Eplerenone

updated

Eplerenone is a mineralocorticoid receptor blocker, FDA-approved as INSPRA in 2002 and labeled for heart failure after a heart attack and for hypertension, with two large placebo-controlled outcome trials, EPHESUS and EMPHASIS-HF, showing lower mortality. A PubMed search on 9 October 2026 returned 15 records on mineralocorticoid antagonists with anabolic steroid terms; none tested eplerenone and none studied one in human steroid users. The fluid retention and fibrosis parts of the supplier claim rest on spironolactone studies, not eplerenone.

Selective mineralocorticoid receptor antagonist

  • FDA approved INSPRA under NDA 021437 on 27 September 2002; the current label covers heart failure after a heart attack and hypertension.
  • EPHESUS randomized 6,632 patients with heart failure after myocardial infarction: over a mean 16 months there were 478 deaths on eplerenone versus 554 on placebo (RR 0.85, 95% CI 0.75 to 0.96).
  • EMPHASIS-HF randomized 2,737 patients with NYHA class II heart failure and stopped early at a median 21 months: cardiovascular death or heart failure hospitalization occurred in 18.3% versus 25.9% (HR 0.63, 95% CI 0.54 to 0.74).
  • A PubMed search on 9 October 2026 for mineralocorticoid antagonists with anabolic steroid terms returned 15 records; none tested eplerenone and none studied one in human steroid users.
  • Hyperkalemia is the label's main warning; serious hyperkalemia occurred in 5.5% versus 3.9% on placebo in EPHESUS.
  • In a head-to-head trial in primary aldosteronism, male gynecomastia occurred in 21.2% on spironolactone versus 4.5% on eplerenone, but diastolic blood pressure fell less on eplerenone.

What is eplerenone approved to do?

FDA approved eplerenone as INSPRA on 27 September 2002. The label covers improving survival in stable adults with symptomatic heart failure and an ejection fraction of 40% or less after a heart attack, and treating hypertension in adults.

INSPRA is labeled to improve survival of stable adults with symptomatic heart failure with reduced ejection fraction (40% or less) after an acute myocardial infarction, and to treat hypertension in adults. The label version used here took effect on 23 June 2025.

FDA approved INSPRA under NDA 021437 on 27 September 2002. Generic eplerenone tablets are approved under ANDAs; the earliest among the records returned was ANDA 206922 on 13 July 2017, which is not confirmed as the first generic. Approvals outside the United States are not covered here.

Eplerenone is C24H30O6 (414.5 g/mol, CAS 107724-20-9, PubChem CID 443872). The INSPRA label gives the same empirical formula and a molecular weight of 414.50.

INSPRA label, version effective 23 June 2025: indications, hyperkalemia, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INSPRA (eplerenone) film-coated oral tablets, prescribing information, label version effective 23 June 2025. Set ID 1a52bedc-8e2c-4116-a296-a87770676b4a.

The label approves INSPRA to improve survival of stable adults with symptomatic heart failure with reduced ejection fraction (40% or less) after an acute myocardial infarction, and to treat hypertension in adults. Hyperkalemia is the main warning, with higher risk in renal impairment, proteinuria, diabetes, and with ACE inhibitors, ARBs, NSAIDs or moderate CYP3A inhibitors. It is contraindicated in all patients with serum potassium above 5.5 mEq/L at initiation, creatinine clearance of 30 mL/min or less, or strong CYP3A inhibitors, and for hypertension also with potassium supplements or potassium-sparing diuretics, spironolactone included. In hypertension trials, trough blood pressure fell 6 to 13 mmHg systolic and 3 to 7 mmHg diastolic more than placebo. Eplerenone binds the mineralocorticoid receptor selectively relative to glucocorticoid, progesterone and androgen receptors, yet gynecomastia and abnormal vaginal bleeding were reported with INSPRA and not with placebo in hypertension trials, with rates rising with duration of therapy. Clearance is mainly by CYP3A4, elimination half-life is 3 to 6 hours, steady state is reached within 2 days, and food does not affect absorption. Analyses of a range of cardiovascular biomarkers in EPHESUS did not confirm a mechanism for the mortality reduction.

Participants / model
Adults with heart failure with reduced ejection fraction after myocardial infarction; adults with hypertension; label PK participants
Treatment
INSPRA film-coated oral tablets
Follow-up
Label version effective 23 June 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, titration or the potassium monitoring schedule.

Read the original source
Drugs@FDA: INSPRA approved 27 September 2002; generics from 2017 in the records returned

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 021437 (INSPRA), with generic eplerenone applications including ANDA 206922. Dates read from the openFDA Drugs@FDA records.

FDA approved INSPRA under NDA 021437 on 27 September 2002. Generic eplerenone tablets are approved under ANDAs; the earliest among the records returned was ANDA 206922 on 13 July 2017.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 2002 to 2017 in the records returned
Study design
FDA application records
Funding
not stated in the source

The generic date is the earliest among the records returned, not a confirmed first generic.

Read the original source
PubChem: eplerenone identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 443872 (eplerenone).

Eplerenone: C24H30O6, 414.5 g/mol, CAS 107724-20-9. The INSPRA label gives the same empirical formula and a molecular weight of 414.50.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the heart failure and hypertension trials find?

In two large placebo-controlled trials, eplerenone lowered death and cardiovascular events in patients with heart failure. The label reports a blood pressure fall in hypertension trials. Serious hyperkalemia was more common on eplerenone in EPHESUS.

EPHESUS randomized 6,632 patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure to eplerenone or placebo on top of optimal medical therapy. Over a mean 16 months there were 478 deaths on eplerenone and 554 on placebo (RR 0.85, 95% CI 0.75 to 0.96). Cardiovascular death or cardiovascular hospitalization was also reduced (RR 0.87, 95% CI 0.79 to 0.95).

EMPHASIS-HF randomized 2,737 patients with NYHA class II heart failure and an ejection fraction of 35% or less to eplerenone or placebo on top of recommended therapy (NCT00232180). It stopped early at a median 21 months. Cardiovascular death or heart failure hospitalization occurred in 18.3% versus 25.9% (HR 0.63, 95% CI 0.54 to 0.74), and death from any cause in 12.5% versus 15.5% (HR 0.76, 95% CI 0.62 to 0.93).

For hypertension, the INSPRA label reports that trough blood pressure fell 6 to 13 mmHg systolic and 3 to 7 mmHg diastolic more than placebo across the doses tested in its hypertension trials.

Both outcome trials enrolled people with heart failure, so the survival results do not apply to healthy people or to people using anabolic steroids.

EPHESUS: 6,632 patients after MI, 478 versus 554 deaths

Randomized controlled trial

Pitt B et al. N Engl J Med. 2003;348(14):1309-21. PMID 12668699.

Over a mean 16 months there were 478 deaths on eplerenone and 554 on placebo (RR 0.85, 95% CI 0.75 to 0.96). Cardiovascular death or cardiovascular hospitalization was also reduced (RR 0.87, 95% CI 0.79 to 0.95). Serious hyperkalemia occurred in 5.5% versus 3.9%, and hypokalemia in 8.4% versus 13.1%.

