ESPE Abstracts (2018) 89 RFC13.5

Pubertal Voice Break: Temporal Relation of Secondary Sexual Characteristics in Healthy Boys

Alexander Siegfried Busch, Casper P Hagen, Kaspar Sørensen, Nanna Kolby, Camilla Eckert-Lind & Anders Juul


Department of Growth and Reproduction, Rigshsopitalet, Copenhagen, Denmark


Introduction: The clinical hallmark of male puberty is testicular enlargement ≥4 ml. While this initial sign largely depends on central reactivation of the hypothalamic-pituitary-gonadal (HPG) axis along with peripheral follicle-stimulating hormone (FSH) action, the attainment of voice-break, activation of sweat- and sebaceous- glands, acne as well as axillary hair development require testosterone action.

Objective: To investigate the temporal relation of emerging secondary sexual characteristics and correlation with testosterone levels during pubertal transition in healthy boys.

Methods: Seven hundred and thirty one healthy Danish boys from the COPENHAGEN Puberty Study [cross-sectional: n=637; longitudinal: n=94, median (range) number of examinations: 10 (2–13)] underwent blood sampling including measurement of reproductive hormones as well as clinical examinations of secondary sexual characteristics. (Mean) BMI z-scores were calculated using the WHO reference. Mean age (95% CI) at pubertal event was assessed by probit analysis (proc lifereg; SAS Institute) integrating censored observations. Data on testicular volume and pubic hair stages as well as reproductive hormones have previously been published (Sørensen, JCEM 2010).

Results: In our cohort, voice-break occurred at 13.6 (95% CI: 13.5–13.8) yrs, activation of sweat glands 12.4 (12.2–12.6) yrs, axillary hair development 13.6 (13. 5–13.8) yrs and acne 14.9 (14.6–15.2) yrs. Testicular enlargement ≥4 ml occurred at 11.6 (11.5–11.8) yrs and pubic hair at 12.2 (12.1–12.4) yrs. All events, except acne, were significantly (P<0.001) negatively associated with mean zBMI score with effect sizes ranging from −0.4 yrs (−0.5 to −0.2) yrs (axillary hair development)up to −0.5 (−0.5 to −0.3) yrs (activation of sweat glands) per zBMI. Serum Testosterone (T) levels in the examination prior to the examination in which voice-break was detected were 8.34 (0.1–26.8) nmol/l and the time from the examination with detectable T (>0.115 nmol/l) to voice break was 1.6 (−1.2 to 3.8) yrs. At time of voice break, testis size (largest testis) was 11.8 (4–20) ml and genital stage was Tanner 3 (2–5).

Conclusions: We provide a comprehensive temporal analysis of pubertal events in a large contemporary cohort of healthy boys. Reference ranges can be directly implemented in a clinical setting. Threshold of T levels for voice-break to occur varied substantially between individuals.

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