The term gynecomastia refers to benign growth of the mammary glands in men. It results from an increase in glandular breast tissue and should be distinguished from pseudogynaecomastia, where there is increased fat accumulation rather than glandular proliferation. Causes and mechanisms of occurrence During childhood, boys have almost as much parenchyma and stromal cells in the mammary glands as girls, so the possibility of developing mammary glands before puberty is the same for both sexes. Of decisive importance is the ratio between androgens and estrogens and their influence on the glands. Estradiol, as the main representative of estrogens, has a stimulating role for the differentiation of cells, the formation of ducts in the breasts and their corresponding growth. Testosterone (main representative of androgens) has opposite effects of estradiol. It suppresses the growth and development of mammary glands. Gynecomastia occurs in conditions that disrupt the normal ratio between testosterone and estradiol with a relative or absolute predominance of female sex hormones. In conditions associated with hyperestrogenia (increased level of estrogens), even with normal testosterone secretion, androgen levels fall due to secondary suppression of testosterone production. Elevated levels of estradiol have a negative feedback effect on the pituitary gland, lowering the levels of luteinizing hormone released from it and subsequently testosterone. Conversely, conditions with baseline low testosterone levels (hypogonadism) lead to a secondary rise in luteinizing hormone levels, which in turn increases estradiol release more than testosterone. Estrogens further lower testosterone levels by increasing levels of sex-hormone-binding globulin. It is a sex hormone transporter protein that has a higher binding affinity for testosterone. Binding to it reduces the levels of circulating free testosterone, which is the biologically active fraction of the hormone. Another mechanism causing the appearance of gynecomastia is a defect in the function of the androgen receptor at the mammary gland level, even with normal testosterone levels. This is usually seen around puberty and rarely persists thereafter (mainly in individuals with a family history of gynecomastia). There are three known physiological conditions in which gynecomastia occurs: Neonatal gynecomastia – caused by female sex hormones that have passed from the mother’s circulation into the fetus. It usually disappears 2-3 weeks after birth; Adolescent gynecomastia – during puberty, estradiol levels rise faster than testosterone and this could lead to gynecomastia,which usually regresses after 18 months; Senile gynecomastia is caused by age-related declining testosterone levels and an increase in subcutaneous fat levels, as part of the normal aging process. There are many non-physiological causes of gynecomastia, and this group includes a number of endocrine diseases – hypogonadism (primary diseases of the testicles, Klinefelter’s syndrome, diseases of the pituitary gland or hypothalamus – secondary and tertiary forms of hypogonadism), Based’s disease (hyperthyroidism leads to an increase in the levels of sex-hormone-binding globulin and the conversion of testosterone into estradiol) non-endocrine chronic diseases (chronic liver diseases, cirrhosis, chronic kidney disease V degree), testicular tumors, tumors of extragonadal origin, chronic use of certain medications, etc. The group of medications causing gynecomastia is large, and the mechanisms for its occurrence are several – an increase in estrogen levels; mimicking estrogen-like effects; lowering testosterone and/or other androgen levels; blocking androgen receptors; increasing prolactin levels or through other unknown mechanisms.