Why are aromatase inhibitors (AIs) not typically used to treat gynecomastia?

Aromatase Inhibitors Are Not Recommended for Gynecomastia Treatment

Aromatase inhibitors (AIs) are not typically used to treat gynecomastia because they have limited effectiveness, lack FDA approval for this indication, and have insufficient evidence supporting their use in clinical practice. 1

Understanding Gynecomastia

Gynecomastia is a benign proliferation of glandular breast tissue in males, occurring due to an imbalance between estrogen and androgen effects at the breast tissue level. It affects 32-65% of males depending on age and diagnostic criteria. 1

• Gynecomastia is common during infancy and puberty, with most cases resolving spontaneously within 24 months 1
• In adults, proper investigation may reveal underlying pathology in 45-50% of cases 1
• The condition is not considered premalignant 1

Why Aromatase Inhibitors Are Not Recommended

Limited Clinical Evidence

• Current clinical practice guidelines specifically recommend against using aromatase inhibitors for gynecomastia treatment in general 1
• Studies with aromatase inhibitors like anastrozole show limited effectiveness in reducing breast tissue, with complete resolution occurring in only a small percentage of patients 2
• The European Association of Andrology (EAA) clinical practice guidelines explicitly state: "We do not recommend the use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or non-aromatizable androgens in the treatment of GM in general" 1

Better Established Alternatives

• Watchful waiting is the recommended approach after treating underlying pathology or discontinuing substances associated with gynecomastia 1
• For persistent cases, surgical treatment is considered the therapy of choice for patients with long-lasting gynecomastia that doesn't respond to medical therapy 1
• Testosterone treatment should only be offered to men with proven testosterone deficiency 1

Specific Limitations of Aromatase Inhibitors

• While AIs can decrease the estradiol/testosterone ratio, this doesn't consistently translate to significant reduction in breast tissue 2
• The longer the duration of gynecomastia before AI administration, the smaller the reduction in breast size 2
• AIs may help with breast tenderness but are less effective at eliminating glandular tissue 2
• Spontaneous resolution of pubertal gynecomastia is common, making it difficult to attribute improvement to AI therapy 2

Proper Management Approach

1. Identify and address underlying causes:

   • Medication review (antipsychotics, antiandrogens, spironolactone, etc.) 3
   • Evaluation for hormonal disorders 1
   • Assessment for substance use (cannabis, anabolic steroids) 3

2. Diagnostic workup should include:

   • Medical history focusing on onset, duration, and potential contributing factors 1
   • Physical examination to confirm glandular tissue and rule out malignancy 1
   • Laboratory tests may include testosterone, estradiol, LH, FSH, prolactin, and other relevant hormones 1
   • Imaging when clinical examination is equivocal 1

3. Treatment options:

   • Watchful waiting after addressing underlying causes 1
   • Surgical treatment for persistent cases (reduction mammoplasty or subcutaneous mastectomy) 1, 4
   • Testosterone replacement only for confirmed hypogonadism 1

Conclusion

While aromatase inhibition theoretically addresses the hormonal imbalance in gynecomastia, clinical evidence does not support their routine use. Current guidelines recommend watchful waiting as the first approach, with surgery reserved for persistent cases. The limited effectiveness of AIs, particularly in established gynecomastia, makes them unsuitable as a standard treatment option.