Hydrochlorothiazide

updated

Hydrochlorothiazide is a long-established diuretic, FDA-approved as generic tablets and in many ARB combinations for edema and hypertension, and a 2011 meta-analysis calls it the most commonly prescribed antihypertensive worldwide. The 13,523-patient Diuretic Comparison Project found cardiovascular outcomes no different from chlorthalidone, but at 12.5 to 25 mg its 24-hour blood pressure effect is weaker than other drug classes and outcome data at those doses are lacking. The supplier claim for steroid-related water retention and hypertension is largely unsupported: a PubMed search on 9 October 2026 returned 14 records and none tested hydrochlorothiazide in steroid users.

Thiazide diuretic

  • Generic hydrochlorothiazide tablets are labeled for edema, including edema with corticosteroid and estrogen therapy, and for hypertension; the label does not mention androgens or anabolic steroids.
  • The Diuretic Comparison Project randomized 13,523 adults aged 65 or older already on hydrochlorothiazide: the composite occurred in 10.0% versus 10.4% on chlorthalidone at a median 2.4 years (HR 1.04, 95% CI 0.94 to 1.16).
  • A meta-analysis of 24-hour ambulatory trials found hydrochlorothiazide 12.5 to 25 mg lowered blood pressure by 6.5/4.5 mmHg, less than ACE inhibitors, ARBs, beta blockers and calcium antagonists.
  • The only direct comparison with eplerenone found (16 adults with diabetes and albuminuria) gave similar blood pressure, but potassium was supplemented on hydrochlorothiazide.
  • A PubMed search on 9 October 2026 for hydrochlorothiazide or thiazides with anabolic steroid terms returned 14 records; none tested it for steroid-related blood pressure or water retention.
  • The label warns of hypokalemia and links the drug to non-melanoma skin cancer, about 1 additional case per 16,000 patients per year overall.

What is hydrochlorothiazide approved to do?

Generic hydrochlorothiazide tablets are FDA-labeled for edema from heart failure, cirrhosis, corticosteroid and estrogen therapy and renal dysfunction, and for hypertension. The label does not mention androgens or anabolic steroids.

Generic hydrochlorothiazide tablets are labeled as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy, as useful in edema from renal dysfunction, and for hypertension, alone or to enhance other antihypertensive drugs in more severe forms. The label does not mention androgens or anabolic steroids. The label version used here took effect on 1 July 2024.

openFDA Drugs@FDA lists single-ingredient generic hydrochlorothiazide (for example ANDA 040907, approved 15 August 2008) and many ARB plus hydrochlorothiazide combination products, among them losartan potassium and hydrochlorothiazide (for example ANDA 091629, approved 6 October 2010) and valsartan and hydrochlorothiazide (for example ANDA 203000, approved 15 March 2019). The original brand application was not among the records returned, so the first U.S. approval date is not established here. Approvals outside the United States are not covered.

Hydrochlorothiazide is C7H8ClN3O4S2 (297.7 g/mol, CAS 58-93-5, PubChem CID 3639).

Generic hydrochlorothiazide label, version effective 1 July 2024: indications, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Hydrochlorothiazide oral tablets (Teva generic label), prescribing information, label version effective 1 July 2024. Set ID e2270db4-2930-4ec5-ac96-2b4542aed367.

Generic hydrochlorothiazide tablets are labeled as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy, as useful in edema from renal dysfunction, and for hypertension, alone or to enhance other antihypertensive drugs in more severe forms. The label does not mention androgens or anabolic steroids, and it states that hydrochlorothiazide does not usually affect normal blood pressure. The drug is not metabolized, plasma half-life is 5.6 to 14.8 hours, and at least 61% of a dose is excreted unchanged within 24 hours. The label links higher doses to marked falls in serum potassium. It warns of fluid and electrolyte imbalance (hyponatremia, hypochloremic alkalosis, and hypokalemia, the last more likely with brisk diuresis, severe cirrhosis or prolonged therapy and able to cause arrhythmia), hypomagnesemia, hyperuricemia or gout, hyperglycemia that can unmask latent diabetes, and increases in cholesterol and triglycerides. It warns of acute myopia and secondary angle-closure glaucoma, says lithium generally should not be given with diuretics, and lists impotence among adverse reactions. Postmarketing, hydrochlorothiazide is associated with increased non-melanoma skin cancer risk: in a Sentinel System study the excess was mainly squamous cell carcinoma, about 1 additional case per 16,000 patients per year overall and 1 per 6,700 patients per year in white patients with a cumulative dose of 50,000 mg or more, and patients are told to protect their skin from the sun and get regular skin cancer screening.

Participants / model
Patients with the labeled edema states and hypertension; label PK participants; patients in postmarketing data
Treatment
Hydrochlorothiazide oral tablets (Teva generic label)
Follow-up
Label version effective 1 July 2024
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, and the label gives no magnitude for the cholesterol and triglyceride increases.

Read the original source
Drugs@FDA: generic hydrochlorothiazide from 2008 and ARB combinations in the records returned

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application records for hydrochlorothiazide, including ANDA 040907, with losartan potassium and hydrochlorothiazide (ANDA 091629) and valsartan and hydrochlorothiazide (ANDA 203000). Dates read from the openFDA Drugs@FDA records.

openFDA Drugs@FDA lists single-ingredient generic hydrochlorothiazide (for example ANDA 040907, approved 15 August 2008) and many ARB plus hydrochlorothiazide combination products, among them losartan potassium and hydrochlorothiazide (for example ANDA 091629, approved 6 October 2010) and valsartan and hydrochlorothiazide (for example ANDA 203000, approved 15 March 2019). The original brand application was not among the records returned, so the first U.S. approval date is not established here.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 2008 to 2019 in the records returned
Study design
FDA application records
Funding
not stated in the source

The ANDAs cited are examples, not confirmed first approvals. The first U.S. approval date is not established.

Read the original source
PubChem: hydrochlorothiazide identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 3639 (hydrochlorothiazide).

Hydrochlorothiazide: C7H8ClN3O4S2, 297.7 g/mol, CAS 58-93-5 (PubChem also lists 8049-49-8 and 125727-50-6 as CAS-like synonyms).

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 do the blood pressure and outcome trials show?

In the 13,523-patient Diuretic Comparison Project, cardiovascular outcomes on hydrochlorothiazide were no different from chlorthalidone. A meta-analysis found hydrochlorothiazide at 12.5 to 25 mg lowered 24-hour blood pressure less than other drug classes, and outcome data at those doses are lacking.

