Low testosterone and non-alcoholic fatty liver disease: Evidence for their independent association in men with chronic spinal cord injury

Abstract

Objective: Non-alcoholic fatty liver disease (NAFLD) has been claimed as a liver phenotype of metabolic syndrome, which in turn is associated with male hypogonadism. We assessed whether an independent association between NAFLD and androgen deficiency could be revealed in men with chronic spinal cord injury (SCI), who exhibit a high prevalence of biochemical androgen deficiency and a combination of risk factors for metabolic syndrome. Design: Fifty-five consecutive men with chronic SCI admitted to a rehabilitation program underwent clinical/ biochemical evaluations and liver ultrasonography. Results: NAFLD was diagnosed in 27 patients (49.1%). Men with NAFLD were older and exhibited significantly higher body mass index, Homeostatic model assessment of insulin resistance, triglycerides and gammaglutamyl transpeptidase values, lower total and free testosterone levels and they were engaged in a significantly poorer weekly leisure time physical activity (LTPA). At the multiple logistic regression analysis, only total and free testosterone levels exhibited a significant independent association with NAFLD. The risk of having NAFLD increased indeed of 1% for each decrement of 1 ng/dL of total testosterone and of 3% for each decrement of 1 pg/mL of free testosterone, after adjustment for confounders. In men with total testosterone < 300 ng/dL (36.4%) the prevalence of NAFLD reached 85%: they had a risk of having NAFLD significantly higher (∼12-fold) than those with total testosterone ≥ 300 ng/dL, after adjustment for confounders. Conclusion: The evidence of an independent association between NAFLD and low testosterone is strongly reinforced by its demonstration in men with chronic SCI, in spite of the many confounders peculiar to this population.

Relevance of low testosterone to nonalcoholic fatty liver disease

“…[44] One blood sample was taken to measure total testosterone levels by chemiluminescence immunoassay, while NAFLD was diagnosed by abdominal US. Twenty-seven out of the 55 patients were diagnosed with NAFLD; all had a higher body mass index (BMI), insulin resistance (HOMA-IR), triglyceride levels, and GGT values, and lower total testosterone and FT levels.…”

Serum testosterone and non‐alcoholic fatty liver disease in men and women in the US

“…22 Furthermore, 1 study reported that parenteral administration of testosterone to increase serum testosterone concentrations to within the normal range led to normalization of ALT levels. 23 Circulating androgen is known to be associated with a genderspecific risk of metabolic complications or NAFLD; associations of low serum testosterone levels with obesity, metabolic syndrome, and NAFLD have been well established in men, 6,7 but studies have suggested that increased androgenicity in healthy post-menopausal women was associated with an unfavourable cardiovascular risk profile. 24,25 In our study, a low serum testosterone level was associated with an increased risk for suspected NAFLD in men, but post-menopausal women with low serum androgen levels were also more prone to developing NAFLD.…”

“…Increasing data support the association between NAFLD and serum testosterone levels. [6][7][8][9][10] Several cross-sectional studies have reported a relatively consistent relationship between low total testosterone levels and NAFLD in men. 6,7 In women, data from the Multi-Ethnic Study of Atherosclerosis (MESA) indicated that post-menopausal women with fatty livers had higher serum total testosterone levels than those without fatty livers, which differed from the results of another study from Greece.…”

“…[6][7][8][9][10] Several cross-sectional studies have reported a relatively consistent relationship between low total testosterone levels and NAFLD in men. 6,7 In women, data from the Multi-Ethnic Study of Atherosclerosis (MESA) indicated that post-menopausal women with fatty livers had higher serum total testosterone levels than those without fatty livers, which differed from the results of another study from Greece. 7,8 Although we reported that hyperandrogenaemia may be an independent risk factor for non-obese NAFLD in premenopausal PCOS patients, 11 other studies have reported that circulating levels of androgens did not correlate with the presence of NAFLD in women with PCOS.…”

Diagnosis and Characterization of Non-Alcoholic Fatty Liver Disease

“…Obstructive sleep apnea syndrome (OSAS) is strongly associated with NAFLD independently of other traditional factors; it is a consequence of the decrease in the lipid metabolism provoked by intermittent hypoxia [182][183][184][185]. Other described diseases associated with NAFLD include osteoporosis [186], psoriasis [187], polycystic syndrome [188] and other endocrinopathies such as hypothyroidism [189], hypopituitarism [190] and hypogonadism [191]. Until now, there is no evidence for screening of all these pathologies for the mere fact that the subject presents NAFLD, so all that needs to be studied is the presence of them if the patient has clinical manifestations related to them.…”