Correlation between gynecomastia and endocrine regulation in patients with metabolic dysfunction-associated fatty liver disease: A cross-sectional study

Table 1 Demographic and clinical characteristics of the study population, n (%)

	Non-GYN (n = 638)	GYN (n = 359)	P value
Demographic and body measurements
Age (years) (mean ± SD)	47.89 ± 9.92	54.± 9.71	< 0.001
Height (m) (mean ± SD)	1.73 ± 0.06	1.72 ± 0.06	0.121
Weight (kg) [M (P25, P75)]	76.50 (71.00, 84.53)	79.50 (72.60, 84.80)	< 0.001
Body mass index (kg/m2) [M (P25, P75)]	25.74 (24.16, 27.29)	26.82 (24.96, 29.00)	< 0.001
Waist circumference (cm) [M (P25, P75)]	89.70 (85.08, 93.40)	90.20 (85.60, 97.70)	0.020
Hip circumference (cm) [M (P25, P75)]	102.35 (97.00, 106.63)	103.30 (99.90, 106.70)	0.018
Waist-to-hip ratio	0.87 (0.86, 0.90)	0.87 (0.85, 0.92)	0.422
Systolic blood pressure (mmHg) [M (P25, P75)]	127.00 (120.00, 134.00)	133 (127.00, 143.00)	< 0.001
Diastolic blood pressure (mmHg) [M (P25, P75)]	76.00 (70.75, 83.00)	81.00 (75.00, 87.00)	< 0.001
Biochemical Parameters
Alanine aminotransferase (U/L) [M (P25, P75)]	27.00 (21.00, 34.00)	50.00 (36.00, 65.00)	< 0.001
Aspartate aminotransferase (U/L) [M (P25, P75)]	28.00 (21.00, 32.00)	46.00 (35.00, 60.00)	< 0.001
Gamma-glutamyltransferase (U/L) [M (P25, P75)]	30.00 (22.00, 42.00)	56.00 (39.00, 76.00)	< 0.001
Creatinine (μmol/L) [M (P25, P75)]	78.80 (71.30, 85.70)	78.10 (70.50, 87.65)	0.902
Uric acid (μmol/L) [M (P25, P75)]	384.00 (345.00, 414.00)	439.00 (388.00, 486.00)	< 0.001
Fasting blood glucose (mmol/L) [M (P25, P75)]	5.31 (4.95, 5.70)	5.82 (5.03, 6.60)	< 0.001
Total cholesterol (mmol/L) [M (P25, P75)]	4.98 (4.31, 5.60)	6.06 (5.09, 6.96)	< 0.001
Triglycerides (mmol/L) [M (P25, P75)]	1.66 (1.26, 2.39)	2.99 (1.82, 4.37)	< 0.001
Low-density lipoprotein (mmol/L) [M (P25, P75)]	2.82 (2.41, 3.22)	3.18 (2.87, 3.66)	< 0.001
High-density lipoprotein (mmol/L) [M (P25, P75)]	1.26 (1.10, 1.39)	1.12 (1.00, 1.26)	< 0.001
Total bilirubin (μmol/L) [M (P25, P75)]	17.60 (14.60, 20.30)	18.7 (16.00, 21.70)	< 0.001
Total protein (g/L) [M (P25, P75)]	72.20 (69.80, 74.30)	71.60 (69.70, 73.90)	0.036
Hormonal parameters
Estradiol (pmol/L) [M (P25, P75)]	84.67 (69.71, 100.03)	112.12 (99.98, 130.00)	< 0.001
Testosterone (nmol/L) [M (P25, P75)]	15.08 (11.36, 19.71)	10.49 (6.80, 14.04)	< 0.001
Estrogen to androgen ratio	5.48 (3.74, 8.39)	10.90 (7.45, 19.03)	< 0.001
Clinical and lifestyle factors
Level			< 0.001
Mild	255 (72.4)	97 (27.6)
Moderate	304 (66.5)	153 (33.5)
Severe	79 (42)	109 (58)
Hypertension			< 0.001
No	540 (70)	228 (30)
Yes	98 (42.8)	131 (57.2)
Diabetes mellitus			< 0.001
No	535 (72.3)	205 (27.7)
Yes	103 (40)	154 (60)
Sporting			< 0.001
No	288 (51.8)	268 (48.2)
Yes	350 (79.4)	91 (20.6)
Smoking			< 0.001
No	343 (70.1)	146 (29.9)
Yes	295 (58.1)	213 (41.9)
Time			< 0.001
1-5 years	185 (78.7)	50 (21.3)
5-10 years	229 (75.3)	75 (24.7)
10-20 years	159 (51.5)	150 (48.5)
≥ 20 years	65 (43.6)	84 (56.4)

GYN: Gynecomastia.

