Aromatase excess syndrome (AEXS) is a rare genetic condition where the body produces too much estrogen due to the overactivity of an enzyme called aromatase. This imbalance in sex hormones can lead to a range of health issues in both males and females. The syndrome results from an excess of estrogen throughout the body.
Understanding Aromatase and Its Function
Aromatase is an enzyme in the body’s endocrine system. Its primary function is to convert androgens, hormones associated with male sexual development, into estrogens, hormones associated with female sexual development. This conversion process is known as aromatization.
This enzyme is present in various tissues, including the gonads (testes and ovaries), brain, fat tissue, and bone. In males, estrogen regulates bone growth, while in females, it guides sexual development before birth and during puberty.
Causes of Aromatase Excess Syndrome
Aromatase excess syndrome is a genetic condition, often inherited in an autosomal dominant pattern. This means a genetic rearrangement involving just one copy of the CYP19A1 gene is enough to cause the disorder. The CYP19A1 gene provides instructions for making the aromatase enzyme.
Mutations in the CYP19A1 gene lead to increased production or activity of the aromatase enzyme. These genetic rearrangements can include duplications, deletions, or inversions of genetic material within or around the CYP19A1 gene. This results in excessive conversion of androgens into estrogens, leading to elevated estrogen levels. The severity of the condition can vary depending on the specific type of genetic rearrangement.
Recognizing the Signs and Symptoms
The signs and symptoms of aromatase excess syndrome stem from elevated estrogen levels and manifest differently in males and females. In males, common manifestations include breast enlargement (gynecomastia) appearing in late childhood or adolescence. Males may also experience an early growth spurt due to advanced bone age, where bones grow and develop more quickly than usual. This accelerated bone maturation can lead to premature fusion of growth plates, resulting in a shorter adult stature.
Females may show signs of early or accelerated puberty, such as early breast development and pubic hair. They can also experience advanced bone age, similar to males, potentially leading to a shorter adult height. Irregular menstrual periods and an increased risk of ovarian cysts have also been observed. While fertility is usually normal, long-term elevated estrogen can lead to potential fertility issues and an increased risk of estrogen-dependent cancers, such as breast and endometrial cancers, if left untreated.
Diagnosis and Treatment Strategies
Diagnosing aromatase excess syndrome involves a combination of clinical evaluation, hormone level assessment, and genetic testing. Doctors observe characteristic symptoms, such as gynecomastia in males or early puberty signs in females. Blood tests measure hormone levels, often revealing high estrogen and low or normal androgen levels. Bone age assessment, usually done through X-rays of the hand and wrist, can show an advanced bone age. Genetic testing for mutations in the CYP19A1 gene confirms the diagnosis.
The primary treatment involves aromatase inhibitors, such as anastrozole or letrozole. These medications work by blocking the aromatase enzyme, reducing the conversion of androgens to estrogens and lowering overall estrogen production. This reduction in estrogen helps reverse or prevent many effects of the syndrome, promoting normal growth patterns, preventing premature puberty, and improving adult height potential. Treatment is often long-term, requiring regular monitoring by endocrinologists to adjust dosages and assess effectiveness. In some cases, male patients may opt for surgical breast reduction if gynecomastia is severe.