spironolactone and Gynecomastia studies

Spironolactone: A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)
spironolactone : A steroid lactone that is 17alpha-pregn-4-ene-21,17-carbolactone substituted by an oxo group at position 3 and an alpha-acetylsulfanyl group at position 7.

Gynecomastia: Enlargement of the BREAST in the males, caused by an excess of ESTROGENS. Physiological gynecomastia is normally observed in NEWBORNS; ADOLESCENT; and AGING males.

Research Excerpts

Excerpt	Relevance	Reference
"The role of spironolactone in resistant hypertension management is unclear."	9.14	Efficacy of spironolactone therapy in patients with true resistant hypertension. ( de Souza, F; Fiszman, R; Muxfeldt, E; Salles, G, 2010)
"The aim of this prospective, randomised, open-label, blinded-end point study was to compare the efficacy and safety of eplerenone versus spironolactone in patients with bilateral idiopathic hyperaldosteronism (IHA)."	9.13	Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism. ( Anagnostis, P; Athyros, VG; Kakafika, AI; Karagiannis, A; Mikhailidis, DP; Pagourelias, ED; Papageorgiou, A; Tziomalos, K, 2008)
"Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication."	9.12	Effect of spironolactone on blood pressure in subjects with resistant hypertension. ( Chapman, N; Dahlöf, B; Dobson, J; Poulter, NR; Sever, PS; Wedel, H; Wilson, S, 2007)
"Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure."	9.09	The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. ( Castaigne, A; Cody, R; Palensky, J; Perez, A; Pitt, B; Remme, WJ; Wittes, J; Zannad, F, 1999)
"The long-term efficacy and tolerance of spironolactone in essential hypertension was evaluated among 20,812 patients referred to the Broussais and St."	7.67	Efficacy and tolerance of spironolactone in essential hypertension. ( Charru, A; Chatellier, G; Corvol, P; DeVries, C; Jeunemaitre, X; Kreft-Jais, C; Menard, J; Plouin, PF, 1987)
" Six of these patients were treated with spironolactone and developed gynecomastia."	7.65	Pathophysiology of spironolactone-induced gynecomastia. ( Kisch, ES; Newmark, SR; Rose, LI; Underwood, RH; Williams, GH, 1977)
"The role of spironolactone in resistant hypertension management is unclear."	5.14	Efficacy of spironolactone therapy in patients with true resistant hypertension. ( de Souza, F; Fiszman, R; Muxfeldt, E; Salles, G, 2010)
"The aim of this prospective, randomised, open-label, blinded-end point study was to compare the efficacy and safety of eplerenone versus spironolactone in patients with bilateral idiopathic hyperaldosteronism (IHA)."	5.13	Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism. ( Anagnostis, P; Athyros, VG; Kakafika, AI; Karagiannis, A; Mikhailidis, DP; Pagourelias, ED; Papageorgiou, A; Tziomalos, K, 2008)
"Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication."	5.12	Effect of spironolactone on blood pressure in subjects with resistant hypertension. ( Chapman, N; Dahlöf, B; Dobson, J; Poulter, NR; Sever, PS; Wedel, H; Wilson, S, 2007)
"Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure."	5.09	The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. ( Castaigne, A; Cody, R; Palensky, J; Perez, A; Pitt, B; Remme, WJ; Wittes, J; Zannad, F, 1999)
"Two groups of patients with water retention due to ascites in cirrhosis of the liver were treated with antialdosterone diuretics (42 cases with K-canrenoate and 48 cases with spironolactone) for prolonged periods of time (an average of more than 5 months)."	5.06	[Controlled study of the effect of long-term administration of canrenoate potassium in cirrhotic ascites]. ( Traina, M; Vizzini, GB, 1986)
"Hydrochlorothiazide (HCT) and spironolactone (SP), alone and in combination, were utilized in the treatment of 79 adult men with mild to moderate essential hypertension."	5.04	Antihypertensive effect and serum potassium homeostasis: comparison of hydrochlorothiazide and spironolactone alone and in combination. ( Nash, DT, 1977)
" Another patient was a 61-year-old man with gynecomastia induced by spironolactone of 6 months duration."	3.78	Two cases of male nipple leiomyoma: idiopathic leiomyoma and gynecomastia-associated leiomyoma. ( Hashimoto, Y; Iizuka, H; Ishida-Yamamoto, A; Mizumoto, T; Nakamura, S; Nishi, K; Takeda, K, 2012)
" Subsequently, gynecomastia developed as a side effect of spironolactone and digoxin treatment."	3.75	[A mourning case that referred with sexual identity disorder secondary to a general medical condition]. ( Ceri, O; Koçak, OM; Soykan, A; Tatlidil, E; Yilmaz, A, 2009)
"The use of spironolactone in the treatment of hypertension has been limited by the occurrence of sexual side effects, mainly menstrual disturbances in women and gynaecomastia in men."	3.67	Antialdosterones: incidence and prevention of sexual side effects. ( Corvol, P; de Gasparo, M; Jeunemaître, X; Ménard, J; Preiswerk, G; Whitebread, SE, 1989)
"The long-term efficacy and tolerance of spironolactone in essential hypertension was evaluated among 20,812 patients referred to the Broussais and St."	3.67	Efficacy and tolerance of spironolactone in essential hypertension. ( Charru, A; Chatellier, G; Corvol, P; DeVries, C; Jeunemaitre, X; Kreft-Jais, C; Menard, J; Plouin, PF, 1987)
"Spirolactones (spironolactone, potassium canrenoate) may produce secundary sexual effects such as gynecomastia in man and menstrual disturbances in women."	3.65	[Sexual side-effects of spironolactones. Possible mechanisms of their anti-androgen action]. ( Bricaire, H; Corvol, P; Mahoudeau, JA; Ménard, J; Valcke, JC, 1976)
" Six of these patients were treated with spironolactone and developed gynecomastia."	3.65	Pathophysiology of spironolactone-induced gynecomastia. ( Kisch, ES; Newmark, SR; Rose, LI; Underwood, RH; Williams, GH, 1977)
"Therapy with spironolactone is often associated with estrogenlike side-effects, including impotence and gynecomastia in men and menstrual irregularity in women."	3.65	Spironolactone and endocrine dysfunction. ( , 1976)
" Spironolactone appears safe in carefully monitored maintenance hemodialysis patients, but did not affect cardiovascular parameters in this small study."	2.90	Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial. ( Anderson, AH; Charytan, DM; Dember, LM; DiCarli, M; Himmelfarb, J; Hsu, JY; Hung, AM; Ikizler, TA; Kimmel, PL; Kliger, AS; Landis, JR; Mehrotra, R; Raj, DS; Sharma, S; Skali, H; Weiner, DE; Williams, M, 2019)

