The COPENHAGEN Puberty Study

NCT01411527 | Completed Results

• 1 other identifier: KF01282214
• Study Type: observational
• Target: 1,957
• Locations: 1 country
• Sites: 1

Brief Summary

By clinical examinations and withdrawing of blood samples from a large number of healthy Danish children, this study will reveal if age of pubertal onset is declining. Furthermore, the extensive normative data will provide detailed insight into normal ranges and individual changes of anthropometrics and hormone levels in healthy children during childhood and adolescence.

Conditions

Puberty

Keywords

Hormones; Endocrine Disrupters; Polymorphism, Genetic

Outcome Measures

Primary Outcomes (1)

• Pubertal Onset

  Pubertal onset (according to Tanner stageing - Marshall \& Tanner 1969 and 1970), i.e. Tanner stages B2+ or G2+ \[Tanner stages included genital stages 1-5 as well as pubic hairs tages 1-6\] Data of both arms were pooled for calculation of means.

  up to 8 year period.

Study Arms (2)

Cross- sectional cohort

Schools were randomly selected and 6203 children (50.0 % girls) were invited to participate. 1864 (1097 girls and 767 boys) (age 5.6-20.0 years) were included, resulting in an overall participation-rate of 30%. Blood samples were drawn, and a thorough clinical examination was performed in all participating children

Longitudinal cohort

209 healthy Danish children (108 girls), were examined and blood samples were drawn every 6 months. In july 2011, the mean (range) number of examinations per child was 7 (2-10). 116 (63 boys and 53 girls) continued from the cross sectional study to the longitudinal study. Thus, the total number of participants in The COPENHAGEN Puberty Study was 2020 children.

Eligibility Criteria

• Age: 5 Years - 20 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

In the cross sectional study, all children at randomly selected schools in Copenhagen were invited (6203 children). 1864 accepted to participate. In the longitudinal study, children at two schools with the highest participating rate were invited to participate in the follow-up study. Ongoing recruitment was continued until at least 100 boys and 100 girls were enrolled in the logitudinal study.

You may qualify if:

• all children accepting to participate were included

You may not qualify if:

• no children were excluded from examination or blood sampling. In case of chronic diseases, medical treatment, or ethnicity the children may be excluded from specific final data analysis.

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• The Ministry of Science, Technology and Innovation, Denmark: collaborator
• European Commission: collaborator

Study Sites (1)

Department of Growth and Reproduction, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (34)

• Courant F, Aksglaede L, Antignac JP, Monteau F, Sorensen K, Andersson AM, Skakkebaek NE, Juul A, Bizec BL. Assessment of circulating sex steroid levels in prepubertal and pubertal boys and girls by a novel ultrasensitive gas chromatography-tandem mass spectrometry method. J Clin Endocrinol Metab. 2010 Jan;95(1):82-92. doi: 10.1210/jc.2009-1140. Epub 2009 Nov 20.

  PMID: 19933393 BACKGROUND

• Aksglaede L, Sorensen K, Petersen JH, Skakkebaek NE, Juul A. Recent decline in age at breast development: the Copenhagen Puberty Study. Pediatrics. 2009 May;123(5):e932-9. doi: 10.1542/peds.2008-2491.

  PMID: 19403485 RESULT

• Sorensen K, Aksglaede L, Petersen JH, Juul A. Recent changes in pubertal timing in healthy Danish boys: associations with body mass index. J Clin Endocrinol Metab. 2010 Jan;95(1):263-70. doi: 10.1210/jc.2009-1478. Epub 2009 Nov 19.

  PMID: 19926714 RESULT

• Sorensen K, Aksglaede L, Munch-Andersen T, Aachmann-Andersen NJ, Petersen JH, Hilsted L, Helge JW, Juul A. Sex hormone-binding globulin levels predict insulin sensitivity, disposition index, and cardiovascular risk during puberty. Diabetes Care. 2009 May;32(5):909-14. doi: 10.2337/dc08-1618. Epub 2009 Feb 5.

