What is the diagnosis and treatment for Aromatase Excess Syndrome (AES)?

From the Guidelines

Aromatase excess syndrome should be treated with aromatase inhibitors such as anastrozole, letrozole, or exemestane to reduce estrogen levels and manage symptoms, with careful monitoring and regular endocrinological follow-up to adjust medication dosages and balance hormone levels. The diagnosis of aromatase excess syndrome (AES) is based on clinical presentation and laboratory findings, including elevated estrogen levels and genetic testing to identify mutations in the CYP19A1 gene. Key features of AES include feminization in males, such as gynecomastia, accelerated growth during childhood, and premature epiphyseal closure leading to short adult stature. Treatment with aromatase inhibitors is aimed at reducing estrogen production and alleviating symptoms, with the goal of improving quality of life and preventing long-term complications such as short stature and osteoporosis. The choice of aromatase inhibitor and dosage should be individualized based on the patient's age, symptoms, and response to treatment, as well as consideration of potential side effects and interactions with other medications. Regular monitoring of hormone levels, bone age, and clinical response is essential to adjust treatment and ensure optimal outcomes, as noted in studies on hormone regulation and endocrine therapy 1. Genetic counseling is also recommended for affected individuals and their families to discuss the risk of transmission and options for genetic testing. In terms of specific treatment regimens, aromatase inhibitors such as anastrozole (1 mg daily), letrozole (2.5 mg daily), or exemestane (25 mg daily) may be used, with the goal of reducing estrogen levels to a normal range and managing symptoms. However, the most recent and highest quality study on this topic is not directly related to AES, but rather to breast cancer treatment, and therefore the treatment approach for AES is based on expert consensus and clinical experience rather than a specific study recommendation 1. Overall, the treatment of aromatase excess syndrome requires a comprehensive and individualized approach, taking into account the patient's unique needs and circumstances, and prioritizing morbidity, mortality, and quality of life as the primary outcomes. Key considerations in the treatment of AES include:

• Reducing estrogen levels to a normal range
• Managing symptoms such as gynecomastia and short stature
• Preventing long-term complications such as osteoporosis
• Individualizing treatment based on patient age, symptoms, and response to treatment
• Regular monitoring of hormone levels, bone age, and clinical response to adjust treatment
• Genetic counseling for affected individuals and their families.

From the Research

Diagnosis of Aromatase Excess Syndrome (AES)

• Aromatase excess syndrome (AEXS) is a rare, autosomal dominant disorder, characterized by enhanced aromatization of androgens and estrogen excess 2, 3, 4, 5, 6
• The diagnosis of AEXS can be suspected on a combination of the clinical picture of an excess of estrogens, increased levels of estrogins with low levels of gonadotropins after the exclusion of an estrogen-producing tumor 4
• Molecular analysis of CYP19A1 mutations is mandatory to confirm AEXS diagnosis 6
• Genetic analysis can reveal submicroscopic rearrangements within the promotor of CYP19A1, such as deletions or duplications, which result in overexpression of aromatase and enhanced aromatization of androgens 2, 3, 4, 5

Treatment of Aromatase Excess Syndrome (AES)

• Treatment with aromatase inhibitors, such as letrozole or anastrozole, can ameliorate gynecomastia and improve physical strength and libido in adult patients 2, 3
• Early treatment with aromatase inhibitors can prevent the development of gynecomastia and increase adult height in patients with AEXS 2, 3
• The use of growth hormone (GH) in combination with aromatase inhibitors may provide a better growth-promoting approach for AEXS patients 5
• Treatment with estrogen receptor modulators and GnRH analogs may also be effective in managing the symptoms of AEXS in female patients 2