Spironolactone has antiandrogenic activity. For this reason, it is 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.[38] Spironolactone is used for the treatment of hirsutism in the United States.[39] 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.[40]
Heart failure
While loop diuretics remain first-line for most people with heart failure, spironolactone 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 spironolactone in patients with NYHA Class II-IV heart failure who have a left ventricular ejection fraction of less than 35%.[41]
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. However, eplerenone may not be as effective as spironolactone or the related medication canrenone in reducing mortality from heart failure.[44]
High blood pressure
About 1 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. 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.[45] There is no evidence of person-oriented outcome at any dose in this group.[45]
Because of the antiandrogenic activity of spironolactone, it can be quite effective in treating acne in women.[62][63][64] In addition, spironolactone reduces oil that is naturally produced in the skin and can be used to treat oily skin.[63][65][52] 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.[63][65] Oftentimes, for women treating acne, spironolactone is prescribed and paired with a birth control pill.[63][65] Positive results in the pairing of these two medications have been observed, although these results may not be seen for up to three months.[63][65] Spironolactone has been reported to produce a 50 to 100% improvement in acne at sufficiently high doses.[66] Response to treatment generally requires 1 to 3 months in the case of acne and up to 6 months in the case of hirsutism.[66] Ongoing therapy is generally required to avoid relapse of symptoms.[66] Spironolactone is commonly used in the treatment of hirsutism in women, and is considered to be a first-line antiandrogen for this indication.[67] Spironolactone can be used in the treatment of female-pattern hair loss (pattern scalp hair loss in women).[68] There is tentative low quality evidence supporting its use for this indication.[69] Although apparently effective, not all cases of female-pattern hair loss are dependent on androgens.[70]
Antiandrogens like spironolactone are male-specific teratogens which can feminize male fetuses due to their antiandrogenic effects.[60][71][72] For this reason, it is recommended that antiandrogens only be used to treat women who are of reproductive age in conjunction with adequate contraception.[60][71][72] Oral contraceptives, which contain an estrogen and a progestin, are typically used for this purpose.[60] 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.[60][73]
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.[68] As an example, spironolactone has been reported to reduce symptoms of acne in males.[74] An additional example is the usefulness of spironolactone as an antiandrogen in transgender women.[75][76][77]
Topical spironolactone has been found to be effective in the treatment of acne as well.[78] As a result, topical pharmaceutical formulations containing 2% or 5% spironolactone cream became available in Italy for the treatment of acne and hirsutism in the early 1990s.[79][80] The products were discontinued in 2006 when the creams were added to the list of doping substances with a decree of the Ministry of Health that year.[80]
Comparison
Spironolactone, the 5α-reductase inhibitorfinasteride, and the nonsteroidal antiandrogenflutamide all appear to have similar effectiveness in the treatment of hirsutism.[67][81][82] However, some clinical research has found that the effectiveness of spironolactone for hirsutism is greater than that of finasteride but is less than that of flutamide.[67] The combination of spironolactone with finasteride is more effective than either alone for hirsutism and the combination of spironolactone with a birth control pill is more effective than a birth control pill alone.[67] One study showed that spironolactone or the steroidal antiandrogencyproterone acetate both in combination with a birth control pill had equivalent effectiveness for hirsutism.[67] Spironolactone is considered to be a first-line treatment for hirsutism, finasteride and the steroidal antiandrogen cyproterone acetate are considered to be second-line treatments, and flutamide is no longer recommended for hirsutism due to liver toxicity concerns.[67] The nonsteroidal antiandrogen bicalutamide is an alternative option to flutamide with improved safety.[83][84]
