Bone metabolism in men: role of aromatase activity

Sex steroid hormones play an important role in the maintenance of bone mass in males and in females. Even though androgens are the major sex steroids in men, direct and indirect evidence emerged suggesting that estrogens may also play a major role in male skeletal health. Since the testes account for only 15% of circulating estrogens in males, the remaining 85% comes from peripheral aromatization of androgen precursors in different tissues, including bone. Human models of aromatase deficiency clearly demonstrated the critical importance of the conversion of androgens into estrogens in regulating male skeletal homeostasis. Aromatase- deficient men showed tall stature due to continued longitudinal growth, unfused epiphyses, high bone turnover, and osteopenia. Interventional studies in adult men using aromatase inhibition confirmed that estrogens are important in controlling bone remodeling. Importantly either inherited (i.e. due to common polymorphisms at the human aromatase CYP19 gene) or acquired (i.e. by diseases or different compounds) variation in aromatase ability to convert androgen precursors into estrogen may also be relevant for skeletal homeostasis.