<unk>  is used primarily to treat heart failure, 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<unk>  is in the treatment of heart failure. On its own,<unk>  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<unk>  as a "potassium-sparing diuretic" has been described as obsolete.<unk>  is also used to treat Bartter's syndrome due to its ability to raise potassium levels.<unk>  has antiandrogenic activity. For this reason, it is frequently used to treat a variety of dermatological conditions in which androgens play a role. Some of these uses include acne, seborrhea, hirsutism, and pattern hair loss in women.<unk>  is the most commonly used medication in the treatment of hirsutism in the United States. High doses of<unk> , which are needed for considerable antiandrogenic effects, are not recommended for men due to the high risk of feminization and other side effects.<unk>  is also commonly used to treat symptoms of hyperandrogenism, such as due to polycystic ovary syndrome, in women. Heart failure While loop diuretics remain first-line for most people with heart failure,<unk>  has shown to reduce both morbidity and mortality in numerous studies and remains an important agent for treating fluid retention, edema, and symptoms of heart failure. Current recommendations from the American Heart Association are to use<unk>  in patients with NYHA Class II-IV heart failure who have a left ventricular ejection fraction of less than 35%. In a randomized evaluation which studied people with severe congestive heart failure, people treated with<unk>  were found to have a relative risk of death of 0.70 or an overall 30% relative risk reduction compared to the placebo group, indicating a significant death and morbidity benefit of the medication. People in the study's intervention arm also had fewer symptoms of heart failure and were hospitalized less frequently. Likewise, it has shown benefit for and is recommended in patients who recently suffered a heart attack and have an ejection fraction less than 40%, who develop symptoms consistent with heart failure, or have a history of diabetes mellitus.<unk>  should be considered a good add-on agent, particularly in those patients "not" yet optimized on ACE inhibitors and beta-blockers. Of note, a recent randomized, double-blinded study of<unk>  in patients with symptomatic heart failure with "preserved" ejection fraction (i.e. >45%) found no reduction in death from cardiovascular events, aborted cardiac arrest, or hospitalizations when<unk>  was compared to placebo. It is recommended that alternatives to<unk>  be considered if serum creatinine is greater than 2.5 mg/dL (221 μmol/L) in males or greater than 2 mg/dL (176.8 μmol/L) in females, if glomerular filtration rate is below 30 mL/min or with a serum potassium of greater than 5.0 mEq/L given the potential for adverse events detailed elsewhere in this article. Doses should be adjusted according to the degree of kidney function as well. According to a systematic review, in heart failure with preserved ejection fraction, treatment with<unk>  did not improve patient outcomes. This is based on the TOPCAT Trial examining this issue, which found that of those treated with placebo had a 20.4% incidence of negative outcome vs 18.6% incidence of negative outcome with<unk> . However, because the p-value of the study was 0.14, and the unadjusted hazard ratio was 0.89 with a 95% confidence interval of 0.77 to 1.04, it is determined the finding had no statistical significance. Hence the finding that patient outcomes are not improved with use of<unk> . More recently, when blood samples from 366 patients in the TOPCAT study were analyzed for presence of canrenone (an active metabolite of<unk> , 30% of blood samples from Russia lacked detectable residues of canrenone. This led to the conclusion that the TOPCAT trial results in Russia do not reflect actual clinical experience with<unk>  in patients with preserved ejection fraction. The TOPCAT study results are now considered to have been invalidated. The study's prime investigator and other prominent research cardiologists are now advising physicians treating heart failure with preserved ejection fraction to consider prescribing<unk>  pending outcome of two multicenter trials of newer medications. Due to its antiandrogenic properties,<unk>  can cause effects associated with low androgen levels and hypogonadism in males. For this reason, men are typically not prescribed<unk>  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 U.S. Food and Drug Administration for the treatment of heart failure, and lacks the antiandrogenic effects of<unk> . As such, it is far more suitable for men for whom long-term medication is being chosen. However, eplerenone may not be as effective as<unk>  or the related medication canrenone in reducing mortality from heart failure. The clinical benefits of<unk>  as a diuretic are typically not seen until 2–3 days after dosing begins. Likewise, the maximal antihypertensive effect may not be seen for 2–3 weeks. Unlike with some other diuretics, potassium supplementation should not be administered while taking<unk> , as this may cause dangerous elevations in serum potassium levels resulting in hyperkalemia and potentially deadly abnormal heart rhythms. High blood pressure About 1 in 100 people with hypertension have elevated levels of aldosterone; in these people, the antihypertensive effect of<unk>  may exceed that of complex combined regimens of other antihypertensives since it targets the primary cause of the elevated blood pressure. However, a Cochrane review found adverse effects at high doses and little effect on blood pressure at low doses in the majority of people with high blood pressure. There is no evidence of person-oriented outcome at any dose in this group. Skin and hair conditions Androgens like 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 (CAIS) 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 (PCOS) or congenital adrenal hyperplasia (CAH), 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<unk> , it can be quite effective in treating acne in women. In addition,<unk>  reduces oil that is naturally produced in the skin and can be used to treat oily skin. Though not the primary intended purpose of the medication, the ability of<unk>  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,<unk>  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.<unk>  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.<unk>  is commonly used in the treatment of hirsutism in women, and is considered to be a first-line antiandrogen for this indication.<unk>  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. Although apparently effective, not all cases of female-pattern hair loss are dependent on androgens. Antiandrogens like<unk>  are male-specific teratogens which can feminize male fetuses due to their antiandrogenic effects. For this reason, it is recommended that antiandrogens only 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, and hence can significantly augment the effectiveness of antiandrogens in the treatment of such conditions.<unk>  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
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