Aromatase excess syndrome

Aromatase excess syndrome (AEXS), also known as familial gynecomastia due to increased aromatase activity or hereditary gynecomastia, is a rare genetic endocrine disorder caused by gain-of-function mutations or genomic rearrangements affecting the CYP19A1 gene, which encodes the aromatase enzyme. Aromatase is responsible for converting androgens (male hormones) into estrogens (female hormones). In this condition, excessive aromatase activity leads to overproduction of estrogen, resulting in hyperestrogenism. The clinical features differ between males and females. Affected males typically present with prepubertal or peripubertal gynecomastia (breast enlargement), which is the hallmark feature of the condition. Males may also experience accelerated bone maturation, short adult stature due to premature epiphyseal fusion, and in some cases, hypogonadism or reduced fertility. Affected females may present with macromastia (excessively large breasts), irregular menstruation, and precocious puberty (early onset of puberty). Both sexes can show elevated serum estrogen levels. Treatment primarily involves the use of aromatase inhibitors, such as anastrozole or letrozole, which block the excessive conversion of androgens to estrogens and can help control symptoms. These medications have been shown to reduce gynecomastia, normalize estrogen levels, and improve predicted adult height in affected children. Surgical intervention, such as reduction mammoplasty, may be considered for significant gynecomastia or macromastia that does not respond adequately to medical therapy. Early diagnosis and treatment are important to prevent complications such as short stature from premature bone fusion.

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