Association between circulating sex hormone levels and diabetic kidney disease in men and postmenopausal women with type 2 diabetes mellitus

doi:10.4239/wjd.v16.i11.111366

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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

Retrospective Study

World J Diabetes. Nov 15, 2025; 16(11): 111366
Published online Nov 15, 2025. doi: 10.4239/wjd.v16.i11.111366

Table 1 Clinical characteristics of patients classified by renal function and sex, n (%)

	Men (n = 249)			Women (n = 107)
	With DKD (n = 73)	Without DKD (n = 176)	P value	With DKD (n = 34)	Without DKD (n = 73)	P value
Baseline information
Age, year	55.11 ± 13.50	52.45 ± 13.26	0.153	66.32 ± 9.13	61.59 ± 8.32	0.009^a
Height, cm	168 (10.5)	170 (9.5)	0.017^a	156.5 (6.5)	158 (7)	0.609
Weight, kg	70.65 (16.56)	69.3 (16.8)	0.7	55.86 ± 9.30	60.07 ± 11.29	0.061
BMI, kg/m²	25.17 (4.93)	24.4 (4.55)	0.054	23.59 (6)	24.5 (4.39)	0.103
SBP, mmHg	128.5 (29.5)	124 (22.5)	0.371	132.29 ± 21.83	131.34 ± 17.52	0.81
DBP, mmHg	83.82 ± 13.24	82.7 ± 10.85	0.487	76.18 ± 12.51	80.27 ± 10.53	0.081
Duration of T2DM, year	13.5 (11.75)	7.5 (8.25)	0.497	13.5 (11.75)	7.5 (8.25)	0.000^a
Current drinking	36 (49.3)	81 (46.0)	0.636	0	0
Current smoking	13 (17.8)	37 (21.0)	0.564	1 (2.9)	4 (5.5)	0.489
Hypertension	42 (57.5)	57 (32.4)	0.000^a	20 (58.8)	28 (38.4)	0.047^a
Antihypertensive therapy
Use of ACEI/ABR/ARNI	28 (38.4)	32 (18.2)	0.001^a	11 (32.4)	17 (23.3)	0.321
Hypoglycemic therapy
Use of biguanides	34 (46.6)	86 (48.9)	0.742	16 (47.1)	34 (46.6)	0.963
Use of DPP-ⅣI	15 (20.5)	39 (22.2)	0.779	10 (29.4)	12 (16.4)	0.122
Use of SGLT-2I	18 (24.7)	48 (27.3)	0.67	10 (29.4)	12 (16.4)	0.122
Use of GLP-1RA	2 (2.7)	6 (3.4)	0.569	1 (2.9)	0	0.318
Use of insulin	19 (26)	40 (22.7)	0.577	11 (32.4)	14 (19.2)	0.134
Diabetes-related complications
CAD	16 (21.9)	23 (13.1)	0.08	8 (23.5)	7 (9.6)	0.053
Peripheral vascular disease	57 (78.1)	121 (68.8)	0.138	31 (91.2)	52 (71.2)	0.021^a
Retinopathy	20 (27.4)	10 (5.7)	0.00¹	11 (32.4)	7 (9.6)	0.003^a
Peripheral neuropathy	44 (60.30)	85 (48.3)	0.085	26 (76.5)	45 (61.6)	0.131
Autonomic neuropathy	26 (35.6)	56 (31.8)	0.562	12 (35.2)	23 (31.5)	0.697
Diabetic foot	2 (2.7)	1 (0.6)	0.206	1 (2.9)	0	0.318
Laboratory indexes
HbA1c	9,1 (7,10.68)	8.5 (6.9,10.4)	0.727	9.55 (2.52)	8.2 (1.93)	0.1
TC, mmol/L	4.7 (1.78)	4.41 (1.64)	0.409	5.18 ± 1.45	4.80 ± 1.11	0.133
TG, mmol/L	1.81 (1.94)	1.4 (1.26)	0.023^a	1.86 (1.09)	1.69 (1.28)	0.218
LDL-C, mmol/L	2.64 (1.80)	2.8 (1.44)	0.47	3.20 ± 1.19	2.93 ± 1.01	0.223
HDL-C, mmol/L	0.93 (0.28)	0.93 (0.3)	0.201	1.07 (0.29)	1.04 (0.26)	0.928
UA, mol/L	430.66 ± 109.886	374.31 ± 97.411	0.000^a	389.10 ± 153.42	349.42 ± 89.48	0.175
Fasting C-peptide, ng/mL	0.65 (0.51)	0.53 (0.41)	0.008^a	0.61 (0.68)	0.6 (0.36)	0.363
Sex hormones
Testosterone, nmol/L	16.85 (10.89)	16.56 (10.00)	0.749	0.78 (0.4)	0.81 (0.44)	0.913
DHEAS, mol/L	3.73 (3.93)	3.96 (3.04)	0.775	2.08 ± 1.21	2.04 ± 1.38	0.891
Androstenedione, nmol/L	3.33 (3.30)	3.28 (3.2)	0.565	1.57 (1.76)	1.28 (1.41)	0.295
E2, pmol/L	119 (69.75)	104 (54.5)	0.008^a	46 (27)	37 (14)	0.085
LH, mIU/mL	5.27 (3.69)	4.31 (3.47)	0.016^a	23.85 (27.33)	15.97 (9.48)	0.000^a
FSH, mIU/mL	6.57 (5.62)	6.7 (6.51)	0.541	59.58 (29.77)	45.45 (19.51)	0.000^a
Renal function indexes
BUN, mmol/L	6.35 (3.3)	5.62 (2.01)	0.000^a	7.40 (4.57)	5.35 (1.73)	0.000^a
Creatinine, mol/L	81.7 (49.8)	65.1 (16.2)	0.000^a	76 (56.85)	51.35 (14.33)	0.000^a
eGFR	90.69 (51.60)	104.92 (21.5)	0.000^a	69.75 (54.51)	98.89 (13.01)	0.000^a
CysC, mg/L	1.19 (0.59)	0.99 (0.24)	0.000^a	1.33 (1.04)	0.97 (0.24)	0.000^a
UACR, mg/g	111.52 (467.92)	12.84 (8.59)	0.000^a	167.85 (847.44)	17.32 (10.61)	0.000^a
24hUARE, mg/24 hours	115.5 (269.1)	13.9 (7.3)	0.000^a	80.8 (275.45)	11.95 (6.48)	0.000^a

