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Aromatase Excess Syndrome

Disease Details

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Description: Aromatase excess syndrome is a rare genetic disorder characterized by the overproduction of estrogen, leading to symptoms such as premature puberty in males and various estrogen-related effects in females.
Type: Aromatase excess syndrome is an endocrine disorder characterized by increased production of estrogen. The type of genetic transmission for this syndrome is autosomal dominant.
Signs And Symptoms: Observed physiological abnormalities of the condition include a dramatic overexpression of aromatase and, accordingly, excessive levels of estrogens including estrone and estradiol and a very high rate of peripheral conversion of androgens to estrogens. In one study, cellular aromatase mRNA expression was found to be at least 10 times higher in a female patient compared to the control, and the estradiol/testosterone ratio after an injection of testosterone in a male patient was found to be 100 times greater than the control. Additionally, in another study, androstenedione, testosterone, and dihydrotestosterone (DHT) were found to be either low or normal in males, and follicle-stimulating hormone (FSH) levels were very low (likely due to suppression by estrogen, which has antigonadotropic effects as a form of negative feedback inhibition on sex steroid production in sufficiently high amounts), whereas luteinizing hormone (LH) levels were normal.According to a recent review, estrone levels have been elevated in 17 of 18 patients (94%), while estradiol levels have been elevated only in 13 of 27 patients (48%). As such, estrone is the main estrogen elevated in the condition. In more than half of patients, circulating androstenedione and testosterone levels are low to subnormal. The ratio of circulating estradiol to testosterone is >10 in 75% of cases. FSH levels are said to be consistently low in the condition, while LH levels are in the low to normal range.It is notable that gynecomastia has been observed in patients in whom estradiol levels are within the normal range. This has been suggested to be due to in situ conversion of adrenal androgens into estrone and then estradiol (via local 17β-HSD) in breast tissue (where aromatase activity may be particularly high).The symptoms of AEXS, in males, include heterosexual precocity (precocious puberty with phenotypically-inappropriate secondary sexual characteristics; i.e., a fully or mostly feminized appearance), severe prepubertal or peripubertal gynecomastia (development of breasts in males before or around puberty), high-pitched voice, sparse facial hair, hypogonadism (dysfunctional gonads), oligozoospermia (low sperm count), small testes, micropenis (an unusually small penis), advanced bone maturation, an earlier peak height velocity (an accelerated rate of growth in regards to height), and short final stature due to early epiphyseal closure. The incidence of gynecomastia appears to be 100%, with 20 of 30 male cases opting for mastectomy according to a review.In females, symptoms of AEXS include isosexual precocity (precocious puberty with phenotypically-appropriate secondary sexual characteristics), macromastia (excessively large breasts), an enlarged uterus, menstrual irregularities, and, similarly to males, accelerated bone maturation and short final height. Of seven females described in one report, three (43%) had macromastia. Pubertal breast hypertrophy in association with AEXS has been described in two young girls.Fertility, though usually affected to one degree or another—especially in males—is not always impaired significantly enough to prevent sexual reproduction, as evidenced by vertical transmission of the condition by both sexes.
Prognosis: Aromatase excess syndrome (AES) is a rare genetic disorder characterized by increased activity of the enzyme aromatase, leading to excessive conversion of androgens to estrogens. This results in elevated estrogen levels and corresponding clinical features.

The prognosis of AES varies depending on the severity of the condition and the effectiveness of treatment. With appropriate management, which may include medications, hormone therapy, or surgery, individuals can often achieve good control of symptoms and maintain a normal quality of life. However, untreated or poorly managed AES can lead to complications such as advanced bone age, short stature, and psychological effects due to early and inappropriate development of secondary sex characteristics. Regular monitoring and individualized treatment plans are essential for optimal long-term outcomes.
Onset: Aromatase excess syndrome typically presents symptoms around puberty. In males, it can cause early closure of growth plates leading to shorter adult height, gynecomastia (development of breast tissue), and other signs of excessive estrogen. In females, the symptoms can be less apparent but may include irregular menstrual cycles and other estrogen-related effects.
Prevalence: The prevalence of aromatase excess syndrome is not well-documented, and specific data is scarce. It is considered a rare condition.
Epidemiology: Aromatase excess syndrome is an extremely rare genetic disorder. Because of its rarity, the exact prevalence and incidence are not well-documented. Cases are sporadic and familial, with limited reports primarily from medical literature and case studies.
Intractability: Aromatase excess syndrome (AES) is generally not considered intractable. Treatment options, such as hormone therapy with aromatase inhibitors, can help manage symptoms effectively. However, the response to treatment can vary among individuals, and continuous medical supervision is often necessary.
Disease Severity: Aromatase excess syndrome is a rare condition. It can cause significant physical changes and developmental issues, especially relating to early puberty and associated growth abnormalities. The severity can vary, leading to potential complications such as reduced adult height, gynecomastia in males, and potential fertility issues in both sexes. It often requires medical management to mitigate these effects.
Healthcare Professionals: Disease Ontology ID - DOID:0090122
Pathophysiology: Aromatase excess syndrome is characterized by the overproduction of estrogen due to excessive activity of the enzyme aromatase. This enzyme converts androgens to estrogens, leading to abnormally high estrogen levels. The pathophysiology involves genetic mutations or rearrangements that increase aromatase activity in various tissues, including adipose tissue and the gonads. This condition can result in symptoms of hyperestrogenism, such as premature puberty in children, gynecomastia in males, and various reproductive and metabolic abnormalities.
Carrier Status: Aromatase excess syndrome is typically caused by mutations or genetic rearrangements that lead to increased activity of the aromatase enzyme. The condition usually follows an autosomal dominant inheritance pattern, meaning that having one copy of the altered gene in each cell is enough to cause the condition. Carrier status is not typically a consideration because individuals with just one copy of the mutation usually exhibit symptoms of the syndrome.
Mechanism: Aromatase excess syndrome (AES) involves increased aromatase activity, leading to elevated levels of estrogen. The mechanism largely involves mutations or rearrangements in the CYP19A1 gene, which codes for the enzyme aromatase. This enzyme converts androgens to estrogens, and its overactivity results in excessive estrogen production.

