{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T06:23:46Z","timestamp":1785911026436,"version":"3.56.0"},"reference-count":32,"publisher":"The Endocrine Society","issue":"5","funder":[{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"publisher","award":["Z01-ES103315"],"award-info":[{"award-number":["Z01-ES103315"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"publisher","award":["ES103363"],"award-info":[{"award-number":["ES103363"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Pubertal girls with higher total body fat (TBF) demonstrate higher androgen levels. The cause of this association is unknown but is hypothesized to relate to insulin resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This work aimed to investigate the association between higher TBF and higher androgens in pubertal girls using untargeted metabolomics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Serum androgens were determined using a quantitative mass spectrometry (MS)\u2013based assay. Metabolomic samples were analyzed using liquid chromatography high-resolution MS. Associations between TBF or body mass index (BMI) z score (exposure) and metabolomic features (outcome) and between metabolomic features (exposure) and serum hormones (outcome) were examined using gaussian generalized estimating equation models with the outcome lagged by one study visit. Benjamini-Hochberg false discovery rate (FDR) adjusted P values were calculated to account for multiple testing. RaMP-DB (relational database of metabolomic pathways) was used to conduct enriched pathway analyses among features nominally associated with body composition or hormones.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Sixty-six pubertal, premenarchal girls (aged 10.9 \u00b1 1.39 SD years; 60% White, 24% Black, 16% other; 63% normal weight, 37% overweight\/obese) contributed an average of 2.29 blood samples. BMI and TBF were negatively associated with most features including raffinose (a plant trisaccharide) and several bile acids. For BMI, RaMP-DB identified many enriched pathways related to bile acids. Androstenedione also showed strong positive associations with raffinose and bile acids.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Metabolomic analyses of samples from pubertal girls did not identify an insulin resistance signature to explain the association between higher TBF and androgens. Instead, we identified potential novel signaling pathways that may involve raffinose or bile acid action at the adrenal gland.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad675","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T06:59:57Z","timestamp":1700290797000},"page":"1328-1333","source":"Crossref","is-referenced-by-count":3,"title":["Pubertal Girls With Overweight\/Obesity Have Higher Androgen Levels\u2014Can Metabolomics Tell us Why?"],"prefix":"10.1210","volume":"109","author":[{"given":"Madison E","family":"Calvert","sequence":"first","affiliation":[{"name":"Pediatric Neuroendocrinology Group, Clinical Research Branch, National Institute of Environmental Health Sciences (NIEHS) , Durham, NC 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha A","family":"Molsberry","sequence":"additional","affiliation":[{"name":"Social & Scientific Systems, a DLH Holdings company , Durham, NC 27703 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten E","family":"Overdahl","sequence":"additional","affiliation":[{"name":"Metabolomics Core Facility, NIEHS , Durham, NC 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan K","family":"Jarmusch","sequence":"additional","affiliation":[{"name":"Metabolomics Core Facility, NIEHS , Durham, NC 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0847-9170","authenticated-orcid":false,"given":"Natalie D","family":"Shaw","sequence":"additional","affiliation":[{"name":"Pediatric Neuroendocrinology Group, Clinical Research Branch, National Institute of Environmental Health Sciences (NIEHS) , Durham, NC 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,11,18]]},"reference":[{"issue":"6","key":"2024073012241296600_dgad675-B1","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1542\/peds.2012-3773","article-title":"Onset of breast development in a longitudinal cohort","volume":"132","author":"Biro","year":"2013","journal-title":"Pediatrics"},{"issue":"4","key":"2024073012241296600_dgad675-B2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jpag.2018.05.002","article-title":"Age of menarche in a longitudinal US cohort","volume":"31","author":"Biro","year":"2018","journal-title":"J Pediatr Adolesc Gynecol"},{"issue":"4","key":"2024073012241296600_dgad675-B3","first-page":"1168","article-title":"Blunted sleep-related luteinizing hormone rise in healthy premenarcheal pubertal girls with elevated body mass index","volume":"94","author":"Bordini","year":"2009","journal-title":"JClinEndocrinolMetab"},{"issue":"4","key":"2024073012241296600_dgad675-B4","doi-asserted-by":"crossref","first-page":"219","DOI":"10.6065\/apem.2016.21.4.219","article-title":"The impact of obesity on hyperandrogenemia in Korean girls","volume":"21","author":"Kang","year":"2016","journal-title":"Ann Pediatr Endocrinol Metab"},{"issue":"5","key":"2024073012241296600_dgad675-B5","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1210\/jc.2005-1852","article-title":"The association of obesity and hyperandrogenemia during the pubertal transition in girls: obesity as a potential factor in the genesis of postpubertal hyperandrogenism","volume":"91","author":"McCartney","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"2024073012241296600_dgad675-B6","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1210\/jc.2018-02313","article-title":"Distinctive reproductive phenotypes in peripubertal girls at risk for polycystic ovary syndrome","volume":"104","author":"Torchen","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2024073012241296600_dgad675-B7","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1210\/clinem\/dgab092","article-title":"Longitudinal investigation of pubertal milestones and hormones as a function of body fat in girls","volume":"106","author":"Ortega","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"2024073012241296600_dgad675-B8","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1038\/oby.2010.58","article-title":"Hyperandrogenemia in obese peripubertal girls: correlates and potential etiological determinants","volume":"18","author":"Knudsen","year":"2010","journal-title":"Obesity (Silver Spring)"},{"issue":"7","key":"2024073012241296600_dgad675-B9","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1210\/jc.2009-0139","article-title":"KLF15 is a transcriptional regulator of the human 17beta-hydroxysteroid dehydrogenase type 5 gene. 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