Participants / model
6,632 patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure
Treatment
Oral eplerenone 25 mg daily, titrated to at most 50 mg, or placebo, on top of optimal medical therapy
Follow-up
Mean 16 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Heart failure population after myocardial infarction; the results do not apply to healthy people or anabolic steroid users.

Read the original source
EMPHASIS-HF: 2,737 patients, stopped early, HR 0.63

Randomized controlled trial

Zannad F et al. N Engl J Med. 2011;364(1):11-21. PMID 21073363.

The trial stopped early. Cardiovascular death or heart failure hospitalization occurred in 18.3% versus 25.9% (HR 0.63, 95% CI 0.54 to 0.74) and death from any cause in 12.5% versus 15.5% (HR 0.76, 95% CI 0.62 to 0.93). Serum potassium above 5.5 mmol/L occurred in 11.8% versus 7.2%.

Participants / model
2,737 patients with NYHA class II heart failure and an ejection fraction of 35% or less
Treatment
Oral eplerenone up to 50 mg daily or placebo, on top of recommended therapy
Follow-up
Stopped early at a median 21 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Chronic systolic heart failure with mild symptoms; the results do not apply to healthy people.

Read the original source
INSPRA label, version effective 23 June 2025: indications, hyperkalemia, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INSPRA (eplerenone) film-coated oral tablets, prescribing information, label version effective 23 June 2025. Set ID 1a52bedc-8e2c-4116-a296-a87770676b4a.

The label approves INSPRA to improve survival of stable adults with symptomatic heart failure with reduced ejection fraction (40% or less) after an acute myocardial infarction, and to treat hypertension in adults. Hyperkalemia is the main warning, with higher risk in renal impairment, proteinuria, diabetes, and with ACE inhibitors, ARBs, NSAIDs or moderate CYP3A inhibitors. It is contraindicated in all patients with serum potassium above 5.5 mEq/L at initiation, creatinine clearance of 30 mL/min or less, or strong CYP3A inhibitors, and for hypertension also with potassium supplements or potassium-sparing diuretics, spironolactone included. In hypertension trials, trough blood pressure fell 6 to 13 mmHg systolic and 3 to 7 mmHg diastolic more than placebo. Eplerenone binds the mineralocorticoid receptor selectively relative to glucocorticoid, progesterone and androgen receptors, yet gynecomastia and abnormal vaginal bleeding were reported with INSPRA and not with placebo in hypertension trials, with rates rising with duration of therapy. Clearance is mainly by CYP3A4, elimination half-life is 3 to 6 hours, steady state is reached within 2 days, and food does not affect absorption. Analyses of a range of cardiovascular biomarkers in EPHESUS did not confirm a mechanism for the mortality reduction.

Participants / model
Adults with heart failure with reduced ejection fraction after myocardial infarction; adults with hypertension; label PK participants
Treatment
INSPRA film-coated oral tablets
Follow-up
Label version effective 23 June 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, titration or the potassium monitoring schedule.

Read the original source

Is eplerenone gentler than spironolactone?

On breast effects, yes in one head-to-head trial: male gynecomastia occurred in 21.2% on spironolactone versus 4.5% on eplerenone. Eplerenone also lowered diastolic blood pressure less, and its label still reports gynecomastia and abnormal vaginal bleeding.

A double-blind randomized trial in adults with hypertension and primary aldosteronism compared 16 weeks of spironolactone with eplerenone. Diastolic blood pressure fell by 5.6 mmHg on eplerenone and 12.5 mmHg on spironolactone (difference -6.9 mmHg, 95% CI -10.6 to -3.3). Overall adverse events did not differ, but male gynecomastia (21.2% versus 4.5%) and female mastodynia (21.1% versus 0.0%) were more frequent with spironolactone. The selectivity advantage came with weaker blood pressure lowering at the doses tested.

In RALES, 1,663 patients with severe heart failure and an ejection fraction of 35% or less were randomized to spironolactone or placebo. Deaths fell from 46% to 35% (RR 0.70, 95% CI 0.60 to 0.82), and gynecomastia or breast pain was reported in 10% of men on spironolactone versus 1% on placebo. This documents spironolactone's anti-androgenic side effect at a low dose in heart failure; it is not a study of anabolic steroid users.

Eplerenone is not free of these effects. The INSPRA label says it binds the mineralocorticoid receptor selectively relative to glucocorticoid, progesterone and androgen receptors, yet in hypertension trials gynecomastia and abnormal vaginal bleeding were reported with INSPRA and not with placebo, with rates rising with duration of therapy.

Head-to-head in primary aldosteronism: gynecomastia 21.2% versus 4.5%, weaker blood pressure fall on eplerenone

Randomized controlled trial

Parthasarathy HK et al. J Hypertens. 2011;29(5):980-90. PMID 21451421.

Diastolic blood pressure fell less on eplerenone (-5.6 mmHg) than on spironolactone (-12.5 mmHg; difference -6.9 mmHg, 95% CI -10.6 to -3.3). Overall adverse events did not differ, but male gynecomastia (21.2% versus 4.5%) and female mastodynia (21.1% versus 0.0%) were more frequent with spironolactone.

Participants / model
Adults with hypertension and biochemical evidence of primary aldosteronism
Treatment
Oral spironolactone 75 to 225 mg daily or eplerenone 100 to 300 mg daily, titrated to effect
Follow-up
16 weeks
Study design
Double-blind randomized trial
Funding
not stated in the source

Eplerenone's selectivity advantage came with weaker blood pressure lowering at the doses tested. Patients had primary aldosteronism.

Read the original source
RALES (spironolactone): 1,663 patients, gynecomastia or breast pain in 10% versus 1% of men

Randomized controlled trial

Pitt B et al. N Engl J Med. 1999;341(10):709-17. PMID 10471456.

Deaths fell from 46% to 35% (RR 0.70, 95% CI 0.60 to 0.82). Gynecomastia or breast pain was reported in 10% of men on spironolactone versus 1% on placebo.

Participants / model
1,663 patients with severe heart failure and an ejection fraction of 35% or less, on an ACE inhibitor and a loop diuretic
Treatment
Oral spironolactone 25 mg daily or placebo
Follow-up
not stated in the source
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Spironolactone, not eplerenone. It documents spironolactone's anti-androgenic side effect at a low dose in heart failure; it is not a study of anabolic steroid users.

Read the original source
INSPRA label, version effective 23 June 2025: indications, hyperkalemia, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INSPRA (eplerenone) film-coated oral tablets, prescribing information, label version effective 23 June 2025. Set ID 1a52bedc-8e2c-4116-a296-a87770676b4a.

