{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:35:16Z","timestamp":1788320116164,"version":"build-2803163510"},"reference-count":127,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000},"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>Metabolic syndrome (MetS) and infertility are two afflictions with a high prevalence in the general population. MetS is a global health problem increasing worldwide, while infertility affects up to 12% of men. Despite the high prevalence of these conditions, the possible impact of MetS on male fertility has been investigated by a few authors only in the last decade. In addition, underlying mechanism(s) connecting the two conditions have been investigated in few preclinical studies. The aim of this review is to summarize and critically discuss available clinical and preclinical studies on the role of MetS (and its treatment) in male fertility. An extensive Medline search was performed identifying studies in the English language. While several studies support an association between MetS and hypogonadism, contrasting results have been reported on the relationship between MetS and semen parameters\/male infertility, and the available studies considered heterogeneous MetS definitions and populations. So far, only two meta-analyses in clinical and preclinical studies, respectively, evaluated this topic, reporting a negative association between MetS and sperm parameters, testosterone and FSH levels, advocating, however, larger prospective investigations. In conclusion, a possible negative impact of MetS on male reproductive potential was reported; however, larger studies are needed.<\/jats:p>","DOI":"10.3390\/ijms22041988","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T21:35:42Z","timestamp":1613597742000},"page":"1988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Metabolic Syndrome and Reproduction"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8343-1807","authenticated-orcid":false,"given":"Francesco","family":"Lotti","sequence":"first","affiliation":[{"name":"Andrology, Female Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1057-8626","authenticated-orcid":false,"given":"Sara","family":"Marchiani","sequence":"additional","affiliation":[{"name":"Andrology, Female Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Corona","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Medical Department, Maggiore-Bellaria Hospital, Azienda-Usl Bologna, 40139 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Maggi","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1210\/er.2008-0024","article-title":"The metabolic syndrome","volume":"29","author":"Cornier","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0140-6736(09)61794-3","article-title":"The metabolic syndrome","volume":"375","author":"Eckel","year":"2010","journal-title":"Lancet"},{"key":"ref_3","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., de Herder, W.W., Dungan, K., Grossman, A., Hershman, J.M., Hofland, H.J., and Kaltsas, G. (2000). Metabolic Syndrome. 2019 Feb 11. Endotext [Internet], MDText.com, Inc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ecl.2004.03.005","article-title":"The metabolic syndrome: Prevalence in worldwide populations","volume":"33","author":"Cameron","year":"2004","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113","DOI":"10.5534\/wjmh.180055","article-title":"Metabolic syndrome and male fertility","volume":"37","author":"Martins","year":"2019","journal-title":"World J. Mens Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.2337\/diab.37.12.1595","article-title":"Role of insulin resistance in human disease","volume":"37","author":"Reaven","year":"1988","journal-title":"Diabetes"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1146\/annurev.me.44.020193.001005","article-title":"Role of insulin resistance in human disease (syndrome X): An expanded definition","volume":"44","author":"Reaven","year":"1993","journal-title":"Annu. Rev. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.diabet.2010.04.003","article-title":"The metabolic syndrome as a predictor of incident diabetes and cardiovascular events in the Health 2000 Study","volume":"36","author":"Pajunen","year":"2010","journal-title":"Diabetes Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1136\/bmj.39477.500197.AD","article-title":"Should we dump the metabolic syndrome?: Yes","volume":"336","author":"Gale","year":"2008","journal-title":"BMJ"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1016\/S0140-6736(08)60731-X","article-title":"Metabolic syndrome-what is the clinical usefulness?","volume":"371","author":"Kahn","year":"2008","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.jacc.2013.05.064","article-title":"Prevalence and Trends of Metabolic Syndrome in the Adult U.S. Population, 1999\u20132010","volume":"62","author":"Harhay","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1007\/s00125-009-1620-4","article-title":"The metabolic syndrome: Useful concept or clinical tool? Report of a WHO expert consultation","volume":"53","author":"Simmons","year":"2010","journal-title":"Diabetologia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1111\/jsm.12832","article-title":"Prevalence of endocrine and metabolic disorders in subjects with erectile dysfunction: A comparative study","volume":"12","author":"Maseroli","year":"2015","journal-title":"J. Sex. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1111\/j.1743-6109.2012.02717.x","article-title":"Hormonal Association and Sexual Dysfunction in Patients with Impaired Fasting Glucose: A Cross-Sectional and Longitudinal Study","volume":"9","author":"Corona","year":"2012","journal-title":"J. Sex. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/14779072.2020.1745632","article-title":"Erectile dysfunction and cardiovascular risk: A review of current findings","volume":"18","author":"Corona","year":"2020","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1161\/CIRCOUTCOMES.112.966903","article-title":"Prediction of cardiovascular events and all-cause mortality with erectile dysfunction a systematic review and meta-analysis of cohort studies","volume":"6","author":"Vlachopoulos","year":"2013","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/j.1743-6109.2010.02126.x","article-title":"Is Metabolic Syndrome a Useless Category in Subjects with High Cardiovascular Risk? Results from a Cohort Study in Men with Erectile Dysfunction","volume":"8","author":"Corona","year":"2011","journal-title":"J. Sex. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/17446651.2019.1657827","article-title":"Metabolically healthy and unhealthy obesity in erectile dysfunction and male infertility","volume":"14","author":"Rastrelli","year":"2019","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1093\/aje\/kwp168","article-title":"Good Semen Quality and Life Expectancy: A Cohort Study of 43,277 Men","volume":"170","author":"Jensen","year":"2009","journal-title":"Am. J. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1093\/humrep\/deu106","article-title":"Semen quality, infertility and mortality in the USA","volume":"29","author":"Eisenberg","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/andr.12477","article-title":"Semen quality associated with subsequent hospitalizations\u2013Can the effect be explained by socio-economic status and lifestyle factors?","volume":"6","author":"Latif","year":"2018","journal-title":"Andrology"},{"key":"ref_22","unstructured":"Ferlin, A., Garolla, A., Ghezzi, M., Selice, R., Palego, P., Caretta, N., Di Mambro, A., Valente, U., De Rocco Ponce, M., and Dipresa, S. (2019). Sperm Count and Hypogonadism as Markers of General Male Health. Eur. Urol. Focus."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1001\/jama.285.19.2486","article-title":"Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III)","volume":"285","author":"Cleeman","year":"2001","journal-title":"J. Am. Med. Assoc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0140-6736(05)67402-8","article-title":"The metabolic syndrome\u2013A new worldwide definition","volume":"366","author":"Alberti","year":"2005","journal-title":"Lancet"},{"key":"ref_25","unstructured":"World Health Organization (1999). Definition and Classification of Diabetes Mellitus and Its Complications Report of a WHO Consultation. Part 1: Diagnosis and Classification of Diabetes Mellitus, World Health Organization. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/66040\/WHO_NCD_NCS_99.2.pdf?sequence=1&isAllowed=y."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"237","DOI":"10.4158\/EP.9.S2.5","article-title":"American College of Endocrinology Position Statement on the Insulin Resistance Syndrome","volume":"9","author":"Einhorn","year":"2003","journal-title":"Endocr. Pract."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1161\/CIRCULATIONAHA.105.169404","article-title":"Diagnosis and management of the metabolic syndrome: An American Heart Association\/National Heart, Lung, and Blood Institute scientific statement","volume":"112","author":"Grundy","year":"2005","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the metabolic syndrome: A joint interim statement of the international diabetes federation task force on epidemiology and prevention; National heart, lung, and blood institute; American heart association; World heart federation; International atherosclerosis society; And international association for the study of obesity","volume":"120","author":"Alberti","year":"2009","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1365-2605.2008.00951.x","article-title":"Hypogonadism, ED, metabolic syndrome and obesity: A pathological link supporting cardiovascular diseases","volume":"32","author":"Corona","year":"2009","journal-title":"Int. J. Androl."},{"key":"ref_30","first-page":"557","article-title":"Hypogonadism and metabolic syndrome","volume":"34","author":"Corona","year":"2011","journal-title":"J. Endocrinol. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1016\/j.ejca.2009.01.031","article-title":"Metabolic syndrome and risk of cancer mortality in men","volume":"45","author":"Jaggers","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.2337\/dc12-0336","article-title":"Metabolic syndrome and risk of cancer: A systematic review and meta-analysis","volume":"35","author":"Esposito","year":"2012","journal-title":"Diabetes Care"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1001\/jama.297.5.509","article-title":"A 27-year-old woman with a diagnosis of polycystic ovary syndrome","volume":"297","author":"Legro","year":"2007","journal-title":"J. Am. Med. Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0140-6736(07)61345-2","article-title":"Polycystic ovary syndrome","volume":"370","author":"Norman","year":"2007","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.beem.2010.07.002","article-title":"Testosterone, cardiovascular disease and the metabolic syndrome","volume":"25","author":"Corona","year":"2011","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/j.1743-6109.2010.01991.x","article-title":"Testosterone and Metabolic Syndrome: A Meta-Analysis Study","volume":"8","author":"Corona","year":"2011","journal-title":"J. Sex. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.metabol.2018.03.024","article-title":"The complex association between metabolic syndrome and male hypogonadism","volume":"86","author":"Dimopoulou","year":"2018","journal-title":"Metabolism"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000485999","article-title":"Metabolic Syndrome in Male Hypogonadism","volume":"49","author":"Rastrelli","year":"2018","journal-title":"Front. Horm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/ijir.2014.3","article-title":"Metabolic syndrome and risk for ED: A meta-analysis","volume":"26","author":"Liu","year":"2014","journal-title":"Int. J. Impot. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1111\/jsm.12885","article-title":"The Relationship between Metabolic Syndrome, Its Components, and Erectile Dysfunction: A Systematic Review and a Meta-Analysis of Observational Studies","volume":"12","author":"Besiroglu","year":"2015","journal-title":"J. Sex. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/pcan.2012.44","article-title":"Metabolic syndrome and lower urinary tract symptoms: The role of inflammation","volume":"16","author":"Gacci","year":"2013","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/bju.12728","article-title":"Metabolic syndrome and benign prostatic enlargement: A systematic review and meta-analysis","volume":"115","author":"Gacci","year":"2015","journal-title":"BJU Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/pcan.2017.1","article-title":"Meta-Analysis of metabolic syndrome and prostate cancer","volume":"20","author":"Gacci","year":"2017","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.1177\/0300060519876823","article-title":"Association between benign prostate hyperplasia and metabolic syndrome in men under 60 years old: A meta-analysis","volume":"47","author":"Wu","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.eururo.2006.02.053","article-title":"Psychobiologic Correlates of the Metabolic Syndrome and Associated Sexual Dysfunction","volume":"50","author":"Corona","year":"2006","journal-title":"Eur. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S561","DOI":"10.1016\/j.dsx.2017.04.005","article-title":"Metabolic syndrome and its components are related to psychological disorders: A population based study","volume":"11","author":"Bagherniya","year":"2017","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.2047-2927.2012.00031.x","article-title":"Seminal, ultrasound and psychobiological parameters correlate with metabolic syndrome in male members of infertile couples","volume":"1","author":"Lotti","year":"2013","journal-title":"Andrology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2164\/jandrol.107.003731","article-title":"The metabolic syndrome and male infertility","volume":"29","author":"Kasturi","year":"2008","journal-title":"J. Androl."},{"key":"ref_49","unstructured":"Baskaran, S., Agarwal, A., Leisegang, K., Pushparaj, P.N., Panner Selvam, M.K., and Henkel, R. (2019). An in-depth bibliometric analysis and current perspective on male infertility research. World J. Mens Health, 37."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nrurol.2018.20","article-title":"Sexual dysfunction and male infertility","volume":"15","author":"Lotti","year":"2018","journal-title":"Nat. Rev. Urol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1089\/met.2012.0122","article-title":"The prevalence of metabolic syndrome in children: A systematic review of the literature","volume":"11","author":"Friend","year":"2013","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2431-13-19","article-title":"The relationship between physical activity, physical fitness and overweight in adolescents: A systematic review of studies published in or after 2000","volume":"13","author":"Rauner","year":"2013","journal-title":"BMC Pediatr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/humrep\/dey371","article-title":"Features of the metabolic syndrome in late adolescence are associated with impaired testicular function at 20 years of