Table 2 Factors influencing gynecomastia in patients with metabolic dysfunction-associated fatty liver disease

	P value	Odds ratio	95%CI
Clinical and lifestyle factors
Level
Mild
Moderate	0.040	1.523	1.176-1.793
Severe	< 0.001	3.627	2.500-5.263
Hypertension
No
Yes	< 0.001	3.166	2.336-4.291
Diabetes mellitus
No
Yes	< 0.001	3.902	2.900-5.291
Sporting
No
Yes	< 0.001	0.279	0.210-0.371
Smoking
No
Yes	< 0.001	1.696	1.305-2.204
Time
1-5 years
5-10 years	0.355	1.212	0.807-1.820
10-20 years	< 0.001	3.491	2.378-5.124
≥ 20 years	< 0.001	4.782	3.049-7.498
Demographic and body measurements
Age	< 0.001	1.056	1.042-1.070
Weight	< 0.001	1.025	1.012-1.037
Body mass index	< 0.001	1.158	1.106-1.213
Waist circumference	0.003	1.020	1.007-1.033
Hip circumference	0.513	0.999	0.995-1.003
Waist-to-hip ratio	0.009	18.955	2.119-169.572
Systolic blood pressure	< 0.001	1.048	1.036-1.059
diastolic blood pressure	< 0.001	1.049	1.034-1.063
Biochemical parameters
Alanine aminotransferase	< 0.001	1.084	1.072-1.096
Aspartate aminotransferase	< 0.001	1.119	1.102-1.136
Gamma-glutamyltransferase	< 0.001	1.054	1.045-1.062
Creatinine	0.753	1.002	0.991-1.012
Uric acid	< 0.001	1.010	1.008-1.012
Fasting blood glucose	< 0.001	1.268	1.151-1.398
Total cholesterol	< 0.001	1.987	1.755-2.250
Triglycerides	< 0.001	1.709	1.545-1.891
Low-density lipoprotein	< 0.001	2.356	1.911-2.904
High-density lipoprotein	< 0.001	0.062	0.031-0.126
Total bilirubin	0.053	1.023	1.000-1.046
Total protein	0.446	0.987	0.954-1.021
Hormonal parameters
Estradiol	< 0.001	1.063	1.054-1.072
Testosterone	< 0.001	0.851	0.828-0.875
Estrogen to androgen ratio	< 0.001	1.173	1.142-1.205

Table 3 The correlation between metabolic dysfunction-associated fatty liver disease and gynecomastia after adjustments

Metabolic dysfunction-associated fatty liver disease	Nonadjusted		Model I		Model II
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Mild	Reference		Reference		Reference
Moderate	1.523 (1.176-1.793)	0.040	1.600 (1.107-1.835)	0.046	1.256 (0.874-1.732)	0.229
Severe	3.627 (2.500-5.263)	< 0.001	3.157 (2.056-4.847)	< 0.001	1.873 (1.038-3.381)	0.037

Model I adjusting for age, hypertension, diabetes mellitus (DM), sporting, smoking, body mass index (BMI) , waist-to-hip ratio (WHR). Model II adjusting for age, hypertension, DM, sporting, smoking, BMI, WHR, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, creatinine, uric acid, high-density lipoprotein, low-density lipoprotein, total bilirubin, total protein, estradiol, testosterone, estrogen/androgen ratio. OR: Odds ratio.

Table 4 General characteristics of study participants grouped by level of metabolic dysfunction-associated fatty liver disease, n (%)