^aP < 0.05.

24hUARE: 24-hour urinary albumin excretion rate; ACEI: Angiotensin-converting enzyme inhibitor; ACR: Albumin creatinine ratio; ARB: Angiotensin receptor blocker; ARNI: Angiotensin receptor-neprilysin inhibitor; BMI: Body mass index; BUN: Blood urea nitrogen; CAD: Coronary artery disease; CysC: Cystatin C; DBP: Diastolic blood pressure; DHEAS: Dehydroepiandrosterone sulfate; DKD: Diabetic kidney disease; DPP-IVI: Dipeptidyl peptidase-IV inhibitor; E2: Estradiol; eGFR: Estimated glomerular filtration rate; FSH: Follicle-stimulating hormone; GLP-1RA: Glucagon-like peptide-1 agonist; HDL-C: High density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol; LH: Luteinizing hormone; SBP: Systolic blood pressure; SGLT-2I: Sodium-glucosecotrasporter-2 inhibitor; T2DM: Type 2 diabetes mellitus; TC: Total cholesterol; TG: Total triglyceride; UA: Uric acid.

Full Size Table

Table 2 Correlation between sex hormones and renal function indexes in men with type 2 diabetes mellitus

r	BUN	Creatinine	eGFR	CysC	UACR	24-hour UARE
Testosterone	0.042	0.003	-0.078	0.11	-0.079	-0.092
DHEAS	-0.163^a	-0.113	0.387^a	-0.193^a	-0.11	-0.07
Androstenedione	-0.08	0.074	0.015	0.072	-0.042	-0.042
E2	-0.1	0.052	0.007	0.150^a	0.156^a	0.193^a
LH	0.199^a	0.248^a	-0.397^a	0.318^a	0.15^a	0.136^a
FSH	0.198^a	0.054	-0.307^a	0.131^a	0.009	-0.124

^aP < 0.05.

BUN: Blood urea nitrogen; CysC: Cystatin C; DHEAS: Dehydroepiandrosterone sulfate; E2: Levels of estradiol; eGFR: Estimated glomerular filtration rate; FSH: Follicle-stimulating hormone; LH: Luteinizing hormone; UACR: Urinary albumin/creatinine ratio; UARE: Urinary albumin excretion rate.

Full Size Table

Table 3 Correlation between sex hormones and renal function indexes in women with type 2 diabetes mellitus

r	BUN	Creatinine	eGFR	CysC	UACR	24-hour UARE
Testosterone	-0.146	-0.087	0.094	-0.176	-0.134	-0.021
DHEAS	-0.051	0.011	0.041	0.002	-0.145	-0.008
Androstenedione	-0.059	0.021	0.036	0.087	0.062	0.029
E2	-0.001	0.278^a	-0.217^a	0.242^a	0.103	0.21
LH	0.295^a	0.379^a	-0.317^a	0.458^a	0.355^a	0.28^a
FSH	0.256^a	0.317^a	-0.306^a	0.345^a	0.322^a	0.258^a

^aP < 0.05.