age","volume":"34","author":"Hart","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Bitew, Z.W., Alemu, A., Ayele, E.G., Tenaw, Z., Alebel, A., and Worku, T. (2020). Metabolic syndrome among children and adolescents in low and middle income countries: A systematic review and meta-analysis. Diabetol. Metab. Syndr., 12.","DOI":"10.1186\/s13098-020-00601-8"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ozturk, U., Sener, N.C., Nalbant, I., Karabacak, O.R., Ulusoy, M.G., and Imamoglu, M.A. (2012). The effect of metabolic syndrome upon the success of varicocelectomy. Sci. World J., 2012.","DOI":"10.1100\/2012\/985201"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"295","DOI":"10.4103\/1008-682X.122341","article-title":"Metabolic syndrome and prostate abnormalities in male subjects of infertile couples","volume":"16","author":"Lotti","year":"2014","journal-title":"Asian J. Androl."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1111\/andr.12232","article-title":"Metabolic syndrome in white European men presenting for primary couple\u2019s infertility: Investigation of the clinical and reproductive burden","volume":"4","author":"Ventimiglia","year":"2016","journal-title":"Andrology"},{"key":"ref_58","first-page":"368","article-title":"Metabolic syndrome in White-European men presenting for secondary couple\u2019s infertility: An investigation of the clinical and reproductive burden","volume":"18","author":"Ventimiglia","year":"2016","journal-title":"Asian J. Androl."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ehala-Aleksejev, K., and Punab, M. (2018). The effect of metabolic syndrome on male reproductive health: A cross-sectional study in a group of fertile men and male partners of infertile couples. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194395"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12610-019-0090-x","article-title":"Metabolic syndrome and smoking are independent risk factors of male idiopathic infertility","volume":"29","author":"Dupont","year":"2019","journal-title":"Basic Clin. Androl."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1530\/EJE-19-0615","article-title":"Relationships between metabolic status, seminal adipokines, and reproductive functions in men from infertile couples","volume":"182","author":"Elfassy","year":"2019","journal-title":"Eur. J. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"100054","DOI":"10.1016\/j.metop.2020.100054","article-title":"Impact of body mass index and metabolic syndrome on sperm DNA fragmentation in males from infertile couples: A cross-sectional study from Vietnam","volume":"7","author":"Le","year":"2020","journal-title":"Metab. Open"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1111\/andr.12808","article-title":"The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: Clinical, seminal and biochemical characteristics","volume":"8","author":"Lotti","year":"2020","journal-title":"Andrology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/and.12060","article-title":"Effect of the metabolic syndrome on male reproductive function: A case-controlled pilot study","volume":"46","author":"Leisegang","year":"2014","journal-title":"Andrologia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/aji.12529","article-title":"Metabolic syndrome is associated with increased seminal inflammatory cytokines and reproductive dysfunction in a case-controlled male cohort","volume":"76","author":"Leisegang","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Elsamanoudy, A.Z., Abdalla, H.A., Hassanien, M., and Gaballah, M.A. (2016). Spermatozoal cell death-inducing DNA fragmentation factor-\u03b1-like effector A (CIDEA) gene expression and DNA fragmentation in infertile men with metabolic syndrome and normal seminogram. Diabetol. Metab. Syndr., 8.","DOI":"10.1186\/s13098-016-0192-y"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/andr.12296","article-title":"Metabolic syndrome and the seminal cytokine network in morbidly obese males","volume":"5","author":"Pilatz","year":"2017","journal-title":"Andrology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/1753-0407.12995","article-title":"Metabolic syndrome and semen quality in adult population","volume":"12","author":"Chen","year":"2020","journal-title":"J. Diabetes"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"251","DOI":"10.4103\/ijem.IJEM_574_18","article-title":"Sertoli cell function in young males with metabolic syndrome","volume":"23","author":"Saikia","year":"2019","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zhao, L., and Pang, A. (2020). Effects of Metabolic Syndrome on Semen Quality and Circulating Sex Hormones: A Systematic Review and Meta-Analysis. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00428"},{"key":"ref_71","unstructured":"World Health Organization (1999). WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction, Cambridge University Press. [4th ed.]."},{"key":"ref_72","unstructured":"World Health Organization (2010). WHO Laboratory Manual for the Examination and Processing of Human Semen, WHO Press. [5th ed.]."