Research

Studies (59)

Authors

Clinical Trials (27)

Trial Overview

Trial Outcomes

Safety - Cardiovascular Death

Timeframe	Studies, this research(%)	All Research%
pre-1990	33 (55.93)	18.7374
1990's	4 (6.78)	18.2507
2000's	15 (25.42)	29.6817
2010's	6 (10.17)	24.3611
2020's	1 (1.69)	2.80

Authors	Studies
Hasegawa, T	1
Nishiwaki, H	1
Ota, E	1
Levack, WM	1
Noma, H	1
Charytan, DM	1
Himmelfarb, J	1
Ikizler, TA	1
Raj, DS	1
Hsu, JY	1
Landis, JR	1
Anderson, AH	1
Hung, AM	1
Mehrotra, R	1
Sharma, S	1
Weiner, DE	1
Williams, M	1
DiCarli, M	1
Skali, H	1
Kimmel, PL	1
Kliger, AS	1
Dember, LM	1
Kiehl, EL	1
Shivapour, DM	1
Goenka, AH	1
Jaber, WA	1
Farag, AA	1
Andrikopoulou, E	1
Hage, FG	1
Kaplan, NM	1
Yilmaz, A	1
Ceri, O	1
Tatlidil, E	1
Koçak, OM	1
Soykan, A	1
Haynes, BA	1
Mookadam, F	1
de Souza, F	1
Muxfeldt, E	1
Fiszman, R	1
Salles, G	1
Nakamura, S	1
Hashimoto, Y	1
Takeda, K	1
Nishi, K	1
Ishida-Yamamoto, A	1
Mizumoto, T	1
Iizuka, H	1
Lindbloom, EJ	1
Koenig, CJ	1
SUSSMAN, RM	1
CLARK, E	1
Lee, TH	1
Garthwaite, SM	1
McMahon, EG	1
Ménard, J	5
Mosenkis, A	1
Townsend, RR	1
Fukuchi, K	1
Sasaki, H	1
Yokoya, T	1
Noguchi, T	1
Goto, Y	1
Hayashida, K	1
Ishida, Y	1
Winter, M	1
Karagiannis, A	2
Tziomalos, K	2
Kakafika, A	1
Florentin, M	1
Athyros, VG	2
Chapman, N	1
Dobson, J	1
Wilson, S	1
Dahlöf, B	1
Sever, PS	1
Wedel, H	1
Poulter, NR	1
Cuculi, F	1
Suter, A	1
Erne, P	1
Teive, HA	1
Munhoz, RP	1
Werneck, LC	1
Mimidis, K	1
Papadopoulos, V	1
Kartalis, G	1
Papageorgiou, A	1
Kakafika, AI	1
Pagourelias, ED	1
Anagnostis, P	1
Mikhailidis, DP	1
Tragl, KH	1
Merino Angulo, J	1
Bilbao Ercoreca, F	1
del Villar Negro, A	1
de la Riva Aguinaco, C	1
Aguirre Errasti, C	1
Kley, HK	1
Holzgreve, H	1
Quietzsch, D	1
Dove, F	1
Ohta, H	1
Pitt, B	1
Zannad, F	1
Remme, WJ	1
Cody, R	1
Castaigne, A	1
Perez, A	1
Palensky, J	1
Wittes, J	1
Yamamoto, S	1
Protivinsky, R	1
Licata, AA	1
Bartter, FC	1
Ehrlich, U	1
Klepzig, H	1
Corvol, P	4
Mahoudeau, JA	1
Valcke, JC	1
Bricaire, H	1
Nash, DT	1
Jefferys, DB	1
Vetter, H	1
Huffman, DH	1
Kampmann, JP	1
Hignite, CE	1
Azarnoff, DL	1
Miyatake, A	1
Noma, K	1
Nakao, K	1
Morimoto, Y	1
Yamamura, Y	1
Zarren, HS	1
Black, PM	1
Caminos-Torres, R	1
Ma, L	1
Snyder, PJ	1
Rose, LI	1
Underwood, RH	1
Newmark, SR	1
Kisch, ES	1
Williams, GH	1
Dupont, A	1
Bellati, G	1
Idéo, G	1
Overdiek, JW	1
Merkus, FW	1
de Gasparo, M	1
Whitebread, SE	1
Preiswerk, G	1
Jeunemaître, X	3
Kreft-Jais, C	2
Chatellier, G	2
Julien, J	1
Degoulet, P	1
Plouin, PF	2
Traina, M	1
Vizzini, GB	1
Charru, A	1
DeVries, C	1
Bokarev, IN	1
Baranova, NV	1
Hussey, HH	1
Bridgman, JF	1
Buckler, JM	1
Keil-Kuri, E	1
Marshall, M	1
Greenblatt, DJ	2
Koch-Weser, J	2

