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At least 19 recordsLinked to original sources
PubMed2000

Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne.

BACKGROUND: Hirsutism is the presence of excessive hair growth in women and is an important cosmetic condition often resulting in severe distress. Hirsutism is most often caused by increased production of male sex hormones also known as androgens. It is also affected by increased sensitivity to androgens in the hair follicles, and the secretory glands around the hair follicles, called sebaceous glands. Spironolactone is an antiandrogen and aldosterone antagonist used to treat hirsutism. Since 1978, many studies have been conducted to determine its effectiveness. OBJECTIVES: The objective of this review was to investigate the effectiveness of spironolactone and/or in combination with steroids (oral contraceptive pill included) in reducing excess hair growth and/or acne in women. SEARCH STRATEGY: All publications of randomised controlled trials of spironolactone versus placebo and/or in combination with steroids (oral contraceptive pill included) were identified. Search strategy was developed by the Menstrual Disorder Group. All accessable electronic databases were searched. In addition, all reference lists of relevant trials were searched and drug companies contacted for details of unpublished trials. SELECTION CRITERIA: All randomised controlled comparisons of spironolactone versus: placebo steroids (oral contraceptive pill included)) spironolactone of varying dosages or spironolactone and steroids versus steroids alone when used to reduce hair growth and acne in women. DATA COLLECTION AND ANALYSIS: Four trials were included in the review, seven trials were excluded. Two other trials are awaiting assessment. All included trials were small (no more than 31 participants) randomised and controlled. Only one trial studied acne as an outcome, the remaining three were concerned with hirsutism. One trial investigated spironolactone versus placebo; one trial was a dosage studies of spironolactone; one trial compared spironolactone with spironolactone in combination with dexamethasone; the remaining trial used topical spironolactone for the treatment of acne. Major outcome measures include the following: - subjective observations - Ferriman and Gallwey hair scores - hormonal and biochemical parameters - side effects - sebum production measurement MAIN RESULTS: All sample populations were small and confidence intervals were wide. There was no significant difference between treatments for any of the observed outcomes. REVIEWER'S CONCLUSIONS: The effectiveness of treatment for either acne vulgaris or hirsutism cannot be determined due to the small sample populations involved in the trials. Its value in clinical practice is difficult to assess from currently available research.

Acne Vulgaris↗
PubMed1998

Water-soluble beta-cyclodextrins in paediatric oral solutions of spironolactone: preclinical evaluation of spironolactone bioavailability from solutions of beta-cyclodextrin derivatives in rats.

Water-soluble derivatives of beta-cyclodextrin have been considered for solubilization of spironolactone in the formulation of a safe liquid preparation for premature infants. The oral absorption of spironolactone was studied in rats to evaluate the need to adjust spironolactone dosage in prospective clinical studies. Spironolactone was administered in solutions of sulphobutyl ether beta-cyclodextrin (SBE7) or dimethyl-beta-cyclodextrin (DM-beta-CyD) and also as spironolactone-containing powder papers (reference preparation). Spironolactone in SBE7 solution was administered intravenously to assess the extent of intestinal absorption from the different formulations. Spironolactone and the metabolites 7alpha-thiospirolactone, 7alpha-thiomethylspirolactone and canrenone were determined in rat serum after intravenous administration of spironolactone. Half-lives for spironolactone, 7alpha-thiomethylspirolactone and canrenone were 0.72 +/- 0.17, 1.5 +/- 0.3 and 2.2 +/- 0.3 h, respectively. Although, according to Cmax values, 7alpha-thiomethylspirolactone was the major serum metabolite in rats, higher AUC (area under the serum concentration-time curve) values were obtained for canrenone. After oral administration of spironolactone the bioavailabilities evaluated from the AUC values of 7alpha-thiomethylspirolactone were 27.5 +/- 9.3%, 81.3 +/- 28.8% and 82.8 +/- 28.6% for powder papers, DM-beta-CyD and SBE7 solutions, respectively. The oral absorption of spironolactone by rats was better after administration of spironolactone in SBE7 and DM-beta-CyD solutions than after administration as powder papers. Both cyclodextrin formulations enhanced spironolactone bioavailability to a similar extent despite some deacetylation of spironolactone in the presence of SBE7. A reduction of spironolactone dosage would be recommended during clinical studies with premature infants. These results indicate that SBE7 could be a safe and suitable excipient for the solubilization of spironolactone in paediatric formulations.

Animals↗
PubMed2000

[Treatment of hirsutism with spironolactone and with spironolactone plus dexamethasone].

