Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat fluid build-up due to liver disease or kidney disease. It is also used to reduce risk of disease progression, hospitalization, and death due to some types of heart failure. Other uses include acne and excessive hair growth in women, low blood potassium that does not improve with supplementation, high blood pressure that is difficult to treat, and early puberty in boys. It is also used to block the effects of testosterone as a part of feminizing hormone therapy. Spironolactone is usually available in tablets, taken by mouth, though topical forms are also available.
Common side effects include electrolyte abnormalities, particularly high blood potassium, nausea, vomiting, headache, rashes, and a decreased desire for sex. In those with liver or kidney problems, extra care should be taken.
If taken during pregnancy, some animal studies suggest that spironolactone may affect the development of sex organs in babies. While this has not occurred in the few human studies available, women who are pregnant or considering pregnancy should discuss spironolactone use with their doctor due to the theoretical risk.
Spironolactone is a steroid that blocks the effects of the hormones aldosterone, and to a lesser degree, testosterone, causing some estrogen-like effects. Spironolactone belongs to a class of medications known as potassium-sparing diuretics.
Spironolactone was discovered in 1957, and was introduced in 1959. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the 52nd most commonly prescribed medication in the United States, with more than 12million prescriptions. Spironolactone has a history of use in the trans community. Its use continues despite the rise of various accessible alternatives such as bicalutamide and cyproterone acetate with more precise action and fewer side effects.
Medical uses Spironolactone is used in the treatment of heart failure with reduced ejection fraction (HFrEF), where evidence shows that it reduces the risk of heart failure hospitalisation and mortality when added to standard therapy.
Multiple studies show that spironolactone improves left ventricular diastolic function in patients with heart failure with preserved ejection fraction HFpEF, though without benefits in death from any cause or overall hospitalisation. One randomised controlled trial showed a modest reduction in hospitalisation due to heart failure. A secondary analysis of TOPCAT suggested possible benefit in patients with both HFpEF and resistant hypertension, but this has not been confirmed in a prospective trial designed for this subgroup. Spironolactone is an effective fourth-line add-on therapy for lowering blood pressure in resistant hypertension that remains uncontrolled despite an ACE inhibitor or ARB, calcium channel blocker, and diuretic.
It is also used to treat edematous conditions such as nephrotic syndrome or ascites in people with liver disease, essential hypertension, low blood levels of potassium, secondary hyperaldosteronism (such as occurs with liver cirrhosis), and Conn's syndrome (primary hyperaldosteronism). The most common use of spironolactone is in the treatment of heart failure. On its own, spironolactone is only a weak diuretic because it primarily targets the distal nephron (collecting tubule), where only small amounts of sodium are reabsorbed, but it can be combined with other diuretics to increase efficacy. The classification of spironolactone as a "potassium-sparing diuretic" has been described as obsolete. Spironolactone is also used to treat Bartter's syndrome due to its ability to raise potassium levels.
Spironolactone, which has antiandrogenic effects, may help improve acne in adult women, with modest benefits demonstrated in recent clinical trials. Its use is limited by short-term outcome data and minimal reporting of side effects. It is considered a possible alternative to antibiotics for hormonal acne. It is also used to manage other androgen-related conditions such as hirsutism, seborrhoea, and female pattern hair loss Spironolactone is used for the treatment of hirsutism in the United States. High doses of spironolactone, which are needed for considerable antiandrogenic effects, are not recommended for men due to the high risk of feminization and other side effects. Spironolactone can be used to treat symptoms of hyperandrogenism, such as due to polycystic ovary syndrome.
Heart failure Although loop diuretics help to treat acute symptoms of heart failure, mineralocorticoid receptor antagonist diuretics (such as spironolactone) can be used long-term to reduce mortality and morbidity associated with certain types of chronic heart failure. A randomized controlled trial in 1999 found that spironolactone reduced death from any cause by 30%, as well as cardiac death and heart failure hospitalisations, in patients with HFrEF on standard therapy. A 2011 randomized controlled trial found similar benefits with eplerenone in HFrEF, supporting the use of mineralocorticoid receptor antagonists in HFrEF when added to contemporary heart failure therapy. Current recommendations from the American Heart Association are to use spironolactone in patients with NYHA Class II-IV heart failure who have a left ventricular ejection fraction of less than 35%.
Spironolactone improves left ventricular diastolic function in patients with heart failure with preserved ejection fraction, but it has no effect on mortality and hospitalization.