},{"key":"ref_73","unstructured":"World Health Organization (2000). WHO Manual for the Standardized Investigation and Diagnosis of the Infertile Couple, Cambridge University Press."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e020293","DOI":"10.1136\/bmjopen-2017-020293","article-title":"Risk of metabolic disorders in childless men: A population-based cohort study","volume":"8","author":"Bungum","year":"2018","journal-title":"BMJ Open"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-32813-4","article-title":"More Prevalent Prescription of Medicine for Hypertension and Metabolic Syndrome in Males from Couples Undergoing Intracytoplasmic Sperm Injection","volume":"8","author":"Elenkov","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1093\/humrep\/des173","article-title":"Higher clusterin immunolabeling and sperm DNA damage levels in hypertensive men compared with controls","volume":"27","author":"Muciaccia","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/clpt.2011.265","article-title":"Low-dose lisinopril in normotensive men with idiopathic oligospermia and infertility: A 5-year randomized, controlled, crossover pilot study","volume":"91","author":"Mbah","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.euf.2018.07.030","article-title":"High Blood Pressure Is a Highly Prevalent but Unrecognised Condition in Primary Infertile Men: Results of a Cross-sectional Study","volume":"6","author":"Cazzaniga","year":"2020","journal-title":"Eur. Urol. Focus"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"59","DOI":"10.5534\/wjmh.2017.35.2.59","article-title":"Hypertension and Male Fertility","volume":"35","author":"Guo","year":"2017","journal-title":"World J. Mens Health"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jri.2013.02.004","article-title":"Interleukin 8 and the male genital tract","volume":"100","author":"Lotti","year":"2013","journal-title":"J. Reprod. Immunol."},{"key":"ref_81","first-page":"e336","article-title":"Elevated body mass index correlates with higher seminal plasma interleukin 8 levels and ultrasonographic abnormalities of the prostate in men attending an andrology clinic for infertility","volume":"34","author":"Lotti","year":"2011","journal-title":"J. Endocrinol. Investig."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/j.1365-2605.2010.01121.x","article-title":"Ultrasonographic and clinical correlates of seminal plasma interleukin-8 levels in patients attending an andrology clinic for infertility","volume":"34","author":"Lotti","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.jsxm.2019.03.006","article-title":"Impact of Metabolically Healthy Obesity in Patients with Andrological Problems","volume":"16","author":"Lotti","year":"2019","journal-title":"J. Sex. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1111\/j.1743-6109.2012.02872.x","article-title":"Clinical Correlates of Erectile Dysfunction and Premature Ejaculation in Men with Couple Infertility","volume":"9","author":"Lotti","year":"2012","journal-title":"J. Sex. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/humupd\/dmu042","article-title":"Ultrasound of the male genital tract in relation to male reproductive health","volume":"21","author":"Lotti","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.2337\/diabetes.54.6.1726","article-title":"A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-\u03b1)-like effector A (CIDEA) in adipocyte lipolysis and obesity","volume":"54","author":"Backlund","year":"2005","journal-title":"Diabetes"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.diabres.2010.10.016","article-title":"Association of the cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) gene V115F (G\/T) polymorphism with phenotypes of metabolic syndrome in a Chinese population","volume":"91","author":"Zhang","year":"2011","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lotti, F., Frizza, F., Balercia, G., Barbonetti, A., Behre, H.M., Calogero, A.E., Cremers, J., Francavilla, F., Isidori, A.M., and Kliesch, S. (2020). The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: Scrotal ultrasound reference ranges and associations with clinical, seminal and biochemical characteristics. Andrology.","DOI":"10.1111\/andr.12951"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/obr.12827","article-title":"High-fat diets reduce male reproductive success in animal models: A systematic review and meta-analysis","volume":"20","author":"Crean","year":"2019","journal-title":"Obes. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1111\/j.1743-6109.2009.01467.x","article-title":"Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome","volume":"6","author":"Filippi","year":"2009","journal-title":"J. Sex. