{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:14:14Z","timestamp":1788372854663,"version":"build-2803163510"},"reference-count":48,"publisher":"Bioscientifica","issue":"9","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CYP19A1 encodes aromatase, the enzyme converting androgens to estrogens, thereby influencing breast tissue development in healthy children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine associations between CYP19A1 single nucleotide polymorphisms (SNPs) and circulating estradiol (E2) and testosterone (T), the E2\/T ratio and age at thelarche in girls, and the presence of gynecomastia in boys.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 1,023 healthy participants (aged 5.9\u201320.0 years) from the Copenhagen Puberty Study were assessed for pubertal status, and serum sex steroid concentrations were measured by LC\u2013MS\/MS. Genotyping of CYP19A1 SNPs (rs727479 A&amp;gt;C, rs2899472 A&amp;gt;C and rs10046 C&amp;gt;T) was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Girls with the AA genotype in rs727479 and rs2899472 showed tendencies toward earlier pubertal onset. In a combined efficacy allele model, each additional allele was associated with 1.6 months earlier puberty (P = 0.06), and girls with 5\u20136 vs 0\u20132 efficacy alleles presented with significantly lower pubertal age (P = 0.02). The CYP19A1 genotype was not associated with E2, T or E2\/T levels. Boys with the CC genotype in rs727479 had the highest prevalence of pubertal gynecomastia (73%, P &amp;lt; 0.01). Boys with gynecomastia showed higher E2 and T (SDS) than unaffected boys (both P &amp;lt; 0.01), with no difference in E2\/T. In age-matched analyses, E2 (SDS) remained elevated in boys with gynecomastia (0.81 vs 0.19, P = 0.04).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CYP19A1 variants may influence pubertal timing in girls. In boys, pubertal gynecomastia appeared to be linked with the CYP19A1 genotype and was associated with elevated E2 concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance statement<\/jats:title>\n                    <jats:p>Aromatase, encoded by CYP19A1, catalyzes the conversion of androgens to estrogens. The contribution of common CYP19A1 genetic variants to variation in pubertal development in healthy children is not fully understood. In this cohort from the Copenhagen Puberty Study, we examined associations between CYP19A1 polymorphisms and circulating sex steroid concentrations, age at puberty and pubertal gynecomastia in boys. By integrating genetic, hormonal and clinical pubertal data, this study provides additional insights into potential links between aromatase-related genetic variation and normal pubertal development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-26-0182","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:29:46Z","timestamp":1786634986000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":0,"title":["<i>CYP19A1<\/i>\n                    variation in healthy children: associations with breast development and pubertal gynecomastia"],"prefix":"10.1530","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2601-3638","authenticated-orcid":true,"given":"Veronica L R","family":"Groendahl","sequence":"first","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital \u2013 Rigshospitalet 1 , ,","place":["Copenhagen, 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Hospital \u2013 Rigshospitalet 1 , ,","place":["Copenhagen, Denmark"]},{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen 2 , ,","place":["Copenhagen, Denmark"]},{"name":"Department of General Pediatrics, University of M\u00fcnster 3 , ,","place":["M\u00fcnster, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper P","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital \u2013 Rigshospitalet 1 , ,","place":["Copenhagen, Denmark"]},{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen 2 , ,","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen H","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital \u2013 Rigshospitalet 1 , ,","place":["Copenhagen, Denmark"]},{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen 2 , ,","place":["Copenhagen, Denmark"]},{"name":"Section of Biostatistics, University of Copenhagen 4 , ,","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine H","family":"Johannsen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital \u2013 Rigshospitalet 1 , ,","place":["Copenhagen, Denmark"]},{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen 2 , ,","place":["Copenhagen, Denmark"]},{"name":"Department of Clinical Biochemistry, Copenhagen University Hospital \u2013 Rigshospitalet 5 , ,","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1832-0307","authenticated-orcid":true,"given":"Kristian","family":"Almstrup","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital \u2013 Rigshospitalet 1 , ,","place":["Copenhagen, Denmark"]},{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen 2 , ,","place":["Copenhagen, Denmark"]},{"name":"Department of Cellular and Molecular Medicine, University of Copenhagen 6 , ,","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Frederiksen","sequence":"additional","affiliation":[{"name":"Department of 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