Molecular mechanisms that lead to AES include:
1. Gene duplications or inversions that increase CYP19A1 gene expression.
2. Promoter mutations that enhance gene transcription.
3. Differential regulation by tissue-specific promoters that are excessively active, especially in gonadal and extragonadal tissues.

These genetic alterations cause increased and abnormal aromatase enzyme activity, leading to heightened estrogen levels and the associated clinical manifestations of AES.
Treatment: Several treatments have been found to be effective in managing AEXS, including aromatase inhibitors and gonadotropin-releasing hormone analogues in both sexes, androgen replacement therapy with non-aromatizable androgens such as DHT in males, and progestogens (which, by virtue of their antigonadotropic properties at high doses, suppress estrogen levels) in females. In addition, male patients often seek bilateral mastectomy, whereas females may opt for breast reduction if warranted.Medical treatment of AEXS is not absolutely necessary, but it is recommended as the condition, if left untreated, may lead to excessively large breasts (which may necessitate surgical reduction), problems with fertility, and an increased risk of endometriosis and estrogen-dependent cancers such as breast and endometrial cancers later in life. At least one case of male breast cancer has been reported.
Compassionate Use Treatment: Aromatase excess syndrome is a rare condition characterized by the overproduction of estrogen due to increased aromatase activity. Treatment options for this syndrome are limited due to its rarity. Here are some potential approaches:

1. **Compassionate Use Treatment**:
- Prescription of aromatase inhibitors (like anastrozole or letrozole) under compassionate use programs in cases where the syndrome causes severe symptoms.

2. **Off-Label Treatments**:
- Use of aromatase inhibitors that are typically prescribed for conditions like breast cancer, but which may help in reducing estrogen levels in patients with aromatase excess syndrome.

3. **Experimental Treatments**:
- Participation in clinical trials aimed at finding new therapies for rare endocrine disorders could be an option. Consult with a healthcare provider to explore available trials.

It is important to work closely with an endocrinologist to manage this condition, as treatment needs to be carefully tailored to the individual.
Lifestyle Recommendations: Aromatase excess syndrome is a rare condition characterized by increased levels of the enzyme aromatase, which converts androgens to estrogens.

Lifestyle recommendations include:
1. **Diet**: Focus on a balanced diet rich in whole foods. Monitoring and managing weight can help, as adipose tissue can influence hormone levels.
2. **Exercise**: Regular physical activity can help regulate hormone levels and improve overall well-being.
3. **Avoidance of Endocrine Disruptors**: Limit exposure to chemicals found in plastics, pesticides, and certain personal care products that can mimic estrogen.
4. **Mental Health**: Managing stress through mindfulness, counseling, or other relaxation techniques can benefit hormonal balance.
5. **Medical Monitoring**: Regular follow-ups with a healthcare provider to monitor hormone levels and adjust treatment as necessary.

Consulting with healthcare professionals for personalized guidance is essential for managing the condition effectively.
Medication: For Aromatase Excess Syndrome (AES), there is limited established pharmacological treatment. Management often involves the use of medications that can inhibit aromatase activity or block the effects of estrogen, such as:

1. Aromatase Inhibitors (e.g., anastrozole, letrozole): These reduce the production of estrogen.
2. Selective Estrogen Receptor Modulators (SERMs) (e.g., tamoxifen): These block the action of estrogen in the body.

Each treatment is tailored to the patient’s specific symptoms and clinical presentation, and careful monitoring by a healthcare provider is necessary.
Repurposable Drugs: Aromatase excess syndrome (AES) is a rare genetic condition characterized by excessive production of estrogen. There is limited information on repurposable drugs for treating AES. However, drugs that can inhibit aromatase activity, such as anastrozole, letrozole, and exemestane, may be considered to manage estrogen levels. These medications are primarily used in the treatment of estrogen-dependent cancers but may be repurposed for AES under medical supervision. It is important to consult with a healthcare professional for personalized treatment options.
Metabolites: Aromatase excess syndrome (AES) is characterized by increased levels of estrogen due to excessive activity of the enzyme aromatase. This abnormal activity leads to the conversion of androgens to estrogens.

Some of the metabolites involved include:
- Estradiol (E2)
- Estrone (E1)
- Androstenedione
- Testosterone

These imbalances and heightened levels of estrogen contribute to the symptoms and complications associated with aromatase excess syndrome.
Nutraceuticals: Aromatase excess syndrome is a rare genetic condition, and there is limited information on the use of nutraceuticals for its management. Nutraceuticals are products derived from food sources with additional health benefits beyond basic nutritional value. No specific nutraceuticals have been proven effective for treating this syndrome. Management typically involves medical treatments that may include medications or surgery to address hormone imbalances and their effects. Always consult with a healthcare professional for personalized advice and treatment options.
Peptides: Aromatase excess syndrome (AES) is a rare genetic condition characterized by excessive conversion of androgens to estrogens due to overactivity of the aromatase enzyme. This enzyme is responsible for the biosynthesis of estrogens from androgens.

Peptides: There is no specific peptide therapy for aromatase excess syndrome. Management typically involves the use of medications that inhibit aromatase or block estrogen receptors to reduce the effects of excess estrogen.

Nan: Nanotechnology is not currently a standard treatment approach for aromatase excess syndrome. The condition is generally managed through hormonal therapies rather than interventions involving nanotechnology.