Spironolactone for PCOS
Primary Recommendation
Spironolactone (100-200 mg daily) combined with oral contraceptive pills is the recommended treatment for hirsutism and acne in women with PCOS who are not attempting to conceive, providing superior antiandrogen effects compared to monotherapy while preventing pregnancy and regulating menstrual cycles. 1
Clinical Algorithm for Spironolactone Use in PCOS
When to Use Spironolactone
Start spironolactone when:
- Hirsutism or acne are primary concerns requiring antiandrogen therapy 1
- Patient is not attempting to conceive (absolute requirement) 1, 2
- Patient has failed or cannot tolerate topical treatments for acne 3
- Combined hormonal and antiandrogen therapy is needed 1
Do NOT use spironolactone when:
- Patient is attempting to conceive—use clomiphene citrate instead 1, 2
- Patient is pregnant or may become pregnant (pregnancy category C with risk of male fetus feminization) 3, 1
- Patient requires treatment primarily for metabolic dysfunction—use lifestyle modification and metformin instead 1
Dosing Strategy
Initial dose: 100 mg daily in the evening 3
Dose range: 50-200 mg daily, with higher doses increasing side effects in a dose-dependent manner 3
Combination therapy (mandatory for sexually active women): Always combine with oral contraceptive pills to prevent pregnancy, regulate menstrual cycles, and reduce menstrual irregularities from spironolactone 3, 1
Alternative combination: Metformin (1700 mg/day) plus low-dose spironolactone (25 mg/day) produces more marked reduction in clinical and biochemical hyperandrogenism than metformin alone, particularly for dehydroepiandrosterone sulfate and hirsutism scores 4
Expected Timeline
Duration to full effect: Several months of treatment is typically required to reach full effectiveness 3
Long-term use: Spironolactone can be used safely for extended periods in women with PCOS without kidney or heart disease 5
Mechanism of Action
Spironolactone works through multiple pathways:
- Decreases testosterone production 3
- Competitively inhibits testosterone and dihydrotestosterone binding to androgen receptors in the skin 3, 1
- May inhibit 5α-reductase 3, 1
- Increases sex hormone-binding globulin 3, 1
Side Effect Profile and Management
Common Side Effects (in order of frequency)
Menstrual irregularities (22-40%): 3, 1
- Most common side effect
- Dose-dependent with relative risk of 4.12 at 200 mg/day compared to lower doses 3
- Significantly reduced when combined with oral contraceptives 3, 1
Diuresis (29%): 1
Breast tenderness (17%): 1
Other effects: Breast enlargement, fatigue, headache, dizziness, nausea (2-4%), polyuria (1-2%) 3, 1
Potassium Monitoring
Who needs monitoring: 1
- Older patients
- Patients with comorbidities (hypertension, diabetes, chronic kidney disease)
- Patients taking medications affecting renal/adrenal function (ACE inhibitors, ARBs, NSAIDs)
Risk assessment: Women with PCOS without kidney or heart disease using spironolactone combined with hormonal contraception have a low incidence of hyperkalemia, with only mild elevations (5.1-5.5 mEq/L) when they occur 5
Concomitant use with drospirenone: Spironolactone combined with drospirenone-containing oral contraceptives did not increase serum potassium or adverse effects requiring treatment discontinuation 3
Efficacy Data
For Idiopathic Hirsutism
Spironolactone (200 mg/day as monotherapy) is as effective as cyproterone acetate combined with estradiol for long-term treatment, with Ferriman-Gallwey scores improving from 21±2 to 14.5±2 over 12 months 6
For PCOS-Related Hirsutism
Spironolactone (200 mg/day) reduces hirsutism effectively but less dramatically than in idiopathic hirsutism, with Ferriman-Gallwey scores improving from baseline to 16±1 at 12 months 6
Spironolactone shows a positive trend for improving hirsutism in PCOS but displays no effect on FSH, LH, menstrual cyclicity, BMI, or HOMA-IR 7
For Acne
Compared to placebo with benzoyl peroxide 2.5% at 12 weeks, spironolactone 50 mg daily combined with benzoyl peroxide achieved greater IGA success (75.0% vs 30.0%; RR 2.50) 3
Critical Pitfalls to Avoid
Never use spironolactone as monotherapy in patients attempting to conceive—this is an absolute contraindication; use clomiphene citrate instead 1, 2
Never use spironolactone without effective contraception in sexually active women due to risk of male fetus feminization 3, 1
Do not use spironolactone as sole therapy for metabolic dysfunction—it does not improve insulin resistance, BMI, or metabolic parameters; use lifestyle modification and metformin for these goals 1, 7
Do not expect immediate results—counsel patients that several months of treatment is required for full effectiveness 3
Do not overlook the need for combination therapy—spironolactone works best when combined with oral contraceptives for optimal hirsutism reduction and menstrual regulation 1, 6