2 inhibitor, use of glucagon-like peptide-1 receptor agonist, hypertension, use of angiotensin-converting enzyme inhibitor/ angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, diabetic retinopathy, diabetic peripheral vascular disease, triglyceride, uric acid, and hemoglobin A1c, multiple linear regression and logistic regression analyses were conducted to identify factors influencing the urinary albumin/creatinine ratio (UACR) and DKD.
RESULTS
In men, dehydroepiandrosterone sulfate levels were inversely associated with log-transformed UACR after adjustment for covariate factors [regression coefficient (β) = -0.691, 95% confidence interval (CI): -1.241 to -0.141 for quartile 4 vs quartile 1; P = 0.006 for trend]. Elevated levels of estradiol were positively associated with DKD [odds ratio (OR) = 3.097, 95%CI: 1.083-8.856 for quartile 4 vs quartile 1; P = 0.041 for trend], and higher luteinizing hormone (LH) levels were similarly associated with DKD (OR = 4.164, 95%CI: 1.30-13.330 for quartile 4 vs quartile 1; P = 0.048 for trend). In postmenopausal women, LH levels were positively correlated with log-transformed UACR and DKD (β = 1.039, 95%CI: 0.284-1.794 for quartile 4 vs quartile 1; P = 0.006 for trend and OR = 15.117, 95%CI: 2.191-104.326 for quartile 4 vs quartile 1; P = 0.004 for trend). Follicle-stimulating hormone (FSH) levels were also positively associated with DKD (OR = 9.588, 95%CI: 1.680-54.709 for quartile 4 vs quartile 1; P = 0.014 for trend).
CONCLUSION
In men with T2DM, elevated levels of estradiol and LH levels were positively associated with increased risk of DKD. In postmenopausal women with T2DM, high FSH and LH levels were positively associated with increased risk of DKD.
Core Tip: This was a retrospective study that comprehensively analyzed the relationship between sex hormones and diabetic kidney disease (DKD) in men and postmenopausal women with type 2 diabetes mellitus. Few studies have focused on the association between gonadal hormones and DKD. In this study, we identified the relationship between gonadotropins and the risk of DKD for the first time and between overall sex hormone levels and DKD, providing a new perspective for the diagnosis and treatment of DKD.
