The Role of Sex Steroids, Sex Hormone-binding Globulin and Leptin in the Development of Pubertal Gynecomastia and its Persistence into Adulthood

Objective: Pubertal gynecomastia (PG) is a benign condition considered to be caused by imbalance between estrogen and testosterone, though this is not frequently evident from serum analysis. This study aimed to determine possible alteration in sex hormone levels, as well as to investigate the role of sex hormone-binding globulin (SHBG) and leptin in PG development and persistence. Methods: A total of 95 boys with PG were included. They were divided into 3 groups considering stage. Anthropometric measurements, hormonal investigations, SHBG and leptin were collected and compared group of 64 controls without PG matched in pubertal status and anthropometrics. Results: Investigations of patients with gonadal Tanner stage 2 proved statistically significant estradiol [120.0 pmol/l (73.4-240.0) vs.77.80 (23.2-120), p=0.023] and decrease in testosterone/estradiol ratio compared to control group. The same is not found in PG groups with Tanner stage 3, 4 5. Difference of the levels of testosterone and Free Androgen Index (FAI) were not found in Tanner stage 2, but significantly lower FAI was determined in mid-pubertal boys with gynecomastia compared to controls [36.0(6.8-197.0) vs.64.0(1.79-140.1), p=0.017]. Additionally, a lack of decrease of SHBG in the PG group with pubertal advancement was observed, which might explain the lower FAI in that cohort. No statistically significant difference leptin level was found. Conclusion: The early rise of estradiol at the beginning of puberty might be responsible for PG, while lack of SHBG reduction with advancement of puberty and lower FAI might have an impact on its development and/or persistence in mid-pubertal boys.