The label approves INSPRA to improve survival of stable adults with symptomatic heart failure with reduced ejection fraction (40% or less) after an acute myocardial infarction, and to treat hypertension in adults. Hyperkalemia is the main warning, with higher risk in renal impairment, proteinuria, diabetes, and with ACE inhibitors, ARBs, NSAIDs or moderate CYP3A inhibitors. It is contraindicated in all patients with serum potassium above 5.5 mEq/L at initiation, creatinine clearance of 30 mL/min or less, or strong CYP3A inhibitors, and for hypertension also with potassium supplements or potassium-sparing diuretics, spironolactone included. In hypertension trials, trough blood pressure fell 6 to 13 mmHg systolic and 3 to 7 mmHg diastolic more than placebo. Eplerenone binds the mineralocorticoid receptor selectively relative to glucocorticoid, progesterone and androgen receptors, yet gynecomastia and abnormal vaginal bleeding were reported with INSPRA and not with placebo in hypertension trials, with rates rising with duration of therapy. Clearance is mainly by CYP3A4, elimination half-life is 3 to 6 hours, steady state is reached within 2 days, and food does not affect absorption. Analyses of a range of cardiovascular biomarkers in EPHESUS did not confirm a mechanism for the mortality reduction.

Participants / model
Adults with heart failure with reduced ejection fraction after myocardial infarction; adults with hypertension; label PK participants
Treatment
INSPRA film-coated oral tablets
Follow-up
Label version effective 23 June 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, titration or the potassium monitoring schedule.

Read the original source

Does eplerenone treat fluid retention from anabolic steroids or growth hormone?

No study tested it. A PubMed search on 9 October 2026 returned 15 records on mineralocorticoid antagonists with anabolic steroid terms; none tested eplerenone and none studied one in human steroid users. A second search with growth hormone terms returned 4 records, none testing eplerenone against growth hormone fluid retention.

Sellers describe eplerenone as targeting aldosterone-driven fluid retention on aromatizing compounds and growth hormone, as preferred over spironolactone on steroid cycles because spironolactone is anti-androgenic, and as protective against steroid-related myocardial fibrosis. The first search covered eplerenone, mineralocorticoid receptor antagonists and spironolactone with anabolic steroid, nandrolone, bodybuilding, stanozolol and trenbolone terms. Three of the 15 records were rat studies of nandrolone with spironolactone. The rest were gynecomastia, breast and herbal reviews, a 1996 trial that gave nandrolone or spironolactone as separate arms to obese postmenopausal women, and older clinical, animal, fish reporter-assay or pharmacology papers.

The second search, eplerenone with growth hormone, somatropin or acromegaly, returned 4 records: a heart failure review, a Cochrane review of cardiac care in muscular dystrophy, a trials listing and a retinal case report. The aromatization (estrogen) mechanism sellers cite has no eplerenone study among these records either.

What exists points at aldosterone, not at eplerenone. In a cross-sectional study of 100 men in recreational strength training, the 37 current steroid users had higher 24-hour systolic blood pressure than controls (132 versus 124 mmHg) and more systolic hypertension (51% versus 17%), with higher plasma aldosterone and noradrenaline and lower MR-proANP than former users and controls. That is an association consistent with raised aldosterone during steroid use. It does not show that blocking the mineralocorticoid receptor corrects fluid retention or blood pressure.

In an 8-subject randomized double-blind study, four 6-day periods of subcutaneous growth hormone raised extracellular volume (18.87 L on placebo, 20.43 L on growth hormone), and captopril (18.82 L) or spironolactone (18.99 L) abolished the rise. Aldosterone rose only with growth hormone plus spironolactone. This supports renin-angiotensin-aldosterone involvement in short-term growth hormone fluid retention, but the mineralocorticoid blocker tested was spironolactone, not eplerenone.

PubMed searches, 9 October 2026: 15 and 4 records, none testing eplerenone for the supplier claims

PubMed search record

PubMed search run on 9 October 2026: (eplerenone[tiab] OR mineralocorticoid receptor antagonist*[tiab] OR spironolactone[tiab]) AND (anabolic steroid*[tiab] OR anabolic-androgenic[tiab] OR anabolic androgenic[tiab] OR nandrolone[tiab] OR bodybuild*[tiab] OR stanozolol[tiab] OR trenbolone[tiab]). 15 records returned. A second search, eplerenone[tiab] AND (growth hormone[tiab] OR somatropin[tiab] OR acromegaly[tiab]), returned 4 records.

The first search returned 15 records. None tested eplerenone, and none studied a mineralocorticoid antagonist in human anabolic steroid users. Three were rat studies of nandrolone with spironolactone; the rest were gynecomastia, breast and herbal reviews, a 1996 trial that gave nandrolone or spironolactone as separate arms to obese postmenopausal women, and older clinical, animal, fish reporter-assay or pharmacology papers. The second search returned 4 records (a heart failure review, a Cochrane review of cardiac care in muscular dystrophy, a trials listing and a retinal case report), none testing eplerenone against growth hormone fluid retention. The anabolic steroid cycle, aromatization and growth hormone uses have no eplerenone study behind them in these records.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists. The link opens the first search.

Read the original source
100 strength-training men: higher aldosterone and blood pressure in current steroid users

Human study

Rasmussen JJ et al. J Hypertens. 2018;36(2):277-285. PMID 28863033.

Current users had higher 24-hour systolic blood pressure than controls (132 versus 124 mmHg) and more systolic hypertension (51% versus 17%). Plasma aldosterone and noradrenaline were higher, and MR-proANP lower, in current users than in former users and controls.

Participants / model
100 men in recreational strength training: 37 current anabolic steroid users, 33 former users and 30 controls
Treatment
Self-administered anabolic steroids (observational); no drug was given by the investigators
Follow-up
Cross-sectional
Study design
Cross-sectional study
Funding
not stated in the source

An association consistent with raised aldosterone during steroid use. It does not show that blocking the mineralocorticoid receptor corrects fluid retention or blood pressure.

Read the original source
GH fluid retention: 8 subjects, spironolactone or captopril abolished the rise

Randomized controlled trial

Møller J et al. Am J Physiol. 1997;272(5 Pt 1):E803-8. PMID 9176179.

Growth hormone raised extracellular volume (18.87 L on placebo, 20.43 L on growth hormone), and captopril (18.82 L) or spironolactone (18.99 L) abolished the rise. Renin and angiotensin II rose in all growth hormone periods, while aldosterone rose only with growth hormone plus spironolactone.

Participants / model
8 subjects
Treatment
Subcutaneous growth hormone (6 IU/m2) or placebo combined with oral captopril, spironolactone or placebo tablets
Follow-up
Four 6-day periods
Study design
Randomized double-blind study
Funding
not stated in the source

Supports renin-angiotensin-aldosterone involvement in short-term growth hormone fluid retention. The mineralocorticoid blocker tested was spironolactone, not eplerenone.

Read the original source

Does eplerenone protect the heart from steroid-related fibrosis?

No study tested eplerenone for fibrosis in steroid users. The closest studies are a rat nandrolone study with spironolactone, two cardiac MRI studies in steroid users that disagree on fibrosis, and an eplerenone trial in hypertrophic cardiomyopathy that missed its between-group comparison.

