Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
E-pub ahead of print

Voice break in boys-temporal relations with other pubertal milestones and likely causal effects of BMI

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Patients' attitudes and preferences towards a freeze-all strategy in ART treatment

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Recurrent pregnancy loss: couples' perspectives on their need for treatment, support and follow up

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Anogenital distance is associated with semen quality but not reproductive hormones in 1106 young men from the general population

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Cumulative live birth rate prognosis based on the number of aspirated oocytes in previous ART cycles

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Decrease in semen quality and Leydig cell function in infertile men: a longitudinal study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Characterisation and localisation of the endocannabinoid system components in the adult human testis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Possible link between FSH and RANKL release from adipocytes in men with impaired gonadal function including Klinefelter syndrome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Characterization of Human Adrenal Steroidogenesis during Fetal Development

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Populations, decreasing fertility, and reproductive health

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

STUDY FUNDING/COMPETING INTEREST(S): This 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, 14-2013-4); The International Center for Research and Research Training in Endocrine Disrupting Effects of Male Reproduction and Child Health. 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 (R44HG006981). Members of the 23andMe Research Team are employees of 23andMe, Inc. and hold stock or stock options in 23andMe.

TRIAL REGISTRATION NUMBER: NCT01411527.

OriginalsprogEngelsk
TidsskriftHuman reproduction (Oxford, England)
ISSN0268-1161
DOI
StatusE-pub ahead of print - 26 jul. 2019

Bibliografisk note

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

ID: 57662592