  PMID: 19196890 RESULT

• Juul A, Sorensen K, Aksglaede L, Garn I, Rajpert-De Meyts E, Hullstein I, Hemmersbach P, Ottesen AM. A common deletion in the uridine diphosphate glucuronyltransferase (UGT) 2B17 gene is a strong determinant of androgen excretion in healthy pubertal boys. J Clin Endocrinol Metab. 2009 Mar;94(3):1005-11. doi: 10.1210/jc.2008-1984. Epub 2008 Dec 16.

  PMID: 19088161 RESULT

• Sorensen K, Aksglaede L, Munch-Andersen T, Aachmann-Andersen NJ, Leffers H, Helge JW, Hilsted L, Juul A. Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty. J Clin Endocrinol Metab. 2009 Aug;94(8):2966-9. doi: 10.1210/jc.2009-0313. Epub 2009 May 5.

  PMID: 19417039 RESULT

• Sorensen K, Aksglaede L, Petersen JH, Leffers H, Juul A. The exon 3 deleted growth hormone receptor gene is associated with small birth size and early pubertal onset in healthy boys. J Clin Endocrinol Metab. 2010 Jun;95(6):2819-26. doi: 10.1210/jc.2009-2484. Epub 2010 Apr 9.

  PMID: 20382688 RESULT

• Sorensen K, Mouritsen A, Mogensen SS, Aksglaede L, Juul A. Insulin sensitivity and lipid profiles in girls with central precocious puberty before and during gonadal suppression. J Clin Endocrinol Metab. 2010 Aug;95(8):3736-44. doi: 10.1210/jc.2010-0731. Epub 2010 May 19.

  PMID: 20484471 RESULT

• Hagen CP, Aksglaede L, Sorensen K, Main KM, Boas M, Cleemann L, Holm K, Gravholt CH, Andersson AM, Pedersen AT, Petersen JH, Linneberg A, Kjaergaard S, Juul A. Serum levels of anti-Mullerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients. J Clin Endocrinol Metab. 2010 Nov;95(11):5003-10. doi: 10.1210/jc.2010-0930. Epub 2010 Aug 18.

  PMID: 20719830 RESULT

• Aksglaede L, Sorensen K, Boas M, Mouritsen A, Hagen CP, Jensen RB, Petersen JH, Linneberg A, Andersson AM, Main KM, Skakkebaek NE, Juul A. Changes in anti-Mullerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. J Clin Endocrinol Metab. 2010 Dec;95(12):5357-64. doi: 10.1210/jc.2010-1207. Epub 2010 Sep 15.

  PMID: 20843948 RESULT

• Mogensen SS, Aksglaede L, Mouritsen A, Sorensen K, Main KM, Gideon P, Juul A. Diagnostic work-up of 449 consecutive girls who were referred to be evaluated for precocious puberty. J Clin Endocrinol Metab. 2011 May;96(5):1393-401. doi: 10.1210/jc.2010-2745. Epub 2011 Feb 23.

  PMID: 21346077 RESULT

• Aksglaede L, Christiansen P, Sorensen K, Boas M, Linneberg A, Main KM, Andersson AM, Skakkebaek NE, Juul A. Serum concentrations of Anti-Mullerian Hormone (AMH) in 95 patients with Klinefelter syndrome with or without cryptorchidism. Acta Paediatr. 2011 Jun;100(6):839-45. doi: 10.1111/j.1651-2227.2011.02148.x. Epub 2011 Feb 25.

  PMID: 21251056 RESULT

• Frederiksen H, Aksglaede L, Sorensen K, Nielsen O, Main KM, Skakkebaek NE, Juul A, Andersson AM. Bisphenol A and other phenols in urine from Danish children and adolescents analyzed by isotope diluted TurboFlow-LC-MS/MS. Int J Hyg Environ Health. 2013 Nov;216(6):710-20. doi: 10.1016/j.ijheh.2013.01.007. Epub 2013 Mar 13.

  PMID: 23491025 RESULT

• Mouritsen A, Hagen CP, Sorensen K, Aksglaede L, Mieritz MG, Main KM, Almstrup K, Rajpert-De Meyts E, Juul A. Androgen receptor CAG repeat length is associated with body fat and serum SHBG in boys: a prospective cohort study. J Clin Endocrinol Metab. 2013 Mar;98(3):E605-9. doi: 10.1210/jc.2012-3778. Epub 2013 Feb 7.

