{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:44:06Z","timestamp":1787013846404,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2016\u201001642"],"award-info":[{"award-number":["2016\u201001642"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypospadias is a common congenital malformation often related to the effect of androgens in utero. While hypogonadism is associated with many potential health risks including metabolic and cardiovascular disease, the risk of clinical hypogonadism and comorbidities in men with hypospadias later in life has not been studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Investigate the risk of hypogonadism and somatic comorbidities in adolescents and men born with hypospadias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We conducted a population\u2010based cohort study using Swedish registers. Associations between hypospadias and hypogonadism, delayed puberty, metabolic, and cardiovascular disease respectively were estimated using Cox proportional hazards regression. Body measurements from military conscription were analysed in a subpopulation as indicators of growth and cardiometabolic risk. We used sibling comparison analyses to control for familial confounding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Using register data, a total of 2,165,255 men including 9,714 men born with hypospadias were followed from the age of 10 to a maximum of 60 years. We found an association between hypospadias and hypogonadism (Hazard ratio (HR)\u00a03.27, 95% confidence interval (CI) 2.33\u20134.59) which was more pronounced in proximal hypospadias. Men with hypospadias had shorter average height than their brothers and the general population. We further found an increased risk of delayed puberty (HR 1.49, 95% CI 1.08\u20132.07), diabetes mellitus type 2 (HR 1.57, 95% CI 1.18\u20132.09) and cardiovascular disease (HR 1.47, 95% CI 1.27\u20131.71).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We found an increased risk of hypogonadism, metabolic and cardiovascular disease in men born with hypospadias, increasing with severity of phenotype, as well as impacted growth. These results indicate discruptions in androgen function past childhood, although some of the associations may be due to other underlying aetiologies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hypospadias is associated with an increased risk of androgen\u2010related comorbidity in adolescence and adulthood. We suggest that this can be considered clinically, while further research is needed, especially in older populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.13229","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T04:57:31Z","timestamp":1658120251000},"page":"1376-1386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Increased androgen\u2010related comorbidity in adolescents and adults born with hypospadias: A population\u2010based study"],"prefix":"10.1111","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4108-1471","authenticated-orcid":false,"given":"Lottie","family":"Phillips","sequence":"first","affiliation":[{"name":"Department of Women's and Children's Health, and Center of Molecular Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Lundholm","sequence":"additional","affiliation":[{"name":"Deparment of Medical Epidemiology and Biostatistics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrik","family":"Kvist","sequence":"additional","affiliation":[{"name":"Department of Medicine, Huddinge Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Almqvist","sequence":"additional","affiliation":[{"name":"Deparment of Medical Epidemiology and Biostatistics Karolinska Institutet  Stockholm Sweden"},{"name":"Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children's Hospital Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agneta","family":"Nordenskj\u00f6ld","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, and Center of Molecular Medicine Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Pediatric Surgery, Astrid Lindgren Children\u00b4s Hospital Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3034-9222","authenticated-orcid":false,"given":"Anna","family":"Skarin Nordenvall","sequence":"additional","affiliation":[{"name":"Deparment of Medical Epidemiology and Biostatistics Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Radiology Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.09.058"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)65334-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dms002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2009.00957.x"},{"issue":"8","key":"e_1_2_8_6_1","first-page":"PC01","article-title":"Fertility potential in adult hypospadias","volume":"10","author":"Kumar S","year":"2016","journal-title":"J Clin Diagn Res"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61126-5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-12-0455"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsxm.2018.06.012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-12-0582"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2018.03.115"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-019-0211-4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-016-0117-y"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-11-450"},{"key":"e_1_2_8_15_1","unstructured":"Socialstyrelsen.The Swedish Medical Birth Register \u2010 A summary of content and quality.https:\/\/www.socialstyrelsen.se\/globalassets\/sharepoint-dokument\/artikelkatalog\/ovrigt\/2003-112-3_20031123.pdf. 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