The combination of spironolactone with a birth control pill in the treatment of acne appears to have similar effectiveness to a birth control pill alone and the combination of a birth control pill with cyproterone acetate, flutamide, or finasteride.[63] However, this was based on low- to very-low-quality evidence.[63] Spironolactone may be more effective than birth control pills in the treatment of acne, and the combination of spironolactone with a birth control pill may have greater effectiveness for acne than either alone.[85] In addition, some clinical research has found that flutamide is more effective than spironolactone in the treatment of acne.[63] In one study, flutamide decreased acne scores by 80% within 3 months, whereas spironolactone decreased symptoms by only 40% in the same time period.[86][87][88] However, the use of flutamide for acne is limited by its liver toxicity.[89][90][91][92] Bicalutamide is a potential alternative to flutamide for acne as well.[93][94] Spironolactone can be considered as a first-line treatment for acne in those who have failed other standard treatments such as topical therapies and under certain other circumstances, although this is controversial due to the side effects of spironolactone and its teratogenicity.[85][61]
There is insufficient clinical evidence to compare the effectiveness of spironolactone with other antiandrogens for female-pattern hair loss.[95] The effectiveness of spironolactone in the treatment of both acne and hirsutism appears to be dose-dependent, with higher doses being more effective than lower doses.[85][96][97] However, higher doses also have greater side effects, such as menstrual irregularities.[63]
A potential side effect of spironolactone is hyperkalemia (high potassium levels), which, in severe cases, can be life-threatening.[8] Hyperkalemia can present as a normal anion-gap metabolic acidosis.[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.[114] Spironolactone may put people at a heightened risk for gastrointestinal issues like nausea, vomiting, diarrhea, cramping, and gastritis.[8][115] In addition, there has been some evidence suggesting an association between use of the medication and bleeding from the stomach and duodenum,[8] though a causal relationship between the two has not been established.[116][117] Also, spironolactone is immunosuppressive in the treatment of sarcoidosis.[118]
Most of the side effects of spironolactone are dose-dependent.[62] Low-dose spironolactone is generally very well tolerated.[62] Even higher doses of spironolactone, such as 100 mg/day, are well tolerated in most individuals.[62] Dose-dependent side effects of spironolactone include menstrual irregularities, breast tenderness and enlargement, orthostatic hypotension, and hyperkalemia.[62] The side effects of spironolactone are usually mild and rarely result in discontinuation.[62]
Spironolactone can cause hyperkalemia, or high blood potassium levels.[111] Rarely, this can be fatal.[111] Of people with heart disease prescribed typical dosages of spironolactone, 10 to 15% develop some degree of hyperkalemia, and 6% develop severe hyperkalemia.[111] At a higher dosage, a rate of hyperkalemia of 24% has been observed.[119] An abrupt and major increase in the rate of hospitalization due to hyperkalemia from 0.2% to 11% and in the rate of death due to hyperkalemia from 0.3 per 1,000 to 2.0 per 1,000 between early 1994 and late 2001 has been attributed to a parallel rise in the number of prescriptions written for spironolactone upon the publication of the Randomized Aldactone Evaluation Study (RALES) in July 1999.[111][119][120][35] However, another population-based study in Scotland failed to replicate these findings.[121][122] The risk of hyperkalemia with spironolactone is greatest in the elderly, in people with renal impairment (e.g., due to chronic kidney disease or diabetic nephropathy), in people taking certain other medications (including ACE inhibitors, angiotensin II receptor blockers, nonsteroidal anti-inflammatory drugs, the antibiotictrimethoprim, and potassiumsupplements), and at higher dosages of spironolactone.[111][35][123][124]