The Diuretic Comparison Project, a pragmatic Veterans Affairs trial, randomized 13,523 adults aged 65 or older who were already taking hydrochlorothiazide to continue it or switch to chlorthalidone (NCT02185417). At a median 2.4 years, the composite of nonfatal MI, stroke, heart failure hospitalization, urgent revascularization for unstable angina and non-cancer death occurred in 10.0% on hydrochlorothiazide versus 10.4% on chlorthalidone (HR 1.04, 95% CI 0.94 to 1.16). Hypokalemia occurred in 4.4% versus 6.0%.

A meta-analysis of randomized trials using 24-hour ambulatory monitoring (14 studies, 1,234 patients at 12.5 to 25 mg; 5 studies, 229 patients at 50 mg) found that hydrochlorothiazide 12.5 to 25 mg lowered 24-hour blood pressure by 6.5/4.5 mmHg, less than ACE inhibitors (12.9/7.7), ARBs (13.3/7.8), beta blockers (11.2/8.5) and calcium antagonists (11.0/8.1). At 50 mg the reduction (12.0/5.4 mmHg) was comparable to other agents. The authors describe hydrochlorothiazide as the most commonly prescribed antihypertensive worldwide and note that outcome data at 12.5 to 25 mg are lacking.

Both results come from people with hypertension, not from anabolic steroid users.

Diuretic Comparison Project: 13,523 veterans aged 65 or older, HR 1.04

Randomized controlled trial

Ishani A et al. N Engl J Med. 2022;387(26):2401-2410. PMID 36516076.

At a median 2.4 years, the composite of nonfatal MI, stroke, heart failure hospitalization, urgent revascularization for unstable angina and non-cancer death occurred in 10.0% on hydrochlorothiazide versus 10.4% on chlorthalidone (HR 1.04, 95% CI 0.94 to 1.16). Hypokalemia occurred in 4.4% on hydrochlorothiazide versus 6.0% on chlorthalidone.

Participants / model
13,523 adults aged 65 or older with hypertension in the Veterans Affairs health system, already taking hydrochlorothiazide
Treatment
Oral hydrochlorothiazide 25 or 50 mg daily (25 mg in 94.5%), continued or switched to chlorthalidone 12.5 or 25 mg daily
Follow-up
Median 2.4 years
Study design
Pragmatic randomized trial
Funding
not stated in the source

Compares hydrochlorothiazide with chlorthalidone in older veterans already taking it, not with placebo and not in anabolic steroid users.

Read the original source
24-hour blood pressure meta-analysis: 6.5/4.5 mmHg at 12.5 to 25 mg

Systematic review and meta-analysis

Messerli FH et al. J Am Coll Cardiol. 2011;57(5):590-600. PMID 21272751.

Hydrochlorothiazide 12.5 to 25 mg lowered 24-hour blood pressure by 6.5/4.5 mmHg, less than ACE inhibitors (12.9/7.7), ARBs (13.3/7.8), beta blockers (11.2/8.5) and calcium antagonists (11.0/8.1). At 50 mg the reduction (12.0/5.4 mmHg) was comparable to other agents. The authors describe hydrochlorothiazide as the most commonly prescribed antihypertensive worldwide and note that outcome data at 12.5 to 25 mg are lacking.

Participants / model
Patients with hypertension in head-to-head randomized trials: 14 studies with 1,234 patients at 12.5 to 25 mg and 5 studies with 229 patients at 50 mg
Treatment
Oral hydrochlorothiazide 12.5 to 50 mg daily
Follow-up
Pooled randomized trials using 24-hour ambulatory monitoring
Study design
Systematic review and meta-analysis
Funding
not stated in the source

Blood pressure lowering only; outcome data at 12.5 to 25 mg are lacking according to the authors.

Read the original source

Does hydrochlorothiazide treat water retention and high blood pressure from anabolic steroids?

No study tested it. A PubMed search on 9 October 2026 returned 14 records on hydrochlorothiazide or thiazides with anabolic steroid terms, and none tested hydrochlorothiazide for steroid-related blood pressure or water retention. The label covers edema with corticosteroid and estrogen therapy but does not mention androgens.

Sellers describe hydrochlorothiazide as treating steroid-induced water retention and hypertension, as blunter and less potassium-sparing than eplerenone, and as a useful add-on when blood pressure stays high despite an ARB and a beta blocker. The PubMed search covered hydrochlorothiazide or thiazides with anabolic steroid, bodybuilding, nandrolone, stanozolol and androgen abuse terms. The 14 records covered drug-induced diabetes, secondary hyperlipidemia, corticosteroid osteoporosis and NSAID reviews, a 1985 review of HDL-raising approaches, a report of six bodybuilders who used hydrochlorothiazide and ephedrine in cutting phases, a single case report of severe hypokalemia, doping-control analytical methods, and a 1964 pediatric rheumatology paper.

The blood pressure problem itself is documented. In a prospective cohort of 100 men performing a self-directed androgen cycle, systolic and diastolic blood pressure rose 6.87 mmHg (95% CI 4.34 to 9.40) and 3.17 mmHg (95% CI 1.29 to 5.04) during use and returned to baseline 3 months after the cycle, and hematocrit rose 0.03 L/L. 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 30 controls (132 versus 124 mmHg) and more systolic hypertension (51% versus 17%), with higher aldosterone and noradrenaline and lower MR-proANP than former users and controls. No antihypertensive or diuretic was tested in either study.

The label lists edema associated with corticosteroid and estrogen therapy and does not mention androgens or anabolic steroids. It also states that hydrochlorothiazide does not usually affect normal blood pressure.

PubMed search, 9 October 2026: 14 records, none testing hydrochlorothiazide for steroid-related blood pressure or water retention

PubMed search record

PubMed search run on 9 October 2026: (hydrochlorothiazide[tiab] OR thiazide*[tiab]) AND (anabolic steroid*[tiab] OR anabolic-androgenic[tiab] OR anabolic androgenic[tiab] OR bodybuild*[tiab] OR nandrolone[tiab] OR stanozolol[tiab] OR androgen abuse[tiab]). 14 records returned.

The search returned 14 records. None tested hydrochlorothiazide for blood pressure or water retention related to anabolic steroids. They covered drug-induced diabetes, secondary hyperlipidemia, corticosteroid osteoporosis and NSAID reviews, a 1985 review of HDL-raising approaches, a report of six bodybuilders who used hydrochlorothiazide and ephedrine in cutting phases, the case report above, doping-control analytical methods, and a 1964 pediatric rheumatology paper.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search 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.

