Hyperandrogenemia is independently associated with elevated alanine aminotransferase activity in young women with polycystic ovary syndrome.

CONTEXT Women with polycystic ovary syndrome (PCOS) have been implicated to have higher levels of alanine aminotransferase (ALT) because of the high prevalence of obesity. OBJECTIVE Our aim was to investigate the relationship between elevated ALT and aspartate aminotransferase (AST) activity and characteristic hyperandrogenism in women with PCOS. DESIGN AND SETTING We conducted a cross-sectional case-control study in a reproductive endocrinology clinic and voluntary annual medical health check-up program of the health management center in a tertiary medical center. PATIENTS A total of 279 women with PCOS and 279 age-frequency-matched healthy women were studied. INTERVENTIONS There were no interventions. MAIN OUTCOME MEASURES All subjects underwent anthropometric measurement, clinical history recorded by questionnaires, and biochemical tests after an overnight fast. RESULTS The prevalence of elevated ALT and AST levels was significantly higher in women with PCOS than healthy control subjects. Multivariate regression analysis for women revealed that the presence of PCOS was significantly associated with elevated ALT but not AST after adjustment for age, obesity, and dyslipidemia. The level of androgenicity represented by free androgen index in women with PCOS was significantly related to elevated ALT and AST levels in multivariate regression models. Women with PCOS who had the highest quartile of free androgen index level had the highest risk of elevated ALT level after adjustment for age, obesity, insulin resistance, and dyslipidemia. CONCLUSIONS The risk of elevated ALT level is significantly higher in women with PCOS than those without, independent of obesity. The elevated ALT levels in women with PCOS were associated with the increased androgen levels, independent of obesity, insulin resistance, and dyslipidemia.

[1]  Henry Völzke,et al.  Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels in men. , 2010, International journal of andrology.

[2]  V. Castracane,et al.  Endocrine factors associated with non-alcoholic fatty liver disease in women with polycystic ovary syndrome: Do androgens play a role? , 2009, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[3]  J. Shyy,et al.  Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1. , 2009, Journal of hepatology.

[4]  A. Mallat,et al.  Cigarette smoke exposure: a novel cofactor of NAFLD progression? , 2009, Journal of hepatology.

[5]  S. Livadas,et al.  In overweight/obese but not in normal-weight women, polycystic ovary syndrome is associated with elevated liver enzymes compared to controls , 2009, Hormones.

[6]  Kayoung Lee,et al.  The roles of obesity and gender on the relationship between metabolic risk factors and non‐alcoholic fatty liver disease in Koreans , 2009, Diabetes/metabolism research and reviews.

[7]  M. Eijkemans,et al.  Indicators for metabolic disturbances in anovulatory women with polycystic ovary syndrome diagnosed according to the Rotterdam consensus criteria. , 2008, Human reproduction.

[8]  W. Goessling,et al.  Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease. , 2008, Gastroenterology.

[9]  S. Yeh,et al.  Androgen receptor is a new potential therapeutic target for the treatment of hepatocellular carcinoma. , 2008, Gastroenterology.

[10]  Chi-Ling Chen,et al.  The relationship between anti-Mullerian hormone, androgen and insulin resistance on the number of antral follicles in women with polycystic ovary syndrome. , 2008, Human reproduction.

[11]  D. Lawlor,et al.  Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999-2004. , 2007, Gastroenterology.

[12]  J. Miquel,et al.  Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. , 2007, Journal of hepatology.

[13]  M. Beckmann,et al.  Long-term administration of testosterone undecanoate every 3 months for testosterone supplementation in female-to-male transsexuals. , 2007, The Journal of clinical endocrinology and metabolism.

[14]  Chi-Ling Chen,et al.  Relationship Between Androgen Levels and Blood Pressure in Young Women With Polycystic Ovary Syndrome , 2007, Hypertension.

[15]  H. Hsu,et al.  Somatic mutations at the trinucleotide repeats of androgen receptor gene in male hepatocellular carcinoma , 2007, International journal of cancer.