Due to its antiandrogenic properties, spironolactone can cause effects associated with low androgen levels and hypogonadism in males. For this reason, men are typically not prescribed spironolactone for any longer than a short period of time, e.g., for an acute exacerbation of heart failure. 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. As such, it is far more suitable for men for whom long-term medication is being chosen. Mineralcortocoid receptor antagonists (MRA) as a class (including spironolactone, canerenone, eplerenone and finerenone) are cornerstones of heart failure with reduced ejection fraction (HFrEF EF≤40%) management, however, the comparative magnitude of effect on mortality between agents remains uncertain. Primarily, evidence explores spironolactone and eplerenone, with limited comparative data available for canerenone. Furthermore, there is limited evidence for benefit of finerenone in a HFrEF patient cohort, a newer agent recently licensed for the treatment of chronic kidney disease (CKD) in type 2 diabetes mellitus.
High blood pressure About one in 100 people with hypertension have elevated levels of aldosterone; in these people, the antihypertensive effect of spironolactone may exceed that of complex combined regimens of other antihypertensives since it targets the primary cause of the elevated blood pressure. Spironolactone has demonstrated consistent and clinically meaningful reductions in blood pressure when used as an add-on therapy in patients with resistant hypertension.
High aldosterone levels Spironolactone is used in the treatment of hyperaldosteronism (high aldosterone levels or mineralocorticoid excess), for instance primary aldosteronism (Conn's syndrome). Antimineralocorticoids including spironolactone and eplerenone are first-line treatments for hyperaldosteronism. They improve blood pressure and potassium levels, as well as left ventricular hypertrophy, albuminuria, and carotid intima-media thickness, in people with primary aldosteronism. In people with hyperaldosteronism due to unilateral aldosterone-producing adrenocortical adenoma, adrenalectomy should be preferred instead of antimineralocorticoids. Spironolactone should not be used to treat primary aldosteronism in pregnancy due to its antiandrogen-related risk of teratogenicity in male fetuses.
Skin and hair conditions Androgens such as testosterone and DHT play a critical role in the pathogenesis of a number of dermatological conditions including oily skin, acne, seborrhea, hirsutism (excessive facial/body hair growth in women), and male pattern hair loss (androgenic alopecia). In demonstration of this, women with complete androgen insensitivity syndrome do not produce sebum or develop acne and have little to no body, pubic, or axillary hair. Moreover, men with congenital 5α-reductase type II deficiency, 5α-reductase being an enzyme that greatly potentiates the androgenic effects of testosterone in the skin, have little to no acne, scanty facial hair, reduced body hair, and reportedly no incidence of male-pattern hair loss. Conversely, hyperandrogenism in women, for instance due to polycystic ovary syndrome or congenital adrenal hyperplasia, is commonly associated with acne and hirsutism, as well as virilization (masculinization) in general. In accordance with the preceding, antiandrogens are highly effective in the treatment of the aforementioned androgen-dependent skin and hair conditions.
Because of the antiandrogenic activity of spironolactone, it can be quite effective in treating acne in women. In addition, spironolactone reduces oil that is naturally produced in the skin, so can be used to treat oily skin. 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. Oftentimes, for women treating acne, spironolactone is prescribed and paired with a birth control pill. Positive results in the pairing of these two medications have been observed, although these results may not be seen for up to three months. Spironolactone has been reported to produce a 50 to 100% improvement in acne at sufficiently high doses. Response to treatment generally requires 1 to 3 months in the case of acne and up to 6 months in the case of hirsutism. Ongoing therapy is generally required to avoid relapse of symptoms. Spironolactone is commonly used in the treatment of hirsutism in women, and is considered to be a first-line antiandrogen for this indication. Spironolactone can be used in the treatment of female-pattern hair loss (pattern scalp hair loss in women). There is tentative low quality evidence supporting its use for this indication.
Antiandrogens such as spironolactone are male-specific teratogens, which can feminize male fetuses due to their antiandrogenic effects. For this reason, antiandrogens are recommended only to be used to treat women who are of reproductive age in conjunction with adequate contraception. Oral contraceptives, which contain an estrogen and a progestin, are typically used for this purpose. Moreover, oral contraceptives themselves are functional antiandrogens and are independently effective in the treatment of androgen-dependent skin and hair conditions, hence can significantly augment the effectiveness of antiandrogens in the treatment of such conditions.
Spironolactone is not generally used in men for the treatment of androgen-dependent dermatological conditions because of its feminizing side effects, but it is effective for such indications in men similarly. As an example, spironolactone has been reported to reduce symptoms of acne in males. An additional example is the usefulness of spironolactone as an antiandrogen in transgender women and nonbinary individuals.