Read the original source
Androgen cycle cohort: systolic pressure up 6.87 mmHg, back to baseline 3 months after

Human study

Smit DL et al. Andrologia. 2022;54(4):e14372. PMID 35014715.

Systolic and diastolic blood pressure rose 6.87 mmHg (95% CI 4.34 to 9.40) and 3.17 mmHg (95% CI 1.29 to 5.04) during use and returned to baseline 3 months after the cycle; hematocrit rose 0.03 L/L.

Participants / model
100 men performing a self-directed androgen cycle
Treatment
Self-administered androgens (observational); no antihypertensive or diuretic was tested
Follow-up
Cycle and 3 months after
Study design
Prospective cohort study
Funding
not stated in the source

Observational. It measures the blood pressure change the supplier claim targets, not any treatment for it.

Read the original source
100 strength-training men: higher 24-hour blood pressure in current steroid users

Human study

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

37 current anabolic steroid users had higher 24-hour systolic blood pressure than 30 controls (132 versus 124 mmHg) and more systolic hypertension (51% versus 17%), with higher aldosterone and noradrenaline and lower MR-proANP than former users and controls.

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

Observational. No treatment was tested.

Read the original source
Generic hydrochlorothiazide label, version effective 1 July 2024: indications, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Hydrochlorothiazide oral tablets (Teva generic label), prescribing information, label version effective 1 July 2024. Set ID e2270db4-2930-4ec5-ac96-2b4542aed367.

Generic hydrochlorothiazide tablets are labeled as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy, as useful in edema from renal dysfunction, and for hypertension, alone or to enhance other antihypertensive drugs in more severe forms. The label does not mention androgens or anabolic steroids, and it states that hydrochlorothiazide does not usually affect normal blood pressure. The drug is not metabolized, plasma half-life is 5.6 to 14.8 hours, and at least 61% of a dose is excreted unchanged within 24 hours. The label links higher doses to marked falls in serum potassium. It warns of fluid and electrolyte imbalance (hyponatremia, hypochloremic alkalosis, and hypokalemia, the last more likely with brisk diuresis, severe cirrhosis or prolonged therapy and able to cause arrhythmia), hypomagnesemia, hyperuricemia or gout, hyperglycemia that can unmask latent diabetes, and increases in cholesterol and triglycerides. It warns of acute myopia and secondary angle-closure glaucoma, says lithium generally should not be given with diuretics, and lists impotence among adverse reactions. Postmarketing, hydrochlorothiazide is associated with increased non-melanoma skin cancer risk: in a Sentinel System study the excess was mainly squamous cell carcinoma, about 1 additional case per 16,000 patients per year overall and 1 per 6,700 patients per year in white patients with a cumulative dose of 50,000 mg or more, and patients are told to protect their skin from the sun and get regular skin cancer screening.

Participants / model
Patients with the labeled edema states and hypertension; label PK participants; patients in postmarketing data
Treatment
Hydrochlorothiazide oral tablets (Teva generic label)
Follow-up
Label version effective 1 July 2024
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, and the label gives no magnitude for the cholesterol and triglyceride increases.

Read the original source

Is hydrochlorothiazide blunter or less potassium-sparing than eplerenone?

The only direct comparison found, in 16 adults with diabetes and albuminuria, gave similar blood pressure on eplerenone and on hydrochlorothiazide with potassium. Potassium was supplemented on hydrochlorothiazide, so that trial does not show the potassium difference. Hydrochlorothiazide lowers potassium rather than sparing it.

In a randomized double-blind crossover trial in 16 adults with diabetes and albuminuria taking enalapril plus amlodipine to reach a blood pressure below 130/80 mmHg, 6 weeks of eplerenone 50 mg and 6 weeks of hydrochlorothiazide 12.5 mg with potassium 10 mEq produced similar blood pressure, serum potassium, glycemia and endothelial function. Myocardial perfusion reserve was higher after eplerenone (median 1.57 versus 1.30). Among 7 records returned by a PubMed search on 9 October 2026 for eplerenone and hydrochlorothiazide in randomized trials, this was the only direct comparison.

Potassium was supplemented on hydrochlorothiazide, so the trial does not measure the potassium difference directly. The hydrochlorothiazide label warns of hypokalemia, more likely with brisk diuresis, severe cirrhosis or prolonged therapy and able to cause arrhythmia, and links higher doses to marked falls in serum potassium. In the Diuretic Comparison Project, hypokalemia occurred in 4.4% on hydrochlorothiazide versus 6.0% on chlorthalidone.

Eplerenone versus hydrochlorothiazide: 16 adults with diabetes, similar blood pressure

Randomized controlled trial

Joffe HV et al. J Clin Endocrinol Metab. 2007;92(7):2552-8. PMID 17488800.

Eplerenone and hydrochlorothiazide with potassium produced similar blood pressure, serum potassium, glycemia and endothelial function; myocardial perfusion reserve was higher after eplerenone (median 1.57 versus 1.30). Among 7 records returned by a PubMed search on 9 October 2026 for eplerenone and hydrochlorothiazide in randomized trials, this was the only direct comparison.

Participants / model
16 adults with diabetes and albuminuria, taking enalapril and amlodipine to reach a blood pressure below 130/80 mmHg
Treatment
Oral eplerenone 50 mg versus hydrochlorothiazide 12.5 mg plus potassium 10 mEq, each for 6 weeks
Follow-up
6 weeks per treatment
Study design
Randomized double-blind crossover trial
Funding
not stated in the source

Potassium was supplemented on hydrochlorothiazide, so the trial does not measure the potassium difference directly.

Read the original source
Generic hydrochlorothiazide label, version effective 1 July 2024: indications, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Hydrochlorothiazide oral tablets (Teva generic label), prescribing information, label version effective 1 July 2024. Set ID e2270db4-2930-4ec5-ac96-2b4542aed367.

