Obesity Is Associated With Earlier Pubertal Onset in Boys

Alexander S. Busch; Brigitte Højgaard; Casper P. Hagen; Grete Teilmann


J Clin Endocrinol Metab. 2020;105(4) 

In This Article


Comparing two large cohorts of obese boys and normal-weight controls, we found testicular enlargement, genital stage ≥ 2, and pubarche to occur earlier or at the same age in obese boys. While we demonstrate that obesity is associated with an earlier timing of the initial sign of male pubertal onset, that is, testicular enlargement, as compared to controls, we did not observe a significant delay in obese boys for any of the investigated pubertal events.

The association between obesity and male pubertal timing is far from clear. Previous studies, including the COPENHAGEN Puberty study that serves as a control group in the present study, consistently showed that zBMI exhibits a negative correlation with pubertal timing across the spectrum of physiological zBMI.[5,17] However, results in obese children and adolescents are diverging: While some studies report a continuous negative correlation in obese boys,[2,4,7] other studies report a delayed onset of puberty in obese boys compared to overweight boys[6,18] indicating a J-shaped association. Challenging the comparison between studies on the relation between obesity and male pubertal timing, studies largely differ concerning: (1) milestones used as measure of puberty, including genital stage ≥ 2, testicular enlargement, pubarche, and voice break; (2) modes of data collection, including clinically assessed and self-reported puberty timing; (3) definitions of obesity, including zBMI > 95th percentile and > 97th percentile as the cut-off[6,7,18,19] (Table 2). In our study, trained physicians assessed different pubertal milestones in both groups by inspection and testicular palpation, while obesity was defined more strictly as zBMI > +2SD (approximately corresponding to the 97th percentile). Examiners were all thoroughly trained by a small team of senior physicians, making it unlikely that our findings are profoundly biased by interobserver variations. In sub-analysis, we further introduced a cut-off at zBMI of > +3SD (approximately corresponding to the 99.9th percentile, which is very obese). Our findings indicate that the negative association between zBMI and pubertal timing wears out as BMI increases rather than delaying pubertal onset in obese boys. Within the obese study cohort, pubarche even occurred significantly earlier in very obese boys with a zBMI > +3SD compared to obese boys (+2SD < zBMI ≤ +3SD). However, given the fact that no previous study has made a distinction between obese and very obese participants, that is, +2SD < zBMI ≤ +3SD versus zBMI > +3SD, the subtle difference between these groups might have been overseen. We further compared all puberty measurements of the obese cohort with reference data on pubertal progression, that is, puberty nomograms. No apparent delay or advancement in pubertal progression in obese boys was observed, as the majority of measurements ranged in the 95% CI.

The question remains why some studies have observed a delay in pubertal onset in obese boys. While indeed some diseases are associated with both obesity and delayed puberty, for example, Prader-Willi Syndrome, it is unlikely that this could explain the diverging results as the prevalence of such diseases is very low. Comparing previous studies reporting a delayed onset on obese boys there is no clear pattern, but we speculate that varying definitions of obesity as well differences between populations within studies contribute to the diverging results.

Concerning a potential mechanism, energy homeostasis and puberty are known to be closely linked.[20] While body fat is mirroring energy storage, BMI in adults or age-specific BMI in children and adolescents are frequently used as a proxy measure for body fat. However, limitations exist, which include a high specificity and low sensitivity of age-specific BMI in identifying children with a high body fat percentage, ignoring so-called "normal weight obese" subjects.[9] Concerning evidence based on genetic data, recent studies demonstrated a significant negative genetic correlation between the BMI and male pubertal timing as well as a causal effect of higher BMI on earlier pubertal timing in boys.[5,10,11] The overlap of the genetic architecture between the male pubertal timing and BMI included genes involved in the metabolic control of GnRH secretion, that is, Brain-derived neurotrophic factor (BDNF), Leptin receptor (LEPR), and Melanocortin 3 Receptor (MC3R), representing key factors in the Leptin/Melanocortin pathway.[10,11] Circulating hormone levels in boys from the control group in the present study have previously been published in detail.[21] Body mass index was negatively associated with Sex hormone binding globulin (SHBG), and SHBG was negatively associated with circulating levels of testosterone, estradiol, and Dehydroepiandrosterone-sulfate (DHEAS). Although we do not have hormone levels available in the obese cohort, the observed relations between BMI, reproductive hormones, and their binding proteins in controls probably contributes to earlier testicular growth in obese boys and adolescents in the present study. A potential explanation for an outwearing association with male pubertal timing and zBMI in cases of very high zBMI includes peripheral conversion of testosterone to estrogen by aromatization in adipose tissue and subsequent inhibition of the hypothalamic-pituitary-gonadal axis.[22,23]

In conclusion, comparing a cohort of obese boys to a population-based reference of normal-weight boys, we demonstrate that obesity is associated with earlier testicular enlargement and equal timing of other pubertal milestones.