Although spironolactone poses an important risk of hyperkalemia in the elderly, in those with kidney or cardiovascular disease, and/or in those taking medications or supplements which increase circulating potassium levels, a large retrospective study found that the rate of hyperkalemia in young women without such characteristics who had been treated with high doses of spironolactone for dermatological conditions did not differ from that of controls.[63][65][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.[63] These findings suggest that hyperkalemia may not be a significant risk in such individuals, and that routine monitoring of circulating potassium levels may be unnecessary in this population.[63][65][125] However, other sources have claimed that hyperkalemia can nonetheless also occur in people with more normal renal function and presumably without such risk factors.[35] Occasional testing on a case-by-case basis in those with known risk factors may be justified.[63] 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.[63] Notably, non-use of routine potassium monitoring with spironolactone in young women would reduce costs associated with its use.[63]
Among young gender-diverse individuals taking spironolactone, hyperkalemia is rare and (if present) transient and asymptomatic. Larger doses do not appear to increase risks in this population.[126] A broader retrospective study found that the rate of hyperkalemia in gender-diverse individuals is correlated with age, with those above 45 years old being more at risk. The finding suggests that patients below or at 45 years old without other conditions that affect potassium handling can be spared from routine monitoring.[127]
Breast changes
Spironolactone can cause breast pain and breast enlargement in women.[128][129] This is "probably because of estrogenic effects on target tissue."[111] At low doses, breast tenderness has been reported in only 5% of women, but at high doses, it has been reported in up to 40% of women.[130][62] Breast enlargement and tenderness may occur in 26% of women at high doses.[86] Some women regard spironolactone-induced breast enlargement as a positive effect.[63]
Spironolactone also commonly and dose-dependently produces gynecomastia (breast development) as a side effect in men.[110][129][131][132] At low doses, the rate is only 5 to 10%,[132] but at high doses, up to or exceeding 50% of men may develop gynecomastia.[110][129][131] In the RALES, 9.1% of men taking 25 mg/day spironolactone developed gynecomastia, compared to 1.3% of controls.[133] Conversely, in studies of healthy men given high-dose spironolactone, gynecomastia occurred in 3 of 10 (30%) at 100 mg/day, in 5 of 8 (62.5%) at 200 mg/day, and in 6 of 9 (66.7%) at 400 mg/day, relative to none of 12 controls.[134][135] The severity of gynecomastia with spironolactone varies considerably, but is usually mild.[110] As with breast enlargement caused by spironolactone in women, gynecomastia due to spironolactone in men is often although inconsistently accompanied by breast tenderness.[110] In the RALES, only 1.7% of men developed breast pain, relative to 0.1% of controls.[133]
The time to onset of spironolactone-induced gynecomastia has been found to be 27 ± 20 months at low doses and 9 ± 12 months at high doses.[133] Gynecomastia induced by spironolactone usually regresses after a few weeks following discontinuation of the medication.[110] However, after a sufficient duration of gynecomastia being present (e.g., one year), hyalinization and fibrosis of the tissue occurs and drug-induced gynecomastia may become irreversible.[136][137]
Menstrual disturbances
Spironolactone at higher doses can cause menstrual irregularities as a side effect in women.[62] These irregularities include metrorrhagia (intermenstrual bleeding), amenorrhea (absence of menstruation), and breakthrough bleeding.[62] They are common during spironolactone therapy, with 10 to 50% of women experiencing them at moderate doses and almost all experiencing them at a high doses.[86][111] For example, about 20% of women experienced menstrual irregularities with 50 to 100 mg/day spironolactone, whereas about 70% experienced menstrual irregularities at 200 mg/day.[62] Most women taking moderate doses of spironolactone develop amenorrhea, and normal menstruation usually returns within two months of discontinuation.[111] Spironolactone produces an irregular and anovulatory pattern of menstrual cycles.[86] It is also associated with metrorrhagia and menorrhagia (heavy menstrual bleeding) in large percentages of women,[128] as well as with polymenorrhea (short menstrual cycles).[138][139] The medication reportedly has no birth control effect.[140]
It has been suggested that the weak progestogenic activity of spironolactone is responsible for these effects, although this has not been established and spironolactone has been shown to possess insignificant progestogenic and antiprogestogenic activity even at high dosages in women.[86][141][142] An alternative proposed cause is inhibition of 17α-hydroxylase and hence sex steroidmetabolism by spironolactone and consequent changes in sex hormone levels.[110] Indeed, CYP17A1genotype is associated with polymenorrhea.[143] Regardless of their mechanism, the menstrual disturbances associated with spironolactone can usually be controlled well by concomitant treatment with a birth control pill, due to the progestin component.[86][144]
