02 Jan Pubertal Gynecomastia: Understanding the physiology

By far, the vast majortiy of patients we see present with idiopathic, pubertal gynecomastia. In non medical terms, this means that secondary to normal hormonal changes during puberty,  some patients can develop more glandular tissues than others.

The primary culprit behind pubertal gynecomastia is an imbalance between estrogen and testosterone levels. Yes, even males have estrogen. While most cases may have normal estrogen and testosterone levels, the slightly different ratios of each relative to the other can result in gyno . While both hormones are present in males, they need to be in a delicate equilibrium. Estrogen stimulates the growth of breast tissue, whereas testosterone inhibits it. When there is a relative increase in estrogen or a decrease in testosterone, the balance is disrupted, potentially leading to the development of gynecomastia. So where is estrogen produced in males if no ovaries are present?

In males, estrogen synthesis primarily occurs in the testes, where cholesterol serves as a precursor for this essential hormone. A key enzyme called aromatase facilitates the conversion of testosterone, a male sex hormone, into estradiol, a form of estrogen. Additionally, a smaller amount of estrogen is produced in peripheral tissues, such as adipose cells.

Once synthesized, estrogen circulates in the bloodstream, predominantly bound to proteins like sex hormone-binding globulin (SHBG) and albumin. This binding helps transport estrogen to target tissues where it can exert its biological effects. A fraction of estrogen remains unbound, allowing it to be free and active in influencing cellular processes.

In males, estrogen exerts its effects by binding to estrogen receptors (ERs). The two main types of estrogen receptors, ERα (alpha) and ERβ (beta), are primarily located in the nuclei of target cells. Upon binding of estrogen to its receptors, a conformational change occurs, allowing the receptor to translocate into the nucleus of the target cell. Within the nucleus, estrogen receptors act as transcription factors, influencing gene expression. This process is fundamental to mediating the physiological effects of estrogen in males.

Estrogen plays diverse roles in male physiology. It contributes to maintaining bone density and health, influencing spermatogenesis in the testes, and impacting cognitive functions and neural pathways in the male brain. These biological effects highlight the significance of estrogen in various aspects of male reproductive and overall health.

The regulation of estrogen in males involves a negative feedback loop. Elevated estrogen levels in males exert negative feedback on the hypothalamus and pituitary gland. This regulatory mechanism helps control the secretion of gonadotropin-releasing hormone (GnRH) and gonadotropins, maintaining a delicate hormonal balance.

Estrogen undergoes metabolism in the liver, leading to the formation of metabolites. These metabolites are subsequently excreted through bile and urine. The kidneys play a crucial role in the excretion of estrogen metabolites, contributing to the overall elimination of estrogen from the male body.

Pubertal gynecomastia is a common occurrence during adolescence, driven by hormonal changes inherent to puberty. Male breast tissue contains estrogen receptors. When estrogen binds to these receptors, it stimulates the proliferation of glandular tissue.