  PMID: 23393169 RESULT

• Mouritsen A, Aksglaede L, Soerensen K, Hagen CP, Petersen JH, Main KM, Juul A. The pubertal transition in 179 healthy Danish children: associations between pubarche, adrenarche, gonadarche, and body composition. Eur J Endocrinol. 2012 Dec 31;168(2):129-36. doi: 10.1530/EJE-12-0191. Print 2013 Feb.

  PMID: 23093700 RESULT

• Hilsted L, Rustad P, Aksglaede L, Sorensen K, Juul A. Recommended Nordic paediatric reference intervals for 21 common biochemical properties. Scand J Clin Lab Invest. 2013 Feb;73(1):1-9. doi: 10.3109/00365513.2012.721519. Epub 2012 Sep 26.

  PMID: 23013046 RESULT

• Mieritz MG, Frederiksen H, Sorensen K, Aksglaede L, Mouritsen A, Hagen CP, Skakkebaek NE, Andersson AM, Juul A. Urinary phthalate excretion in 555 healthy Danish boys with and without pubertal gynaecomastia. Int J Androl. 2012 Jun;35(3):227-35. doi: 10.1111/j.1365-2605.2012.01279.x.

  PMID: 22612475 RESULT

• Frederiksen H, Sorensen K, Mouritsen A, Aksglaede L, Hagen CP, Petersen JH, Skakkebaek NE, Andersson AM, Juul A. High urinary phthalate concentration associated with delayed pubarche in girls. Int J Androl. 2012 Jun;35(3):216-26. doi: 10.1111/j.1365-2605.2012.01260.x. Epub 2012 Mar 19.

  PMID: 22428786 RESULT

• Hagen CP, Aksglaede L, Sorensen K, Mouritsen A, Andersson AM, Petersen JH, Main KM, Juul A. Individual serum levels of anti-Mullerian hormone in healthy girls persist through childhood and adolescence: a longitudinal cohort study. Hum Reprod. 2012 Mar;27(3):861-6. doi: 10.1093/humrep/der435. Epub 2012 Jan 2.

  PMID: 22215627 RESULT

• Busch AS, Hagen CP, Main KM, Pereira A, Corvalan C, Almstrup K, Mericq V, Juul A. Genetic Variation of Follicle-Stimulating Hormone Action Is Associated With Age at Testicular Growth in Boys. J Clin Endocrinol Metab. 2017 May 1;102(5):1740-1749. doi: 10.1210/jc.2016-4013.

  PMID: 28323923 RESULT

• Busch AS, Hagen CP, Almstrup K, Juul A. Circulating MKRN3 Levels Decline During Puberty in Healthy Boys. J Clin Endocrinol Metab. 2016 Jun;101(6):2588-93. doi: 10.1210/jc.2016-1488. Epub 2016 Apr 8.

  PMID: 27057785 RESULT

• Almstrup K, Lindhardt Johansen M, Busch AS, Hagen CP, Nielsen JE, Petersen JH, Juul A. Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood. Sci Rep. 2016 Jun 28;6:28657. doi: 10.1038/srep28657.

  PMID: 27349168 RESULT

• Busch AS, Ljubicic ML, Upners EN, Fischer MB, Hagen CP, Fluck CE, Johannsen TH, Frederiksen H, Juul A. Serum steroid metabolome dynamics in infancy: a longitudinal cohort study of healthy infants. Eur J Endocrinol. 2025 Sep 30;193(4):403-411. doi: 10.1093/ejendo/lvaf193.

  PMID: 40974100 DERIVED

• Sorensen K, Hagen CP, Juul A. Higher peak height velocity in early maturing girls depends on insulin rather than fat mass or IGF-I. Eur J Endocrinol. 2024 Sep 30;191(4):381-388. doi: 10.1093/ejendo/lvae115.