Mood changes
Research is mixed on whether antimineralocorticoids like spironolactone have positive or negative effects on mood.[145][146][147] In any case, it is possible that spironolactone might have the capacity to increase the risk of depressive symptoms.[145][146][147] However, a 2017 hybrid systematic review found that the incidence of depression in women treated with spironolactone for acne was less than 1%.[63] Likewise, a 10-year observational study found that the incidence of depression in 196 transgender women taking high-dose spironolactone in combination with an estrogen was less than 1%.[148]
Long-term administration of spironolactone gives the histologic characteristic of "spironolactone bodies" in the adrenal cortex. Spironolactone bodies are eosinophilic, round, concentrically laminated cytoplasmic inclusions surrounded by clear halos in preparations stained with hematoxylin and eosin.[159]
Pregnancy and breastfeeding
Spironolactone is able to cross the placenta.[128] It has been found to be present in the breast milk of lactating mothers.[8] However, only very small amounts of spironolactone and its metabolite canrenone enter breast milk, and the amount received by an infant during breastfeeding (<0.5% of the mother's dose) is considered to be insignificant.[160]
A study found that spironolactone was not associated with teratogenicity in the offspring of rats.[161][162][163] Because it is an antiandrogen, however, spironolactone could theoretically have the potential to cause feminization of male fetuses at sufficient doses.[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).[161][163] Another study found permanent, dose-related reproductive tract abnormalities rat offspring of both sexes at lower doses (50 to 100 mg/kg per day).[163]
In practice however, although experience is limited, spironolactone has never been reported to cause observable feminization or any other congenital defects in humans.[161][162][164][165] Among 31 human newborns exposed to spironolactone in the first trimester, there were no signs of any specific birth defects.[165] A case report described a woman who was prescribed spironolactone during pregnancy with triplets and delivered all three (one boy and two girls) healthy; there was no feminization in the boy.[165] In addition, spironolactone has been used at high doses to treat pregnant women with Bartter's syndrome, and none of the infants (three boys, two girls) showed toxicity, including feminization in the male infants.[160][161] There are similar findings, albeit also limited, for another antiandrogen, cyproterone acetate (prominent genital defects in male rats, but no human abnormalities (including feminization of male fetuses) at both a low dose of 2 mg/day or high doses of 50 to 100 mg/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.[161][166]
A 2019 systematic review found insufficient evidence that spironolactone causes birth defects in humans.[167] However, there was also insufficient evidence to be certain that it does not.[167]
There is no specific antidote for overdose of spironolactone.[8] Treatment may consist of induction of vomiting or stomach evacuation by gastric lavage.[8] The treatment of spironolactone overdose is supportive, with the purpose of maintaining hydration, electrolyte balance, and vital functions.[8] Spironolactone should be discontinued in people with impaired kidney function or hyperkalemia.[8]
Interactions
Spironolactone often increases serum potassium levels and can cause hyperkalemia, a very serious condition. Therefore, it is recommended that people using this medication avoid potassium supplements and salt substitutes containing potassium.[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. Doctors may also recommend that some patients may be advised to limit dietary consumption of potassium-rich foods. However, recent data suggests that both potassium monitoring and dietary restriction of potassium intake is unnecessary in healthy young women taking spironolactone for acne[125] and in healthy young gender-diverse individuals taking spironolactone for hormone therapy.[127] Spironolactone together with trimethoprim/sulfamethoxazole increases the likelihood of hyperkalemia, especially in the elderly. The trimethoprim portion acts to prevent potassium excretion in the distal tubule of the nephron.[170]
