{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:17:41Z","timestamp":1783059461858,"version":"3.54.6"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Klinefelter syndrome (KS; 47, XXY) usually involves male sex development and gender identity. Small studies suggest gender incongruence may be more common in KS, but feminizing gender\u2011affirming hormone therapy in this group has been scarcely reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate current feminizing hormone therapy in individuals with KS and the number of individuals with KS attending our gender clinic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We conducted a care evaluation of individuals with KS referred to the Center of Expertise on Gender Dysphoria (Amsterdam UMC) between February 1972 and May 2025, collecting data on KS diagnosis, testosterone use, referral age, feminizing hormone therapy, and hormone concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight (0.12%) people had KS. Median age at KS diagnosis was 25.3 years (IQR 16.9\u201337.5,\n                      <jats:italic>n<\/jats:italic>\n                      = 8), and at gender clinic intake 45.3 years (IQR 34.2\u201352.2,\n                      <jats:italic>n<\/jats:italic>\n                      = 8). Among estradiol users, median age was 45.7 years (IQR 42.4\u201357.1,\n                      <jats:italic>n<\/jats:italic>\n                      = 6). None of those retaining their testes use testosterone blockers (follow\u2011up: median 5.4 years (3.6\u20137.7),\n                      <jats:italic>n<\/jats:italic>\n                      = 5).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In KS, estradiol alone may sufficiently suppress testosterone. KS prevalence in our cohort does not exceed that of the general population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Given KS\u2011related hypogonadism, estradiol monotherapy may be an appropriate first\u2011line feminizing hormone therapy, avoiding routine use of testosterone blockers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70290","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:28:41Z","timestamp":1783056521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Feminizing Therapy in People With Klinefelter Syndrome and Gender Incongruence: Considerations for Treatment Without Testosterone Blockers"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1721-7470","authenticated-orcid":false,"given":"Maaike","family":"Kroon","sequence":"first","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam Center of Expertise on Gender Dysphoria  Amsterdam The Netherlands"},{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam Department of Endocrinology and Metabolism  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"},{"name":"Amsterdam Public Health, Health Behaviors and Chronic Diseases  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamira Klaziene","family":"Klooker","sequence":"additional","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam Center of Expertise on Gender Dysphoria  Amsterdam The Netherlands"},{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam Department of Endocrinology and Metabolism  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine Elisabeth","family":"Hannema","sequence":"additional","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam Center of Expertise on Gender Dysphoria  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"},{"name":"Amsterdam UMC location University of Amsterdam, Paediatric Endocrinology  Amsterdam The Netherlands"},{"name":"Amsterdam Reproduction and Development  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Den Heijer","sequence":"additional","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam Center of Expertise on Gender Dysphoria  Amsterdam The Netherlands"},{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam Department of Endocrinology and Metabolism  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"},{"name":"Amsterdam Public Health, Health Behaviors and Chronic Diseases  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"issue":"2","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/sj.ejhg.5201956","article-title":"Is the Prevalence of Klinefelter Syndrome Increasing?","volume":"16","author":"Morris J. K.","year":"2008","journal-title":"European Journal of Human Genetics"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2025.102002"},{"issue":"4","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1210\/er.2017-00212","article-title":"Klinefelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology","volume":"39","author":"Gravholt C. H.","year":"2018","journal-title":"Endocrine Reviews"},{"issue":"4","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1210\/endrev\/bnaf005","article-title":"New Horizons in Klinefelter Syndrome: Current Evidence, Gaps, and Research Priorities","volume":"46","author":"Lucas\u2010Herald A. 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O.","year":"2023","journal-title":"Endocrine Connections"},{"key":"e_1_2_11_8_1","first-page":"55","volume-title":"47, XXY Klinefelter Syndrome: Clinical Characteristics and Age\u2010specific Recommendations for Medical Management","author":"Aksglaede L.","year":"2013"},{"issue":"5","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.jsxm.2018.02.021","article-title":"Gender Dysphoria and Gender Change in Disorders of Sex Development\/Intersex Conditions: Results From the dsd\u2010LIFE Study","volume":"15","author":"Kreukels B. P. 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