Aromatase excess syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Aromatase excess syndrome is a condition characterized by elevated levels of the female sex hormone estrogen in both males and females. Males with aromatase excess syndrome experience breast enlargement (gynecomastia) in late childhood or adolescence. The bones of affected males grow and develop more quickly and stop growing sooner than usual (advanced bone age). As a result males have an early growth spurt, typically during late childhood, with short stature as an adult. Affected females rarely show signs and symptoms of the condition, but they may have increased breast growth (macromastia), irregular menstrual periods, and short stature. The ability to have children (fertility) is usually normal in both males and females with aromatase excess syndrome.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Rearrangements of genetic material involving the CYP19A1 gene cause aromatase excess syndrome. The CYP19A1 gene provides instructions for making an enzyme called aromatase. This enzyme converts a class of hormones called androgens, which are involved in male sexual development, to different forms of estrogen. In females, estrogen guides female sexual development before birth and during puberty. In both males and females, estrogen plays a role in regulating bone growth.

The condition can result from several types of genetic rearrangements involving the CYP19A1 gene. These rearrangements alter the activity of the gene and lead to an increase in aromatase production. In affected males, the increased aromatase and subsequent conversion of androgens to estrogen are responsible for the gynecomastia and limited bone growth characteristic of aromatase excess syndrome. Increased estrogen in females can cause symptoms such as irregular menstrual periods and short stature.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means a genetic rearrangement involving one copy of the CYP19A1 gene in each cell is sufficient to cause the disorder.

In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new genetic changes and occur in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The prevalence of aromatase excess syndrome is unknown; more than 20 cases have been described in the medical literature.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Elevated aromatase activity · Very frequent (99-80%)

Enzyme activity of aromatase above the upper limit of normal.

Gynecomastia · Very frequent (99-80%)

Abnormal development of large mammary glands in males resulting in breast enlargement.

Increased serum estrone · Very frequent (99-80%)

An elevation above normal limits of the concentration of estrone in the circulation.

Accelerated skeletal maturation · Frequent (79-30%)

An abnormally increased rate of skeletal maturation. Accelerated skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.

Decreased circulating follicle stimulating hormone concentration · Frequent (79-30%)

A reduction of the circulating level of follicle-stimulating hormone (FSH).

Hypogonadotropic hypogonadism · Frequent (79-30%)

Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones: follicle stimulating hormone (FSH) and luteinizing hormone (LH).

Increased serum estradiol · Frequent (79-30%)

An elevation above normal limits of the concentration of estradiol in the circulation.

Sparse facial hair · Frequent (79-30%)

Reduced number or density of facial hair.

Abnormally high-pitched voice · Occasional (29-5%)

A persistent (minutes to hours) abnormal increase in the pitch (frequency) of the voice for the context or social situation or significantly different from baseline of the individual.

Breast hypertrophy · Occasional (29-5%)

The presence of hypertrophy of the breast.

Decreased testicular size · Occasional (29-5%)

Reduced volume of the testicle (the male gonad).

Irregular menstruation · Occasional (29-5%)

Abnormally high variation in the amount of time between periods.

Male hypogonadism · Occasional (29-5%)

Decreased functionality of the male gonad, i.e., of the testis, with reduced spermatogenesis or testosterone synthesis.

Mild short stature · Occasional (29-5%)

A mild degree of short stature, more than -2 SD but not more than -3 SD from mean corrected for age and sex.

Other findings in the same source

From: Orphanet

Additional reported features include Precocious puberty in females (Occasional (29-5%)); Premature thelarche (Occasional (29-5%)); Decreased serum testosterone concentration (Occasional (29-5%)); Enlarged uterus (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Aromatase excess syndrome is Endocrinology, with a endocrinologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which hormone or metabolic finding is important in this case?
• How should test timing and current medicines be taken into account?
• What follow-up would show whether the care plan is working?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Aromatase excess syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.