Spironolactone has been reported to induce the enzymesCYP3A4 and certain UDP-glucuronosyltransferases (UGTs), which can result in interactions with various medications.[17][171][172] However, it has also been reported that metabolites of spironolactone irreversibly inhibit CYP3A4.[173] In any case, spironolactone has been found to reduce the bioavailability of oral estradiol, which could be due to induction of estradiol metabolism via CYP3A4.[174] Spironolactone has also been found to inhibitUGT2B7.[175] Spironolactone can also have numerous other interactions, most commonly with other cardiac and blood pressure medications, for instance digoxin.[8]
Licorice, which has indirect mineralocorticoid activity by inhibiting mineralocorticoid metabolism, has been found to inhibit the antimineralocorticoid effects of spironolactone.[176][177][178] Moreover, the addition of licorice to spironolactone has been found to reduce the antimineralocorticoid side effects of spironolactone in women treated with it for hyperandrogenism, and licorice hence may be used to reduce these side effects in women treated with spironolactone as an antiandrogen who are bothered by them.[176][177] On the opposite end of the spectrum, spironolactone is useful in reversing licorice-induced hypokalemia.[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.[37][181]
Some research has suggested that spironolactone might be able to interfere with the effectiveness of antidepressant treatment. As the medication acts as an antimineralocorticoid, it is thought that it might be able to reduce the effectiveness of certain antidepressants by interfering with normalization of the hypothalamic–pituitary–adrenal axis and by increasing levels of glucocorticoids such as cortisol.[182][183] However, other research contradicts this hypothesis and has suggested that spironolactone might actually produce antidepressant effects, for instance studies showing antidepressant-like effects of spironolactone in animals.[184]
Spironolactone has been found in some studies to increase levels of estradiol, an estrogen, although many other studies have found no changes in estradiol levels.[109][134] The mechanism of how spironolactone increases estradiol levels is unclear, but it may involve inhibition of the inactivation of estradiol into estrone and enhancement of the peripheral conversion of testosterone into estradiol.[202][203] It is notable that spironolactone has been found in vitro to act as a weak inhibitor of 17β-hydroxysteroid dehydrogenase 2, an enzyme that is involved in the conversion of estradiol into estrone.[204][205] Increased levels of estradiol with spironolactone may be involved in its preservation of bone density and in its side effects such as breast tenderness, breast enlargement, and gynecomastia in women and men.[202][206][207]
In response to the antimineralocorticoid activity spironolactone, and in an attempt to maintain homeostasis, the body increases aldosterone production in the adrenal cortex.[208][209][210] Some studies have found that levels of cortisol, a glucocorticoid hormone that is also produced in the adrenal cortex, are increased as well.[209][210][211] Spironolactone “acts at the basolateral side of the upper-distal tubule as well as in the collecting tubule,” and does not have glucocorticoid-like effects at these specific sites; it can sometimes be prescribed as an alternative to glucocorticoids for patients with Glucocorticoid-Remediable Aldosteronism characterized by aldosterone excess,[141][212][97][213] In patients “receiving spironolactone, there was a significant positive correlation between the change in cortisol and the change in HbA1c (r = 0.489, P = .003).”[214] Patients taking spironolactone must be monitored for side effects including dizziness, headache, fatigue, diarrhea, hypertriglyceridemia and elevated liver enzymes.[215][216]
The pharmacokinetics of spironolactone have not been studied well, which is in part because it is an old medication that was developed in the 1950s.[135] Nonetheless, much has been elucidated about the pharmacokinetics of spironolactone over the decades.[221][222][223][11][224][225][226][227]
Absorption
Levels of spironolactone and its major active metabolites after a single oral dose of 100 mg spironolactone in humans.[228]
