Mechanisms of hepatic steatosis formation in adolescent boys with hypoandrogenism
Keywords:adolescent boys, hypoandrogenism, hepatic steatosis, free radical oxidation, antioxidant protection
There has been an increase the prevalence of andrological diseases in all age groups in recent decades, including those with comorbid conditions such as pathology of the cardiovascular system and liver, which are manifestations of metabolic syndrome.
Research aim: to investigate the relationship between formation of hepatic steatosis and hypoandrogenism (HA) in adolescent boys.
Materials and methods. The study involved 42 adolescent boys aged 14–18 years with laboratory confirmed HA in whom total testosterone levels were less than 12.0 nmol/l. Sex hormones, gonadotropins, insulin levels, biochemical parameters of liver function, the state of free radical oxidation and antioxidant protection were determined in patients. Based on ultrasound examination adolescents with HA were divided into 2 groups: group 1 – 15 adolescents with signs of liver steatosis; group 2 – 27 adolescents with normal ultrasound parameters of a liver. The control group consisted of 38 boys of the same age with normal indicators of physical and sexual development without signs of pathology of the hepatobiliary system.
Results. Individual assessment of sexual development allowed to diagnose I degree of delayed sexual development in 44.7%, II degree in 38.3% and III degree in 17.0% of adolescents. HA negatively affects the physical development of most boys (78.7%), due to short stature (40.0%), weight deficiency (20.0%) and overweight (18.7%). Factor analysis allowed to build a factor model of hepatic steatosis formation in adolescents with delayed sexual development and HA, which describes 76.0% of the sample and consists of five factors.
Conclusion. Atherogenic changes of the lipid profile, androgen deficiency, insulin resistance, activation of cytolytic processes in the liver and oxidative stress formation due to a decrease in the effectiveness of antioxidant protection are important in the pathogenesis of hepatic steatosis in boys with HA. A factor model of the hepatic steatosis development in adolescent boys with HA gives grounds for the development of therapeutic and preventive measures in adolescent boys with HA and comorbid liver pathology.
Lutov, Y.V. Metabolic syndrome in men – a dynamic multiforme transsystemic comorbid state. Thesis for MD degree. Novosibirsk (2018): 342 p.
Kolesnikova, L.I., Darenskaya, M.A., Kolesnikov, S.I. “Free radical oxidation: a pathophysiologist’s view.” Bulletin of Siberian Medicine 16.4 (2017): 16–29. DOI: 10.20538/1682-0363-2017-4-16–29
Parkhomenko, L.K., et al. “Hepatic manifestations of metabolic syndrome in boys with hypoandrogenism.” Ukrainian Journal of Pediatric Endocrinology 1 (2019): 36–44. DOI: 10.30978/UJPE2019-1-38
Plekhova, O.I., et al. Assessment of state development of boys (standards): guidelines. Kharkiv. SI ICAHC NAMS (2010): 25 р.
On approval of protocols for providing medical care to children in the specialty “Pediatric Endocrinology”. Order of the Ministry of Health of Ukraine. Adopted on April 27, 2006, No. 254. Available from: [http://www.moz.gov.ua/ua/portal/dn_20060427_254.html].
Roytberg, G.E., Platonova, O.E., Sharhun, O.O. “Features of the ultrasound picture of the hepatobiliary system and pancreas in patients with non-alcoholic fatty liver disease.” NovaInfo. Ru 2.59 (2017): 400–5.
Tyuzikov, I.A., et al. “Male infertility and insulin resistance: are there pathogenetic links and who, when and how should diagnose and treat them?” Experimental and Clinical Urology 2 (2014): 68–75.
