{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:46:49Z","timestamp":1789152409911,"version":"build-2803163510"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPESP (Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["[Grants 2007\/07731-0, 2011\/05991-0, and 2015\/04040-2]"],"award-info":[{"award-number":["[Grants 2007\/07731-0, 2011\/05991-0, and 2015\/04040-2]"]}]},{"name":"UNIMED ASSIS"},{"name":"Pro-Rector for Research at UNESP"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Data regarding the use and effect of hormonal contraceptives on bone mass acquisition during adolescence are contradictory. The present study was designed to evaluate bone metabolism in two groups of healthy adolescents using combined oral contraceptives (COC).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A total of 168 adolescents were recruited from 2014 to 2020 in a non-randomized clinical trial and divided into three groups. The COC1 group used 20 \u03bcg Ethinylestradiol (EE)\/150 \u03bcg Desogestrel and the COC2 group used 30 \u03bcg EE\/3 mg Drospirenone over a period of two years. These groups were compared to a control group of adolescent non-COC users. The adolescents were submitted to bone densitometry by dual-energy X-ray absorptiometry and measurement of bone biomarkers, bone alkaline phosphatase (BAP), and osteocalcin (OC) at baseline and 24 months after inclusion in the study. The three groups studied were compared at the different time points by ANOVA, followed by Bonferroni\u2019s multiple comparison test.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Incorporation of bone mass was greater in non-users at all sites analyzed (4.85 g in lumbar Bone mineral content (BMC)) when compared to adolescents of the COC1 and COC2 groups, with a respective increase of 2.15 g and loss of 0.43g in lumbar BMC (P = 0.001). When comparing subtotal BMC, the control increased 100.83 g, COC 1 increased 21.46 g, and COC 2 presented a reduction of 1.47 g (P = 0.005). The values of bone markers after 24 months are similar for BAP, being 30.51 U\/L (\u00b1 11.6) for the control group, 34.95 U\/L (\u00b1 10.8) for COC1, and 30.29 U\/L for COC 2 (\u00b1 11.5) (P = 0.377). However, when we analyzed OC, we observed for control, COC 1, and COC 2 groups, respectively, 13.59 ng\/mL (\u00b1 7.3), 6.44 ng\/mL (\u00b1 4.6), and 9.48 ng\/mL (\u00b1 5.9), with P = 0.003. Despite loss to follow-up occurring in the three groups, there were no significant differences between the variables in adolescents at baseline who remained in the study during the 24-month follow-up and those who were excluded or lost to follow-up.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Bone mass acquisition was compromised in healthy adolescents using combined hormonal contraceptives when compared to controls. This negative impact seems to be more pronounced in the group that used contraceptives containing 30 \u03bcg EE.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Clinical trial registration<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.ensaiosclinicos.gov.br\/\" xlink:type=\"simple\">http:\/\/www.ensaiosclinicos.gov.br<\/jats:ext-link>, RBR-5h9b3c. \u201cLow-dose combined oral contraceptive use is associated with lower bone mass in adolescents\u201d.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0285885","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T17:39:53Z","timestamp":1686245993000},"page":"e0285885","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Bone impact after two years of low-dose oral contraceptive use during adolescence"],"prefix":"10.1371","volume":"18","author":[{"given":"Lilian Rodrigues","family":"Orsolini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7017-766X","authenticated-orcid":true,"given":"Tamara Beres Lederer","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talita Domingues","family":"Caldeir\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Cristiane da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anapaula da Concei\u00e7\u00e3o Bisi","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talita Poli","family":"Biason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Altamir Santos","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helio Rubens","family":"Carvalho Nunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"pone.0285885.ref001","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/s00774-005-0631-6","article-title":"Bone mineral density in girls and boys at different pubertal stages: relation with gonadal steroids, bone formation markers, and growth parameters","volume":"23","author":"D Yilmaz","year":"2005","journal-title":"J Bone Miner Metab"},{"key":"pone.0285885.ref002","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1136\/adc.44.235.291","article-title":"Variations in Pattern of Pubertal Changes in Girls","volume":"44","author":"WA Marshall","year":"1969","journal-title":"Arch Dis Childh"},{"key":"pone.0285885.ref003","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.jped.2014.04.008","article-title":"Relationship between chronological and bone ages and pubertal stage of breasts with bone biomarkers and bone mineral density in adolescents","volume":"90","author":"CMT Fortes","year":"2014","journal-title":"J Pediatr (Rio J)"},{"key":"pone.0285885.ref004","doi-asserted-by":"crossref","first-page":"878","DOI":"10.3390\/ijerph15050878","article-title":"Exercise Early and Often: Effects of Physical Activity and Exercise on Women\u2019s Bone Health","volume":"15","author":"KL Troy","year":"2018","journal-title":"Int J Environ Res Public Health"},{"key":"pone.0285885.ref005","first-page":"1353","article-title":"Physiology and Pathophysiology of Bone Remodeling","volume":"45","author":"L Raisz","year":"1999","journal-title":"Clin Chem"},{"key":"pone.0285885.ref006","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/13625180902838828","article-title":"Oral contraception usage in relation to bone mineral density and bone turnover in adolescent girls","volume":"14","author":"M Lattakova","year":"2009","journal-title":"Eur J Contracept Reprod Health Care"},{"key":"pone.0285885.ref007","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1172\/JCI117034","article-title":"Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. 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