The bioavailability of spironolactone when taken by mouth is 60 to 90%.[11][12][13] The bioavailability of spironolactone and its metabolites increases significantly (+22–95% increases in levels) when spironolactone is taken with food, although it is uncertain whether this further increases the therapeutic effects of the medication.[229][230][231] The increase in bioavailability is thought to be due to promotion of the gastric dissolution and absorption of spironolactone, as well as due to a decrease of the first-pass metabolism.[229][232][233] The relationship between a single dose of spironolactone and plasma levels of canrenone, a major active metabolite of spironolactone, has been found to be linear across a dose range of 25 to 200 mg spironolactone.[195]Steady-state concentrations of spironolactone are achieved within 8 to 10 days of treatment initiation.[186][234]
Little or no systemic absorption has been observed with topical spironolactone.[235]
Distribution
Spironolactone and its metabolite canrenone are highly plasma protein bound, with percentages of 88.0% and 99.2%, respectively.[11][14] Spironolactone is bound equivalently to albumin and α1-acid glycoprotein, while canrenone is bound only to albumin.[11][14] Spironolactone and its metabolite 7α-thiospironolactone show very low or negligible affinity for sex hormone-binding globulin (SHBG).[236][237] In accordance, a study of high-dosage spironolactone treatment found no change in steroid binding capacity related to SHBG or to corticosteroid-binding globulin (CBG), suggesting that spironolactone does not displace steroid hormones from their carrier proteins.[238] This is in contradiction with widespread statements that spironolactone increases free estradiol levels by displacing estradiol from SHBG.[97][239]
Spironolactone is rapidly and extensively metabolized in the liver upon oral administration and has a very short terminal half-life of 1.4 hours.[11][12] The major metabolites of spironolactone are 7α-thiomethylspironolactone (7α-TMS), 6β-hydroxy-7α-thiomethylspironolactone (6β-OH-7α-TMS), and canrenone (7α-desthioacetyl-δ6-spironolactone).[11][12][185] These metabolites have much longer elimination half-lives than spironolactone of 13.8 hours, 15.0 hours, and 16.5 hours, respectively, and are responsible for the therapeutic effects of the medication.[11][12] As such, spironolactone is a prodrug.[243] The 7α-thiomethylated metabolites of spironolactone were not known for many years and it was originally thought that canrenone was the major active metabolite of the medication, but subsequent research identified 7α-TMS as the major metabolite.[11][185][186] Other known but more minor metabolites of spironolactone include 7α-thiospironolactone (7α-TS), which is an important intermediate to the major metabolites of spironolactone,[17] as well as the 7α-methyl ethyl ester of spironolactone and the 6β-hydroxy-7α-methyl ethyl ester of spironolactone.[15]
Spironolactone, also known as 7α-acetylthiospirolactone, is a steroidal17α-spirolactone, or more simply a spirolactone.[107] It can most appropriately be conceptualized as a derivative of progesterone,[133][249][234] itself also a potent antimineralocorticoid, in which a hydroxyl group has been substituted at the C17α position (as in 17α-hydroxyprogesterone), the acetyl group at the C17β position has been cyclized with the C17α hydroxyl group to form a spiro 21-carboxylic acid γ-lactonering, and an acetylthio group has been substituted in at the C7α position.[250][251][252] These structural modifications of progesterone confer increased oralbioavailability and potency,[253] potent antiandrogenic activity, and strongly reduced progestogenic activity.[254] The C7α substitution is likely responsible for or involved in the antiandrogenic activity of spironolactone, as 7α-thioprogesterone (SC-8365), unlike progesterone,[255] is an antiandrogen with similar affinity to the AR as that of spironolactone.[256] In addition, the C7α substitution appears to be responsible for the loss of progestogenic activity and good oral bioavailability of spironolactone, as SC-5233, the analogue of spironolactone without a C7α substitution, has potent progestogenic activity but very poor oral bioavailability similarly to progesterone.[255][257][258]
Names
Spironolactone is also known by the following equivalent chemical names:[250][251][252]