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Randomized, Controlled Trial of L-arginine and Spironolactone in Dialysis-dependant End Stage Renal Disease[NCT01855334]	Phase 4	0 participants (Actual)	Interventional	2013-09-30	Withdrawn (stopped due to change of funding leading to major redesign)
Effect of Spironolactone on the Progression of Coronary Calcification in Peritoneal Dialysis Patients[NCT03314493]	Phase 3	33 participants (Actual)	Interventional	2014-11-07	Completed
Protective Mechanisms of Aldosterone Antagonists and Their Effects on Cardiovascular Damage in Chronic Renal Failure: Clinical and Experimental Studies[NCT00277693]	Phase 4	0 participants	Interventional		Recruiting
Aldosterone bloCkade for Health Improvement EValuation in End-stage Renal Disease[NCT03020303]	Phase 3	2,750 participants (Anticipated)	Interventional	2017-07-07	Recruiting
[NCT01687699]	Phase 4	157 participants (Actual)	Interventional	2008-04-30	Completed
Subjects With Severe Heart Failure and End-Stage Renal Disease on Hemodialysis: A Pilot Study to Assess Safety and Tolerability of Spironolactone[NCT00328809]	Phase 4	0 participants (Actual)	Interventional	2013-06-30	Withdrawn (stopped due to personnel shortage)
Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent End-Stage Renal Disease (ESRD) (SPin-D) Trial[NCT02285920]	Phase 2	129 participants (Actual)	Interventional	2014-11-30	Completed
Role of Renin Angiotensin Blockade in Peritoneal Fibrosis in Peritoneal Dialysis Patients[NCT00865449]	Phase 3	20 participants (Actual)	Interventional	2008-07-31	Completed
Assessment of the Effects of the Combination of Spironolactone to Conventional Pharmacotherapy in Dialysis Patients[NCT01128101]	Phase 4	60 participants (Anticipated)	Interventional	2011-03-31	Recruiting
Effect of Add-on Spironolactone to Losartan Versus Losartan Alone on Peritoneal Membrane Among Continuous Ambulatory Peritoneal Dialysis Patients: An Open-Label Randomized-Controlled Trial[NCT03953950]	Phase 4	84 participants (Anticipated)	Interventional	2019-10-31	Not yet recruiting
The Effects of Losartan and Spironolactone on Residual Renal Function Preservation in Peritoneal Dialysis Patients[NCT02190318]		96 participants (Anticipated)	Interventional	2013-11-30	Recruiting
ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST), Phase III b[NCT01848639]	Phase 3	823 participants (Actual)	Interventional	2013-06-30	Completed
Double-blind Placebo-Controlled Randomized Clinical Trial of Mineralocorticoid Receptor Blockade With Eplerenone After Renal Transplantation : Effect on Graft Function at 3 Months.[NCT02490904]	Phase 3	132 participants (Anticipated)	Interventional	2016-10-19	Active, not recruiting
Pilot Trial of Hemodialysis Patient Aldosterone antagoniSm With Eplerenone Trial[NCT01650012]		158 participants (Actual)	Interventional	2013-03-31	Completed
Phase II Trial to Evaluate the Efficacy and Safety of Spironolactone in Hemodialysis Patients[NCT01691053]	Phase 2	118 participants (Actual)	Interventional	2012-12-31	Completed
HYpertension Therapy With Valsartan Versus EpleRenone for Obese Patients: A Randomized Clinical Trial[NCT03476616]	Phase 4	330 participants (Anticipated)	Interventional	2018-09-01	Not yet recruiting
Addition of Spironolactone in Patients With Resistant Arterial Hypertension[NCT00524615]	Phase 4	160 participants (Anticipated)	Interventional	2007-09-30	Recruiting
South Danish Hypertension and Diabetes Study[NCT01062763]	Phase 3	119 participants (Actual)	Interventional	2010-03-31	Completed
A Randomised Open Label, Blinded End Point Trial to Compare the Effects of Spironolactone With Chlortalidone on LV Mass in Stage 3 Chronic Kidney Disease (SPIRO-CKD)[NCT02502981]	Phase 4	154 participants (Actual)	Interventional	2014-06-30	Active, not recruiting
MINeralocorticoid Receptor Antagonist Pretreatment to MINIMISE Reperfusion Injury After ST-Elevation Myocardial Infarction (STEMI)[NCT01882179]	Phase 3	61 participants (Actual)	Interventional	2013-11-30	Completed
Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy-- a Multicenter Randomized Control Trial[NCT02948998]	Phase 4	260 participants (Anticipated)	Interventional	2018-05-14	Not yet recruiting
Congestive Heart Failure Atrial Arrhythmia Monitoring and Pacing (CHAMP)[NCT00156728]	Phase 4	172 participants	Interventional	2003-10-31	Completed
Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure?[NCT00291720]	Phase 2	120 participants (Actual)	Interventional	2005-04-30	Completed
Randomized Clinical Trial of Radiofrequency Ablation for Atrial Fibrillation in Patients With Heart Failure With Preserved Ejection Fraction for Reduced Healthcare Utilization[NCT04327596]		2 participants (Actual)	Interventional	2021-01-25	Terminated (stopped due to lack of enrollment)
A Prospective, Randomized Trial Using a reproduciBLe volUmE-Measurement stratEGy in the surGical Reconstruction of the Ischemic Cardiomyopathic Heart[NCT00326690]		0 participants (Actual)	Interventional	2005-11-30	Withdrawn (stopped due to Unable to recruit and enroll patients)
Exercise Intolerance in Elderly Diastolic Heart Failure[NCT00123955]	Phase 3	80 participants (Actual)	Interventional	2005-04-30	Completed
Mineralocorticoid Receptor, Coronary Microvascular Function, and Cardiac Efficiency in Hypertension[NCT05593055]	Phase 4	75 participants (Anticipated)	Interventional	2023-08-25	Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Number of Cardiovascular deaths defined as death due to myocardial infarction, congestive heart failure, cardiac valvular disease, arrhythmia, sudden death, stroke, or peripheral arterial disease (NCT02285920)
Timeframe: 0 - 40 weeks

