Evaluation of 451 Danish boys with delayed puberty: diagnostic use of a new puberty nomogram and effects of oral testosterone therapy

J Clin Endocrinol Metab. 2015 Apr;100(4):1376-85. doi: 10.1210/jc.2014-3631. Epub 2015 Jan 16.


Context: Few data exist on the diagnostic criteria, and on the effects of puberty induction, in boys with constitutional delay in growth and puberty (CDGP).

Objective: To develop puberty nomograms based on Danish boys with normal pubertal development. To evaluate the different diagnostic criteria and the effect of oral testosterone undecanoate (TU) in boys with CDGP.

Design: A cross-sectional and longitudinal study of Danish boys with normal pubertal development (COPENHAGEN puberty study). A retrospective observational study of 451 boys evaluated for delayed puberty between 1990 and 2013.

Setting: Tertiary referral center for pediatric endocrinology.

Participants: One hundred and sixty-four (36%) boys evaluated for CDGP were excluded due to missing data, reclassification, or associated comorbidities, yielding 287 (64%) eligible for analysis.

Main outcome measures: The number of patients with CDGP classified by the puberty nomogram (genital stage < -2 SD for age) versus the classical criteria (genital stage 1 at ≥ 14 years). The effect of one year of oral TU treatment on pubertal progression, circulating hormones, height, and predicted adult height (PAH).

Results: Seventy-eight (27%) of the 287 boys had delayed pubertal onset according to the classical criteria, whereas 173 (60%) of the 287 boys had impaired pubertal progression according to the puberty nomogram. Ninety-six (56%) of these 173 boys were treated with oral TU for 0.8 years (0.5; 1.3) [median (25th; 75th percentiles)], which resulted in beneficial effects on pubertal progression. Height increased from -1.9 SD (-2.5; -1.2) to -1.5 SD (-2.1; -0.7) (P < .001), and PAH increased from 172.3 cm (170.3; 182.8) to 178.1 cm (171.4; 191.7) (P = .001) following one year of treatment.

Conclusions: The puberty nomogram evaluates both delayed pubertal onset as well as delayed pubertal progression and allows separation of normal versus abnormal pubertal development. Oral TU treatment was followed by pubertal induction and progression and short-term growth without compromising final height.

Trial registration: ClinicalTrials.gov NCT02034487.

Publication types

  • Clinical Trial
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Body Height / drug effects
  • Child
  • Cross-Sectional Studies
  • Denmark / epidemiology
  • Growth Charts
  • Hormone Replacement Therapy* / methods
  • Humans
  • Longitudinal Studies
  • Male
  • Nomograms*
  • Puberty / physiology
  • Puberty, Delayed / diagnosis*
  • Puberty, Delayed / drug therapy*
  • Puberty, Delayed / epidemiology
  • Retrospective Studies
  • Testosterone / administration & dosage*
  • Young Adult


  • Testosterone

Associated data

  • ClinicalTrials.gov/NCT02034487