The natriuretic effects of progesterone were demonstrated in 1955, and the development of spironolactone as a synthetic antimineralocorticoid analogue of progesterone shortly followed this.[133][249][260][261] Spironolactone was first synthesized in 1957,[28][260][261] was patented between 1958 and 1961,[262][263] and was first marketed, as an antimineralocorticoid, in 1959.[264][265] Gynecomastia was first reported with spironolactone in 1962,[107][266] and the antiandrogenic activity of the medication was first described in 1969.[267] This shortly followed the discovery in 1967 that gynecomastia is an important and major side effect of AR antagonists.[268][269] Spironolactone was first studied in the treatment of hirsutism in women in 1978.[270][176][271][272][273] It has since become the most widely used antiandrogen for dermatological indications in women in the United States.[103][274][275][276] Spironolactone was first studied as an antiandrogen in transgender women in 1986, and has since become widely adopted for this purpose as well, particularly in the United States where cyproterone acetate is not available.[277][278][279]
Early oral spironolactone tablets showed poor absorption.[280] The formulation was eventually changed to a micronized formulation with particle sizes of less than 50 μg, which resulted in approximately 4-fold increased potency.[280][281]
Society and culture
Generic names
Generic spironolactone for veterinary use
The English, French, and generic name of the medication is spironolactone and this is its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, USPTooltip United States Pharmacopeia, BANTooltip British Approved Name, DCFTooltip Dénomination Commune Française, and JANTooltip Japanese Accepted Name.[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).[105][106][282]
Spironolactone is also known by its developmental code names SC-9420 and NSC-150339.[105][106][250]
Brand names
Spironolactone is marketed under a various brand names throughout the world.[105][106] The original brand name of spironolactone is Aldactone.[105][106] Other brand names include Aldactone-A, Berlactone, CaroSpir, Espironolactona, Espironolactona Genfar, Novo-Spiroton, Prilactone (veterinary), Spiractin, Spiridon, Spirix, Spiroctan, Spiroderm (discontinued),[5] Spirogamma, Spirohexal, Spirolon, Spirolone, Spiron, Spironolactone Actavis, Spironolactone Orion, Spironolactone Teva, Spirotone, Tempora (veterinary), Uractone, Uractonum, Verospiron, and Vivitar.[105][106]
Spironolactone is also formulated in combination with a variety of other medications, including with hydrochlorothiazide as Aldactazide, with hydroflumethiazide as Aldactide, Lasilacton, Lasilactone, and Spiromide, with altizide as Aldactacine and Aldactazine, with furosemide as Fruselac, with benazepril as Cardalis (veterinary), with metolazone as Metolactone, with bendroflumethiazide as Sali-Aldopur, and with torasemide as Dytor Plus, Torlactone, and Zator Plus.[106]
Availability
Spironolactone is marketed throughout the world.[105][106]
Research
Prostate conditions
Spironolactone has been studied at a high dosage in the treatment of benign prostatic hyperplasia (BPH; enlarged prostate).[283][284][285] It was found to be better than placebo in terms of symptom relief following three months of treatment.[283][284] However, this was not maintained after six months of treatment, by which point the improvements had largely disappeared.[283][284][285] Moreover, no difference was observed between spironolactone and placebo with regard to volume of residual urine or prostate size.[283][284] Gynecomastia was observed in about 5% of people.[284] On the basis of these results, it has been said that spironolactone has no place in the treatment of BPH.[284]
Spironolactone has been found to block Epstein–Barr virus (EBV) production and that of other human herpesviruses by inhibiting the function of an EBV protein SM, which is essential for infectious virus production.[288] This effect of spironolactone was determined to be independent of its antimineralocorticoid actions.[288]
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Uusikaupunki Le bâtiment principal en 2007. Localisation Pays Finlande Commune Uusikaupunki Adresse Ratapihankatu 423500 Uusikaupunki Coordonnées géographiques 60° 47′ 50″ nord, 21° 25′ 33″ est Gestion et exploitation Exploitant VR Code UIC 10001214 Services Marchandises Caractéristiques Ligne(s) Turku à Uusikaupunki Historique Mise en service 1er septembre 1924 Fermeture 1er janvier 1993 (voyageurs) Architecte Thure Hellström modifier La ga...
Myles MoylanMyles MoylanLahir17 Desember 1838Amesbury, Massachusetts, Amerika SerikatMeninggal11 Desember 1909San Diego, California, Amerika SerikatDikebumikanGreenwood Memorial Park, San Diego, California, Amerika SerikatPengabdianAmerika SerikatDinas/cabangAngkatan Darat Amerika SerikatLama dinas1857–1893Pangkat MayorKomandanCompany A, Resimen Kavaleri ke-7Perang/pertempuranPerang Saudara Amerika Pertempuran Cekungan Wilson Pertempuran Benteng Henry Pertempuran Benteng Donelson Perte...
