SUN-714 - Impact of Hypogonadism on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Male Individuals

Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern, affecting approximately one third of the adult population. While the relationship between MASLD and hypogonadism has been previously explored, those studies usually relied on serum-based surrogate markers of liver disease or liver ultrasound; or failed to measure testosterone using gold-standard techniques. Therefore, the aim of this study was to describe the association between MASLD and liver fibrosis staging with hypogonadism in unselected men from the US population.

Methods
Data from NHANES 2021-2023 was analyzed, including adult individuals with complete data on transient elastography (TE) and sex hormone measurements by mass spectrometry. MASLD was defined based on controlled attenuation parameter ≥274 dB/m. Clinically significant and advanced liver fibrosis were defined based on liver stiffness measurement (LSM) by TE (Fibroscan®) of ≥8.2 kPa and ≥9.7 kPa, respectively. Hypogonadism was defined as total testosterone < 250 ng/dL. Free testosterone was calculated based on Vermeulen equation based on total testosterone, albumin and sex hormone-binding globulin (SHBG).

Results
A total of 2,328 male individuals (46±1 years, 29.0±0.3 kg/m2, 15% with diabetes, 36% with MASLD) were included. Hypogonadism was found in 11.9% of the population. Prevalence of MASLD, clinically significant fibrosis (F2-F4), and advanced fibrosis (F3-F4) were significantly higher in the hypogonadism group: 65.7% vs. 41.0% (p < 0.001); 26.6% vs. 10.3%, (p < 0.001); 20.3% vs. 6.7%, (p < 0.001), respectively. SHBG was significantly lower in those with hypogonadism: 38.4 ± 0.6 vs. 25.0 ± 1.3 nmol/L, (p < 0.001). Moreover, 94% of male with a diagnosis of hypogonadism based on total testosterone had free testosterone levels below lower limit of normal (i.e., 66pg/mL). When stratifying by body mass index (BMI), a higher prevalence of clinically significant fibrosis in patients with hypogonadism was observed in all groups, lean [BMI < 25.0]: 11.0% vs. 4.5%; overweight [BMI 25.0-29.9]: 13.5% vs. 5.7%, and obese [BMI≥30.0]: 34.5% vs. 20.2%. Higher prevalence of clinically significant fibrosis in patients with hypogonadism was also observed in all age groups ≥25 years (i.e., 25-34, 35-44, 45-64, and ≥65 years). Among individuals with MASLD, the prevalence of hypogonadism was 18.1% vs. 8.6% in those without MASLD, (p < 0.003).

Conclusion
In a population representative of the US, MASLD and clinically significant fibrosis are common in individuals with hypogonadism, and this is independent of BMI and age groups. Therefore, the presence of hypogonadism in male individuals may warrant screening for liver fibrosis. However, more studies are warranted to further understand the clinical impact of the association between hypogonadism and MASLD.

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