Safety - Combined Incidence of Potassium >6.5 mEq/L or Serious Hyperkalemia

Intervention	Participants (Count of Participants)
Placebo	1
Spironolactone 12.5 mg	0
Spironolactone 25 mg	2
Spironolactone 50 mg	1

The number of participants who had serum potassium >6.5 mEq/L or serious hyperkalemia was assessed by treatment arm. (NCT02285920)
Timeframe: 0 - 40 Weeks

Safety - Hyperkalemia Requiring Adjustment in Treatment

Intervention	Participants (Count of Participants)
Placebo	13
Spironolactone 12.5 mg	5
Spironolactone 25 mg	5
Spironolactone 50 mg	10

Hyperkalemia requiring adjustment in dialysate potassium concentration, or discontinuation of study medication (NCT02285920)
Timeframe: 0 - 40 weeks

Safety - Number of Participants With Serious Hyperkalemia

Intervention	Participants (Count of Participants)
Placebo	13
Spironolactone 12.5 mg	2
Spironolactone 25 mg	5
Spironolactone 50 mg	7

Number of patients with serious hyperkalemia requiring hospitalization, emergency/unscheduled dialysis or resin therapy (NCT02285920)
Timeframe: 0 - 40 weeks

Safety - Number of Participants With Serum Potassium >6.5 mEq/L

Intervention	Participants (Count of Participants)
Placebo	6
Spironolactone 12.5 mg	2
Spironolactone 25 mg	0
Spironolactone 50 mg	7

The number of participants who had serum potassium >6.5 mEq/L was assessed by treatment arm. (NCT02285920)
Timeframe: 0 - 40 weeks

Safety - Participants With Serious Hypotension

Intervention	Participants (Count of Participants)
Placebo	9
Spironolactone 12.5 mg	4
Spironolactone 25 mg	4
Spironolactone 50 mg	8

The number of participants experiencing serious hypotension, defined as hypotension requiring hospitalization or ED visit and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). (NCT02285920)
Timeframe: 0 - 40 weeks

Study Drug Tolerability

Intervention	Participants (Count of Participants)
Placebo	0
Spironolactone 12.5 mg	2
Spironolactone 25 mg	0
Spironolactone 50 mg	3

Tolerability is defined as number of participants who experienced permanent study drug discontinuation or dose reduction. (NCT02285920)
Timeframe: 0 - 36 weeks

Efficacy - Change in Mitral Annular E' Velocity

Intervention	Participants (Count of Participants)
Placebo	16
Spironolactone 12.5 mg	5
Spironolactone 25 mg	6
Spironolactone 50 mg	8

Change in mitral annular E' velocity measured using Tissue Doppler Index (TDI) echocardiography. Efficacy outcomes were considered exploratory with a goal of detecting signals rather than clearly demonstrating efficacy. (NCT02285920)
Timeframe: Baseline to 36 weeks

Efficacy - Secondary Cardiac Outcome Measure - Left Ventricular Ejection Fraction (LVEF)

Intervention	cm/second (Mean)
	Baseline MA E'	36 Week MA E'	Change between baseline - 36 weeks
Placebo	7.4	7.5	0.1
Spironolactone 12.5 mg	7.6	7.4	-0.2
Spironolactone 25 mg	7.8	7.7	-0.1
Spironolactone 50 mg	7.0	7.3	0.3