[16]  C. Bodian,et al.  Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[17]  Yoosoo Chang,et al.  Higher concentrations of alanine aminotransferase within the reference interval predict nonalcoholic fatty liver disease. , 2007, Clinical chemistry.

[18]  Jin-Tung Liang,et al.  Association of metabolic syndrome with proximal and synchronous colorectal neoplasm. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[19]  A. Lazenby,et al.  The Prevalence of Nonalcoholic Steatohepatitis is Greater in Morbidly Obese Men Compared to Women , 2006, Obesity surgery.

[20]  M. Holmqvist,et al.  Long‐term follow‐up of patients with NAFLD and elevated liver enzymes , 2006, Hepatology.

[21]  C. K. Hsiao,et al.  Low sex hormone-binding globulin is associated with low high-density lipoprotein cholesterol and metabolic syndrome in women with PCOS. , 2006, Human reproduction.

[22]  A. Diehl,et al.  Nonalcoholic steatohepatitis and nonalcoholic Fatty liver disease in young women with polycystic ovary syndrome. , 2006, The Journal of clinical endocrinology and metabolism.

[23]  R. Legro,et al.  Adolescent girls with polycystic ovary syndrome have an increased risk of the metabolic syndrome associated with increasing androgen levels independent of obesity and insulin resistance. , 2006, The Journal of clinical endocrinology and metabolism.

[24]  G. Farrell,et al.  Nonalcoholic fatty liver disease: From steatosis to cirrhosis , 2006, Hepatology.

[25]  S. Sanderson,et al.  The natural history of nonalcoholic fatty liver disease: a population-based cohort study. , 2005, Gastroenterology.

[26]  Tomi-Pekka Tuomainen,et al.  The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study. , 2005, The Journal of clinical endocrinology and metabolism.

[27]  J. Schwimmer,et al.  Abnormal aminotransferase activity in women with polycystic ovary syndrome. , 2005, Fertility and sterility.

[28]  I. Suh,et al.  Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study , 2004, BMJ : British Medical Journal.

[29]  C. Nishida,et al.  Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies , 2004, The Lancet.

[30]  R. Fisher,et al.  Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values , 2003, Hepatology.

[31]  F. Brancati,et al.  The prevalence and etiology of elevated aminotransferase levels in the United States , 2003, American Journal of Gastroenterology.

[32]  H. Hsu,et al.  Dominance of functional androgen receptor allele with longer CAG repeat in hepatitis B virus-related female hepatocarcinogenesis. , 2002, Cancer research.

[33]  M. Kaplan.  Alanine Aminotransferase Levels: What's Normal? , 2002, Annals of Internal Medicine.

[34]  Mauro Salizzoni,et al.  Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. , 2002, Gastroenterology.

[35]  P. Angulo,et al.  Nonalcoholic fatty liver disease. , 2002, Revista de gastroenterologia de Mexico.

[36]  G. Marchesini,et al.  Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. , 2001, Diabetes.

[37]  E. Diamanti-Kandarakis,et al.  A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. , 1999, The Journal of clinical endocrinology and metabolism.

[38]  J. Delattre,et al.  Factors associated with serum alanine transaminase activity in healthy subjects: Consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C , 1998, Hepatology.

[39]  N. Nagasue,et al.  Effects of castration and androgen replacement on tumour growth of human hepatocellular carcinoma in nude mice. , 1996, Journal of hepatology.

[40]  E. Papavassiliou,et al.  Increased androgen bioavailability is associated with non-alcoholic fatty liver disease in women with polycystic ovary syndrome. , 2010, Human reproduction.

[41]  D. Ehrmann,et al.  Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. , 2006, The Journal of clinical endocrinology and metabolism.

[42]  D. Grobbee,et al.  Endogenous sex hormones and metabolic syndrome in aging men. , 2005, The Journal of clinical endocrinology and metabolism.

[43]  B. Fauser,et al.  Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). , 2004, Human reproduction.