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dc.contributor.authorBusch, ASen
dc.contributor.authorHollis, Benjaminen
dc.contributor.authorDay, Felixen
dc.contributor.authorSørensen, Ken
dc.contributor.authorAksglaede, Len
dc.contributor.authorPerry, Johnen
dc.contributor.authorOng, Kennethen
dc.contributor.authorJuul, Aen
dc.contributor.authorHagen, CPen
dc.date.accessioned2019-07-01T23:30:34Z
dc.date.available2019-07-01T23:30:34Z
dc.date.issued2019-08en
dc.identifier.issn0268-1161
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/294253
dc.description.abstractAbstract STUDY QUESTION: How is timing of voice break related to other male pubertal milestones as well as to BMI? SUMMARY ANSWER: We provide a comprehensive temporal analysis of male pubertal milestones, including reproductive hormone dynamics, confirm voice break as a late milestone of male puberty and report a likely causal relationship between higher BMI and earlier age at voice break in men. WHAT IS KNOWN ALREADY: Voice break represents a late pubertal milestone and recalled age at voice break is frequently used in epidemiological studies as a measure of puberty. In contrast, clinical studies use mainly testicular enlargement and/or genital tanner stage as the marker of pubertal onset. However, neither correlation of pubertal milestones nor reproductive hormone dynamics have been assessed in detail previously. Further, although BMI and puberty timing are known to be closely linked, cause and effect between these traits are not known. STUDY DESIGN, SIZE, DURATION: The study included a population-based mixed cross-sectional and longitudinal cohort (2006-2014, COPENHAGEN Puberty Study) of 730 healthy Danish boys. Data for 55,871 male research participants from the 23andMe study were obtained, including genome-wide single nucleotide polymorphism data and age at voice break. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed a detailed evaluation of pubertal milestones and reproductive hormone levels (study population 1). A Mendelian randomization (MR) approach was used to determine the likely causal link between BMI and timing of voice break (study population 2). MAIN RESULTS AND THE ROLE OF CHANCE: Voice break occurred at mean age 13.6 (95% CI: 13.5-13.8) years. At voice break, mean (95% CI) testosterone levels, LH levels and bi-testicular volume were 10.9 (10.0-11.7) nmol/L, 2.4 (2.2-2.5) IU/L and 24 (23-25) mL, respectively. Voice break correlated moderately strongly with timing of male pubertal milestones, including testicular enlargement, gonadarche, pubarche, sweat odor, axillary hair growth and testosterone above limit of detection (r2 range: 0.43-0.61). Timing of all milestones was negatively associated with age-specific BMI (all p≤0.001). MR analyses inferred likely causal effects of higher BMI on earlier voice break in males (-0.35 years/approximate SD, p<0.001). LIMITATIONS, REASONS FOR CAUTION: Participation rate of the population-based cohort was 25%. Further, boys that were followed longitudinally were examined approximately every 6 months limiting the time resolution of pubertal milestones. Using adult BMI as exposure instead of prepubertal BMI in the MR analysis and the known inaccuracies of the testosterone immunoassay at low testosterone levels may be further limitations. WIDER IMPLICATIONS OF THE FINDINGS: We provide valuable normative data on the temporal relation of male pubertal milestones. Further, the likely causal relationship between BMI and puberty timing highlights the importance of preventing obesity in childhood.
dc.description.sponsorshipThis work was supported by Danish Agency for Science, Technology and Innovation (09-067 180); Danish Ministry of the Environment, CeHoS (MST-621-00 065); Capital Region of Denmark (R129-A3966); Ministry of Higher Education and Science (DFF-1331-00 113); Innovation Fund Denmark (InnovationsFonden, grant no. 14-2013-4); The International Center for Research and Research Training in Endocrine Disrupting Effects of Male Reproduction and Child Health (EDMaRC). B.H., F.R.D., J.R.B.P. and K.K.O. are supported by the Medical Research Council (MC_UU_12015/2). The 23andMe study is supported by the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981). Members of the 23andMe Research Team are employees of 23andMe, Inc., and hold stock or stock options in 23andMe.
dc.format.mediumPrinten
dc.languageengen
dc.publisherOxford University Press
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectHumansen
dc.subjectTestosteroneen
dc.subjectBody Mass Indexen
dc.subjectLongitudinal Studiesen
dc.subjectAge Factorsen
dc.subjectPubertyen
dc.subjectVoiceen
dc.subjectAdolescenten
dc.subjectChilden
dc.subjectDenmarken
dc.subjectMaleen
dc.subjectYoung Adulten
dc.subjectPediatric Obesityen
dc.titleVoice break in boys-temporal relations with other pubertal milestones and likely causal effects of BMI.en
dc.typeArticle
prism.endingPage1522
prism.issueIdentifier8en
prism.publicationDate2019en
prism.publicationNameHuman reproduction (Oxford, England)en
prism.startingPage1514
prism.volume34en
dc.identifier.doi10.17863/CAM.41352
dcterms.dateAccepted2019-06-10en
rioxxterms.versionofrecord10.1093/humrep/dez118en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-08en
dc.contributor.orcidDay, Felix [0000-0003-3789-7651]
dc.contributor.orcidAksglaede, L [0000-0001-7885-7467]
dc.contributor.orcidPerry, John [0000-0001-6483-3771]
dc.contributor.orcidOng, Kenneth [0000-0003-4689-7530]
dc.identifier.eissn1460-2350
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/2)
cam.orpheus.successThu Jan 30 10:42:38 GMT 2020 - Embargo updated*
rioxxterms.freetoread.startdate2020-08-31


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