BACKGROUND: Spironolactone has an anti androgenic effect, inhibiting the binding of androgens to their receptor. This antagonistic effect is the basis for the use of spironolactone in the treatment of hirsutism. AIM: To study the effectiveness and safety of spironolactone in the treatment of hirsute women and of the association of spironolactone plus dexamethasone in the treatment of hirsutism with glucocorticoid sensitive hyperandrogenism. PATIENTS AND METHOD: Sixteen women (group 1) with peripheral hirsutism (defined as those with normal androgens levels, normal menstrual cycles and ovulation) and 24 women (group 2) with glucocorticoid sensitive hyperandrogenic hirsutism were studied. Group 1 was treated with spironolactone 50 mg hid and group 2 with same spironolactone dose plus dexamethasone 0.5 mg at 23 h during one month and 0.25 mg thereafter. Patients were followed during one year. RESULTS: After one year of treatment, a 54% reduction in Moncada hirsutism escore was observed in group 1 and 52% reduction in group 2. Observed secondary effects of spironolactone were increases in diuresis, fatigability, acne aggravation and seborrhea in two patients. Two additional patients had spotting. No secondary effect attributable to glucocorticoid use were observed. CONCLUSIONS: Spironolactone is effective and safe in the treatment of hirsutism. Androgenic supression did no increases its effectiveness, underscoring the peripheral anti androgenic activity os spironolactone.

Adolescent↗
PubMedDate not supplied

Readministration of spironolactone in the spironolactone-intolerant patient.

We report a successful practical protocol for readministration of spironolactone in a patient with cirrhosis and severe ascites whose initial exposure to spironolactone resulted in erythema multiforme. Because salt and water restriction and other diuretics were ineffective, readministration of spironolactone was considered appropriate. In the absence of in vitro or in vivo diagnostic tests for drug allergy to spironolactone, serial increasing doses from 1 mg to 400 mg were administered over a 14 day period and tolerated uneventfully. A mild maculopapular rash appeared a month later but resolved despite continuation of spironolactone. The patient has now received spironolactone successfully for a total of 20 months without evidence of subsequent drug hypersensitivity. Although proven drug hypersensitivity attributable to spironolactone is very rare, when allergic manifestations have occurred in a patient who may require readministration of spironolactone, we believe that the suggested protocol for test-dosing be considered.

Drug Hypersensitivity↗
PubMed1977

Renin levels and spironolactone treatment in general practice: similar blood pressure lowering effect of spironolactone in low and normal renin patients.

We examined the predictive value of plasma renin activity (PRA) in ambulatory patients in the selection of hypertensive patients for treatment with spironolactone. The patients were classified as frusemide responders or non-responders according to their PRA response to 80 mg frusemide orally. After an initial 4 weeks placebo period forty-five patients with the clinical diagnosis of benign hypertension (WHO stage I-II) entered a 4 X 4 week double blind treatment period during which they received spironolactone (Aldactone) 400, 300, 200 and 100 mg/day, respectively. Five out of the forty-five patients who started the trial were withdrawn on account of side-effects and five patients for other reasons. Of the thirty-five patients who completed the study eighteen belonged to the group of non-responders to frusemide, seventeen to the responders. A gradual and significant decrease in mean blood pressure occurred during the period with the high doses of spironolactone, without any significant difference between the groups. The blood pressure lowering effect obtained with the initial high doses was maintained during the consecutive periods when the doses was reduced to a half or even a fourth, in both groups. We conclude that PRA measurement in ambulatory patients is of little, if any, value for the selection of hypertensives for spironolactone treatment; this in contrast to similar selections performed on hospitalized patients.

Adult↗
PubMed1976

A comparison of the dissolution and bioavailability characteristics of three spironolactone tablet formulations, including preliminary data on two spironolactone metabolites.

The bioavailabilities of three spironolactone tablet formulations specially selected for major differences in in vitro dissolution tests were compared in normal male volunteers by measuring plasma and urinary levels of the pharmacologically active spironolactone metabolite canrenone. It was possible to demonstrate small but statistically significant differences in plasma canrenone concentration-time curves derived from the three formulations together with significant differences in the time course of urinary canrenone excretion. The bioavailabilities of the three formulations did not differ significantly although the tablet with the poorest in vitro dissolution produced a significant delayed peak canrenone concentration. The dissolution rate methodology and results are described and an approach to the development of improved in vitro dissolution tests for spironolactone is suggested. The use of a new method for canrenone estimation resulted in the incidental detection of two other quantitatively significant spironolactone metabolites and preliminary information is given on these.