Church in Adelaide, South Australia Church in South Australia, AustraliaSt Peter's CathedralCathedral Church of St Peter34°54′46″S 138°35′53″E / 34.91278°S 138.59806°E / -34.91278; 138.59806LocationAdelaide, South AustraliaCountryAustraliaDenominationAnglican Church of AustraliaWebsitestpeters-cathedral.org.auHistoryStatusCathedralFounded29 June 1869 (1869-06-29)Founder(s)Bishop Augustus ShortDedicationSt Peter the ApostleConsecrated1 Ja...
Chinese bakery product traditionally eaten during the Mid-Autumn Festival For the American chocolate-marshmallow confection, see Moon pie. For the animated character, see Final Space. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Mooncake – news · newspapers · books · scholar · JSTOR (September 2021) (Lear...
American actor and director (1895–1985) Edward BuzzellEdward Buzzell in Easy to Wed (1946)Born(1895-11-13)November 13, 1895Brooklyn, New York City, U.S.DiedJanuary 11, 1985(1985-01-11) (aged 89)Los Angeles, California, U.S.Occupation(s)Actor, director, producer, writerYears active1929–1961Spouses Ona Munson (m. 1926; div. 1931) Sara Clark (1934–1934) Lorraine Miller &#...
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article is missing information about the party's ideology. Please expand the article to include this information. Further details may exist on the talk page. (March 2015) This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenge...
Радянський диктатор Йосип Сталін та міністр закордонних справ Третього Райху Йоахим фон Ріббентроп у Кремлі після підписання Пакту Молотова-Ріббентропа (серпень 1939) Співпраця між Німеччиною та Радянською Росією (пізніше — Радянським Союзом) бере початок від кінця Перш...
Tom Daschle Retrato oficial, 2003 Senador de los Estados Unidospor Dakota del Sur 6 de enero de 1987-3 de enero de 2005Predecesor James AbdnorSucesor John Thune Líder de la mayoría en el Senado de los Estados Unidos 6 de junio de 2001-3 de enero de 2003Predecesor Trent LottSucesor Bill Frist 3 de enero de 2001-20 de enero de 2001Predecesor Trent LottSucesor Trent Lott Miembro de la Cámara de Representantes de los Estados Unidospor Dakota del Sur 3 de enero de 1979-3 de enero de 1987Predece...
Чемпіонат України з футболу 2022—2023 років — 32-й чемпіонат України з футболу. Зміст 1 Прем'єр-ліга 2 Перехідні матчі за право виступати в Прем'єр-лізі 3 Перша ліга 3.1 Група А 3.2 Група Б 3.3 Чемпіонська група 3.4 Група вибування 4 Перехідні матчі за право виступати в першій лізі 5 �...
Constituency of the Haryana legislative assembly in India Kaithal Assembly constituencyConstituency for the Haryana Legislative AssemblyConstituency detailsCountryIndiaRegionNorth IndiaStateHaryanaLS constituencyKurukshetraEstablished1967Member of Legislative Assembly14th Haryana Legislative AssemblyIncumbent Leela Ram PartyBharatiya Janata PartyElected year2019 Kaithal Assembly constituency is one of the 90 constituencies in the Haryana Legislative Assembly of Haryana a northern state of Ind...
Australian rugby league club, based at The Entrance, NSW The Entrance TigersClub informationFull nameThe Entrance District Rugby League Football ClubNickname(s)The Tigers,Colours Orange Black WhiteFounded1934; 89 years ago (1934)Entered Competition 1947; 76 years ago (1947)Current detailsGround(s)EDSACC Oval, Bateau BayCompetitionCentral Coast Rugby League20191stRecordsPremierships18 (CCDRL 1949, 1956, 1957, 1961, 1989, 1993, 1995, 2000, ...
