{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:33:46Z","timestamp":1793198026050,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100005039","name":"Leiden University Medical Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005039","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001717","name":"Leiden University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Estrogens play a large role in female and male physiology and are routinely determined in the clinical setting. For interpretation, distinct reference intervals (RIs) are applied for men, pre-, and postmenopausal women. Adipose tissue is a potent producer of estrogens and influences the circulating estrogen concentrations, although its impact on estrogen RIs is currently unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We determined estradiol and estrone concentrations in 6671 middle-aged participants of a large cohort oversampled for persons with a Body Mass Index (BMI) \u226527\u2005kg\/m2. We investigated partitioning based on sex, age, menopausal status, and BMI by assessing the proportion of subgroups outside each limit of a shared 95% RI (ideally 2.5%) and calculating RIs for justified subgroups according to CLSI EP28-A3c.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>As expected, the strongest partitioning factor was sex, followed by menopausal status for women. When using a shared RI for all BMI categories, 4.9% and 5.2% of values in men with obesity and 11.4% and 7.7% of values in postmenopausal women with obesity fell above the RI for estradiol and estrone, respectively. Within postmenopausal women, differences in the upper reference limit were found, being 138, 157, and 210\u2005pmol\/L for estradiol and 32, 41, and 74\u2005pmol\/L for estrone for normal weight, overweight, and obesity, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Laboratory professionals and clinicians should be aware that BMI affects estrogen concentrations to such an extent that it may influence clinical interpretation. Ideally, their RIs should be stratified by BMI category to reflect the increased estrogen concentrations associated with higher BMI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag194","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:26:41Z","timestamp":1792416401000},"page":"658-666","source":"Crossref","is-referenced-by-count":0,"title":["BMI as a partitioning factor for estradiol and estrone reference intervals in middle-aged men and postmenopausal women"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4520-7385","authenticated-orcid":false,"given":"Mirjam","family":"Kruijt","sequence":"first","affiliation":[{"name":"Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, Location University of Amsterdam and Location Vrije Universiteit Amsterdam , 1105AZ Amsterdam ,","place":["the Netherlands"]},{"name":"Gastroenterology, Endocrinology and Metabolism Institute , 1105AZ Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5470-0673","authenticated-orcid":false,"given":"Ren\u00e9e","family":"de Mutsert","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center , 2333ZA Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-1168","authenticated-orcid":false,"given":"Astrid","family":"van Hylckama Vlieg","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center , 2333ZA Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2558-7496","authenticated-orcid":false,"given":"Frits R","family":"Rosendaal","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center , 2333ZA Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1161-0301","authenticated-orcid":false,"given":"Jacquelien J","family":"Hillebrand","sequence":"additional","affiliation":[{"name":"Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, Location University of Amsterdam and Location Vrije Universiteit Amsterdam , 1105AZ Amsterdam ,","place":["the Netherlands"]},{"name":"Gastroenterology, Endocrinology and Metabolism Institute , 1105AZ Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3620-5617","authenticated-orcid":false,"given":"Martin","family":"den Heijer","sequence":"additional","affiliation":[{"name":"Gastroenterology, Endocrinology and Metabolism Institute , 1105AZ Amsterdam ,","place":["the Netherlands"]},{"name":"Department of Endocrinology and Metabolism and Center of Expertise on Gender Dysphoria, Amsterdam UMC, Location Vrije Universiteit Amsterdam , 1081HV Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6712-9955","authenticated-orcid":false,"given":"Annemieke C","family":"Heijboer","sequence":"additional","affiliation":[{"name":"Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, Location University of Amsterdam and Location Vrije Universiteit Amsterdam , 1105AZ Amsterdam ,","place":["the Netherlands"]},{"name":"Gastroenterology, Endocrinology and Metabolism Institute , 1105AZ Amsterdam ,","place":["the Netherlands"]},{"name":"Amsterdam Reproduction and Development Research Institute , 1105AZ Amsterdam ,","place":["the 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