{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:44:31Z","timestamp":1792154671620,"version":"4.4.0"},"reference-count":108,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human sex hormone-binding globulin (SHBG) is a glycoprotein produced by the liver that binds sex steroids with high affinity and specificity. Clinical observations and reports in the literature have suggested a negative correlation between circulating SHBG levels and markers of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Decreased SHBG levels increase the bioavailability of androgens, which in turn leads to progression of ovarian pathology, anovulation and the phenotypic characteristics of polycystic ovarian syndrome (PCOS). This review will use a case report to illustrate the inter-relationships between SHBG, NAFLD and PCOS. In particular, we will review the evidence that low hepatic SHBG production may be a key step in the pathogenesis of PCOS. Furthermore, there is emerging evidence that serum SHBG levels may be useful as a diagnostic biomarker and therapeutic target for managing women with PCOS.<\/jats:p>","DOI":"10.3390\/ijms21218191","type":"journal-article","created":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T20:05:25Z","timestamp":1604261125000},"page":"8191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":192,"title":["Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome"],"prefix":"10.3390","volume":"21","author":[{"given":"Xianqin","family":"Qu","sequence":"first","affiliation":[{"name":"School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Donnelly","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Nottingham, Derby DE22 3DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wolf, W.M., Wattick, R.A., Kinkade, O.N., and Olfert, M.D. (2018). Geographical Prevalence of Polycystic Ovary Syndrome as Determined by Region and Race\/Ethnicity. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15112589"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1093\/humrep\/dew218","article-title":"The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis","volume":"31","author":"Bozdag","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.metabol.2017.09.016","article-title":"Polycystic ovarian syndrome (PCOS): Long-term metabolic consequences","volume":"86","author":"Anagnostis","year":"2018","journal-title":"Metabolism"},{"key":"ref_4","unstructured":"Dunaif, A., Givens, J.R., Haseltine, F.P., and Merriam, G.R. (1992). Diagnostic criteria for polycystic ovary syndrome. Polycystic Ovary Syndrome, Blackwell Science."},{"key":"ref_5","first-page":"1","article-title":"Diagnosis of polycystic ovary syndrome: From NIH criteria to ESHRE-ASRM guidelines","volume":"56","author":"Carmina","year":"2004","journal-title":"Minerva Ginecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.fertnstert.2008.06.035","article-title":"The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: The complete task force report","volume":"91","author":"Azziz","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_7","unstructured":"Johnson, T., Kaplan, L., Ouyang, P., Rizza, R., and Health, N.I.O. (2012). Evidence-Based Methodology Workshop on Polycystic Ovary Syndrome."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1093\/humrep\/dey256","article-title":"Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"33","author":"Teede","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/09513590.2019.1631278","article-title":"Comparing pregnancy, childbirth, and neonatal outcomes in women with different phenotypes of polycystic ovary syndrome and healthy women: A prospective cohort study","volume":"36","author":"Foroozanfard","year":"2020","journal-title":"Gynecol. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2147\/TACG.S200341","article-title":"Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives","volume":"12","author":"Khan","year":"2019","journal-title":"Appl. Clin. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1080\/14767058.2016.1265933","article-title":"Risk factors for stillbirth in a socio-economically disadvantaged urban Australian population","volume":"30","author":"Wijs","year":"2017","journal-title":"J. Matern-Fetal Neonatal Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"359","DOI":"10.17219\/acem\/59380","article-title":"The pathogenesis and treatment of polycystic ovary syndrome: What's new?","volume":"26","author":"Bednarska","year":"2017","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Teede, H., Deeks, A., and Moran, L. (2010). Polycystic ovary syndrome: A complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med., 8.","DOI":"10.1186\/1741-7015-8-41"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/cen.13828","article-title":"Comorbidities and complications of polycystic ovary syndrome: An overview of systematic reviews","volume":"89","author":"Gilbert","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1093\/humupd\/dmv029","article-title":"Pregnancy complications in women with polycystic ovary syndrome","volume":"21","author":"Palomba","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.fertnstert.2008.06.045","article-title":"Risk of gestational diabetes mellitus in women with polycystic ovary syndrome: A systematic review and a meta-analysis","volume":"92","author":"Toulis","year":"2009","journal-title":"Fertil Steril."