J Clin Endocrinol Metab. 2015 Oct;100(10):3752-9. doi: 10.1210/jc.2015-2836. Epub 2015 Aug 19.
A Longitudinal Study of Growth, Sex Steroids, and IGF-1 in Boys With Physiological Gynecomastia.

Mieritz MG1, Rakęt LL1, Hagen CP1, Nielsen JE1, Talman ML1, Petersen JH1, Sommer SH1, Main KM1, Jřrgensen N1, Juul A1.
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Abstract
CONTEXT:
Physiological gynecomastia is common and affects a large proportion of otherwise healthy adolescent boys. It is thought to be caused by an imbalance between estrogen and testosterone, although this is rarely evident in analyses of serum.
OBJECTIVE:
This study aimed to describe the frequency of physiological gynecomastia and to determine possible etiological factors (eg, auxology and serum hormone levels) in a longitudinal setup.
DESIGN, SETTINGS, AND PARTICIPANTS:
A prospective cohort study of 106 healthy Danish boys (5.8-16.4 years) participated in the longitudinal part of the COPENHAGEN Puberty Study. The boys were examined every 6 months during an 8-year follow-up. Median number of examinations was 10 (2-15).
MAIN OUTCOME MEASUREMENTS:
Blood samples were analyzed for FSH, LH, testosterone, estradiol, SHBG, inhibin B, anti-Müllerian hormone, IGF-1, and IGF binding protein-3 by immunoassays. Auxological parameters, pubertal development, and the presence of gynecomastia were evaluated at each visit.
RESULTS:
Fifty-two of 106 boys (49%) developed gynecomastia, of which 10 (19%) presented with intermittent gynecomastia. Boys with physiological gynecomastia reached peak height velocity at a significantly younger age than boys who did not develop gynecomastia (13.5 versus 13.9 years, P = .027), and they had significantly higher serum levels of IGF-1 (P = .000), estradiol (P = .013), free testosterone (P < .001), and FSH (P = .030) during pubertal transition. However, no differences in serum LH or in the estradiol to testosterone ratio were found.
CONCLUSIONS:
Gynecomastia is frequent in pubertal boys. Increased IGF-1 levels and pubertal growth appear to be associated, whereas changes in estrogen to testosterone ratio seem negligible.