BUN: Blood urea nitrogen; CysC: Cystatin C; DHEAS: Dehydroepiandrosterone sulfate; E2: Estradiol; eGFR: Estimated glomerular filtration rate; FSH: Follicle-stimulating hormone; UACR: Urinary albumin/creatinine ratio; UARE: Urinary albumin excretion rate; LH: Luteinizing hormone.

Full Size Table

Table 4 Association of sex hormone level quartiles with diabetic kidney disease in men

	Odds ratio (95%CI)		β (95%CI)
	Model 1¹	Model 2²	β (95%CI)
Testosterone
Q1	Reference	Reference	Reference
Q2	0.984 (0.442 2.19)	0.794 (0,305, 2.069)	0.046 (-0.477, 0.570)
Q3	0.97 (0.435, 2.159)	0.915 (0.354, 2.362)	0.141 (-0.372, 0.655)
Q4	1.319 (0.579, 3.006)	1.243 (0.469, 3.294)	0.204 (-0.330, 0.739)
P for trend	0.52	0.619	0.405
Per SD increase	1.017 (0.749, 1.381)	1.034 (0.717, 1.491)	0.037 (-0.149, 0.224)
DHEAS
Q1	Reference	Reference	Reference
Q2	1.319 (0.605, 2.873)	0.880 (0.350, 2.214)	-0.345 (-0.830, -0.140)
Q3	0.52 (0.209, 1.295)	0.273 (0.089, 0.838)^a	-1.014 (-1.525, -0.503)^a
Q4	1.595 (0.664, 3.833)	1.273 (0.439, 3.694)	-0.691 (-1.241, -0.141)^a
P for trend	0.526	0.969	0.006^a
Per SD increase	1.023 (0.738, 1.417)	0.868 (0.586, 1.286)	-0.328 (-0.530, -0.127)^a
Androstenedione
Q1	Reference	Reference	Reference
Q2	1.641 (0.732, 3.675)	1.933 (0.764, 4.886)	0.103 (-0.393, 0.599)
Q3	1.221 (0.538, 2.771)	1.006 (0.393, 2.576)	-0.074 (-0.567, 0.418)
Q4	1.641 (0.733, 3.671)	1.454 (0.551, 3.838)	-0.120 (-0.632, 0.392)
P for trend	0.364	0.772	0.504
Per SD increase	1.021 (0.986, 1.056)	1.023 (0.718, 1.458)	-0.035 (-0.219, 0.149)
E2
Q1	Reference	Reference
Q2	1.695 (0.706, 4.069)	2.066 (0.726, 5.885)	0.152 (-0.363, 0.668)
Q3	2.113 (0.899, 4.97)	2.627 (0.947, 7.293)	0.291 (-0.234, 0.815)
Q4	2.616 (1.1, 6.222)^a	3.097 (1.083, 8.856)^a	0.451 (-0.088, 0.989)
P for trend	0.029^a	0.041^a	0.088
Per SD increase	1.411 (1.053, 1.891)^a	1.527 (1.077, 2.165)^a	0.219 (0.027, 0.411)^a
LH
Q1	Reference	Reference
Q2	3.228 (1.276, 8.166)^a	3.423 (1.139, 10.283)^a	0.719 (0.210, 1.227)^a
Q3	3.398 (1.345, 8.582)^a	3.359 (1.142, 9.879)^a	0.600 (0.093, 1.106)^a
Q4	4.008 (1.507, 10.659)^a	4.164 (1.300, 13.330)^a	0.568 (0.020, 1.116)^a
P for trend	0.02^a	0.048^a	0.151
Per SD increase	1.192 (0.89, 1.597)	1.175 (0.819, 1.687)	0.032 (-0.164, 0.228)
FSH
Q1	Reference	Reference	Reference
Q2	0.604 (0.269, 1.354)	0.554 (0.213, 1.441)	-0.103 (-0.619, 0.413)
Q3	0.705 (0.309, 1.609)	0.629 (0.234, 1.685)	0.002 (-0.532, 0.537)
Q4	0.56 (0.232, 1.352)	0.706 (0.257, 1.945)	-0.375 (-0.933, 0.183)
P for trend	0.328	0.766	0.174
Per SD increase	0.856 (0.618, 1.186)	0.927 (0.629, 1.364)	-0.076 (-0.269, 0.117)

^aP < 0.05.

