Abstract

Background: Gynecomastia (defined by breast tissue) and pseudogynecomastia (defined by adipose tissue) is frequent in pubertal boys. However, the underlying pathomechanisms are not fully understood so far. An association to growth hormone axis- IGF-1 axis and sex hormones has been discussed. Methods: We analyzed serum steroid hormones (progesterone, estradiol [E2], estriol, estrone, cortisol, cortisone, testosterone [T], dihydrotestosterone [DHT]) by liquid chromatography-tandem mass spectrometry, as well as gonadotropins, prolactin, IGF-1 and IGFBP-3 in 124 pubertal boys with breast swelling (mean age 14 +/-2 years). The steroid hormones were compared to those of 84 healthy pubertal boys (mean age 14 +/-2 years) without breast swelling. The differential diagnosis of either gynecomastia or pseudogynecomastia was determined by ultrasound. Puberty was defined by testes volumes > 3ml on each side. Results: A total of 86 boys suffered from gynecomastia and 38 from pseudogynecomastia. In boys with gynecomastia the ratio E2/T (median 22, interquartile range [IQR] 8–75) was significantly (p<0.05) higher compared to boys with pseudogynecomastia (median 12 IQR 5–21) or healthy boys without breast swelling (median 18 IQR 6–44). DHT concentrations were significantly (p<0.001) lower in boys with gynecomastia (median 0.13 IQR 0.02–0.38 nM/L) or pseudogynecomastia (median 0.18 IQR 0.05–0.32 nM/L) compared to healthy boys (median 0.41 IQR 0.22–0.66 nM/L). T concentrations were significantly (p<0.05) lower in boys with gynecomastia (median 1.8 IQR 0.7–4.2 nM/L) compared to boys with pseudogynecomastia (median 4.3 IQR 1.4–6.9 nM/L) or healthy boys without breast swelling (median 3.1 IQR 0.6–7.6 nM/L). The ratio DHT/T was significantly (p<0.001) lower in boys with gynecomastia (median 0.09 IQR 0.02–0.17) or pseudogynecomastia (median 0.04 IQR 0.02–0.16) compared to healthy Boys without breast swelling (median 0.13 IQR 0.05–0.28). Boys with gynecomastia did not differ from boys with pseudogynecomastia according to the other steroid hormones, prolactin, IGF-1, or IGFBP-3 concentrations. Conclusions: Gynecomastia is characterized by a higher E2 to T ratio compared to healthy boys without breast swelling due to a relative T deficiency in the presence of similar E2 levels. The lower DHT/T ratio in gynecomastia and pseudogynecomastia compared to healthy boys without breast swelling points towards a functional 5 alpha reductase deficiency.

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