In male Wistar rats (14 per group) given nandrolone decanoate for 10 weeks, with or without swimming training, cardiac hypertrophy developed (10% with nandrolone, 17% with nandrolone plus training) with higher collagen volume fraction and collagen type III. Spironolactone or losartan in drinking water prevented the collagen increase and the rise in cardiac ACE activity, aldosterone synthase, 11-beta-HSD2, TGF-beta and osteopontin. This is the closest steroid-fibrosis evidence for mineralocorticoid blockade, and it is rat evidence with spironolactone, not eplerenone.

In a cardiac MRI study, 13 male bodybuilders who had used steroids for at least 2 years and were on cycle had higher absolute left ventricular mass than 8 training-matched non-users (220 versus 163 g, no longer different when indexed to fat-free mass), lower right ventricular ejection fraction (51% versus 59%) and lower peak left ventricular longitudinal strain. No participant showed focal fibrosis.

A second MRI study of 20 strength-trained steroid users, 20 strength-trained non-users and 7 sedentary controls found lower native T1 in users than in non-users (888 versus 1020 ms), lower left ventricular strain and higher LV mass index. Focal myocardial fibrosis was found in 2 users, and extracellular volume was similar across the three groups (28%, 28% and 30%). The authors describe human data on myocardial fibrosis in steroid users as conflicting.

In a randomized double-blind trial in 61 patients with nonobstructive hypertrophic cardiomyopathy, 12 months of eplerenone 50 mg (30 patients) lowered native T1, an MRI index of diffuse fibrosis, within the group (1,315 to 1,259 ms, P = 0.041), while placebo (31 patients) did not change. The between-group difference (3.7% reduction versus 1.1% increase) was not significant (P = 0.07), and functional status and diastolic function did not change. The authors call for larger and longer trials. This is disease-population evidence, not evidence in steroid users.

Rat nandrolone study: spironolactone prevented the collagen increase

Animal study

Do Carmo EC et al. Med Sci Sports Exerc. 2011;43(10):1836-48. PMID 21407130.

Nandrolone decanoate, with or without swimming training, produced cardiac hypertrophy (10% with nandrolone, 17% with nandrolone plus training) and higher collagen volume fraction and collagen type III. Spironolactone or losartan in drinking water prevented the collagen increase and the rise in cardiac ACE activity, aldosterone synthase, 11-beta-HSD2, TGF-beta and osteopontin.

Participants / model
Male Wistar rats, 14 per group
Treatment
Nandrolone decanoate 10 mg/kg per week, route not stated in the abstract; spironolactone 10 mg/kg per day or losartan in drinking water
Follow-up
10 weeks of nandrolone
Study design
Animal study
Funding
not stated in the source

The closest steroid-fibrosis evidence for mineralocorticoid blockade. It is rat evidence with spironolactone, not eplerenone.

Read the original source
Cardiac MRI: 13 bodybuilders on cycle versus 8 non-users, no focal fibrosis

Human study

Angell PJ et al. Eur J Appl Physiol. 2014;114(5):921-8. PMID 24463601.

Users had higher absolute left ventricular mass (220 versus 163 g, no longer different when indexed to fat-free mass), lower right ventricular ejection fraction (51% versus 59%) and lower peak left ventricular longitudinal strain. No participant showed focal fibrosis.

Participants / model
21 strength-trained men: 13 male bodybuilders who had used anabolic steroids for at least 2 years and were on cycle, and 8 training-matched non-users
Treatment
Self-administered anabolic steroids (observational)
Follow-up
Cross-sectional
Study design
Cross-sectional cardiac MRI study
Funding
not stated in the source

Observational. No eplerenone or other blocker was tested.

Read the original source
Cardiac MRI: 47 participants, focal fibrosis in 2 users, extracellular volume similar

Human study

de Souza FR et al. Int J Sports Med. 2022;43(2):183-191. PMID 34341973.

Native T1 was lower in users than in non-users (888 versus 1020 ms), with lower left ventricular strain and higher LV mass index. Focal myocardial fibrosis was found in 2 users, and extracellular volume was similar across the three groups (28%, 28% and 30%). The authors describe human data on myocardial fibrosis in steroid users as conflicting.

Participants / model
47 participants: 20 strength-trained anabolic steroid users, 20 strength-trained non-users and 7 sedentary controls
Treatment
Self-administered anabolic steroids (observational)
Follow-up
Cross-sectional
Study design
Cross-sectional cardiac MRI study
Funding
not stated in the source

Observational. No eplerenone or other blocker was tested.

Read the original source
Eplerenone in HCM: 61 patients, 12 months, between-group native T1 difference not significant

Randomized controlled trial

Papapostolou S et al. JACC Heart Fail. 2025;13(7):102415. PMID 40243979.

Eplerenone lowered native T1, an MRI index of diffuse fibrosis, within the group (1,315 to 1,259 ms, P = 0.041), while placebo did not change. The between-group difference (3.7% reduction versus 1.1% increase) was not significant (P = 0.07), and functional status and diastolic function did not change. The authors call for larger and longer trials.

Participants / model
61 patients with nonobstructive hypertrophic cardiomyopathy: 30 on eplerenone and 31 on placebo
Treatment
Oral eplerenone 50 mg daily or placebo
Follow-up
12 months
Study design
Randomized double-blind trial
Funding
not stated in the source

Disease-population evidence, not evidence in anabolic steroid users.

Read the original source

How does eplerenone work, and what does the body do with it?

Eplerenone binds the mineralocorticoid receptor selectively. Clearance is mainly by CYP3A4 and the elimination half-life is 3 to 6 hours. The EPHESUS biomarker analyses did not confirm a mechanism for the mortality reduction.

The INSPRA label says eplerenone binds the mineralocorticoid receptor selectively relative to glucocorticoid, progesterone and androgen receptors. It also says analyses of a range of cardiovascular biomarkers in EPHESUS did not confirm a mechanism for the mortality reduction.

Clearance is mainly by CYP3A4. Elimination half-life is 3 to 6 hours, steady state is reached within 2 days, and food does not affect absorption.

Whether blocking aldosterone corrects the estrogen-related effects of aromatizing compounds, as sellers claim, is not addressed by any eplerenone study in the records reviewed.

INSPRA label, version effective 23 June 2025: indications, hyperkalemia, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INSPRA (eplerenone) film-coated oral tablets, prescribing information, label version effective 23 June 2025. Set ID 1a52bedc-8e2c-4116-a296-a87770676b4a.

