Gynecomastia: Etiological Analysis Beyond Hormonal Imbalance

Background: Gynecomastia is a benign enlargement of the male breast with multiple causes. This retrospective study evaluated whether serum estradiol (E2), testosterone (T), or the E2/T ratio differed between patients and controls, while explicitly accounting for the limited hormonal subset and lack of statistical significance. Methods: We retrospectively reviewed 68 men with benign gynecomastia (1996-2000) and 10 healthy controls. Analyses were conducted in two predefined populations: a full etiologic cohort (n = 68) and a hormonal-analysis subset (37 patients and 10 controls). Serum E2 and T were measured in 37 patients and all controls, and the E2/T ratio was calculated. The E2/T ratio was analyzed primarily as a continuous variable rather than relying solely on a control-derived threshold. Results: Gynecomastia was most frequent in adult and middle-aged men. Idiopathic cases were most common, followed by drug-related, hormonal, and disease-related causes. The mean E2/T ratio was higher in patients (12.0 ± 1.8) than controls (7.1 ± 0.5), but this difference did not reach statistical significance (E2: p = 0.21; T: p = 0.34; E2/T: p = 0.07). Among tested patients, 13.5% had low T, 24.3% high E2, and 43.2% elevated E2/T ratios. Liver disease and drugs such as H₂ blockers and psychoactive agents contributed in some cases, while 50% were idiopathic. Conclusions: Because hormone comparisons were non-significant and based on a limited subset, these data do not support an independent association between gynecomastia and circulating E2, T, or the E2/T ratio. Clinical evaluation should consider age, comorbidities, and medications in addition to hormonal factors.