"Secondary outcome measures include other echocardiographic markers of systolic and diastolic function~• Change in left ventricular ejection fraction between Baseline and 36 weeks" (NCT02285920)
Timeframe: Baseline - 36 weeks

Efficacy - Secondary Cardiac Outcome Measures - Left Ventricular Global Longitudinal Strain (LVGLS)

Intervention	percent ejection fraction (Mean)
	LVEF Baseline	LVEF 36-Week	LVEF Change
Placebo	68.9	70.7	1.8
Spironolactone 12.5 mg	65.9	66.9	1.0
Spironolactone 25 mg	66.0	65.3	-0.7
Spironolactone 50 mg	68.2	69.5	1.3

"Secondary outcome measures include other echocardiographic markers of systolic and diastolic function,~• Change in myocardial strain and strain rate between baseline and 36 weeks" (NCT02285920)
Timeframe: Baseline - 36 weeks

Efficacy - Secondary Cardiac Outcome Measures - Ratio of Mitral Peak Velocity to Diastolic Mitral Annular Velocity (E/E')

Intervention	% of myocardial shortening (Mean)
	LVGLS Baseline	LVGLS 36-week	LVGLS Change
Placebo	-17.2	-18.1	-0.8
Spironolactone 12.5 mg	-16.7	-17.0	-0.3
Spironolactone 25 mg	-17.2	-17.0	0.2
Spironolactone 50 mg	-17.4	-18.2	-0.7

"Secondary outcome measures include other echocardiographic markers of systolic and diastolic function,~• E/E' is the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E')" (NCT02285920)
Timeframe: Baseline - 36 weeks

Efficacy - Secondary Cardiac Outcome Measures Left Ventricular Mass Index (LVMI)

Intervention	ratio (Mean)
	E/E' Baseline	E/E' 36-Week	E/E' Change
Placebo	10.7	11.5	0.9
Spironolactone 12.5 mg	11.8	12.2	0.4
Spironolactone 25 mg	9.2	10.6	1.4
Spironolactone 50 mg	12.5	11.9	-0.6

"Secondary outcome measures include other echocardiographic markers of systolic and diastolic function,~• Change in left ventricular mass index (LVMI) between baseline and 36 weeks" (NCT02285920)
Timeframe: Baseline - 36 weeks

Adverse Effects

Change of Diastolic Blood Pressure

Intervention	g/m^2 (Mean)
	LVMI Baseline	LVMI 36-Week	LVMI Change
Placebo	105.2	94.8	-10.4
Spironolactone 12.5 mg	115.5	104.6	-10.9
Spironolactone 25 mg	116.4	109.1	-7.3
Spironolactone 50 mg	106.3	96.5	-9.8

Intervention	participants (Number)
Addition of Spironolactone	4
Placebo	0

Change of diastolic blood pressure from baseline to study end at four months. (NCT01062763)
Timeframe: 4 months

Change of of Systolic Blood Pressure

Intervention	mm Hg (Mean)
Addition of Spironolactone	-3.9
Placebo	-0.3

Change of systolic blood pressure from baseline to study end at four months. (NCT01062763)
Timeframe: 4 months

Concentric Left Ventricular Remodeling

Intervention	mm Hg (Mean)
Addition of Spironolactone	-9.6
Placebo	-0.7

"Left ventricle measurements by MRI:~Mass/end diastolic volume ratio: g/ml" (NCT00123955)
Timeframe: Baseline, 9 month

Exercise Intolerance

Left Ventricular Diastolic Stiffness

Intervention	g/ml (Mean)
	baseline	9 month
Placebo	1.7	1.6
Spironolactone	1.8	1.7

Intervention	ml/kg/min (Mean)
	Baseline	4 months	9 months
Placebo	13.3	13.5	13.9
Spironolactone	13.5	13.6	13.8

"Echocardiography Doppler measurement of left ventricular diastolic function:~Early mitral annulus velocity (lateral) (Ea; cm/s)" (NCT00123955)
Timeframe: Baseline, 4 month and 9 month

Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score

Intervention	cm/s (Mean)
	baseline	4 month	9 month
Placebo	6.8	6.8	6.6
Spironolactone	7.0	7.0	7.4

"The Minnesota Living with Heart Failure Questionnaire (MLHF) is a self-administered disease-specific questionnaire for patients with Heart Failure, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on HRQoL, from 0 (none) to 5 (very much). It provides a total score (range 0-105, from best to worst HRQoL), as well as scores for two dimensions, physical (8 items, range 0-40) and emotional (5 items, range 0-25). The other eight items (of the total of 21) are only considered for the calculation of the total score.~Scale of 0-105:The higher the score the worse the heart failure related Quality of Life." (NCT00123955)
Timeframe: Baseline, 4 and 9 months