The label approves INSPRA to improve survival of stable adults with symptomatic heart failure with reduced ejection fraction (40% or less) after an acute myocardial infarction, and to treat hypertension in adults. Hyperkalemia is the main warning, with higher risk in renal impairment, proteinuria, diabetes, and with ACE inhibitors, ARBs, NSAIDs or moderate CYP3A inhibitors. It is contraindicated in all patients with serum potassium above 5.5 mEq/L at initiation, creatinine clearance of 30 mL/min or less, or strong CYP3A inhibitors, and for hypertension also with potassium supplements or potassium-sparing diuretics, spironolactone included. In hypertension trials, trough blood pressure fell 6 to 13 mmHg systolic and 3 to 7 mmHg diastolic more than placebo. Eplerenone binds the mineralocorticoid receptor selectively relative to glucocorticoid, progesterone and androgen receptors, yet gynecomastia and abnormal vaginal bleeding were reported with INSPRA and not with placebo in hypertension trials, with rates rising with duration of therapy. Clearance is mainly by CYP3A4, elimination half-life is 3 to 6 hours, steady state is reached within 2 days, and food does not affect absorption. Analyses of a range of cardiovascular biomarkers in EPHESUS did not confirm a mechanism for the mortality reduction.

Participants / model
Adults with heart failure with reduced ejection fraction after myocardial infarction; adults with hypertension; label PK participants
Treatment
INSPRA film-coated oral tablets
Follow-up
Label version effective 23 June 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, titration or the potassium monitoring schedule.

Read the original source

What risks does the label report?

Hyperkalemia is the label's main warning, with higher risk in renal impairment, proteinuria, diabetes, and with ACE inhibitors, ARBs, NSAIDs or moderate CYP3A inhibitors. The label contraindicates strong CYP3A inhibitors in all patients.

Hyperkalemia is the main warning. Risk is higher in renal impairment, proteinuria and diabetes, and with ACE inhibitors, ARBs, NSAIDs or moderate CYP3A inhibitors. The label calls for serum potassium to be measured before starting and during early treatment; its schedule is not reproduced here.

INSPRA is contraindicated in all patients with serum potassium above 5.5 mEq/L at initiation, creatinine clearance of 30 mL/min or less, or strong CYP3A inhibitors. For hypertension it is also contraindicated in type 2 diabetes with microalbuminuria, serum creatinine above 2.0 mg/dL in men or 1.8 mg/dL in women, creatinine clearance below 50 mL/min, and with potassium supplements or potassium-sparing diuretics, spironolactone included.

In EPHESUS, serious hyperkalemia occurred in 5.5% versus 3.9% on placebo and hypokalemia in 8.4% versus 13.1%. In EMPHASIS-HF, serum potassium above 5.5 mmol/L occurred in 11.8% versus 7.2%. Gynecomastia and abnormal vaginal bleeding were reported with INSPRA and not with placebo in hypertension trials.

These figures come from people with heart failure or hypertension. No eplerenone study in people using anabolic steroids or growth hormone was found, so how these risks behave alongside steroids or growth hormone is unmeasured.

INSPRA label, version effective 23 June 2025: indications, hyperkalemia, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INSPRA (eplerenone) film-coated oral tablets, prescribing information, label version effective 23 June 2025. Set ID 1a52bedc-8e2c-4116-a296-a87770676b4a.

The label approves INSPRA to improve survival of stable adults with symptomatic heart failure with reduced ejection fraction (40% or less) after an acute myocardial infarction, and to treat hypertension in adults. Hyperkalemia is the main warning, with higher risk in renal impairment, proteinuria, diabetes, and with ACE inhibitors, ARBs, NSAIDs or moderate CYP3A inhibitors. It is contraindicated in all patients with serum potassium above 5.5 mEq/L at initiation, creatinine clearance of 30 mL/min or less, or strong CYP3A inhibitors, and for hypertension also with potassium supplements or potassium-sparing diuretics, spironolactone included. In hypertension trials, trough blood pressure fell 6 to 13 mmHg systolic and 3 to 7 mmHg diastolic more than placebo. Eplerenone binds the mineralocorticoid receptor selectively relative to glucocorticoid, progesterone and androgen receptors, yet gynecomastia and abnormal vaginal bleeding were reported with INSPRA and not with placebo in hypertension trials, with rates rising with duration of therapy. Clearance is mainly by CYP3A4, elimination half-life is 3 to 6 hours, steady state is reached within 2 days, and food does not affect absorption. Analyses of a range of cardiovascular biomarkers in EPHESUS did not confirm a mechanism for the mortality reduction.

Participants / model
Adults with heart failure with reduced ejection fraction after myocardial infarction; adults with hypertension; label PK participants
Treatment
INSPRA film-coated oral tablets
Follow-up
Label version effective 23 June 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, titration or the potassium monitoring schedule.

Read the original source
EPHESUS: 6,632 patients after MI, 478 versus 554 deaths

Randomized controlled trial

Pitt B et al. N Engl J Med. 2003;348(14):1309-21. PMID 12668699.

Over a mean 16 months there were 478 deaths on eplerenone and 554 on placebo (RR 0.85, 95% CI 0.75 to 0.96). Cardiovascular death or cardiovascular hospitalization was also reduced (RR 0.87, 95% CI 0.79 to 0.95). Serious hyperkalemia occurred in 5.5% versus 3.9%, and hypokalemia in 8.4% versus 13.1%.

Participants / model
6,632 patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure
Treatment
Oral eplerenone 25 mg daily, titrated to at most 50 mg, or placebo, on top of optimal medical therapy
Follow-up
Mean 16 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Heart failure population after myocardial infarction; the results do not apply to healthy people or anabolic steroid users.

Read the original source
EMPHASIS-HF: 2,737 patients, stopped early, HR 0.63

Randomized controlled trial

Zannad F et al. N Engl J Med. 2011;364(1):11-21. PMID 21073363.

The trial stopped early. Cardiovascular death or heart failure hospitalization occurred in 18.3% versus 25.9% (HR 0.63, 95% CI 0.54 to 0.74) and death from any cause in 12.5% versus 15.5% (HR 0.76, 95% CI 0.62 to 0.93). Serum potassium above 5.5 mmol/L occurred in 11.8% versus 7.2%.

Participants / model
2,737 patients with NYHA class II heart failure and an ejection fraction of 35% or less
Treatment
Oral eplerenone up to 50 mg daily or placebo, on top of recommended therapy
Follow-up
Stopped early at a median 21 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Chronic systolic heart failure with mild symptoms; the results do not apply to healthy people.

Read the original source

Why does eplerenone sit in S tier?

FDA approval since 2002, two large placebo-controlled outcome trials showing lower mortality, and more than two decades of use support the S for the approved uses. The grade does not cover the supplier claims for steroid or growth hormone use.

The S applies to heart failure after myocardial infarction and to hypertension. The supplier claim is a separate question. It is partly supported on selectivity: spironolactone caused more gynecomastia in the head-to-head trial, though eplerenone lowered blood pressure less.

The fluid retention and fibrosis parts rest on spironolactone, not eplerenone, in an 8-subject growth hormone study and a rat nandrolone study. Human MRI data on fibrosis in steroid users conflict, the eplerenone MRI trial reviewed (in hypertrophic cardiomyopathy) missed its between-group comparison, and no record reviewed tested eplerenone in steroid users.

INSPRA label, version effective 23 June 2025: indications, hyperkalemia, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INSPRA (eplerenone) film-coated oral tablets, prescribing information, label version effective 23 June 2025. Set ID 1a52bedc-8e2c-4116-a296-a87770676b4a.