Generic hydrochlorothiazide tablets are labeled as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy, as useful in edema from renal dysfunction, and for hypertension, alone or to enhance other antihypertensive drugs in more severe forms. The label does not mention androgens or anabolic steroids, and it states that hydrochlorothiazide does not usually affect normal blood pressure. The drug is not metabolized, plasma half-life is 5.6 to 14.8 hours, and at least 61% of a dose is excreted unchanged within 24 hours. The label links higher doses to marked falls in serum potassium. It warns of fluid and electrolyte imbalance (hyponatremia, hypochloremic alkalosis, and hypokalemia, the last more likely with brisk diuresis, severe cirrhosis or prolonged therapy and able to cause arrhythmia), hypomagnesemia, hyperuricemia or gout, hyperglycemia that can unmask latent diabetes, and increases in cholesterol and triglycerides. It warns of acute myopia and secondary angle-closure glaucoma, says lithium generally should not be given with diuretics, and lists impotence among adverse reactions. Postmarketing, hydrochlorothiazide is associated with increased non-melanoma skin cancer risk: in a Sentinel System study the excess was mainly squamous cell carcinoma, about 1 additional case per 16,000 patients per year overall and 1 per 6,700 patients per year in white patients with a cumulative dose of 50,000 mg or more, and patients are told to protect their skin from the sun and get regular skin cancer screening.

Participants / model
Patients with the labeled edema states and hypertension; label PK participants; patients in postmarketing data
Treatment
Hydrochlorothiazide oral tablets (Teva generic label)
Follow-up
Label version effective 1 July 2024
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, and the label gives no magnitude for the cholesterol and triglyceride increases.

Read the original source
Diuretic Comparison Project: 13,523 veterans aged 65 or older, HR 1.04

Randomized controlled trial

Ishani A et al. N Engl J Med. 2022;387(26):2401-2410. PMID 36516076.

At a median 2.4 years, the composite of nonfatal MI, stroke, heart failure hospitalization, urgent revascularization for unstable angina and non-cancer death occurred in 10.0% on hydrochlorothiazide versus 10.4% on chlorthalidone (HR 1.04, 95% CI 0.94 to 1.16). Hypokalemia occurred in 4.4% on hydrochlorothiazide versus 6.0% on chlorthalidone.

Participants / model
13,523 adults aged 65 or older with hypertension in the Veterans Affairs health system, already taking hydrochlorothiazide
Treatment
Oral hydrochlorothiazide 25 or 50 mg daily (25 mg in 94.5%), continued or switched to chlorthalidone 12.5 or 25 mg daily
Follow-up
Median 2.4 years
Study design
Pragmatic randomized trial
Funding
not stated in the source

Compares hydrochlorothiazide with chlorthalidone in older veterans already taking it, not with placebo and not in anabolic steroid users.

Read the original source

Does the resistant hypertension trial support hydrochlorothiazide as an add-on?

No. PATHWAY-2 tested spironolactone, bisoprolol and doxazosin as add-ons in 335 patients with drug-resistant hypertension, and it did not test hydrochlorothiazide. Spironolactone lowered home systolic blood pressure the most.

In PATHWAY-2, patients aged 18 to 79 with clinic systolic pressure of 140 mmHg or more (135 with diabetes) and home systolic pressure of 130 mmHg or more despite at least 3 months of three drugs at maximally tolerated doses rotated through 12 weeks each of spironolactone, bisoprolol, doxazosin modified release and placebo, added to their baseline drugs (335 randomized; NCT02369081).

Spironolactone lowered home systolic blood pressure more than placebo (-8.70 mmHg, 95% CI -9.72 to -7.69), more than the average of bisoprolol and doxazosin (-4.26 mmHg), and more than bisoprolol alone (-4.48 mmHg, 95% CI -5.50 to -3.46). Serum potassium exceeded 6.0 mmol/L on one occasion in 6 of 285 patients on spironolactone. The trial did not test hydrochlorothiazide as the added drug, so it says nothing about hydrochlorothiazide in this role.

PATHWAY-2: 335 patients, spironolactone lowered home systolic pressure most; hydrochlorothiazide not tested

Randomized controlled trial

Williams B et al. Lancet. 2015;386(10008):2059-2068. PMID 26414968.

Spironolactone lowered home systolic blood pressure more than placebo (-8.70 mmHg, 95% CI -9.72 to -7.69), more than the average of bisoprolol and doxazosin (-4.26 mmHg), and more than bisoprolol alone (-4.48 mmHg, 95% CI -5.50 to -3.46). Serum potassium exceeded 6.0 mmol/L on one occasion in 6 of 285 patients on spironolactone.

Participants / model
335 patients aged 18 to 79 with drug-resistant hypertension (clinic systolic pressure of 140 mmHg or more, 135 with diabetes, and home systolic pressure of 130 mmHg or more despite at least 3 months of three drugs at maximally tolerated doses)
Treatment
12-week periods of oral spironolactone, bisoprolol, doxazosin modified release or placebo, added to baseline drugs, in rotation
Follow-up
12 weeks per treatment
Study design
Randomized crossover trial
Funding
not stated in the source

The trial did not test hydrochlorothiazide as the added drug.

Read the original source

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

The label lists hydrochlorothiazide for edema and hypertension and states it does not usually affect normal blood pressure. The drug is not metabolized, plasma half-life is 5.6 to 14.8 hours, and at least 61% of a dose is excreted unchanged within 24 hours.

The sources reviewed describe hydrochlorothiazide as a diuretic used for edema and hypertension and give no further receptor or transporter detail. The label states that it does not usually affect normal blood pressure.

The drug is not metabolized. Plasma half-life is 5.6 to 14.8 hours, and at least 61% of a dose is excreted unchanged within 24 hours.

Generic hydrochlorothiazide label, version effective 1 July 2024: indications, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Hydrochlorothiazide oral tablets (Teva generic label), prescribing information, label version effective 1 July 2024. Set ID e2270db4-2930-4ec5-ac96-2b4542aed367.

Generic hydrochlorothiazide tablets are labeled as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy, as useful in edema from renal dysfunction, and for hypertension, alone or to enhance other antihypertensive drugs in more severe forms. The label does not mention androgens or anabolic steroids, and it states that hydrochlorothiazide does not usually affect normal blood pressure. The drug is not metabolized, plasma half-life is 5.6 to 14.8 hours, and at least 61% of a dose is excreted unchanged within 24 hours. The label links higher doses to marked falls in serum potassium. It warns of fluid and electrolyte imbalance (hyponatremia, hypochloremic alkalosis, and hypokalemia, the last more likely with brisk diuresis, severe cirrhosis or prolonged therapy and able to cause arrhythmia), hypomagnesemia, hyperuricemia or gout, hyperglycemia that can unmask latent diabetes, and increases in cholesterol and triglycerides. It warns of acute myopia and secondary angle-closure glaucoma, says lithium generally should not be given with diuretics, and lists impotence among adverse reactions. Postmarketing, hydrochlorothiazide is associated with increased non-melanoma skin cancer risk: in a Sentinel System study the excess was mainly squamous cell carcinoma, about 1 additional case per 16,000 patients per year overall and 1 per 6,700 patients per year in white patients with a cumulative dose of 50,000 mg or more, and patients are told to protect their skin from the sun and get regular skin cancer screening.