Article	Year
Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial. Kidney international, 2019, Volume: 95, Issue:4 Topics: Adult; Aged; Aldosterone; Cardiovascular Diseases; Diastole; Dose-Response Relationship, Drug; Doubl	2019
Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension (Dallas, Tex. : 1979), 2010, Volume: 55, Issue:1 Topics: Blood Pressure; Blood Pressure Monitoring, Ambulatory; Breast Diseases; Diuretics; Follow-Up Studies	2010
Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension (Dallas, Tex. : 1979), 2007, Volume: 49, Issue:4 Topics: Aged; Antihypertensive Agents; Blood Pressure; Breast; Drug Resistance; Female; Gynecomastia; Humans	2007
Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension (Dallas, Tex. : 1979), 2007, Volume: 49, Issue:4 Topics: Aged; Antihypertensive Agents; Blood Pressure; Breast; Drug Resistance; Female; Gynecomastia; Humans	2007
Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension (Dallas, Tex. : 1979), 2007, Volume: 49, Issue:4 Topics: Aged; Antihypertensive Agents; Blood Pressure; Breast; Drug Resistance; Female; Gynecomastia; Humans	2007
Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension (Dallas, Tex. : 1979), 2007, Volume: 49, Issue:4 Topics: Aged; Antihypertensive Agents; Blood Pressure; Breast; Drug Resistance; Female; Gynecomastia; Humans	2007
Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism. Expert opinion on pharmacotherapy, 2008, Volume: 9, Issue:4 Topics: Adult; Antihypertensive Agents; Blood Pressure; Dose-Response Relationship, Drug; Drug Administratio	2008
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine, 1999, Sep-02, Volume: 341, Issue:10 Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Diuretics; Double-Blind Method; Drug	1999
Antihypertensive effect and serum potassium homeostasis: comparison of hydrochlorothiazide and spironolactone alone and in combination. Journal of medicine, 1977, Volume: 8, Issue:5 Topics: Adult; Aged; Blood Urea Nitrogen; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combi	1977
Gynaecomastia after spironolactone and potassium canrenoate. Lancet (London, England), 1986, Mar-15, Volume: 1, Issue:8481 Topics: Ascites; Canrenoic Acid; Gynecomastia; Humans; Liver Cirrhosis; Male; Pregnadienes; Prospective Stud	1986
[Controlled study of the effect of long-term administration of canrenoate potassium in cirrhotic ascites]. Minerva medica, 1986, Jan-28, Volume: 77, Issue:3-4 Topics: Adult; Aged; Ascites; Canrenoic Acid; Clinical Trials as Topic; Drug Evaluation; Female; Gynecomasti	1986