The label approves INSPRA to improve survival of stable adults with symptomatic heart failure with reduced ejection fraction (40% or less) after an acute myocardial infarction, and to treat hypertension in adults. Hyperkalemia is the main warning, with higher risk in renal impairment, proteinuria, diabetes, and with ACE inhibitors, ARBs, NSAIDs or moderate CYP3A inhibitors. It is contraindicated in all patients with serum potassium above 5.5 mEq/L at initiation, creatinine clearance of 30 mL/min or less, or strong CYP3A inhibitors, and for hypertension also with potassium supplements or potassium-sparing diuretics, spironolactone included. In hypertension trials, trough blood pressure fell 6 to 13 mmHg systolic and 3 to 7 mmHg diastolic more than placebo. Eplerenone binds the mineralocorticoid receptor selectively relative to glucocorticoid, progesterone and androgen receptors, yet gynecomastia and abnormal vaginal bleeding were reported with INSPRA and not with placebo in hypertension trials, with rates rising with duration of therapy. Clearance is mainly by CYP3A4, elimination half-life is 3 to 6 hours, steady state is reached within 2 days, and food does not affect absorption. Analyses of a range of cardiovascular biomarkers in EPHESUS did not confirm a mechanism for the mortality reduction.

Participants / model
Adults with heart failure with reduced ejection fraction after myocardial infarction; adults with hypertension; label PK participants
Treatment
INSPRA film-coated oral tablets
Follow-up
Label version effective 23 June 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, titration or the potassium monitoring schedule.

Read the original source
Drugs@FDA: INSPRA approved 27 September 2002; generics from 2017 in the records returned

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 021437 (INSPRA), with generic eplerenone applications including ANDA 206922. Dates read from the openFDA Drugs@FDA records.

FDA approved INSPRA under NDA 021437 on 27 September 2002. Generic eplerenone tablets are approved under ANDAs; the earliest among the records returned was ANDA 206922 on 13 July 2017.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 2002 to 2017 in the records returned
Study design
FDA application records
Funding
not stated in the source

The generic date is the earliest among the records returned, not a confirmed first generic.

Read the original source
EPHESUS: 6,632 patients after MI, 478 versus 554 deaths

Randomized controlled trial

Pitt B et al. N Engl J Med. 2003;348(14):1309-21. PMID 12668699.

Over a mean 16 months there were 478 deaths on eplerenone and 554 on placebo (RR 0.85, 95% CI 0.75 to 0.96). Cardiovascular death or cardiovascular hospitalization was also reduced (RR 0.87, 95% CI 0.79 to 0.95). Serious hyperkalemia occurred in 5.5% versus 3.9%, and hypokalemia in 8.4% versus 13.1%.

Participants / model
6,632 patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure
Treatment
Oral eplerenone 25 mg daily, titrated to at most 50 mg, or placebo, on top of optimal medical therapy
Follow-up
Mean 16 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Heart failure population after myocardial infarction; the results do not apply to healthy people or anabolic steroid users.

Read the original source
EMPHASIS-HF: 2,737 patients, stopped early, HR 0.63

Randomized controlled trial

Zannad F et al. N Engl J Med. 2011;364(1):11-21. PMID 21073363.

The trial stopped early. Cardiovascular death or heart failure hospitalization occurred in 18.3% versus 25.9% (HR 0.63, 95% CI 0.54 to 0.74) and death from any cause in 12.5% versus 15.5% (HR 0.76, 95% CI 0.62 to 0.93). Serum potassium above 5.5 mmol/L occurred in 11.8% versus 7.2%.

Participants / model
2,737 patients with NYHA class II heart failure and an ejection fraction of 35% or less
Treatment
Oral eplerenone up to 50 mg daily or placebo, on top of recommended therapy
Follow-up
Stopped early at a median 21 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Chronic systolic heart failure with mild symptoms; the results do not apply to healthy people.

Read the original source
Head-to-head in primary aldosteronism: gynecomastia 21.2% versus 4.5%, weaker blood pressure fall on eplerenone

Randomized controlled trial

Parthasarathy HK et al. J Hypertens. 2011;29(5):980-90. PMID 21451421.

Diastolic blood pressure fell less on eplerenone (-5.6 mmHg) than on spironolactone (-12.5 mmHg; difference -6.9 mmHg, 95% CI -10.6 to -3.3). Overall adverse events did not differ, but male gynecomastia (21.2% versus 4.5%) and female mastodynia (21.1% versus 0.0%) were more frequent with spironolactone.

Participants / model
Adults with hypertension and biochemical evidence of primary aldosteronism
Treatment
Oral spironolactone 75 to 225 mg daily or eplerenone 100 to 300 mg daily, titrated to effect
Follow-up
16 weeks
Study design
Double-blind randomized trial
Funding
not stated in the source

Eplerenone's selectivity advantage came with weaker blood pressure lowering at the doses tested. Patients had primary aldosteronism.

Read the original source
GH fluid retention: 8 subjects, spironolactone or captopril abolished the rise

Randomized controlled trial

Møller J et al. Am J Physiol. 1997;272(5 Pt 1):E803-8. PMID 9176179.

Growth hormone raised extracellular volume (18.87 L on placebo, 20.43 L on growth hormone), and captopril (18.82 L) or spironolactone (18.99 L) abolished the rise. Renin and angiotensin II rose in all growth hormone periods, while aldosterone rose only with growth hormone plus spironolactone.

Participants / model
8 subjects
Treatment
Subcutaneous growth hormone (6 IU/m2) or placebo combined with oral captopril, spironolactone or placebo tablets
Follow-up
Four 6-day periods
Study design
Randomized double-blind study
Funding
not stated in the source

Supports renin-angiotensin-aldosterone involvement in short-term growth hormone fluid retention. The mineralocorticoid blocker tested was spironolactone, not eplerenone.

Read the original source
Rat nandrolone study: spironolactone prevented the collagen increase

Animal study

Do Carmo EC et al. Med Sci Sports Exerc. 2011;43(10):1836-48. PMID 21407130.

Nandrolone decanoate, with or without swimming training, produced cardiac hypertrophy (10% with nandrolone, 17% with nandrolone plus training) and higher collagen volume fraction and collagen type III. Spironolactone or losartan in drinking water prevented the collagen increase and the rise in cardiac ACE activity, aldosterone synthase, 11-beta-HSD2, TGF-beta and osteopontin.

Participants / model
Male Wistar rats, 14 per group
Treatment
Nandrolone decanoate 10 mg/kg per week, route not stated in the abstract; spironolactone 10 mg/kg per day or losartan in drinking water
Follow-up
10 weeks of nandrolone
Study design
Animal study
Funding
not stated in the source

The closest steroid-fibrosis evidence for mineralocorticoid blockade. It is rat evidence with spironolactone, not eplerenone.