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"214","DOI":"10.5001\/omj.2017.40","article-title":"Gestational Diabetes Mellitus and Metabolic Disorder Among the Different Phenotypes of Polycystic Ovary Syndrome","volume":"32","author":"Ashrafi","year":"2017","journal-title":"Oman Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1542\/peds.2015-1430","article-title":"The Diagnosis of Polycystic Ovary Syndrome in Adolescents","volume":"136","author":"Rosenfield","year":"2015","journal-title":"Pediatrics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/S0140-6736(12)60072-5","article-title":"Adolescence: A foundation for future health","volume":"379","author":"Sawyer","year":"2012","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/cen.13755","article-title":"Simplified 4-item criteria for polycystic ovary syndrome: A bridge too far?","volume":"89","author":"Indran","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"122","DOI":"10.5114\/pedm.2019.87177","article-title":"Difficulties in diagnostics of polycystic ovary syndrome in adolescents - a preliminary study","volume":"25","author":"Milczarek","year":"2019","journal-title":"Pediatr. Endocrinol. Diabetes Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1080\/01443615.2017.1318840","article-title":"Metabolic effect of obesity on polycystic ovary syndrome in adolescents: A meta-analysis","volume":"37","author":"Li","year":"2017","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1093\/humrep\/del175","article-title":"Low sex hormone-binding globulin is associated with low high-density lipoprotein cholesterol and metabolic syndrome in women with PCOS","volume":"21","author":"Chen","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1093\/humrep\/deu200","article-title":"Irregular menstruation and hyperandrogenaemia in adolescence are associated with polycystic ovary syndrome and infertility in later life: Northern Finland Birth Cohort 1986 study","volume":"29","author":"West","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1159\/000184787","article-title":"Sex hormone-binding globulin: Gene organization and structure\/function analyses","volume":"45","author":"Hammond","year":"1996","journal-title":"Horm. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1210\/jcem-64-4-825","article-title":"Sex hormone-binding globulin secretion by human hepatocarcinoma cells is increased by both estrogens and androgens","volume":"64","author":"Lee","year":"1987","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1095\/biolreprod.111.092593","article-title":"Diverse roles for sex hormone-binding globulin in reproduction","volume":"85","author":"Hammond","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1210\/jcem-53-1-58","article-title":"Transport of steroid hormones: Binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma","volume":"53","author":"Dunn","year":"1981","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.cca.2017.06.009","article-title":"New biomarkers for diagnosis and management of polycystic ovary syndrome","volume":"471","author":"Karakas","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_30","first-page":"625","article-title":"Reference intervals for testosterone, androstenedione and SHBG levels in healthy females and males from birth until old age","volume":"51","author":"Elmlinger","year":"2005","journal-title":"Clin. Lab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.metabol.2009.06.033","article-title":"Sex hormone-binding globulin and lipid profile in pubertal children","volume":"59","author":"Oya","year":"2010","journal-title":"Metabolism"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0015-0282(16)53212-9","article-title":"Effect of low-dose oral contraceptive on gonadotropins, androgens, and sex hormone binding globulin in nonhirsute women","volume":"53","author":"Murphy","year":"1990","journal-title":"Fertil Steril."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0378-5122(94)00869-9","article-title":"A longitudinal study of the perimenopausal transition: Altered profiles of steroid and pituitary hormones, SHBG and bone mineral density","volume":"21","author":"Rannevik","year":"1995","journal-title":"Maturitas"},{"key":"ref_34","first-page":"3979","article-title":"Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene","volume":"117","author":"Selva","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4953","DOI":"10.1007\/s11033-019-04946-w","article-title":"Endogenous SHBG levels correlate with that of glucose transporters in insulin resistance model cells","volume":"46","author":"Feng","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"ref_36","first-page":"160","article-title":"Regulation of production and secretion of sex hormone-binding globulin in HepG2 cell cultures by hormones and growth factors","volume":"80","author":"Loukovaara","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1677\/JME-09-0025","article-title":"Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha","volume":"43","author":"Selva","year":"2009","journal-title":"J. Mol. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.mce.2009.09.020","article-title":"Sex hormone-binding globulin gene expression in the liver: Drugs and the metabolic syndrome","volume":"316","author":"Pugeat","year":"2010","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.cca.2019.09.010","article-title":"Sex hormone-binding globulin and polycystic ovary syndrome","volume":"499","author":"Zhu","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1210\/me.2007-0531","article-title":"Down-regulation of hepatic HNF4alpha gene expression during hyperinsulinemia via SREBPs","volume":"23","author":"Xie","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1080\/09513590.2017.1411474","article-title":"SHBG expression is correlated with PI3K\/AKT pathway activity in a cellular model of human insulin resistance","volume":"34","author":"Feng","year":"2018","journal-title":"Gynecol. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"108480","DOI":"10.1016\/j.jnutbio.2020.108480","article-title":"Sex hormone-binding globulin overexpression protects against high fat diet induced obesity in transgenic male mice","volume":"85","author":"Villena","year":"2020","journal-title":"J. Nutr. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"909","DOI":"10.2337\/dc08-1618","article-title":"Sex hormone-binding globulin levels predict insulin sensitivity, disposition index, and cardiovascular risk during puberty","volume":"32","author":"Aksglaede","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1530\/EC-19-0044","article-title":"Does sex hormone-binding globulin cause insulin resistance during pubertal growth?","volume":"8","author":"Le","year":"2019","journal-title":"Endocr. Connect."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/oby.20077","article-title":"Liver fat and SHBG affect insulin resistance in midlife women: The Study of Women\u2019s Health Across the Nation (SWAN)","volume":"21","author":"Kavanagh","year":"2013","journal-title":"Obesity"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"315","DOI":"10.12891\/ceog1779.2015","article-title":"Exploring the significance of sex hormone-binding globulin examination in the treament of women with polycystic ovarian syndrome (PCOS)","volume":"42","author":"Lin","year":"2015","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1210\/jcem.85.8.6738","article-title":"Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome","volume":"85","author":"Pasquali","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1210\/jcem-67-3-460","article-title":"Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin","volume":"67","author":"Plymate","year":"1988","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_49","first-page":"654","article-title":"Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal weight and obese men","volume":"80","author":"Pasquali","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Dapas, M., Lin, F.T., Nadkarni, G.N., Sisk, R., Legro, R.S., Urbanek, M., Hayes, M.G., and Dunaif, A. (2020). Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis. PLoS Med., 17.","DOI":"10.1371\/journal.pmed.1003132"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of Insulin Action and Insulin Resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nrm4074","article-title":"Transcriptional regulation of hepatic lipogenesis","volume":"16","author":"Wang","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E2780","DOI":"10.1210\/jc.2014-2640","article-title":"Sex hormone-binding globulin gene expression and insulin resistance","volume":"99","author":"Winters","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1210\/jc.2018-00740","article-title":"Sex Hormone-Binding Globulin Expression Correlates With Acetyl-Coenzyme A Carboxylase and Triglyceride Content in Human Liver","volume":"104","author":"Hernandez","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1007\/s10620-016-4054-0","article-title":"Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease","volume":"61","author":"Softic","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.tem.2016.06.005","article-title":"The Sweet Path to Metabolic Demise: Fructose and Lipid Synthesis","volume":"27","author":"Herman","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1210\/en.2008-1289","article-title":"Peroxisome-proliferator receptor gamma represses hepatic sex hormone-binding globulin expression","volume":"150","author":"Selva","year":"2009","journal-title":"Endocrinology"},{"key":"ref_58","first-page":"1626","article-title":"Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: A multicenter, double blind, placebo-controlled trial","volume":"86","author":"Azziz","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G.A., Beguinot, F., and Miele, C. (2019). Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092358"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1210\/me.2011-1321","article-title":"Molecular Mechanism of TNF\u03b1-Induced Down-Regulation of SHBG Expression","volume":"26","author":"Lecube","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1210\/me.2012-1152","article-title":"IL1\u03b2 down-regulation of sex hormone-binding globulin production by decreasing HNF-4\u03b1 via MEK-1\/2 and JNK MAPK pathways","volume":"26","author":"Hernandez","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.1210\/en.2014-1072","article-title":"Adiponectin upregulates SHBG production: Molecular mechanisms and potential implications","volume":"155","author":"Lecube","year":"2014","journal-title":"Endocrinology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1038\/s41598-017-03078-0","article-title":"Lower SHBG level is associated with higher leptin and lower adiponectin levels as well as metabolic syndrome, independent of testosterone","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3062319","DOI":"10.1155\/2018\/3062319","article-title":"Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages","volume":"2018","author":"Yamazaki","year":"2018","journal-title":"Mediators Inflamm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8196","DOI":"10.4081\/ejtm.2019.8196","article-title":"The relationship between components of metabolic syndrome and plasma level of sex hormone-binding globulin","volume":"29","author":"Alinezhad","year":"2019","journal-title":"Eur. J. Transl. Myol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1055\/s-0043-123348","article-title":"Serum Sex Hormone Binding Globulin (SHBG) Relation with Different Components of Metabolic Syndrome in Men with Type 2 Diabetes","volume":"50","author":"Siddiqui","year":"2018","journal-title":"Horm. Metab. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.diabres.2019.04.028","article-title":"Sex hormone binding globulin for prediction of gestational diabetes mellitus in pre-conception and pregnancy: A systematic review","volume":"152","author":"Faal","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.annepidem.2005.07.055","article-title":"Sex hormone-binding globulin and serum testosterone are inversely associated with C-reactive protein levels in postmenopausal women at high risk for cardiovascular disease","volume":"16","author":"Joffe","year":"2006","journal-title":"Ann. Epidemiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jcct.2018.09.010","article-title":"Association of endogenous sex hormone levels with coronary artery calcium progression among post-menopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"13","author":"Subramanya","year":"2019","journal-title":"J. Cardiovasc. Comput. Tomogr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/1753-0407.12550","article-title":"Relationship between dietary carbohydrates intake and circulating sex hormone-binding globulin levels in postmenopausal women","volume":"10","author":"Huang","year":"2018","journal-title":"J. Diabetes"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.sxmr.2019.06.006","article-title":"Sex Hormone Binding Globulin: A Review of its Interactions With Testosterone and Age, and its Impact on Mortality in Men With Type 2 Diabetes","volume":"7","author":"Ramachandran","year":"2019","journal-title":"Sex. Med. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6301","DOI":"10.1210\/jc.2019-01317","article-title":"Higher Serum Sex Hormone-Binding Globulin Levels Are Associated With Incident Cardiovascular Disease in Men","volume":"104","author":"Gyawali","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4574","DOI":"10.2174\/1381612825666190117102111","article-title":"Diagnosis of Non-alcoholic Fatty Liver Disease (NAFLD): Current Concepts","volume":"24","author":"Papatheodoridi","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S2213-8587(18)30154-2","article-title":"Non-alcoholic fatty liver disease: Causes, diagnosis, cardiometabolic consequences, and treatment strategies","volume":"7","author":"Stefan","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s12020-015-0640-8","article-title":"Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: A novel hepato-ovarian axis?","volume":"51","author":"Targher","year":"2016","journal-title":"Endocrine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1007\/s40618-017-0708-9","article-title":"Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: Systematic review and meta-analysis","volume":"40","author":"Rocha","year":"2017","journal-title":"J. Endocrinol. Invest."},{"key":"ref_77","first-page":"545","article-title":"Sex Hormone-Binding Globulin Reduction in Metabolic Disorders May Play a Role in NAFLD Development","volume":"158","author":"Hernandez","year":"2017","journal-title":"Endocrinology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4571","DOI":"10.1210\/en.2015-1677","article-title":"SHBG-C57BL\/ksJ-db\/db: A New Mouse Model to Study SHBG Expression and Regulation During Obesity Development","volume":"156","author":"Selva","year":"2015","journal-title":"Endocrinology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"dgaa574","DOI":"10.1210\/clinem\/dgaa574","article-title":"Sex Hormone Relations to Histologic Severity of Pediatric Nonalcoholic Fatty Liver Disease","volume":"105","author":"Mueller","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/obr.12762","article-title":"Metabolic syndrome in polycystic ovary syndrome: A systematic review, meta-analysis and meta-regression","volume":"20","author":"Lim","year":"2019","journal-title":"Obes. Rev."},{"key":"ref_81","first-page":"1004","article-title":"Sex hormone binding globulin, but not testosterone, is associated with the metabolic syndrome in overweight and obese women with polycystic ovary syndrome","volume":"36","author":"Moran","year":"2013","journal-title":"J. Endocrinol. Invest."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"7","DOI":"10.5603\/GP.2019.0002","article-title":"Metabolic and hormonal effects of a combined Myo-inositol and d-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS)","volume":"90","author":"Januszewski","year":"2019","journal-title":"Ginekol. Pol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/19396368.2017.1410591","article-title":"Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis","volume":"64","author":"Deswal","year":"2018","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1210\/jc.2006-2012","article-title":"Clinical review: Identifying children at risk for polycystic ovary syndrome","volume":"92","author":"Rosenfield","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1055\/s-0034-1371092","article-title":"Childhood obesity and its impact on the development of adolescent PCOS","volume":"32","author":"Anderson","year":"2014","journal-title":"Semin. Reprod. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"17315528","DOI":"10.1515\/JPEM.2007.20.1.41","article-title":"Intractable early childhood obesity as the initial sign of insulin resistant hyperinsulinism and precursor of polycystic ovary syndrome","volume":"20","author":"Littlejohn","year":"2007","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.fertnstert.2013.04.001","article-title":"Prevalence of polycystic ovary syndrome in adolescents","volume":"100","author":"Christensen","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1080\/01443615.2017.1345875","article-title":"Clinical and metabolic characteristics of Turkish adolescents with polycystic ovary syndrome","volume":"38","author":"Ates","year":"2018","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12020-019-02085-7","article-title":"Nonalcoholic fatty liver disease in women with polycystic ovary syndrome","volume":"67","author":"Paschou","year":"2020","journal-title":"Endocrine"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.bpobgyn.2016.03.003","article-title":"Hepatic manifestations of women with polycystic ovary syndrome","volume":"37","author":"Chen","year":"2016","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Kumarendran, B., O\u2019Reilly, M.W., Manolopoulos, K.N., Toulis, K.A., Gokhale, K.M., Sitch, A.J., Wijeyaratne, C.N., Coomarasamy, A., Arlt, W., and Nirantharakumar, K. (2018). Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database. PLoS Med., 15.","DOI":"10.1371\/journal.pmed.1002542"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/ijo.2017.116","article-title":"High-free androgen index is associated with increased risk of non-alcoholic fatty liver disease in women with polycystic ovary syndrome, independent of obesity and insulin resistance","volume":"41","author":"Cai","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1210\/jc.2005-2774","article-title":"Nonalcoholic steatohepatitis and nonalcoholic Fatty liver disease in young women with polycystic ovary syndrome","volume":"91","author":"Setji","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1093\/humrep\/dew076","article-title":"Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome","volume":"31","author":"Macut","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/ijo.2008.61","article-title":"Polycystic ovary syndrome in adolescents","volume":"32","author":"Franks","year":"2008","journal-title":"Int. J. Obes."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/ncpendmet0637","article-title":"The reproductive phenotype in polycystic ovary syndrome","volume":"3","author":"Chang","year":"2007","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1258\/000456306776865188","article-title":"The LH\/FSH ratio has little use in diagnosing polycystic ovarian syndrome","volume":"43","author":"Cho","year":"2006","journal-title":"Ann. Clin. Biochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1111\/cen.13808","article-title":"Inter-related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in PCOS","volume":"89","author":"Shorakae","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1210\/jc.2015-4275","article-title":"Enhanced Inflammatory Transcriptome in the Granulosa Cells of Women With Polycystic Ovarian Syndrome","volume":"101","author":"Adams","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1095\/biolreprod61.4.993","article-title":"Tumor necrosis factor-alpha stimulates proliferation of rat ovarian theca-interstitial cells","volume":"61","author":"Spaczynski","year":"1999","journal-title":"Biol. Reprod."},{"key":"ref_101","first-page":"352","article-title":"The Effect of Curcumin on TNF-\u03b1, IL-6 and CRP Expression in a Model of Polycystic Ovary Syndrome as an Inflammation State","volume":"18","author":"Mohammadi","year":"2017","journal-title":"J. Reprod. Infertil."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1016\/j.fertnstert.2011.07.155","article-title":"Resveratrol potentiates effects of simvastatin on inhibition of rat ovarian theca-interstitial cell steroidogenesis","volume":"96","author":"Ortega","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jep.2018.09.006","article-title":"Paeoniflorin extract reverses dexamethasone-induced testosterone over-secretion through downregulation of cytochrome P450 17A1 expression in primary murine theca cells","volume":"229","author":"Ong","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1142\/S0192415X17500252","article-title":"Targeting Insulin Resistance to Treat the Underlying Basis of Polycystic Ovary Syndrome with Chinese Herbal Medicine","volume":"45","author":"Ong","year":"2017","journal-title":"Am. J. Chin. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1000183","DOI":"10.4172\/2161-1017.1000183","article-title":"Successful Treatment of Polycystic Ovarian Syndrome, Nonalcoholic Fatty Liver Disease and Infertility with Chinese Herbal Medicine: A Case Report","volume":"4","author":"Qu","year":"2015","journal-title":"Endocrinol. Metab. Synd."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/hropen\/hoy021","article-title":"Evidence summaries and recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome: Assessment and treatment of infertility","volume":"2019","author":"Costello","year":"2019","journal-title":"Hum. Reprod. Open"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12958-017-0313-y","article-title":"Risks, benefits size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndrome","volume":"15","year":"2017","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e113","DOI":"10.2196\/resprot.9024","article-title":"Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis","volume":"7","author":"Amiri","year":"2018","journal-title":"JMIR Res. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/8191\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:27:57Z","timestamp":1760178477000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/8191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,1]]},"references-count":108,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21218191"],"URL":"https:\/\/doi.org\/10.3390\/ijms21218191","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,1]]}}}