Spironolactone gynecomastia

Hyperkalemia (increase in potassium in the blood), a serious event, may be seen with the administration of potassium-sparing diuretics. Hyperkalemia is most likely to occur in patients with an inadequate fluid intake and urine output, those with diabetes or renal disease tiie elderly, and those who are severely ill. In patients taking spironolactone, gynecomastia (breast enlargement in tiie male) may occur. This reaction appears to be related to both dosage and duration of therapy. The gynecomastia is usually reversible when therapy is discontinued, but in rare instances, some breast enlargement may remain. 

Gynecomastia may be associated with the use of spironolactone and is reversible upon withdrawal of the dmg. 

Spironolactone antagonizes the effects of aldosterone by binding at the aldosterone receptor in the cytosol of the late distal tubules and renal collecting ducts. Side effects of spironolactone are gynecomastia, decreased Hbido, and impotency. 

Fbtassium-sparing diuretics Avoid eating foods high in potassium and avoid the use of salt substitutes containing potassium. Read food labels carefully. Do not use a salt substitute unless a particular brand has been approved by the primary health care provider. Avoid the use of potassium supplements. Male patients taking spironolactone may experience gynecomastia. This is usually reversible when therapy is discontinued. 

Doses should be titrated at intervals no more frequent than every 2 to 3 days. Because spironolactone is used for its antialdosterone effects, much higher doses (up to 400 mg/day) are used than those used when treating hypertension. If intolerable side effects such as gynecomastia occur with spironolactone, other potassium-sparing diuretics may be used, but clinical trials have not shown equivalent efficacy.22... 

The answer is c. (Hardmanr pp 706-708.) Spironolactone is an aldosterone antagonist that acts on the mineralocorticoid receptor It is a Kksparing diuretic. It can also function as an androgen antagonist, which could explain the gynecomastia and erectile dysfunction. Women with hirsutism are sometimes treated with spironolactone. 

Potassium-sparing diuretics may cause hyperkalemia, especially in patients with chronic kidney disease or diabetes, and in patients receiving concurrent treatment with an ACE inhibitor, ARB, NSAID, or potassium supplement. Eplerenone has an increased risk for hyperkalemia and is contraindicated in patients with impaired renal function or type 2 diabetes with proteinuria. Spironolactone may cause gynecomastia in up to 10% of patients, but this effect occurs rarely with eplerenone. 

Spironolactone may induce painful gynecomastia and impotence in the male, and menstrual irregularities in the female. 

The diuretic effect of spironolactone develops fully only with continuous administration for several days. Two possible explanations are (1) the conversion of spironolactone into and accumulation of the more slowly eliminated metabolite canrenone (2) an inhibition of aldosterone-stimulated protein synthesis would become noticeable only if existing proteins had become nonfunctional and needed to be replaced by de novo synthesis. A particular adverse effect results from interference with gonadal hormones, as evidenced by the development of gynecomastia (enlargement of male breast). Clinical uses include conditions of increased aldosterone secretion, e.g., liver cirrhosis with ascites. 

Spironolactone is poorly absorbed after oral administration and has a delayed onset of action it may take several days until a peak effect is produced. It has a somewhat slower onset of action than triamterene and amiloride (discussed later), but its natriuretic effect is modestly more pronounced, especially during long-term therapy. Spironolactone is rapidly and extensively metabolized, largely to the active metabohte canrenone. Canrenone and potassium canrenoate, its K+ salt, are available for clinical use in some countries outside the United States. Canrenone has a half-life of approximately 10 to 35 hours. The metabolites of spironolactone are excreted in both the urine and feces. New selective aldosterone receptor antagonists (SARA), such as eplerenone, have been developed but have not yet been introduced into clinical practice. Eplerenone and canrenone exhibit fewer steroidlike side effects (gynecomastia, hirsutism). 

Primary advantage of eplerenone over spironolactone is a potentially decreased incidence of endocrine-related adverse effects, such as gynecomastia or sexual dysfunction... 

Synthetic steroids may cause endocrine abnormalities by actions on other steroid receptors. Gynecomastia, impotence, and benign prostatic hyperplasia all have been reported with spironolactone. Such effects have not been reported with eplerenone because it is much more selective than spironolactone for the mineralocorticoid receptor, being virtually inactive on androgen or progesterone receptors. 

Spironolactone as a diuretic is discussed in Chapter 15. The drug has benefits in heart failure greater than those predicted from its diuretic effects alone (see Chapter 13). Adverse effects reported for spironolactone include hyperkalemia, cardiac arrhythmia, menstrual abnormalities, gynecomastia, sedation, headache, gastrointestinal disturbances, and skin rashes. 

Adverse effects Renal function may deteriorate with the decreased circulating fluid volume, especially after the addition of another diuretic drug acting on the RAAS system, and careful monitoring of serum creatinine is essential. Serum potassium should be monitored within one week of initiation and at least every four weeks for the first three months and every three months thereafter. It should also be monitored at any dose change in spironolactone or if there is a change in concomitant medications that affects the potassium balance. The spironolactone dose (standard 25 mg per day) should be reduced if potassium levels are <5.4 mEq/L, and treatment should be discontinued if painful gynecomastia or serious renal dysfunction or hyperkalemia result. 

The only frequent adverse effects were gynecomastia, breast pain, or both in 10% of men. The rate of discontinuation because of these events was 2%. The risk of gynecomastia should not be an argument against the use of spironolactone in men with severe heart failure, since it reduces both morbidity and death. 

Epierenone has been reported to produce less gynecomastia than spironolactone (6,7). In patients with gynecomastia from spironolactone, epierenone can be substituted and gynecomastia status reassessed. 

Because of its antiandrogenic action, spironolactone causes gynecomastia, reduced hbido, and erectile failure in 4—30% of men. These effects seem to be both dose- and time-dependent. 

Rose LI, Underwood RH, Newmark SR, Kisch ES, Williams GH. Pathophysiology of spironolactone-induced gynecomastia. Ann Intern Med 1977 87(4) 398-403. 

In the past,. spironolactone has not enjoyed widespread UK for several well-documented reasons.First, its maximal effectiveness is usually not observed for 3 to S seeks. Second, its residual hormonal side effects have pro-J ja d unacceptable rates of gynecomastia in males and men-iimal irregularities in females, especially when doses exceeded 50 to 100 mg/day. These hormonal side effects can tv largely avoided by giving spironolactone in doses of 12.5 m25 mg/day. 

The results from EPHESUS have raised the question of which aldosterone blocker, spironolactone or eplerenone, should be used preferentially. Currently, there are no data to support that the more selective but more expensive eplerenone is superior to or should be preferred to the less expensive generic spironolactone unless a patient has experienced gynecomastia, breast pain, or impotence while receiving spironolactone. Einally, it should be noted that hyperkalemia is just as likely to appear with both these agents. 

Like other diuretics, spironolactone should be initiated at a low dose and increased to treat symptoms. Spironolactone may be initiated at doses of 12.5 to 25 mg/day. Spironolactone shonld be avoided in severe renal failnre. Hyperkalemia and gynecomastia are the most common side effects. Eplerenone is a viable alternative to... 

---