Spironolactone, sold under the brand name Aldactone among others, is a diuretic medication primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease.

[4] Common side effects include electrolyte abnormalities, particularly high blood potassium, nausea, vomiting, headache, rashes, and a decreased desire for sex.

[42] Spironolactone improves left ventricular diastolic function in patients with heart failure with preserved ejection fraction, however it has no effect on mortality and hospitalization.

A newer medication, eplerenone, has been approved by the US Food and Drug Administration (FDA) for the treatment of heart failure, and lacks the antiandrogenic effects of spironolactone.

[47] They improve blood pressure and potassium levels, as well as left ventricular hypertrophy, albuminuria, and carotid intima-media thickness, in people with primary aldosteronism.

[52][53] In demonstration of this, women with complete androgen insensitivity syndrome (CAIS) do not produce sebum or develop acne and have little to no body, pubic, or axillary hair.

[56][57][58][59][60] Conversely, hyperandrogenism in women, for instance due to polycystic ovary syndrome (PCOS) or congenital adrenal hyperplasia (CAH), is commonly associated with acne and hirsutism as well as virilization (masculinization) in general.

[64][66][53] Though not the primary intended purpose of the medication, the ability of spironolactone to be helpful with problematic skin and acne conditions was discovered to be one of the beneficial side effects and has been quite successful.

[68] One study showed that spironolactone or the steroidal antiandrogen cyproterone acetate both in combination with a birth control pill had equivalent effectiveness for hirsutism.

[64] Despite paradoxical reactions, spironolactone is used off-label as a component of feminizing hormone therapy in transgender women, especially in the United States (where cyproterone acetate is not available), usually in addition to an estrogen.

When coupled with estradiol, effects in transgender women include decreased male pattern body hair, induction of breast development and of feminization in general, and reduced spontaneous erections.

[100][101][102][103][104][failed verification] It has also been marketed in the form of 2% and 5% topical cream in Italy for the treatment of acne and hirsutism under the brand name Spiroderm, but this product is no longer available.

[104][failed verification][106] Spironolactone has poor water solubility, and for this reason, only oral and topical formulations have been developed; other routes of administration such as intravenous injection are not used.

[109] At very high doses (400 mg/day), spironolactone has also been associated with testicular atrophy and reversibly reduced fertility, including semen abnormalities such as decreased sperm count and motility in cis men.

[8] It has been reported that the addition of spironolactone to loop diuretics in people with heart failure was associated with a higher risk of hyperkalemia and acute kidney injury.

[64][66][125] This was the conclusion of a 2017 hybrid systematic review of studies of spironolactone for acne in women as well, which found that hyperkalemia was rare and was invariably mild and clinically insignificant.

[64] Side effects of spironolactone which may be indicative of hyperkalemia and if persistent could justify serum potassium testing include nausea, fatigue, and particularly muscle weakness.

Spironolactone bodies are eosinophilic, round, concentrically laminated cytoplasmic inclusions surrounded by clear halos in preparations stained with hematoxylin and eosin.

[161][162] In accordance, a subsequent study found that partial feminization of the genitalia occurred in the male offspring of rats that received doses of spironolactone that were five times higher than those normally used in humans (200 mg/kg per day).

[165] In any case, spironolactone is nonetheless not recommended during pregnancy due to theoretical concerns relating to feminization of males and also to potential alteration of fetal potassium levels.

[8] Symptoms following an acute overdose of spironolactone may include drowsiness, confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, and diarrhea.

[169] Physicians must be careful to monitor potassium levels in both males and females who are taking spironolactone as a diuretic, especially during the first twelve months of use and whenever the dosage is increased.

[179][180] Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to attenuate the diuresis and natriuresis induced by spironolactone, but, not to affect its antihypertensive effect.

[11] The antimineralocorticoid activity of spironolactone is responsible for its therapeutic efficacy in the treatment of edema, high blood pressure, heart failure, hyperaldosteronism, and ascites due to cirrhosis.

[188][189] It is also responsible for many of the side effects of spironolactone, such as urinary frequency, dehydration, hyponatremia, low blood pressure, fatigue, dizziness, metabolic acidosis, decreased kidney function, and its risk of hyperkalemia.

[190] Due to the antimineralocorticoid activity of spironolactone, levels of aldosterone are significantly increased by the medication, probably reflecting an attempt of the body to maintain homeostasis.

[64][109][134][141][172] In any case, the levels of most steroid hormones, including testosterone and cortisol, are usually unchanged by spironolactone in humans, which may in part be related to compensatory upregulation of their synthesis.

[109][134][201] The weak steroidogenesis inhibition of spironolactone might contribute to its antiandrogenic efficacy to some degree and may explain its side effect of menstrual irregularities in women.

"[214] Patients taking spironolactone must be monitored for side effects including dizziness, headache, fatigue, diarrhea, hypertriglyceridemia and elevated liver enzymes.

[105][106][250][282] Its name is spironolactonum in Latin, Spironolacton in German, espironolactona in Spanish and Portuguese, and spironolattone in Italian (which is also its DCITTooltip Denominazione Comune Italiana).