Breast enlargement at puberty in males has been viewed as an imbalance of the Estrogen:Androgen ratio. Previous studies have revealed controversial results regarding the serum estradiol(E2) and Testosterone(T) concentrations and E2:T ratio. Since total E2 and T in these patients is not always altered, we hypothesized that the free E2 fraction may be elevated or the ratio between it and free T may be altered causing breast enlargement. We determined the total and free E2, Testosterone, their ratio and SHBG levels in 13 pubertal males (TIII-TV) with gynecomastia of 1-4 years duration of which 8 were obese(BMI≥25) and 5 were lean(BMI<25), and a control group of 9 non-obese pubertal males(TIII-TV) without any evidence of gynecomastia. In addition to this, S. Estrone(E1), DHEA, Androstenedione (Ao), DHEA:E1 and Ao:E1 ratios were also measured and compared in the obese and the lean patients. Mammography revealed the presence of excessive fibroglandular tissue(≥3×2 cms) in all the patients. Table

Table 1

Neither T, nor E2:T or free E2:free T ratios were significantly different between the 2 groups. Comparison between the obese and the lean group of patients revealed that the SHBG levels were significantly lower in the obese patients compared with the lean patients (p 0.05), and the control group (p 0.055). E1 levels were significantly higher in the lean patients compared with the obese patients (p=0.04). None of the other parameters measured were significantly different when the obese and lean patients were compared. We concluded that the concentration of free E2, free T, free E2:T, SHBG and E2:T, in patients with gynecomastia is not significantly different from that of the controls. Hence, changes in the circulating free E2, free T or their ratio do not seem to account for the pathogenesis of this condition. Further investigations in this area should focus on differences in the responsiveness of the target tissue to E2 or localized differences in the E2 production.