Read the original source
Eplerenone in HCM: 61 patients, 12 months, between-group native T1 difference not significant

Randomized controlled trial

Papapostolou S et al. JACC Heart Fail. 2025;13(7):102415. PMID 40243979.

Eplerenone lowered native T1, an MRI index of diffuse fibrosis, within the group (1,315 to 1,259 ms, P = 0.041), while placebo did not change. The between-group difference (3.7% reduction versus 1.1% increase) was not significant (P = 0.07), and functional status and diastolic function did not change. The authors call for larger and longer trials.

Participants / model
61 patients with nonobstructive hypertrophic cardiomyopathy: 30 on eplerenone and 31 on placebo
Treatment
Oral eplerenone 50 mg daily or placebo
Follow-up
12 months
Study design
Randomized double-blind trial
Funding
not stated in the source

Disease-population evidence, not evidence in anabolic steroid users.

Read the original source
PubMed searches, 9 October 2026: 15 and 4 records, none testing eplerenone for the supplier claims

PubMed search record

PubMed search run on 9 October 2026: (eplerenone[tiab] OR mineralocorticoid receptor antagonist*[tiab] OR spironolactone[tiab]) AND (anabolic steroid*[tiab] OR anabolic-androgenic[tiab] OR anabolic androgenic[tiab] OR nandrolone[tiab] OR bodybuild*[tiab] OR stanozolol[tiab] OR trenbolone[tiab]). 15 records returned. A second search, eplerenone[tiab] AND (growth hormone[tiab] OR somatropin[tiab] OR acromegaly[tiab]), returned 4 records.

The first search returned 15 records. None tested eplerenone, and none studied a mineralocorticoid antagonist in human anabolic steroid users. Three were rat studies of nandrolone with spironolactone; the rest were gynecomastia, breast and herbal reviews, a 1996 trial that gave nandrolone or spironolactone as separate arms to obese postmenopausal women, and older clinical, animal, fish reporter-assay or pharmacology papers. The second search returned 4 records (a heart failure review, a Cochrane review of cardiac care in muscular dystrophy, a trials listing and a retinal case report), none testing eplerenone against growth hormone fluid retention. The anabolic steroid cycle, aromatization and growth hormone uses have no eplerenone study behind them in these records.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists. The link opens the first search.

Read the original source

Studies and sources

INSPRA label, version effective 23 June 2025: indications, hyperkalemia, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INSPRA (eplerenone) film-coated oral tablets, prescribing information, label version effective 23 June 2025. Set ID 1a52bedc-8e2c-4116-a296-a87770676b4a.

The label approves INSPRA to improve survival of stable adults with symptomatic heart failure with reduced ejection fraction (40% or less) after an acute myocardial infarction, and to treat hypertension in adults. Hyperkalemia is the main warning, with higher risk in renal impairment, proteinuria, diabetes, and with ACE inhibitors, ARBs, NSAIDs or moderate CYP3A inhibitors. It is contraindicated in all patients with serum potassium above 5.5 mEq/L at initiation, creatinine clearance of 30 mL/min or less, or strong CYP3A inhibitors, and for hypertension also with potassium supplements or potassium-sparing diuretics, spironolactone included. In hypertension trials, trough blood pressure fell 6 to 13 mmHg systolic and 3 to 7 mmHg diastolic more than placebo. Eplerenone binds the mineralocorticoid receptor selectively relative to glucocorticoid, progesterone and androgen receptors, yet gynecomastia and abnormal vaginal bleeding were reported with INSPRA and not with placebo in hypertension trials, with rates rising with duration of therapy. Clearance is mainly by CYP3A4, elimination half-life is 3 to 6 hours, steady state is reached within 2 days, and food does not affect absorption. Analyses of a range of cardiovascular biomarkers in EPHESUS did not confirm a mechanism for the mortality reduction.

Participants / model
Adults with heart failure with reduced ejection fraction after myocardial infarction; adults with hypertension; label PK participants
Treatment
INSPRA film-coated oral tablets
Follow-up
Label version effective 23 June 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, titration or the potassium monitoring schedule.

Read the original source
Drugs@FDA: INSPRA approved 27 September 2002; generics from 2017 in the records returned

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 021437 (INSPRA), with generic eplerenone applications including ANDA 206922. Dates read from the openFDA Drugs@FDA records.

FDA approved INSPRA under NDA 021437 on 27 September 2002. Generic eplerenone tablets are approved under ANDAs; the earliest among the records returned was ANDA 206922 on 13 July 2017.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 2002 to 2017 in the records returned
Study design
FDA application records
Funding
not stated in the source

The generic date is the earliest among the records returned, not a confirmed first generic.

Read the original source
EPHESUS: 6,632 patients after MI, 478 versus 554 deaths

Randomized controlled trial

Pitt B et al. N Engl J Med. 2003;348(14):1309-21. PMID 12668699.

Over a mean 16 months there were 478 deaths on eplerenone and 554 on placebo (RR 0.85, 95% CI 0.75 to 0.96). Cardiovascular death or cardiovascular hospitalization was also reduced (RR 0.87, 95% CI 0.79 to 0.95). Serious hyperkalemia occurred in 5.5% versus 3.9%, and hypokalemia in 8.4% versus 13.1%.

Participants / model
6,632 patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure
Treatment
Oral eplerenone 25 mg daily, titrated to at most 50 mg, or placebo, on top of optimal medical therapy
Follow-up
Mean 16 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Heart failure population after myocardial infarction; the results do not apply to healthy people or anabolic steroid users.

Read the original source
EMPHASIS-HF: 2,737 patients, stopped early, HR 0.63

Randomized controlled trial

Zannad F et al. N Engl J Med. 2011;364(1):11-21. PMID 21073363.

The trial stopped early. Cardiovascular death or heart failure hospitalization occurred in 18.3% versus 25.9% (HR 0.63, 95% CI 0.54 to 0.74) and death from any cause in 12.5% versus 15.5% (HR 0.76, 95% CI 0.62 to 0.93). Serum potassium above 5.5 mmol/L occurred in 11.8% versus 7.2%.

Participants / model
2,737 patients with NYHA class II heart failure and an ejection fraction of 35% or less
Treatment
Oral eplerenone up to 50 mg daily or placebo, on top of recommended therapy
Follow-up
Stopped early at a median 21 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Chronic systolic heart failure with mild symptoms; the results do not apply to healthy people.

Read the original source
RALES (spironolactone): 1,663 patients, gynecomastia or breast pain in 10% versus 1% of men

Randomized controlled trial

Pitt B et al. N Engl J Med. 1999;341(10):709-17. PMID 10471456.

Deaths fell from 46% to 35% (RR 0.70, 95% CI 0.60 to 0.82). Gynecomastia or breast pain was reported in 10% of men on spironolactone versus 1% on placebo.

Participants / model
1,663 patients with severe heart failure and an ejection fraction of 35% or less, on an ACE inhibitor and a loop diuretic
Treatment
Oral spironolactone 25 mg daily or placebo
Follow-up
not stated in the source
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Spironolactone, not eplerenone. It documents spironolactone's anti-androgenic side effect at a low dose in heart failure; it is not a study of anabolic steroid users.