Participants / model
Patients with the labeled edema states and hypertension; label PK participants; patients in postmarketing data
Treatment
Hydrochlorothiazide oral tablets (Teva generic label)
Follow-up
Label version effective 1 July 2024
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, and the label gives no magnitude for the cholesterol and triglyceride increases.

Read the original source

What risks does the label report?

The label warns of fluid and electrolyte imbalance, especially hypokalemia, plus hypomagnesemia, gout, hyperglycemia, raised cholesterol and triglycerides, acute myopia and angle-closure glaucoma. Postmarketing data link it to non-melanoma skin cancer, and a bodybuilder case report shows severe hypokalemia with diuretic misuse.

The label warns of fluid and electrolyte imbalance: hyponatremia, hypochloremic alkalosis and hypokalemia, the last more likely with brisk diuresis, severe cirrhosis or prolonged therapy and able to cause arrhythmia. It also warns of hypomagnesemia, hyperuricemia or gout, hyperglycemia that can unmask latent diabetes, and increases in cholesterol and triglycerides; the label gives no magnitude for the lipid changes. It warns of acute myopia and secondary angle-closure glaucoma, says lithium generally should not be given with diuretics, and lists impotence among adverse reactions.

Postmarketing, hydrochlorothiazide is associated with increased non-melanoma skin cancer risk. In a Sentinel System study the excess was mainly squamous cell carcinoma, about 1 additional case per 16,000 patients per year overall and 1 per 6,700 patients per year in white patients with a cumulative dose of 50,000 mg or more. Patients are told to protect their skin from the sun and get regular skin cancer screening.

A 22-year-old bodybuilder who misused triamterene and hydrochlorothiazide together with fluid restriction developed generalized cramps, sensory disturbance, quadriparesis and urinary retention, with serum potassium of 1.8 mmol/L and a corrected QT of 625 ms. He recovered within 2 days of intravenous fluids and potassium. This is a single case report, and the authors warn about self-medication with diuretics and anabolic steroids in bodybuilding.

Sport anti-doping rules for diuretics are not covered here, and no study of hydrochlorothiazide in anabolic steroid users was found.

Generic hydrochlorothiazide label, version effective 1 July 2024: indications, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Hydrochlorothiazide oral tablets (Teva generic label), prescribing information, label version effective 1 July 2024. Set ID e2270db4-2930-4ec5-ac96-2b4542aed367.

Generic hydrochlorothiazide tablets are labeled as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy, as useful in edema from renal dysfunction, and for hypertension, alone or to enhance other antihypertensive drugs in more severe forms. The label does not mention androgens or anabolic steroids, and it states that hydrochlorothiazide does not usually affect normal blood pressure. The drug is not metabolized, plasma half-life is 5.6 to 14.8 hours, and at least 61% of a dose is excreted unchanged within 24 hours. The label links higher doses to marked falls in serum potassium. It warns of fluid and electrolyte imbalance (hyponatremia, hypochloremic alkalosis, and hypokalemia, the last more likely with brisk diuresis, severe cirrhosis or prolonged therapy and able to cause arrhythmia), hypomagnesemia, hyperuricemia or gout, hyperglycemia that can unmask latent diabetes, and increases in cholesterol and triglycerides. It warns of acute myopia and secondary angle-closure glaucoma, says lithium generally should not be given with diuretics, and lists impotence among adverse reactions. Postmarketing, hydrochlorothiazide is associated with increased non-melanoma skin cancer risk: in a Sentinel System study the excess was mainly squamous cell carcinoma, about 1 additional case per 16,000 patients per year overall and 1 per 6,700 patients per year in white patients with a cumulative dose of 50,000 mg or more, and patients are told to protect their skin from the sun and get regular skin cancer screening.

Participants / model
Patients with the labeled edema states and hypertension; label PK participants; patients in postmarketing data
Treatment
Hydrochlorothiazide oral tablets (Teva generic label)
Follow-up
Label version effective 1 July 2024
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, and the label gives no magnitude for the cholesterol and triglyceride increases.

Read the original source
Case report: bodybuilder, potassium 1.8 mmol/L, corrected QT 625 ms

Case report

Pfisterer N et al. Clin J Sport Med. 2020;30(5):e172-e174. PMID 31770156.

A 22-year-old bodybuilder who misused triamterene and hydrochlorothiazide together with fluid restriction developed generalized cramps, sensory disturbance, quadriparesis and urinary retention, with serum potassium of 1.8 mmol/L and a corrected QT of 625 ms. He recovered within 2 days of intravenous fluids and potassium. The authors warn about self-medication with diuretics and anabolic steroids in bodybuilding.

Participants / model
One 22-year-old bodybuilder
Treatment
Self-administered oral triamterene and hydrochlorothiazide
Follow-up
Single presentation; recovery within 2 days
Study design
Case report
Funding
not stated in the source

A single case; it shows a possible hypokalemia harm, not how common it is.

Read the original source

Why does hydrochlorothiazide sit in S tier?

A long-established approved antihypertensive, widely prescribed, with a 13,523-patient trial showing outcomes no different from chlorthalidone, supports the S for the approved uses. The grade carries caveats and does not cover the supplier's steroid claims, which are largely unsupported.

The S applies to edema and hypertension as labeled. It carries two caveats: at 12.5 to 25 mg the 24-hour blood pressure effect is weaker than other drug classes and outcome data at those doses are lacking, and the label carries a non-melanoma skin cancer signal.

The supplier claim is largely unsupported. Hydrochlorothiazide lowers potassium rather than sparing it. The label covers edema with estrogen and corticosteroid therapy but not androgens. The only direct eplerenone comparison found gave similar blood pressure. PATHWAY-2 found spironolactone, not bisoprolol, the most effective add-on in resistant hypertension and did not test hydrochlorothiazide. No study tested hydrochlorothiazide in steroid users, where a bodybuilder case shows the hypokalemia hazard.

Generic hydrochlorothiazide label, version effective 1 July 2024: indications, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Hydrochlorothiazide oral tablets (Teva generic label), prescribing information, label version effective 1 July 2024. Set ID e2270db4-2930-4ec5-ac96-2b4542aed367.