¹Adjusts for age, body mass index, systolic blood pressure, diastolic blood pressure, duration of diabetes.

²Model 1 + use of sodium-glucosecotrasporter-2 inhibitor, use of glucagon-like peptide-1 agonist, hypertension, use of angiotensin converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, diabetic retinopathy, diabetic peripheral vascular disease, total triglycerides, uric acid, glycated hemoglobin.

β: Regression coefficient; CI: Confidence interval; DHEAS: Dehydroepiandrosterone sulfate; E2: Estradiol; FSH: Follicle-stimulating hormone; LH: Luteinizing hormone; Q: Quartile; SD: Standard deviation.

Full Size Table

Table 5 Association of sex hormone level quartiles with diabetic kidney disease in postmenopausal women

	Odds ratio (95%CI)		β (95%CI)
	Model 1¹	Model 2²	β (95%CI)
Testosterone
Q1	Reference	Reference	Reference
Q2	2.111 (0.593, 7.518)	3.135 (0.657, 14.955)	0.066 (-0.704, 0.836)
Q3	0.712 (0.173, 2.926)	1.296 (0.255, 6.599)	-0.225 (-0.989, 0.539)
Q4	1.707 (0.451, 6.469)	3.072 (0.497, 18.976)	0.373 (-0.422, 1.169)
P for trend	0.679	0.413	0.448
Per SD increase	2.698 (0.349, 20.834)	3.418 (0.239, 48.900)	0.421 (0.164, 0.678)^a
DHEAS
Q1	Reference	Reference	Reference
Q2	1.692 (0.406, 7.045)	4.559 (0.638, 32.536)	0.558 (-0.216, 1.333)
Q3	4.713 (1.185, 18.745)^a	18.084 (2.483,131.683)^a	0.512 (-0.240, 1.264)
Q4	1.432 (0.316, 6.484)	2.425 (0.321, 18.320)	0.032 (-0.733, 0.797)
P for trend	0.426	0.203	0.911
Per SD increase	1.294 (0.806, 2.08)	1.396 (0.764, 2.553)	0.056 (-0.213, 0.325)
Androstenedione
Q1	Reference	Reference	Reference
Q2	1.273 (0.212, 7.625)	1.527 (0.215, 10.855)	0.373 (-0.649, 1.395)
Q3	2.843 (0.822, 9.831)	3.393 (0.736, 15.630)	0.465 (-0.224, 1.154)
Q4	2.772 (0.802, 9.576)	3.707 (0.700, 19.626)	0.457 (-0.259, 1.173)
P for trend	0.154	0.171	0.281
Per SD increase	1.453 (0.911, 2.317)	1.390 (0.788, 2.453)	0.224 (-0.046, 0.494)
E2
LnE2	1.678 (0.690, 4.085)	1.383 (0.429, 4.453)	0.260 (-0.267, 0.786)
Per SD increase	1.324 (0.818, 2.144)	1.192 (0.632, 2.246)	0.123 (-0.163, 0.410)
LH
Q1	Reference	Reference	Reference
Q2	2.22 (0.408, 12.076)	1.972 (0.301, 12.917)	0.110 (-0.592, 0.813)
Q3	2.971 (0.573, 15.397)	1.508 (0.240, 9.471)	0.222 (-0.516, 0.959)
Q4	18.73 (3.5, 100.231)^a	15.117 (2.191, 104.326)^a	1.039 (0.284, 1.794)^a
P for trend	0^a	0.004^a	0.006^a
Per SD increase	4.562 (2.141, 9.72)^a	4.213 (1.808, 9.816)^a	0.549 (0.294, 0.804)^a
FSH
Q1	Reference	Reference	Reference
Q2	2.748 (0.528, 14.295)	3.607 (0.568, 22.912)	-0.099 (-0.825, 0.627)
Q3	3.278 (0.654, 16.432)	2.213 (0.360, 13.602)	0.151 (-0.617, 0.920)
Q4	13.661 (2.739, 68.125)^a	9.588 (1.680, 54,709)^a	0.641 (-0.109, 1.390)
P for trend	0^a	0.014^a	0.006^a
Per SD increase	3.162 (1.67, 5.988)^a	2.590 (1.320, 5.083)^a	0.549 (0.294, 0.804)^a

^aP < 0.05.

¹Adjusts for age, body mass index, systolic blood pressure, diastolic blood pressure, duration of diabetes.

Full Size Table

Citation: 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
URL: https://www.wjgnet.com/1948-9358/full/v16/i11/111366.htm
DOI: https://dx.doi.org/10.4239/wjd.v16.i11.111366