  PMID: 39292994 DERIVED

• Busch AS, Ljubicic ML, Upners EN, Fischer MB, Kolby N, Eckert-Lind C, Jespersen K, Andersson AM, Frederiksen H, Johannsen TH, Hegaard HK, Sharif H, Hagen CP, Juul A. Cohort profile: The COPENHAGEN Minipuberty Study-A longitudinal prospective cohort of healthy full-term infants and their parents. Paediatr Perinat Epidemiol. 2021 Sep;35(5):601-611. doi: 10.1111/ppe.12777. Epub 2021 Jun 22.

  PMID: 34156716 DERIVED

• Albrethsen J, Ljubicic ML, Juul A. Longitudinal Increases in Serum Insulin-like Factor 3 and Testosterone Determined by LC-MS/MS in Pubertal Danish Boys. J Clin Endocrinol Metab. 2020 Oct 1;105(10):dgaa496. doi: 10.1210/clinem/dgaa496.

  PMID: 32761207 DERIVED

• Busch AS, Hojgaard B, Hagen CP, Teilmann G. Obesity Is Associated with Earlier Pubertal Onset in Boys. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz222. doi: 10.1210/clinem/dgz222.

  PMID: 31761939 DERIVED

• Busch AS, Hollis B, Day FR, Sorensen K, Aksglaede L, Perry JRB, Ong KK, Juul A, Hagen CP. Voice break in boys-temporal relations with other pubertal milestones and likely causal effects of BMI. Hum Reprod. 2019 Aug 1;34(8):1514-1522. doi: 10.1093/humrep/dez118.

  PMID: 31348498 DERIVED

• Busch AS, Hagen CP, Assens M, Main KM, Almstrup K, Juul A. Differential Impact of Genetic Loci on Age at Thelarche and Menarche in Healthy Girls. J Clin Endocrinol Metab. 2018 Jan 1;103(1):228-234. doi: 10.1210/jc.2017-01860.

  PMID: 29077908 DERIVED

• Kolby N, Busch AS, Aksglaede L, Sorensen K, Petersen JH, Andersson AM, Juul A. Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty. J Clin Endocrinol Metab. 2017 Oct 1;102(10):3830-3838. doi: 10.1210/jc.2017-01192.

  PMID: 28938419 DERIVED

• Lindhardt Johansen M, Hagen CP, Mieritz MG, Wolthers OD, Heuck C, Petersen JH, Juul A. Pubertal Progression and Reproductive Hormones in Healthy Girls With Transient Thelarche. J Clin Endocrinol Metab. 2017 Mar 1;102(3):1001-1008. doi: 10.1210/jc.2016-2871.

  PMID: 28009526 DERIVED

• Bisgaard A, Sorensen K, Johannsen TH, Helge JW, Andersson AM, Juul A. Significant gender difference in serum levels of fibroblast growth factor 21 in Danish children and adolescents. Int J Pediatr Endocrinol. 2014;2014(1):7. doi: 10.1186/1687-9856-2014-7. Epub 2014 May 23.

  PMID: 24883065 DERIVED

• Nielsen J, Jensen RB, Juul A. Increased sex hormone-binding globulin levels in children and adolescents with thyrotoxicosis. Horm Res Paediatr. 2013;79:157-61. doi: 10.1159/000348837. Epub 2013 Mar 27.

  PMID: 23548728 DERIVED

• Hagen CP, Sorensen K, Anderson RA, Juul A. Serum levels of antimullerian hormone in early maturing girls before, during, and after suppression with GnRH agonist. Fertil Steril. 2012 Nov;98(5):1326-30. doi: 10.1016/j.fertnstert.2012.07.1118. Epub 2012 Aug 14.

  PMID: 22901847 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

serum, white cells, urine

Results Point of Contact

• Title: Anders Juul
• Organization: Rigshospitalet

Anders.Juul@regionh.dk

+45 3545 5085

Study Officials

• Anders Juul, PhD, DMSc

  Rigshospitalet, dept. of Growth and Reproduction

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 3, 2011
• First Posted: August 8, 2011
• Study Start: July 1, 2006
• Primary Completion: December 1, 2016
• Study Completion: December 31, 2016
• Last Updated: October 10, 2019
• Results First Posted: October 10, 2019

Record last verified: 2019-09

Locations

DK (1)