What are the recommendations for using spironolactone (aldosterone antagonist) during pregnancy?

Spironolactone Use During Pregnancy

Spironolactone is contraindicated during pregnancy due to its potential to cause feminization of male fetuses and should be avoided in pregnant women or those planning pregnancy. 1

Mechanism of Risk

Spironolactone poses specific risks during pregnancy due to its anti-androgenic properties:

• Acts as an aldosterone receptor antagonist with potent anti-androgenic activity 2
• Can affect sex differentiation of male fetuses during embryogenesis 1
• Animal studies have shown feminization of male fetuses when administered during late embryogenesis 1
• May cause endocrine dysfunction in female fetuses 1

Evidence Base

The FDA drug label clearly states the risks:

• Pregnancy Category C classification 2
• Animal studies show feminization of male fetuses when administered at 200 mg/kg/day between gestation days 13-21 1
• Offspring exposed during late pregnancy showed changes in reproductive tract development and endocrine dysfunction that persisted into adulthood 1

Human data are limited but concerning:

• One case report described a pregnant woman accidentally exposed to spironolactone (240 mg/day) at 16 weeks gestation for one week, with no adverse effects on the male infant 3
• However, this single case does not outweigh the established risks from animal studies and theoretical concerns

Alternative Treatments During Pregnancy

For women requiring aldosterone antagonist therapy during pregnancy:

For Hypertension/Heart Failure:

• ACE inhibitors, ARBs, direct renin inhibitors, and spironolactone are all contraindicated during pregnancy 2
• Hydralazine and long-acting nitrates can be used safely instead of ACE inhibitors/ARBs 2
• β-1-selective blockers are preferred as they have not shown teratogenic effects 2
• Diuretics should be used sparingly (furosemide and hydrochlorothiazide are most frequently used) 2

For Primary Aldosteronism:

• Eplerenone (FDA pregnancy category B) may be considered as it lacks anti-androgenic effects 4, 5
• However, data on eplerenone in pregnancy remains limited 6, 4
• For unilateral adrenal adenomas causing primary aldosteronism, laparoscopic adrenalectomy can be considered in the second trimester if medical therapy fails 4, 5

For Acne/Hirsutism:

• Women should discontinue spironolactone before attempting pregnancy 7
• Alternative treatments should be considered for women with acne who are pregnant or planning pregnancy

Recommendations for Clinical Practice

1. Screen for pregnancy before initiating spironolactone therapy in women of childbearing potential 7
2. Advise effective contraception for women taking spironolactone 2
3. Discontinue spironolactone when pregnancy is detected or planned 1
4. Switch to pregnancy-safe alternatives when treating conditions that would otherwise warrant spironolactone 2
5. Consider the risk-benefit ratio carefully in cases where no suitable alternative exists, and inform the patient of potential risks to male fetuses 1

Special Considerations

• Breastfeeding: Limited data suggest spironolactone metabolites appear in breast milk in clinically inconsequential amounts 1
• Women with heart failure, cirrhosis, or poorly controlled hypertension during pregnancy have additional risks that must be managed appropriately 1
• For women with primary aldosteronism planning pregnancy, adrenalectomy should ideally be performed prior to conception if they have a unilateral form 4

The evidence clearly demonstrates that the risks of spironolactone use during pregnancy outweigh potential benefits in most clinical scenarios, and alternative treatments should be utilized.