Article	Year
Male breast uptake in rubidium-82 PET due to spironolactone-induced gynecomastia. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 2015, Volume: 22, Issue:5 Topics: Aged, 80 and over; Breast; Breast Neoplasms, Male; Diagnosis, Differential; Fibrosis; Gynecomastia;	2015
Spironolactone-induced bilateral gynecomastia in a man detected by SPECT myocardial perfusion imaging. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 2017, Volume: 24, Issue:2 Topics: Gynecomastia; Humans; Male; Middle Aged; Myocardial Perfusion Imaging; Spironolactone; Tomography, E	2017
ARAs to the RESCUE. Journal of the American Society of Hypertension : JASH, 2016, Volume: 10, Issue:3 Topics: Aldosterone; Eplerenone; Gynecomastia; Humans; Hyperaldosteronism; Hypertension; Hypokalemia; Meta-A	2016
[A mourning case that referred with sexual identity disorder secondary to a general medical condition]. Turk psikiyatri dergisi = Turkish journal of psychiatry, 2009,Summer, Volume: 20, Issue:2 Topics: Bereavement; Depression; Digoxin; Erectile Dysfunction; Female; Gender Identity; Gynecomastia; Human	2009
Two cases of male nipple leiomyoma: idiopathic leiomyoma and gynecomastia-associated leiomyoma. The American Journal of dermatopathology, 2012, Volume: 34, Issue:3 Topics: Actins; Aged; Breast Neoplasms, Male; Desmin; Gynecomastia; Humans; Leiomyoma; Male; Middle Aged; Mi	2012
Spironolactone for congestive heart failure. The Journal of family practice, 1999, Volume: 48, Issue:10 Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Drug Administration Schedule; Drug T	1999
Spironolactone and gynaecomastia. Lancet (London, England), 1963, Jan-05, Volume: 1, Issue:7271 Topics: Gynecomastia; Humans; Male; Spironolactone	1963
SPIRONOLACTONE THERAPY AND GYNECOMASTIA. JAMA, 1965, Jul-12, Volume: 193 Topics: Drug Therapy; Geriatrics; Gynecomastia; Heart Diseases; Humans; Male; Spironolactone; Toxicology	1965
Ask the doctor. I am a 50-year-old man with congestive heart failure. My doctor has me on all the usual drugs, and a couple of years ago added spironolactone. I did okay with it for a while, but then began to notice that my breasts were getting bigger and Harvard heart letter : from Harvard Medical School, 2003, Volume: 14, Issue:2 Topics: Diuretics; Eplerenone; Gynecomastia; Heart Failure; Humans; Male; Middle Aged; Spironolactone	2003
The evolution of aldosterone antagonists. Molecular and cellular endocrinology, 2004, Mar-31, Volume: 217, Issue:1-2 Topics: Aldosterone; Animals; Cardiovascular Diseases; Clinical Trials as Topic; Eplerenone; Gynecomastia; H	2004
The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Molecular and cellular endocrinology, 2004, Mar-31, Volume: 217, Issue:1-2 Topics: Antihypertensive Agents; Cardiovascular Diseases; Chlorthalidone; Clinical Trials as Topic; Erectile	2004
Ga-67 citrate and F-18 FDG uptake in spironolactone-induced gynecomastia. Clinical nuclear medicine, 2005, Volume: 30, Issue:2 Topics: Artifacts; Citrates; Diuretics; Fluorodeoxyglucose F18; Gallium; Gynecomastia; Heart Failure; Humans	2005
[Old man with bosom]. MMW Fortschritte der Medizin, 2006, Jun-29, Volume: 148, Issue:26 Topics: Aged; Aged, 80 and over; Diuretics; Gynecomastia; Humans; Male; Mineralocorticoid Receptor Antagonis	2006
Eplerenone relieves spironolactone-induced painful gynaecomastia in a patient with primary aldosteronism. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2007, Volume: 22, Issue:1 Topics: Administration, Oral; Aldosterone; Clinical Trials as Topic; Eplerenone; Gynecomastia; Humans; Hyper	2007
Spironolactone-induced gynecomastia. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 2007, Feb-27, Volume: 176, Issue:5 Topics: Aged; Gynecomastia; Humans; Male; Mineralocorticoid Receptor Antagonists; Spironolactone	2007
Worsening of motor symptoms and gynecomastia during spironolactone treatment in a patient with Parkinson's disease and congestive heart failure. Movement disorders : official journal of the Movement Disorder Society, 2007, Aug-15, Volume: 22, Issue:11 Topics: Aged; Gynecomastia; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Movement Di	2007
Eplerenone relieves spironolactone-induced painful gynaecomastia in patients with decompensated hepatitis B-related cirrhosis. Scandinavian journal of gastroenterology, 2007, Volume: 42, Issue:12 Topics: Ascites; Eplerenone; Gynecomastia; Hepatitis B, Chronic; Humans; Liver Cirrhosis; Mineralocorticoid	2007
[Iatrogenic and environmentally caused diseases of the endocrine system in the aged]. Aktuelle Gerontologie, 1983, Volume: 13, Issue:5 Topics: Aged; Cortisone; Cushing Syndrome; Digitalis Glycosides; Endocrine System Diseases; Environmental Ex	1983
[Bilateral metastatic gynecomastia. An unusual manifestation of small-cell pulmonary carcinoma]. Revista clinica espanola, 1983, Jan-15, Volume: 168, Issue:1 Topics: Breast Neoplasms; Carcinoma, Small Cell; Gynecomastia; Humans; Liver Cirrhosis, Alcoholic; Lung Neop	1983
[Diagnostic procedures in gynecomastia]. Deutsche medizinische Wochenschrift (1946), 1984, Nov-30, Volume: 109, Issue:48 Topics: Adolescent; Adult; Diagnosis, Differential; Digitalis; Estradiol Congeners; Gynecomastia; Humans; Hy	1984
[Therapy of cardiac insufficiency with diuretics]. Fortschritte der Medizin, 1982, Aug-26, Volume: 100, Issue:31-32 Topics: Amiloride; Benzothiadiazines; Blood Glucose; Diuretics; Drug Administration Schedule; Female; Furose	1982
[Iatrogenic gynecomastia in aldosterone-antagonist therapy]. Zeitschrift fur die gesamte innere Medizin und ihre Grenzgebiete, 1981, Feb-01, Volume: 36, Issue:3 Topics: Breast Neoplasms; Gynecomastia; Humans; Male; Middle Aged; Spironolactone	1981
Another cause of gynecomastia. Hospital practice (Office ed.), 1994, Apr-15, Volume: 29, Issue:4 Topics: Female; Gynecomastia; Humans; Male; Spironolactone	1994