Generic hydrochlorothiazide tablets are labeled as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy, as useful in edema from renal dysfunction, and for hypertension, alone or to enhance other antihypertensive drugs in more severe forms. The label does not mention androgens or anabolic steroids, and it states that hydrochlorothiazide does not usually affect normal blood pressure. The drug is not metabolized, plasma half-life is 5.6 to 14.8 hours, and at least 61% of a dose is excreted unchanged within 24 hours. The label links higher doses to marked falls in serum potassium. It warns of fluid and electrolyte imbalance (hyponatremia, hypochloremic alkalosis, and hypokalemia, the last more likely with brisk diuresis, severe cirrhosis or prolonged therapy and able to cause arrhythmia), hypomagnesemia, hyperuricemia or gout, hyperglycemia that can unmask latent diabetes, and increases in cholesterol and triglycerides. It warns of acute myopia and secondary angle-closure glaucoma, says lithium generally should not be given with diuretics, and lists impotence among adverse reactions. Postmarketing, hydrochlorothiazide is associated with increased non-melanoma skin cancer risk: in a Sentinel System study the excess was mainly squamous cell carcinoma, about 1 additional case per 16,000 patients per year overall and 1 per 6,700 patients per year in white patients with a cumulative dose of 50,000 mg or more, and patients are told to protect their skin from the sun and get regular skin cancer screening.

Participants / model
Patients with the labeled edema states and hypertension; label PK participants; patients in postmarketing data
Treatment
Hydrochlorothiazide oral tablets (Teva generic label)
Follow-up
Label version effective 1 July 2024
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, and the label gives no magnitude for the cholesterol and triglyceride increases.

Read the original source
Drugs@FDA: generic hydrochlorothiazide from 2008 and ARB combinations in the records returned

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application records for hydrochlorothiazide, including ANDA 040907, with losartan potassium and hydrochlorothiazide (ANDA 091629) and valsartan and hydrochlorothiazide (ANDA 203000). Dates read from the openFDA Drugs@FDA records.

openFDA Drugs@FDA lists single-ingredient generic hydrochlorothiazide (for example ANDA 040907, approved 15 August 2008) and many ARB plus hydrochlorothiazide combination products, among them losartan potassium and hydrochlorothiazide (for example ANDA 091629, approved 6 October 2010) and valsartan and hydrochlorothiazide (for example ANDA 203000, approved 15 March 2019). The original brand application was not among the records returned, so the first U.S. approval date is not established here.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 2008 to 2019 in the records returned
Study design
FDA application records
Funding
not stated in the source

The ANDAs cited are examples, not confirmed first approvals. The first U.S. approval date is not established.

Read the original source
Diuretic Comparison Project: 13,523 veterans aged 65 or older, HR 1.04

Randomized controlled trial

Ishani A et al. N Engl J Med. 2022;387(26):2401-2410. PMID 36516076.

At a median 2.4 years, the composite of nonfatal MI, stroke, heart failure hospitalization, urgent revascularization for unstable angina and non-cancer death occurred in 10.0% on hydrochlorothiazide versus 10.4% on chlorthalidone (HR 1.04, 95% CI 0.94 to 1.16). Hypokalemia occurred in 4.4% on hydrochlorothiazide versus 6.0% on chlorthalidone.

Participants / model
13,523 adults aged 65 or older with hypertension in the Veterans Affairs health system, already taking hydrochlorothiazide
Treatment
Oral hydrochlorothiazide 25 or 50 mg daily (25 mg in 94.5%), continued or switched to chlorthalidone 12.5 or 25 mg daily
Follow-up
Median 2.4 years
Study design
Pragmatic randomized trial
Funding
not stated in the source

Compares hydrochlorothiazide with chlorthalidone in older veterans already taking it, not with placebo and not in anabolic steroid users.

Read the original source
24-hour blood pressure meta-analysis: 6.5/4.5 mmHg at 12.5 to 25 mg

Systematic review and meta-analysis

Messerli FH et al. J Am Coll Cardiol. 2011;57(5):590-600. PMID 21272751.

Hydrochlorothiazide 12.5 to 25 mg lowered 24-hour blood pressure by 6.5/4.5 mmHg, less than ACE inhibitors (12.9/7.7), ARBs (13.3/7.8), beta blockers (11.2/8.5) and calcium antagonists (11.0/8.1). At 50 mg the reduction (12.0/5.4 mmHg) was comparable to other agents. The authors describe hydrochlorothiazide as the most commonly prescribed antihypertensive worldwide and note that outcome data at 12.5 to 25 mg are lacking.

Participants / model
Patients with hypertension in head-to-head randomized trials: 14 studies with 1,234 patients at 12.5 to 25 mg and 5 studies with 229 patients at 50 mg
Treatment
Oral hydrochlorothiazide 12.5 to 50 mg daily
Follow-up
Pooled randomized trials using 24-hour ambulatory monitoring
Study design
Systematic review and meta-analysis
Funding
not stated in the source

Blood pressure lowering only; outcome data at 12.5 to 25 mg are lacking according to the authors.

Read the original source
Eplerenone versus hydrochlorothiazide: 16 adults with diabetes, similar blood pressure

Randomized controlled trial

Joffe HV et al. J Clin Endocrinol Metab. 2007;92(7):2552-8. PMID 17488800.

Eplerenone and hydrochlorothiazide with potassium produced similar blood pressure, serum potassium, glycemia and endothelial function; myocardial perfusion reserve was higher after eplerenone (median 1.57 versus 1.30). Among 7 records returned by a PubMed search on 9 October 2026 for eplerenone and hydrochlorothiazide in randomized trials, this was the only direct comparison.

Participants / model
16 adults with diabetes and albuminuria, taking enalapril and amlodipine to reach a blood pressure below 130/80 mmHg
Treatment
Oral eplerenone 50 mg versus hydrochlorothiazide 12.5 mg plus potassium 10 mEq, each for 6 weeks
Follow-up
6 weeks per treatment
Study design
Randomized double-blind crossover trial
Funding
not stated in the source

Potassium was supplemented on hydrochlorothiazide, so the trial does not measure the potassium difference directly.

Read the original source
PATHWAY-2: 335 patients, spironolactone lowered home systolic pressure most; hydrochlorothiazide not tested

Randomized controlled trial

Williams B et al. Lancet. 2015;386(10008):2059-2068. PMID 26414968.

Spironolactone lowered home systolic blood pressure more than placebo (-8.70 mmHg, 95% CI -9.72 to -7.69), more than the average of bisoprolol and doxazosin (-4.26 mmHg), and more than bisoprolol alone (-4.48 mmHg, 95% CI -5.50 to -3.46). Serum potassium exceeded 6.0 mmol/L on one occasion in 6 of 285 patients on spironolactone.

