What medication is most likely to cause breast tenderness in a patient taking spironolactone?

Spironolactone is the medication most likely to cause breast tenderness due to its action as an aldosterone antagonist and its effects on hormone levels. It has anti-androgen effects and can increase levels of progesterone and estrogen, which are hormones that can lead to tenderness in the breast tissue. This medication is commonly used to treat conditions like hypertension and edema but is also known for its impact on hormone-related side effects.

The other medications listed do not have a significant direct relationship with breast tenderness. Digoxin, primarily used to treat heart conditions, does not typically affect breast tissue. Amlodipine, a calcium channel blocker utilized for hypertension and angina, also lacks this side effect. Metoprolol, a beta-blocker used for heart-related conditions, generally does not influence breast tissue either. Therefore, among these options, spironolactone is most directly associated with breast tenderness.