Adolescent↗
PubMed2003

Potential beneficial as well as detrimental effects of chronic treatment with lisinopril and (or) spironolactone on isolated hearts following low-flow ischemia in normal and infarcted rats.

This study was designed to demonstrate potential beneficial as well as detrimental effects of lisinopril and spironolactone given in combination. In patients with congestive heart failure or myocardial infarction, the use of angiotensin-converting enzyme (ACE) inhibitors may inhibit aldosterone production. Spironolactone, a specific aldosterone receptor antagonist may exert other independent and additive effects to those of ACE inhibitors. Given the consequences of aldosterone on ischemic hearts, we evaluated the protective effects of spironolactone or lisinopril and combined spironolactone-lisinopril therapy during low-flow ischemia and reperfusion in isolated rat hearts. Normal and infarcted (left coronary artery ligature) male Wistar rats were submitted to chronic action of drugs (0.8 mg.kg-1.day-1 for lisinopril and 8 or 50 mg.kg-1.day-1 for spironolactone) for 1 month. Hearts were rapidly excised and perfused (constant pressure) for a 40-min period of stabilization followed by a 25-min period of global low-flow ischemia and a 30-min reperfusion. In normal rats, spironolactone decreased ischemic and reperfusion contracture, reduced ventricular tachycardia, suppressed action-potential duration dispersion, and increased reactive hyperemia leading to an improvement of contractile recovery. Lisinopril also decreased ventricular tachycardia and action-potential duration dispersion concomitantly with increased reactive hyperemia and better contractile recovery. These beneficial effects of the drugs were lost when the two treatments were combined (lisinopril and 50 mg.kg-1.day-1 spironolactone), despite a synergistic effect on plasmatic K+ and Mg2+. However, an interaction between the ACE inhibitor and spironolactone potentiating the effects of either drug alone was observed with a lower dose of spironolactone (lisinopril and 8 mg.kg-1.day-1 spironolactone). Similar beneficial effects have been noted in infarcted rat hearts on reactive hyperemia, ventricular tachycardia, and contractile recovery with the combined treatment and for both spironolactone concentrations (8 or 50 mg). Chronic spironolactone treatment produces similar beneficial effects to ACE inhibitor treatment on normal rat hearts during an ischemia-reperfusion protocol. Synergistic effects have been observed with the combined therapy when a lower dose of spironolactone was utilized in normal and infarcted rats. However, in the case of a high dose of spironolactone, the two effective drugs seem to cancel each other but only in normal rats.

Action Potentials↗
PubMed1984

Effect of spironolactone on fluid volumes and adrenal steroids in primary aldosteronism.

Plasma volume (PV) and extracellular fluid volume (ECF) were determined in 7 patients with essential hypertension (controls) and in 10 patients with primary aldosteronism, while on a high Na diet (342 mEq/day) and on a low Na diet (12 mEq/day). The volume studies were repeated in 6 of the primary aldosteronism patients during treatment with spironolactone for over 3 months. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), cortisol concentration, and serum Na and K concentrations were measured in all patients while on a Na-restricted diet (85 mEq/day) as well as on high-Na and low-Na diets. There were no significant changes in arterial pressure during different Na diets in any groups of patients with essential hypertension, or primary aldosteronism with and without spironolactone therapy. Spironolactone treatment normalized the arterial pressure in patients with primary aldosteronism at all Na intakes. These patients had greater values for PV and ECF than did those with essential hypertension. Spironolactone treatment reduced PV during the low-Na diet, but did not alter it during the high-Na diet. Spironolactone did not produce significant changes in ECF during either the high-Na or low-Na diets. Although there were no changes in PV and ECF in patients with primary aldosteronism due to changes in Na intake, both PV and ECF were significantly less in these patients during spironolactone treatment and in patients with essential hypertension during low-Na intake than during high-Na intake. With primary aldosteronism, PRA was depressed and PAC was elevated when compared to essential hypertension, these were not altered by different Na diets in the patients with primary aldosteronism as they were in those with essential hypertension. During treatment with spironolactone the PRA was restored to normal and showed normal changes with variations in dietary Na, but PAC remained elevated during spironolactone. Plasma cortisol was the same among those with essential hypertension and patients with untreated and spironolactone-treated primary aldosteronism. Serum K was less in untreated primary aldosteronism during all Na diets than in essential hypertension, but during spironolactone it was restored to normal. These results suggest that in primary aldosteronism the reduction in arterial pressure by spironolactone treatment does not occur simply by reductions in body fluid volumes. The long-term treatment of patients with primary aldosteronism with spironolactone does not inhibit the production of aldosterone, possibly because of enhanced activity of the renin-angiotensin system and an increase in serum K.

