Is Spironolactone (potassium-sparing diuretic) safe to use during pregnancy, especially in a patient with a history of heart failure or fluid retention?

Spironolactone Should Be Avoided During Pregnancy

Spironolactone should not be given during pregnancy due to risk of antiandrogenic effects on male fetal development, particularly feminization of male genitalia during the first trimester. 1, 2

Evidence-Based Contraindication

FDA Classification and Mechanism of Harm

• The FDA classifies spironolactone as Pregnancy Category C and explicitly states it should be avoided in pregnant women or the pregnant woman should be advised of potential risk to a male fetus 2
• Animal studies demonstrate feminization of male fetuses when exposed to spironolactone during embryogenesis, with dose-dependent decreases in male reproductive organ weights and persistent endocrine dysfunction 2
• The critical mechanism involves spironolactone competing with dihydrotestosterone for androgen receptor binding and inhibiting enzymes in androgen biosynthesis, disrupting normal male sexual differentiation during the first 6-8 weeks of pregnancy 3, 4

Guideline Consensus

• The European Society of Cardiology explicitly recommends that aldosterone antagonists should be avoided during pregnancy, specifically noting spironolactone can be associated with antiandrogenic effects in the first trimester 1
• All major cardiology societies agree that spironolactone and other mineralocorticoid receptor antagonists should be avoided due to these antiandrogenic risks 3

Limited Human Data Shows Concerning Pattern

While human data remains scarce, the available evidence supports caution:

• Of 6 reported cases of spironolactone exposure during pregnancy, 5 resulted in normal male genital development, but 1 case presented with ambiguous genitalia in a newborn whose mother received spironolactone until week 5 of gestation 3
• A recent 2024 case report described accidental exposure to high-dose spironolactone (240 mg/day) at 16 weeks gestation for 1 week, resulting in a healthy male infant with normal genitalia, but this single case does not establish safety 4

The risk-benefit calculation clearly favors avoidance given the availability of safer alternatives and the irreversible nature of potential genital abnormalities. 3, 2

Safe Alternatives for Heart Failure During Pregnancy

First-Line Alternatives

• Hydralazine and long-acting nitrates can be used instead of ACE inhibitors/ARBs/aldosterone antagonists for afterload reduction in heart failure 1, 3
• Beta-1 selective beta-blockers (metoprolol) are indicated for all heart failure patients if tolerated; atenolol should specifically be avoided 1
• Furosemide and hydrochlorothiazide are the most frequently used diuretics when pulmonary congestion is present, though they should only be used when necessary as they may decrease placental blood flow 1

Inotropic Support When Needed

• Dopamine and levosimendan can be used if inotropic drugs are required 1

Critical Pre-Conception Planning

For Women of Childbearing Age Currently on Spironolactone

• All women of childbearing age taking spironolactone must receive counseling about pregnancy avoidance and use reliable contraception 3
• Spironolactone should be discontinued before attempting pregnancy, with transition to pregnancy-safe alternatives like hydralazine, nitrates, and beta-1 selective beta-blockers 3
• For women with severe heart failure where discontinuation poses significant maternal risk, pregnancy should be carefully planned with cardiology consultation and alternative agents maximized 3

Contraception Requirements

• Concomitant use of oral contraceptives or hormonal IUD is frequently recommended while on spironolactone 3
• Baseline pregnancy testing is mandatory before initiating spironolactone 3

Special Circumstance: Accidental Exposure

If spironolactone exposure occurs during pregnancy:

• Immediate discontinuation is essential 3
• Detailed fetal ultrasound assessment of genital development should be performed, particularly if exposure occurred during the first trimester 4
• The risk appears highest during the first 6-8 weeks when male sexual differentiation occurs 3
• Exposure after the first trimester may carry lower risk, but data is extremely limited 4

Emerging Alternatives Under Investigation

Newer-generation mineralocorticoid receptor antagonists (like eplerenone) have higher selectivity for the mineralocorticoid receptor with reduced antiandrogenic effects, but data for use during pregnancy remains lacking and these agents cannot currently be recommended 1, 5