	Metabolic dysfunction-associated fatty liver disease			P value
	Mild (n = 352)	Moderate (n = 457)	Severe (n = 188)
Demographic and body measurements
Age (years) (mean ± SD)	47.59 ± 11.007	51.25 ± 11.200	52.49 ± 10.635	< 0.001
Height (m) (mean ± SD)	1.73 ± 0.06	1.72 ± 0.06	1.72 ± 0.06	0.084
Weight (kg) [M (P25, P75)]	77.5 (71.8, 83.9)	77.0 (71.1, 84.7)	77.7 (71.4, 84.7)	0.750
Waist circumference (cm) [M (P25, P75)]	89.8 (85.1, 93.2)	89.6 (85.4, 94.0)	91.8 (85.6, 102.2)	0.013
Hip circumference (cm) [M (P25, P75)]	103.3 (98.9, 106.7)	102.6 (98.0, 106.6)	101.7 (97.0, 107.0)	0.369
Body mass index (kg/m2) [M (P25, P75)]	25.89 (24.47, 27.62)	26.13 (24.3, 27.99)	26.50 (24.5, 28.78)	0.041
Waist-to-hip ratio	0.87 (0.85, 0.89)	0.87 (0.86, 0.89)	0.90 (0.86, 0.93)	< 0.001
Systolic blood pressure (mmHg) [M (P25, P75)]	129 (121, 136)	128 (121, 136)	132 (127, 142)	< 0.001
Diastolic blood pressure (mmHg) [M (P25, P75)]	78 (71, 84)	77 (71, 84)	80 (75, 86)	< 0.001
Biochemical parameters
Alanine aminotransferase (U/L) [M (P25, P75)]	28 (22, 40)	33 (23, 48)	42 (29, 61)	< 0.001
Aspartate aminotransferase (U/L) [M (P25, P75)]	29 (22, 36)	30 (23, 42)	38 (29, 49)	< 0.001
Gamma-glutamyltransferase (U/L) [M (P25, P75)]	34 (24, 50)	36 (25, 55)	44 (30, 63)	< 0.001
Creatinine (μmol/L) [M (P25, P75)]	78.6 (72.0, 85.9)	78.8 (70.6, 87.9)	77.9 (71.3, 85.4)	0.983
Uric acid (μmol/L) [M (P25, P75)]	389 (343, 432)	400 (357, 449)	410 (372, 460)	< 0.001
Fasting blood glucose (mmol/L) [M (P25, P75)]	5.32 (4.95, 5.98)	5.39 (4.98, 5.99)	5.58 (5.02, 6.33)	0.029
Total cholesterol (mmol/L) [M (P25, P75)]	5.16 (4.38, 6.02)	5.40 (4.47, 6.06)	5.27 (4.57, 6.32)	0.290
Triglycerides (mmol/L) [M (P25, P75)]	1.73 (1.31, 3.01)	2.08 (1.41, 3.18)	2.22 (1.52, 3.61)	0.002
Low-density lipoprotein (mmol/L) [M (P25, P75)]	2.88 (2.45, 3.32)	2.99 (2.52, 3.31)	3.14 (2.75, 3.70)	< 0.001
High-density lipoprotein (mmol/L) [M (P25, P75)]	1.22 (1.06, 1.36)	1.22 (1.08, 1.33)	1.15 (1.04, 1.31)	0.018
Total bilirubin (μmol/L) [M (P25, P75)]	17.4 (14.5, 20.3)	17.9 (15.0, 21.3)	18.9 (16.7, 21.5)	0.002
Total protein (g/L) [M (P25, P75)]	72.4 (70.2, 74.7)	71.9 (69.5, 73.9)	71.5 (69.5, 74.0)	0.002
Hormonal parameters
Estradiol (pmol/L) [M (P25, P75)]	79.52 ± 20.10	96.02 ± 19.40	128.38 ± 20.37	< 0.001
Testosterone (nmol/L) [M (P25, P75)]	16.46 (12.99, 20.47)	12.81 (9.10, 16.90)	8.66 (5.64, 12.45)	< 0.001
Estrogen to androgen ratio	4.74 (3.31, 6.93)	7.40 (5.27, 11.26)	14.20 (9.87, 24.19)	< 0.001
Clinical and lifestyle factors
Gynecomastia				< 0.001
No	255 (72.4)	304 (66.5)	79 (42)
Yes	97 (27.6)	153 (33.5)	109 (58)
Hypertension				0.099
No	279 (79.3)	355 (77.7)	134 (71.3)
Yes	73 (20.7)	102 (22.3)	54 (28.7)
Diabetes mellitus				0.016
No	268 (76.1)	348 (76.1)	124 (66)
Yes	84 (23.9)	109 (23.9)	64 (34)
Sporting				0.017
No	185 (52.6)	249 (54.5)	122 (64.9)
Yes	167 (47.4)	208 (45.5)	66 (35.1)
Smoking				0.949
No	175 (49.7)	223 (51)	91 (48.4)
Yes	177 (50.3)	234 (49)	97 (51.6)
Time				0.004
1-5 years	85 (24.1)	113(24.7)	37 (19.7)
5-10 years	115 (32.7)	140 (30.6)	49 (26.1)
10-20 years	102 (29)	151 (33)	56 (29.8)
≥ 20 years	50 (14.2)	53 (11.6)	46 (24.4)

Table 5 Performance indicators for sex hormone screening for the development of gynecomastia in patients with metabolic dysfunction-associated fatty liver disease

	Area under the curve	Youden’s index	Cut-off value	P value	95%Cl	Sensitivity	Specificity
E2	0.837	0.552	92.9	< 0.001	0.813-0.861	89.1%	66.1%
ETR	0.804	0.471	6.89	< 0.001	0.777-0.831	81.1%	66%
E2_ETR	0.843	0.545	0.29	< 0.001	0.819-0.866	84.4%	70.1%

ETR: Estrogen to androgen ratio; E2: Estradiol.