Participants / model
335 patients aged 18 to 79 with drug-resistant hypertension (clinic systolic pressure of 140 mmHg or more, 135 with diabetes, and home systolic pressure of 130 mmHg or more despite at least 3 months of three drugs at maximally tolerated doses)
Treatment
12-week periods of oral spironolactone, bisoprolol, doxazosin modified release or placebo, added to baseline drugs, in rotation
Follow-up
12 weeks per treatment
Study design
Randomized crossover trial
Funding
not stated in the source

The trial did not test hydrochlorothiazide as the added drug.

Read the original source
Case report: bodybuilder, potassium 1.8 mmol/L, corrected QT 625 ms

Case report

Pfisterer N et al. Clin J Sport Med. 2020;30(5):e172-e174. PMID 31770156.

A 22-year-old bodybuilder who misused triamterene and hydrochlorothiazide together with fluid restriction developed generalized cramps, sensory disturbance, quadriparesis and urinary retention, with serum potassium of 1.8 mmol/L and a corrected QT of 625 ms. He recovered within 2 days of intravenous fluids and potassium. The authors warn about self-medication with diuretics and anabolic steroids in bodybuilding.

Participants / model
One 22-year-old bodybuilder
Treatment
Self-administered oral triamterene and hydrochlorothiazide
Follow-up
Single presentation; recovery within 2 days
Study design
Case report
Funding
not stated in the source

A single case; it shows a possible hypokalemia harm, not how common it is.

Read the original source
PubMed search, 9 October 2026: 14 records, none testing hydrochlorothiazide for steroid-related blood pressure or water retention

PubMed search record

PubMed search run on 9 October 2026: (hydrochlorothiazide[tiab] OR thiazide*[tiab]) AND (anabolic steroid*[tiab] OR anabolic-androgenic[tiab] OR anabolic androgenic[tiab] OR bodybuild*[tiab] OR nandrolone[tiab] OR stanozolol[tiab] OR androgen abuse[tiab]). 14 records returned.

The search returned 14 records. None tested hydrochlorothiazide for blood pressure or water retention related to anabolic steroids. They covered drug-induced diabetes, secondary hyperlipidemia, corticosteroid osteoporosis and NSAID reviews, a 1985 review of HDL-raising approaches, a report of six bodybuilders who used hydrochlorothiazide and ephedrine in cutting phases, the case report above, doping-control analytical methods, and a 1964 pediatric rheumatology paper.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search 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.

Read the original source

Studies and sources

Generic hydrochlorothiazide label, version effective 1 July 2024: indications, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Hydrochlorothiazide oral tablets (Teva generic label), prescribing information, label version effective 1 July 2024. Set ID e2270db4-2930-4ec5-ac96-2b4542aed367.

Generic hydrochlorothiazide tablets are labeled as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy, as useful in edema from renal dysfunction, and for hypertension, alone or to enhance other antihypertensive drugs in more severe forms. The label does not mention androgens or anabolic steroids, and it states that hydrochlorothiazide does not usually affect normal blood pressure. The drug is not metabolized, plasma half-life is 5.6 to 14.8 hours, and at least 61% of a dose is excreted unchanged within 24 hours. The label links higher doses to marked falls in serum potassium. It warns of fluid and electrolyte imbalance (hyponatremia, hypochloremic alkalosis, and hypokalemia, the last more likely with brisk diuresis, severe cirrhosis or prolonged therapy and able to cause arrhythmia), hypomagnesemia, hyperuricemia or gout, hyperglycemia that can unmask latent diabetes, and increases in cholesterol and triglycerides. It warns of acute myopia and secondary angle-closure glaucoma, says lithium generally should not be given with diuretics, and lists impotence among adverse reactions. Postmarketing, hydrochlorothiazide is associated with increased non-melanoma skin cancer risk: in a Sentinel System study the excess was mainly squamous cell carcinoma, about 1 additional case per 16,000 patients per year overall and 1 per 6,700 patients per year in white patients with a cumulative dose of 50,000 mg or more, and patients are told to protect their skin from the sun and get regular skin cancer screening.

Participants / model
Patients with the labeled edema states and hypertension; label PK participants; patients in postmarketing data
Treatment
Hydrochlorothiazide oral tablets (Teva generic label)
Follow-up
Label version effective 1 July 2024
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing, and the label gives no magnitude for the cholesterol and triglyceride increases.

Read the original source
Drugs@FDA: generic hydrochlorothiazide from 2008 and ARB combinations in the records returned

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application records for hydrochlorothiazide, including ANDA 040907, with losartan potassium and hydrochlorothiazide (ANDA 091629) and valsartan and hydrochlorothiazide (ANDA 203000). Dates read from the openFDA Drugs@FDA records.

openFDA Drugs@FDA lists single-ingredient generic hydrochlorothiazide (for example ANDA 040907, approved 15 August 2008) and many ARB plus hydrochlorothiazide combination products, among them losartan potassium and hydrochlorothiazide (for example ANDA 091629, approved 6 October 2010) and valsartan and hydrochlorothiazide (for example ANDA 203000, approved 15 March 2019). The original brand application was not among the records returned, so the first U.S. approval date is not established here.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 2008 to 2019 in the records returned
Study design
FDA application records
Funding
not stated in the source

The ANDAs cited are examples, not confirmed first approvals. The first U.S. approval date is not established.

Read the original source
Diuretic Comparison Project: 13,523 veterans aged 65 or older, HR 1.04

Randomized controlled trial

Ishani A et al. N Engl J Med. 2022;387(26):2401-2410. PMID 36516076.

At a median 2.4 years, the composite of nonfatal MI, stroke, heart failure hospitalization, urgent revascularization for unstable angina and non-cancer death occurred in 10.0% on hydrochlorothiazide versus 10.4% on chlorthalidone (HR 1.04, 95% CI 0.94 to 1.16). Hypokalemia occurred in 4.4% on hydrochlorothiazide versus 6.0% on chlorthalidone.

Participants / model
13,523 adults aged 65 or older with hypertension in the Veterans Affairs health system, already taking hydrochlorothiazide
Treatment
Oral hydrochlorothiazide 25 or 50 mg daily (25 mg in 94.5%), continued or switched to chlorthalidone 12.5 or 25 mg daily
Follow-up
Median 2.4 years
Study design
Pragmatic randomized trial
Funding
not stated in the source

Compares hydrochlorothiazide with chlorthalidone in older veterans already taking it, not with placebo and not in anabolic steroid users.