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"E519","DOI":"10.1152\/ajpendo.00377.2018","article-title":"Physical activity counteracts metabolic syndrome-induced hypogonadotropic hypogonadism and erectile dysfunction in the rabbit","volume":"316","author":"Morelli","year":"2019","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.mce.2014.11.005","article-title":"Metabolic syndrome-associated sperm alterations in an experimental rabbit model: Relation with metabolic profile, testis and epididymis gene expression and effect of tamoxifen treatment","volume":"401","author":"Marchiani","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1530\/REP-10-0472","article-title":"Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism","volume":"142","author":"Mallidis","year":"2011","journal-title":"Reproduction"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.mce.2013.09.017","article-title":"Metabolic syndrome induces inflammation and impairs gonadotropin-releasing hormone neurons in the preoptic area of the hypothalamus in rabbits","volume":"382","author":"Morelli","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1016\/j.fertnstert.2010.12.009","article-title":"Metformin improves semen characteristics of oligo-terato-asthenozoospermic men with metabolic syndrome","volume":"95","author":"Morgante","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/and.12366","article-title":"Effect of metformin therapy and dietary supplements on semen parameters in hyperinsulinaemic males","volume":"47","author":"Bosman","year":"2015","journal-title":"Andrologia"},{"key":"ref_97","first-page":"5994","article-title":"FSH treatment for normogonadotropic male infertility: A synergistic role for metformin?","volume":"23","author":"Condorelli","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/j.1439-0272.2011.01206.x","article-title":"Cytochemical evaluation of sperm chromatin and DNA integrity in couples with unexplained recurrent spontaneous abortions","volume":"44","author":"Talebi","year":"2012","journal-title":"Andrologia"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1071\/RD18256","article-title":"Metformin inhibits human spermatozoa motility and signalling pathways mediated by protein kinase A and tyrosine phosphorylation without affecting mitochondrial function","volume":"31","author":"Bragado","year":"2019","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Liu, C.Y., Chang, T.C., Lin, S.H., Wu, S.T., Cha, T.L., and Tsao, C.W. (2020). Metformin Ameliorates Testicular Function and Spermatogenesis in Male Mice with High-Fat and High-Cholesterol Diet-Induced Obesity. Nutrients, 12.","DOI":"10.3390\/nu12071932"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"560","DOI":"10.4103\/aja.aja_141_19","article-title":"Metformin treatment of high-fat diet-fed obese male mice restores sperm function and fetal growth, without requiring weight loss","volume":"22","author":"McPherson","year":"2020","journal-title":"Asian J. Androl."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"111085","DOI":"10.1016\/j.biopha.2020.111085","article-title":"The effect of Nigella sativa oil and metformin on male seminal parameters and testosterone in Wistar rats exposed to an obesogenic diet","volume":"133","author":"Leisegang","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1134\/S0012496620040031","article-title":"Normalization of Testicular Steroidogenesis and Spermatogenesis in Male Rats with Type 2 Diabetes Mellitus under the Conditions of Metformin Therapy","volume":"493","author":"Derkach","year":"2020","journal-title":"Dokl. Biol. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1007\/s10815-015-0506-2","article-title":"Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet","volume":"32","author":"Yan","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"18546","DOI":"10.1038\/s41598-019-54799-3","article-title":"Association between high-fat diet feeding and male fertility in high reproductive performance mice","volume":"9","author":"Giaccagli","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Abd El-Hakim, Y.M., Abdel-Rahman Mohamed, A., Khater, S.I., Hamed Arisha, A., Metwally, M.M.M., Nassan, M.A., and Hassan, M.E. (2020). Chitosan-Stabilized Selenium Nanoparticles and Metformin Synergistically Rescue Testicular Oxidative Damage and Steroidogenesis-Related Genes Dysregulation in High-Fat Diet\/Streptozotocin-Induced Diabetic Rats. Antioxidants, 10.","DOI":"10.3390\/antiox10010017"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/s12011-020-02082-2","article-title":"Co-administration of Selenium Nanoparticles and Metformin Abrogate Testicular Oxidative Injury by Suppressing Redox Imbalance, Augmenting Sperm Quality and Nrf2 Protein Expression in Streptozotocin-Induced Diabetic Rats","volume":"198","author":"Ebokaiwe","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/andr.12739","article-title":"Malaysian propolis and metformin mitigate subfertility in streptozotocin-induced diabetic male rats by targeting steroidogenesis, testicular lactate transport, spermatogenesis and mating behaviour","volume":"8","author":"Nna","year":"2020","journal-title":"Andrology"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Rindone, G.M., Gorga, A., Pellizzari, E.H., Del Carmen Camberos, M., Galardo, M.N., Da Ros, V.G., Buffone, M.G., Meroni, S.B., and Riera, M.F. (2020). Postnatal metformin treatment alters rat Sertoli cell proliferation and daily sperm production. Andrology, Dec 11. Epub ahead of