What medication is likely causing this patient's gynecomastia, given the presence of spironolactone (aldosterone antagonist) in their treatment regimen?

Spironolactone is the Cause of This Patient's Gynecomastia

Spironolactone is definitely causing this patient's gynecomastia, as it is a well-documented side effect that occurs in approximately 9-14% of male patients taking this medication. 1, 2

Mechanism of Spironolactone-Induced Gynecomastia

Spironolactone causes gynecomastia through several mechanisms:

1. Anti-androgenic activity - it competitively inhibits binding of testosterone and dihydrotestosterone to androgen receptors 3
2. Decreased testosterone production 3
3. Inhibition of 5-alfa-reductase 3
4. Increased steroid hormone-binding globulin 3

These effects create an imbalance in the estrogen/androgen ratio, which is the primary mechanism for development of gynecomastia 4, 5.

Clinical Presentation and Incidence

The FDA label specifically warns about gynecomastia as a significant adverse effect, noting that:

• Approximately 9% of male patients with heart failure treated with spironolactone develop gynecomastia 1
• The risk increases in a dose-dependent manner 1
• Onset varies widely from 1-2 months to over a year after starting treatment 1
• It can present unilaterally (as in this case report) or bilaterally 6

According to clinical studies, the incidence of gynecomastia with spironolactone ranges from:

• 1.8% in a large cardiology practice study 7
• 14.28% in patients with liver cirrhosis 8

Management Options

For this patient, management options include:

1. Discontinuation of spironolactone - Gynecomastia is usually reversible once the medication is stopped 1

2. Medication substitution options:

   • Eplerenone - A selective mineralocorticoid receptor antagonist with significantly lower rates of gynecomastia (0% vs 14.28% in comparative studies) 8, 2
   • Amiloride - An alternative potassium-sparing diuretic that works through a different mechanism 3

3. Dose reduction - Consider lowering the dose if the clinical condition allows, as gynecomastia is dose-dependent 1

Time Course for Resolution

If spironolactone is discontinued, improvement typically follows this pattern:

• Pain in the breast tissue subsides within approximately one month
• Reduction in breast tissue size follows over subsequent months 6

Prevention and Monitoring

For future patients requiring spironolactone:

• Inform male patients about the risk of gynecomastia before starting treatment
• Monitor for early signs of breast tenderness or enlargement
• Consider eplerenone as a first-line alternative in male patients where gynecomastia would be particularly concerning 2, 8
• Use the lowest effective dose of spironolactone when it must be used 1

In conclusion, this patient's gynecomastia is almost certainly caused by spironolactone, and management should focus on medication substitution or discontinuation if clinically appropriate.