Read the original source
24-hour blood pressure meta-analysis: 6.5/4.5 mmHg at 12.5 to 25 mg

Systematic review and meta-analysis

Messerli FH et al. J Am Coll Cardiol. 2011;57(5):590-600. PMID 21272751.

Hydrochlorothiazide 12.5 to 25 mg lowered 24-hour blood pressure by 6.5/4.5 mmHg, less than ACE inhibitors (12.9/7.7), ARBs (13.3/7.8), beta blockers (11.2/8.5) and calcium antagonists (11.0/8.1). At 50 mg the reduction (12.0/5.4 mmHg) was comparable to other agents. The authors describe hydrochlorothiazide as the most commonly prescribed antihypertensive worldwide and note that outcome data at 12.5 to 25 mg are lacking.

Participants / model
Patients with hypertension in head-to-head randomized trials: 14 studies with 1,234 patients at 12.5 to 25 mg and 5 studies with 229 patients at 50 mg
Treatment
Oral hydrochlorothiazide 12.5 to 50 mg daily
Follow-up
Pooled randomized trials using 24-hour ambulatory monitoring
Study design
Systematic review and meta-analysis
Funding
not stated in the source

Blood pressure lowering only; outcome data at 12.5 to 25 mg are lacking according to the authors.

Read the original source
PATHWAY-2: 335 patients, spironolactone lowered home systolic pressure most; hydrochlorothiazide not tested

Randomized controlled trial

Williams B et al. Lancet. 2015;386(10008):2059-2068. PMID 26414968.

Spironolactone lowered home systolic blood pressure more than placebo (-8.70 mmHg, 95% CI -9.72 to -7.69), more than the average of bisoprolol and doxazosin (-4.26 mmHg), and more than bisoprolol alone (-4.48 mmHg, 95% CI -5.50 to -3.46). Serum potassium exceeded 6.0 mmol/L on one occasion in 6 of 285 patients on spironolactone.

Participants / model
335 patients aged 18 to 79 with drug-resistant hypertension (clinic systolic pressure of 140 mmHg or more, 135 with diabetes, and home systolic pressure of 130 mmHg or more despite at least 3 months of three drugs at maximally tolerated doses)
Treatment
12-week periods of oral spironolactone, bisoprolol, doxazosin modified release or placebo, added to baseline drugs, in rotation
Follow-up
12 weeks per treatment
Study design
Randomized crossover trial
Funding
not stated in the source

The trial did not test hydrochlorothiazide as the added drug.

Read the original source
Eplerenone versus hydrochlorothiazide: 16 adults with diabetes, similar blood pressure

Randomized controlled trial

Joffe HV et al. J Clin Endocrinol Metab. 2007;92(7):2552-8. PMID 17488800.

Eplerenone and hydrochlorothiazide with potassium produced similar blood pressure, serum potassium, glycemia and endothelial function; myocardial perfusion reserve was higher after eplerenone (median 1.57 versus 1.30). Among 7 records returned by a PubMed search on 9 October 2026 for eplerenone and hydrochlorothiazide in randomized trials, this was the only direct comparison.

Participants / model
16 adults with diabetes and albuminuria, taking enalapril and amlodipine to reach a blood pressure below 130/80 mmHg
Treatment
Oral eplerenone 50 mg versus hydrochlorothiazide 12.5 mg plus potassium 10 mEq, each for 6 weeks
Follow-up
6 weeks per treatment
Study design
Randomized double-blind crossover trial
Funding
not stated in the source

Potassium was supplemented on hydrochlorothiazide, so the trial does not measure the potassium difference directly.

Read the original source
Androgen cycle cohort: systolic pressure up 6.87 mmHg, back to baseline 3 months after

Human study

Smit DL et al. Andrologia. 2022;54(4):e14372. PMID 35014715.

Systolic and diastolic blood pressure rose 6.87 mmHg (95% CI 4.34 to 9.40) and 3.17 mmHg (95% CI 1.29 to 5.04) during use and returned to baseline 3 months after the cycle; hematocrit rose 0.03 L/L.

Participants / model
100 men performing a self-directed androgen cycle
Treatment
Self-administered androgens (observational); no antihypertensive or diuretic was tested
Follow-up
Cycle and 3 months after
Study design
Prospective cohort study
Funding
not stated in the source

Observational. It measures the blood pressure change the supplier claim targets, not any treatment for it.

Read the original source
100 strength-training men: higher 24-hour blood pressure in current steroid users

Human study

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

37 current anabolic steroid users had higher 24-hour systolic blood pressure than 30 controls (132 versus 124 mmHg) and more systolic hypertension (51% versus 17%), with higher aldosterone and noradrenaline and lower MR-proANP than former users and controls.

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

Observational. No treatment was tested.

Read the original source
Case report: bodybuilder, potassium 1.8 mmol/L, corrected QT 625 ms

Case report

Pfisterer N et al. Clin J Sport Med. 2020;30(5):e172-e174. PMID 31770156.

A 22-year-old bodybuilder who misused triamterene and hydrochlorothiazide together with fluid restriction developed generalized cramps, sensory disturbance, quadriparesis and urinary retention, with serum potassium of 1.8 mmol/L and a corrected QT of 625 ms. He recovered within 2 days of intravenous fluids and potassium. The authors warn about self-medication with diuretics and anabolic steroids in bodybuilding.

Participants / model
One 22-year-old bodybuilder
Treatment
Self-administered oral triamterene and hydrochlorothiazide
Follow-up
Single presentation; recovery within 2 days
Study design
Case report
Funding
not stated in the source

A single case; it shows a possible hypokalemia harm, not how common it is.

Read the original source
PubChem: hydrochlorothiazide identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 3639 (hydrochlorothiazide).

Hydrochlorothiazide: C7H8ClN3O4S2, 297.7 g/mol, CAS 58-93-5 (PubChem also lists 8049-49-8 and 125727-50-6 as CAS-like synonyms).

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 Hydrochlorothiazide in S tier?

S fits a long-established approved medicine, widely prescribed for hypertension and edema, with a 13,523-patient trial showing cardiovascular outcomes no different from chlorthalidone. The grade carries caveats: at 12.5 to 25 mg its blood pressure effect is weaker than other classes, outcome data at those doses are lacking, and the label carries a non-melanoma skin cancer signal. It does not extend to the supplier's steroid claims.