print.","DOI":"10.1111\/andr.12957"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.rbmo.2014.07.009","article-title":"The effects of liraglutide on male fertility: A case report","volume":"29","author":"Fontoura","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.jsps.2019.01.003","article-title":"Gliclazide alone or in combination with atorvastatin ameliorated reproductive damage in streptozotocin-induced type 2 diabetic male rats","volume":"27","author":"Sezer","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/S0015-0282(16)49901-2","article-title":"Successful treatment of oligospermic and azoospermic men with alpha 1-blocker and beta-stimulator: New treatment for idiopathic male infertility","volume":"46","author":"Yamamoto","year":"1986","journal-title":"Fertil Steril"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/S0015-0282(16)49663-9","article-title":"Evidence for contractility of the human seminiferous tubule confirmed by its response to noradrenaline and acetylcholine","volume":"46","author":"Miyake","year":"1986","journal-title":"Fertil. Steril."},{"key":"ref_114","first-page":"167","article-title":"Seminal parameters of ejaculates collected successively with sixty minute interval in infertile men: Effect of combination of prazosin and terbutaline on these parameters","volume":"23","author":"Karacagil","year":"1991","journal-title":"Andrologia"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e12641","DOI":"10.1111\/and.12641","article-title":"Effect of captopril on semen quality","volume":"49","author":"Banihani","year":"2017","journal-title":"Andrologia"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrurol.2015.145","article-title":"Adverse effects of common medications on male fertility","volume":"12","author":"Samplaski","year":"2015","journal-title":"Nat. Rev. Urol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/andr.12366","article-title":"The impact of drugs on male fertility: A review","volume":"5","author":"Semet","year":"2017","journal-title":"Andrology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/j.1939-4640.1997.tb01902.x","article-title":"Manidipine improves spermatogenesis in the stroke-prone spontaneously hypertensive rat","volume":"18","author":"Akagashi","year":"1997","journal-title":"J. Androl."},{"key":"ref_119","first-page":"e13592","article-title":"Effect of statin on semen quality characteristics","volume":"52","author":"Banihani","year":"2020","journal-title":"Andrologia"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e12995","DOI":"10.1111\/and.12995","article-title":"Semen parameters are unaffected by statin use in men evaluated for infertility","volume":"50","author":"Keihani","year":"2018","journal-title":"Andrologia"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1211\/jpp.60.11.0002","article-title":"A possible negative effect of co-administered amlodipine and atorvastatin on semen volume and spermatozoa in men","volume":"60","author":"Cai","year":"2008","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/0026-0495(93)90272-P","article-title":"Long-term endocrine function in hypercholesterolemic patients treated with pravastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor","volume":"42","author":"Dobs","year":"1993","journal-title":"Metabolism"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1159\/000457881","article-title":"Protective Effects of Fluvastatin on Reproductive Function in Obese Male Rats Induced by High-Fat Diet through Enhanced Signaling of mTOR","volume":"41","author":"Cui","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.lfs.2015.09.015","article-title":"Rosuvastatin ameliorates diabetes-induced reproductive damage via suppression of oxidative stress, inflammatory and apoptotic pathways in male rats","volume":"141","author":"Heeba","year":"2015","journal-title":"Life Sci."},{"key":"ref_125","first-page":"38","article-title":"Comparison of the Effects of Clofibrate and Silafibrate on Sperm Parameters Quality and Sex Hormones in Male Rats","volume":"15","author":"Delashoub","year":"2018","journal-title":"Urol. J."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1007\/s11695-018-3557-5","article-title":"Impact of Bariatric Surgery on Male Sex Hormones and Sperm Quality: A Systematic Review and Meta-Analysis","volume":"29","author":"Lee","year":"2019","journal-title":"Obes. Surg."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1365-2605.2009.00965.x","article-title":"Following the common association between testosterone deficiency and diabetes mellitus, can testosterone be regarded as a new therapy for diabetes?","volume":"32","author":"Corona","year":"2009","journal-title":"Int. J. Androl."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1988\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:25:25Z","timestamp":1760160325000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,17]]},"references-count":127,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22041988"],"URL":"https:\/\/doi.org\/10.3390\/ijms22041988","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,17]]}}}