Khripun, I.A., et al. “Testosterone as a tool of metabolic control of men’s health (Review).” Medical Herald of the South of Russia 4 (2014): 19–22. DOI: 10.21886/2219-8075-2014-4-19-22
Tsygankova, O.V., et al. “Association of sex hormones with components of insulin-glucose homeostasis.” Obesity and Metabolism 15.2 (2018): 3–10. DOI: 10.14341/OMET9482
Barbonetti, A., et al. “Low testosterone and non-alcoholic fatty liver disease: Evidence for their independent association in men with chronic spinal cord injury.” The journal of spinal cord medicine 39.4 (2016): 443–9. DOI: 10.1179/2045772314Y.0000000288
Hermoso, D., et al. “Association between metabolic syndrome, hepatic steatosis, and testosterone deficiency: evidences from studies with men and rodents.” The Aging Male (2020): 1–20. DOI: 10.1080/13685538.2020.1764927
Kravchun, N., Zemlianitsyna, O., Dunayeva, I., et al. “Definition of non-alcohol fatty liver disease (NAFLD) stage by independent non-invasive fibrosis markers and elastography.” Diabetes 68 Suppl 1 (2019): 1902. DOI: 10.2337/db19-1902-P
Lonardo, A., et al. “NAFLD in some common endocrine diseases: prevalence, pathophysiology, and principles of diagnosis and management.” Int J Mol Sci 20.11 (2019): 2841. DOI: 10.3390/ijms20112841
Lonardo, A., et al. “'Endocrine NAFLD' a hormonocentric perspective of nonalcoholic fatty liver disease pathogenesis.” Journal of Hepatology 44.6 (2006): 1196–1207. DOI: 10.1016/j.jhep.2006.03.005
Mody, A., et al. “Relevance of low testosterone to non-alcoholic fatty liver disease.” Cardiovasc Endocrinol 4.3 (2015): 83–9. DOI: 10.1097%2FXCE.000000000000005
Mulligan, T., et al. “Prevalence of hypogonadism in males aged at least 45 years: the HIM study.” Int J Clin Pract 60.7 (2006): 762–9. DOI: 10.1111/j.1742-1241.2006.00992.x
Mushannen, T., et al. “Obesity and hypogonadism – a narrative review highlighting the need for high-quality data in adolescents.” Children 6.5 (2019): 63. DOI: 10.3390/children6050063
Nikolaenko, L., et al. “Testosterone replacement ameliorates nonalcoholic fatty liver disease in castrated male rats.” Endocrinology 155.2 (2014): 417–28. DOI: 10.1210/en.2013-1648
Onat, A., et al. “Fatty liver disease: Disparate predictive ability for cardiometabolic risk and all-cause mortality.” World J Gastroenterol 21.48 (2015): 13555–65. DOI: 10.3748/wjg.v21. i48.13555
Pivonello, R., et al. “Metabolic disorders and male hypogonadotropic hypogonadism.” Front Endocrinol (Lausanne) 10 (2019): 345. DOI: 10.3389/fendo.2019.00345
Polyzos, S., et al. “Nonalcoholic fatty liver disease in males with low testosterone concentrations.” Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14.5 (2020): 1571–7. DOI: 10.1016/j. dsx.2020.07.049
Rastrelli, G., et al. “Metabolic syndrome in male hypogonadism.” Front Horm Res 49 (2018): 131–55. DOI: 10.1159/000485999
Sakr, H., et al. “Possible mechanisms underlying fatty liver in a rat model of male hypogonadism:
A protective role for testosterone.” Steroids 135 (2018): 21–30. DOI: 10.1016/j.steroids.2018.04.004
Sankhla, M., et al. “Relationship of oxidative stress with obesity and its role in obesity induced metabolic syndrome.” Clin Lab 58.5–6 (2012): 385–92.
Solbach, P. “Testosterone-receptor positive hepatocellular carcinoma in a 29-year old bodybuilder with a history of anabolic androgenic steroid abuse: a case report.” BMC Gastroenterol 15 (2015): 60. DOI: 10.1186/s12876-015-0288-0
Stancampiano, M.R., et al. “Testosterone therapy in adolescent boys: the need for a structured approach.” Horm Res Paediatr 92.4 (2019): 215–28. DOI: 10.1159/000504670
Ventimiglia, E., et al. “Metabolic syndrome in White-European men presenting for secondary couple's infertility: an investigation of the clinical and reproductive burden.” Asian J Androl 19.3 (2017): 368–73. DOI: 10.4103/1008-682X.175783.
Copyright (c) 2021 Л.К. Пархоменко, Л.А. Страшок, С.І. Турчина, З.В. Єлоєва, Т.М. Клименко, Г.В. Косовцова, Д.А. Кашкалда, Е.М. Завеля, М.Ю. Ісакова, А.В. Єщенко, Т.П. Костенко
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.