ABSTRACT
INTRODUCTION Gynecomastia is a benign proliferation of glandular tissue of the breast in males, which results in concentric enlargement of one or both mammary regions. Mammary tissue is present in children of both sexes, and development of breasts depends on hormonal stimulation. The growth and differentiation of mammary tissue in the male is controlled by stimulatory and inhibitory hormones (1). Estradiol binds to estrogen receptors (ER and ER) and stimulates glandular cell growth, whereas testosterone binds to the androgen receptor (AR), which seem to inhibit growth and differentiation of breast tissue (2). Gynecomastia may be the result of increased estradiol levels that may occur from direct gonadal or adrenal sources, or from peripheral conversion of androgens (3,4). Thus, the principal determinant of breast development is the balance between androgenic and estrogenic stimulation. Testosterone is converted enzymatically to estradiol by aromatase (encoded by the CYP19 gene). Likewise androstenedione is aromatized to estrone by aromatase. Any changes in the ratio between testosterone and estradiol (either from decreased testosterone or increased estradiol) may stimulate dormant mammary gland tissue to proliferate and lead to the development of gynecomastia (1). Familial cases of gynecomastia due to aromatase excess syndrome have been described (5,6), but in many cases the testosterone-to-estradiol ratio is normal in circulation. Aromatase activity is present in gonads, adipose tissue, and breast tissue. Most likely local aromatase activity in breast tissue may be increased in patients with gynecomastia (4). Clearly marked differences in the sensitivity of breast tissue to estrogens exist between subjects. Other hormones like growth hormone (GH) and insulin-like growth factor I (IGF-I) seem to have permissive effects increasing the activity of other hormones on breast tissue. Thus, development of gynecomastia is a well-known side effect of GH treatment in adult males in some cases (7). Thyroxine increases sex hormone binding globulin (SHBG) and subsequently lowers free testosterone levels which may result in increased glandular growth (8). Prolactin stimulates lactation, but it is not directly related to breast development. Indirectly, however, prolactin decreases gonadotropin secretion and lowers testosterone, which in turn may stimulate male breast development. Thus, in some cases hyperprolactinemia may result in gynecomastia (9).