Read the original source
Head-to-head in primary aldosteronism: gynecomastia 21.2% versus 4.5%, weaker blood pressure fall on eplerenone

Randomized controlled trial

Parthasarathy HK et al. J Hypertens. 2011;29(5):980-90. PMID 21451421.

Diastolic blood pressure fell less on eplerenone (-5.6 mmHg) than on spironolactone (-12.5 mmHg; difference -6.9 mmHg, 95% CI -10.6 to -3.3). Overall adverse events did not differ, but male gynecomastia (21.2% versus 4.5%) and female mastodynia (21.1% versus 0.0%) were more frequent with spironolactone.

Participants / model
Adults with hypertension and biochemical evidence of primary aldosteronism
Treatment
Oral spironolactone 75 to 225 mg daily or eplerenone 100 to 300 mg daily, titrated to effect
Follow-up
16 weeks
Study design
Double-blind randomized trial
Funding
not stated in the source

Eplerenone's selectivity advantage came with weaker blood pressure lowering at the doses tested. Patients had primary aldosteronism.

Read the original source
100 strength-training men: higher aldosterone and blood pressure in current steroid users

Human study

Rasmussen JJ et al. J Hypertens. 2018;36(2):277-285. PMID 28863033.

Current users had higher 24-hour systolic blood pressure than controls (132 versus 124 mmHg) and more systolic hypertension (51% versus 17%). Plasma aldosterone and noradrenaline were higher, and MR-proANP lower, in current users than in former users and controls.

Participants / model
100 men in recreational strength training: 37 current anabolic steroid users, 33 former users and 30 controls
Treatment
Self-administered anabolic steroids (observational); no drug was given by the investigators
Follow-up
Cross-sectional
Study design
Cross-sectional study
Funding
not stated in the source

An association consistent with raised aldosterone during steroid use. It does not show that blocking the mineralocorticoid receptor corrects fluid retention or blood pressure.

Read the original source
GH fluid retention: 8 subjects, spironolactone or captopril abolished the rise

Randomized controlled trial

Møller J et al. Am J Physiol. 1997;272(5 Pt 1):E803-8. PMID 9176179.

Growth hormone raised extracellular volume (18.87 L on placebo, 20.43 L on growth hormone), and captopril (18.82 L) or spironolactone (18.99 L) abolished the rise. Renin and angiotensin II rose in all growth hormone periods, while aldosterone rose only with growth hormone plus spironolactone.

Participants / model
8 subjects
Treatment
Subcutaneous growth hormone (6 IU/m2) or placebo combined with oral captopril, spironolactone or placebo tablets
Follow-up
Four 6-day periods
Study design
Randomized double-blind study
Funding
not stated in the source

Supports renin-angiotensin-aldosterone involvement in short-term growth hormone fluid retention. The mineralocorticoid blocker tested was spironolactone, not eplerenone.

Read the original source
Rat nandrolone study: spironolactone prevented the collagen increase

Animal study

Do Carmo EC et al. Med Sci Sports Exerc. 2011;43(10):1836-48. PMID 21407130.

Nandrolone decanoate, with or without swimming training, produced cardiac hypertrophy (10% with nandrolone, 17% with nandrolone plus training) and higher collagen volume fraction and collagen type III. Spironolactone or losartan in drinking water prevented the collagen increase and the rise in cardiac ACE activity, aldosterone synthase, 11-beta-HSD2, TGF-beta and osteopontin.

Participants / model
Male Wistar rats, 14 per group
Treatment
Nandrolone decanoate 10 mg/kg per week, route not stated in the abstract; spironolactone 10 mg/kg per day or losartan in drinking water
Follow-up
10 weeks of nandrolone
Study design
Animal study
Funding
not stated in the source

The closest steroid-fibrosis evidence for mineralocorticoid blockade. It is rat evidence with spironolactone, not eplerenone.

Read the original source
Cardiac MRI: 13 bodybuilders on cycle versus 8 non-users, no focal fibrosis

Human study

Angell PJ et al. Eur J Appl Physiol. 2014;114(5):921-8. PMID 24463601.

Users had higher absolute left ventricular mass (220 versus 163 g, no longer different when indexed to fat-free mass), lower right ventricular ejection fraction (51% versus 59%) and lower peak left ventricular longitudinal strain. No participant showed focal fibrosis.

Participants / model
21 strength-trained men: 13 male bodybuilders who had used anabolic steroids for at least 2 years and were on cycle, and 8 training-matched non-users
Treatment
Self-administered anabolic steroids (observational)
Follow-up
Cross-sectional
Study design
Cross-sectional cardiac MRI study
Funding
not stated in the source

Observational. No eplerenone or other blocker was tested.

Read the original source
Cardiac MRI: 47 participants, focal fibrosis in 2 users, extracellular volume similar

Human study

de Souza FR et al. Int J Sports Med. 2022;43(2):183-191. PMID 34341973.

Native T1 was lower in users than in non-users (888 versus 1020 ms), with lower left ventricular strain and higher LV mass index. Focal myocardial fibrosis was found in 2 users, and extracellular volume was similar across the three groups (28%, 28% and 30%). The authors describe human data on myocardial fibrosis in steroid users as conflicting.

Participants / model
47 participants: 20 strength-trained anabolic steroid users, 20 strength-trained non-users and 7 sedentary controls
Treatment
Self-administered anabolic steroids (observational)
Follow-up
Cross-sectional
Study design
Cross-sectional cardiac MRI study
Funding
not stated in the source

Observational. No eplerenone or other blocker was tested.

Read the original source
Eplerenone in HCM: 61 patients, 12 months, between-group native T1 difference not significant

Randomized controlled trial

Papapostolou S et al. JACC Heart Fail. 2025;13(7):102415. PMID 40243979.

Eplerenone lowered native T1, an MRI index of diffuse fibrosis, within the group (1,315 to 1,259 ms, P = 0.041), while placebo did not change. The between-group difference (3.7% reduction versus 1.1% increase) was not significant (P = 0.07), and functional status and diastolic function did not change. The authors call for larger and longer trials.

Participants / model
61 patients with nonobstructive hypertrophic cardiomyopathy: 30 on eplerenone and 31 on placebo
Treatment
Oral eplerenone 50 mg daily or placebo
Follow-up
12 months
Study design
Randomized double-blind trial
Funding
not stated in the source

Disease-population evidence, not evidence in anabolic steroid users.

Read the original source
PubChem: eplerenone identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 443872 (eplerenone).

Eplerenone: C24H30O6, 414.5 g/mol, CAS 107724-20-9. The INSPRA label gives the same empirical formula and a molecular weight of 414.50.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

Why is Eplerenone in S tier?

S fits an approved medicine with two large placebo-controlled outcome trials showing lower mortality and more than two decades of use for heart failure after a heart attack and for hypertension. The grade covers the approved uses. It does not extend to the supplier claims for steroid or growth hormone use, which no eplerenone study tests.