Adrenal Cortex Hormones↗
PubMed1987

The metabolism and biopharmaceutics of spironolactone in man.

Spironolactone, a competitive aldosterone antagonist, has been used for almost 30 years in those disorders associated with primary or secondary hyperaldosteronism. This review is confined to its metabolism and biopharmaceutics in man. Spironolactone undergoes extensive metabolism with no unchanged drug appearing in the urine. Its metabolites can be divided into two main categories: those in which the sulfur of the parent molecule is removed and those in which the sulfur is retained. The dethioacetylated metabolite canrenone, belonging to the former category, was long considered to be the major active metabolite of spironolactone. For this reason pharmacokinetic studies have focussed on its kinetic behaviour. However, pharmacodynamic studies indicated that canrenone could only partly explain spironolactone's action. Furthermore, with the advent of modern high-performance liquid chromatographic techniques to measure canrenone concentrations, it was shown that previously employed assay techniques were unspecific and consequently considerably overestimated true canrenone levels. Recently, it was demonstrated that after a single oral dose of spironolactone, 7 alpha-thiomethylspirolactone is the main metabolite and that unchanged spironolactone reaches maximum serum concentrations which are in the same order of magnitude as canrenone. Both spironolactone and 7 alpha-thiomethylspirolactone are known to possess anti-mineralocorticoid activity, and they may be mainly responsible for the activity of spironolactone. It also appears likely that endocrine side effects of spironolactone, such as gynaecomastia, are mediated by these sulfur-containing compounds. The oral absorption of spironolactone is improved by using micronized drug or inclusion complexes of spironolactone with cyclodextrins. Concomitant food intake has also been shown to enhance the bioavailability, by increasing the absorption and decreasing the first-pass effect of spironolactone.

Aged↗
PubMedDate not supplied

Myocardial changes after spironolactone in spontaneous hypertensive rats. A laser scanning confocal microscopy study.

The present study aims to objectivate by laser scanning confocal microscopy, the cardiac structure of the spontaneously hypertensive rats (SHR) treated with different doses of spironolactone, either alone or in combination with an angiotensin converting enzyme inhibitor or with a calcium channel blocker. Thirty SHRs were divided into six groups and treated during 13 weeks as follows: control, spironolactone (5, 10 and 30 mg/kg/day), spironolactone + enalapril and spironolactone + verapamil. Spironolactone action on the SHR blood pressure (BP) was dose-dependent. The cardiac hypertrophy was affected by the treatment with spironolactone (high dose) or a combination of spironolactone and Enalapril. The myocardial structure was less affected by the spironolactone monotherapy (at all doses) showing hypertrophied cardiac myocytes, focal areas of the reactive fibrosis, inflammatory infiltrate. The treatment with spironolactone in combination with enalapril or verapamil prevented these alterations. In conclusion, the monotherapy with spironolactone had only a limited effect in the preservation of the myocardial structure and in the attenuation of the interstitial fibrosis in SHRs, even after high dose. This action on the myocardium is more efficient when the spironolactone (even in medium dose) was associated with enalapril or verapamil.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

The spironolactone renaissance.

Until recently, spironolactone was considered only as an antagonist at the aldosterone receptors of the epithelial cells of the kidney and was used clinically in the treatment of hyperaldosteronism and, occasionally, as a K(+)-sparing diuretic. The spironolactone renaissance started with the experimental finding that spironolactone reversed aldosterone-induced cardiac fibrosis by a cardiac action. Experimentally, spironolactone also has direct effects on blood vessels. Spironolactone reduces vascular fibrosis and injury, inhibits angiogenesis, reduces vascular tone and reduces portal hypertension. The rationale for the Randomized Aldactone Evaluation Study (RALES) of spironolactone in heart failure was that 'aldosterone escape' occurred through non-angiotensin II mechanisms. The RALES clinical trial was stopped early when it was shown that there was a 30% reduction in risk of death among the spironolactone patients. In RALES, spironolactone also reduced hospitalisation for worsening heart failure and improved the symptoms of heart failure. Other recent clinical trials have shown that spironolactone reduces cardiac and vascular collagen turnover, improves heart variability, reduces ventricular arrhythmias, improves endothelial dysfunction and dilates blood vessels in human heart failure and these effects probably all contribute to the increased survival in heart failure. Spironolactone may also be useful in the treatment of left ventricular hypertrophy, portal hypertension and cirrhosis. There have also been some recent small clinical trials of spironolactone as an anti-androgen showing potential in acne, hirsutism and precocious puberty.

Aldosterone↗