[99mTc(V)-DMSA accumulation in gynecomastia]. Kaku igaku. The Japanese journal of nuclear medicine, 1998, Volume: 35, Issue:9 Topics: Digoxin; Furosemide; Gynecomastia; Humans; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuti	1998
Disappearance of spironolactone-induced gynecomastia with triamteren. Internal medicine (Tokyo, Japan), 2001, Volume: 40, Issue:6 Topics: Diuretics; Gynecomastia; Humans; Male; Middle Aged; Remission Induction; Spironolactone; Triamterene	2001
[Spironolactone in respiratory insufficiency. Partial report, 12th Reichenhall Colloquium, 15-17 June 1979 in Bad Reichenhall]. Fortschritte der Medizin, 1979, Oct-04, Volume: 97, Issue:37 Topics: Digitalis Glycosides; Drug Synergism; Gynecomastia; Heart; Humans; Male; Pulmonary Circulation; Resp	1979
Spironolactone-induced gynaecomastia related to allergic reaction to "Darvon compound". Lancet (London, England), 1976, Oct-23, Volume: 2, Issue:7991 Topics: Dextropropoxyphene; Drug Hypersensitivity; Drug Interactions; Gynecomastia; Humans; Male; Middle Age	1976
[Long term therapy over nine years with Spironolacton in hydropic cardiac insufficiency]. Medizinische Klinik, 1976, Sep-17, Volume: 71, Issue:38 Topics: Aged; Blood Pressure; Body Weight; Cardiac Glycosides; Cardiomegaly; Diuretics; Drug Therapy, Combin	1976
[Sexual side-effects of spironolactones. Possible mechanisms of their anti-androgen action]. La Nouvelle presse medicale, 1976, Mar-13, Volume: 5, Issue:11 Topics: Adult; Animals; Canrenoic Acid; Cytosol; Depression, Chemical; Dihydrotestosterone; Follicle Stimula	1976
Painful gynaecomastia treated with tamoxifen. British medical journal, 1979, Apr-28, Volume: 1, Issue:6171 Topics: Aged; Bronchial Neoplasms; Digoxin; Gynecomastia; Humans; Male; Middle Aged; Spironolactone; Tamoxif	1979
[Gynecomastia in spironolactone therapy]. Deutsche medizinische Wochenschrift (1946), 1979, May-25, Volume: 104, Issue:21 Topics: Gynecomastia; Humans; Male; Spironolactone	1979
Gynecomastia induced in normal males by spironolactone. Clinical pharmacology and therapeutics, 1978, Volume: 24, Issue:4 Topics: Adult; Androstenedione; Estrogens; Gynecomastia; Humans; Luteinizing Hormone; Male; Metabolic Cleara	1978
Increased serum oestrone and oestradiol following spironolactone administration in hypertensive men. Clinical endocrinology, 1978, Volume: 9, Issue:6 Topics: Adult; Estradiol; Estrone; Gynecomastia; Humans; Hypertension; Male; Middle Aged; Sexual Behavior; S	1978
Unilateral gynecomastia and impotence during low-dose spironolactone administration in men. Military medicine, 1975, Volume: 140, Issue:6 Topics: Dose-Response Relationship, Drug; Erectile Dysfunction; Gynecomastia; Humans; Male; Middle Aged; Spi	1975
Gynecomastia and semen abnormalities induced by spironolactone in normal men. The Journal of clinical endocrinology and metabolism, 1977, Volume: 45, Issue:2 Topics: Adult; Canrenoic Acid; Canrenone; Estradiol; Follicle Stimulating Hormone; Gynecomastia; Humans; Lut	1977
Pathophysiology of spironolactone-induced gynecomastia. Annals of internal medicine, 1977, Volume: 87, Issue:4 Topics: Adult; Estradiol; Estrogens; Gynecomastia; Humans; Hypertension; Male; Metabolic Clearance Rate; Mid	1977
Spironolactone and endocrine dysfunction. Annals of internal medicine, 1976, Volume: 85, Issue:5 Topics: Adolescent; Adrenal Cortex Hormones; Adult; Age Factors; Androgen Antagonists; Animals; Child, Presc	1976
Disappearance of spironolactone-induced gynaecomastia during treatment with potassium canrenoate. Lancet (London, England), 1985, Sep-28, Volume: 2, Issue:8457 Topics: Canrenoic Acid; Gynecomastia; Humans; Hyperaldosteronism; Male; Middle Aged; Pregnadienes; Spironola	1985
Spironolactone metabolism and gynaecomastia. Lancet (London, England), 1986, May-10, Volume: 1, Issue:8489 Topics: Gynecomastia; Humans; Kinetics; Liver Cirrhosis; Male; Middle Aged; Spironolactone	1986
Antialdosterones: incidence and prevention of sexual side effects. Journal of steroid biochemistry, 1989, Volume: 32, Issue:1B Topics: Blood Pressure; Female; Fludrocortisone; Gynecomastia; Humans; Hypertension; Male; Menstruation Dist	1989
Long-term experience of spironolactone in essential hypertension. Kidney international. Supplement, 1988, Volume: 26 Topics: Blood Pressure; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studi	1988
Efficacy and tolerance of spironolactone in essential hypertension. The American journal of cardiology, 1987, Oct-01, Volume: 60, Issue:10 Topics: Aged; Blood Pressure; Creatinine; Dose-Response Relationship, Drug; Drug Evaluation; Female; Gynecom	1987
[Complications of verospirone therapy]. Klinicheskaia meditsina, 1987, Volume: 65, Issue:9 Topics: Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Dyspepsia; Female; Gynecomastia; Humans;	1987
Editorial: Gynecomastia. JAMA, 1974, Jun-10, Volume: 228, Issue:11 Topics: Age Factors; Antidepressive Agents; Busulfan; Child; Child, Preschool; Digitalis Glycosides; Estroge	1974
Letter: Drug-induced gynaecomastia. British medical journal, 1974, Aug-24, Volume: 3, Issue:5929 Topics: 17-Ketosteroids; Adult; Depression, Chemical; Diethylpropion; Estrogens; Estrone; Gynecomastia; Huma	1974
[Sprironolactone-induced gynecomastia]. Zeitschrift fur Allgemeinmedizin, 1972, Jul-10, Volume: 48, Issue:19 Topics: Aged; Edema; Gynecomastia; Humans; Male; Pulmonary Heart Disease; Spironolactone	1972
Gynecomastia and impotence: complications of spironolactone therapy. JAMA, 1973, Jan-01, Volume: 223, Issue:1 Topics: Erectile Dysfunction; Gynecomastia; Humans; Male; Middle Aged; Spironolactone	1973
Adverse reactions to spironolactone. A report from the Boston Collaborative Drug Surveillance Program. JAMA, 1973, Jul-02, Volume: 225, Issue:1 Topics: Adult; Aged; Blood Urea Nitrogen; Coma; Dehydration; Diarrhea; Female; Gynecomastia; Headache; Heart	1973

spironolactone and Gynecomastia