What is the recommended treatment regimen for a female patient of reproductive age with hirsutism, particularly polycystic ovary syndrome (PCOS), using spironolactone (an anti-androgen medication)?

Spironolactone for Hirsutism in PCOS

For women with hirsutism related to PCOS, prescribe spironolactone 50-200 mg daily combined with an oral contraceptive pill, alongside mechanical hair removal methods, as this combination provides superior results to monotherapy. 1

Recommended Treatment Regimen

Starting Dose and Titration

• Begin with spironolactone 50 mg twice daily (100 mg/day total) on days 4-21 of the menstrual cycle to minimize side effects, particularly metrorrhagia which occurs in 56% of patients at higher doses (200 mg/day). 2
• The dose can be titrated up to 200 mg daily if needed for adequate response, though 100 mg daily is often sufficient. 1
• Starting at 50 mg twice daily significantly reduces the incidence of menstrual irregularities compared to 100 mg twice daily. 2

Mandatory Combination with Oral Contraceptives

• Spironolactone must be combined with an oral contraceptive pill in all sexually active women of reproductive age because it is pregnancy category C and carries risk of feminization of male fetuses. 1
• Any combined OCP formulation is effective; specifically studied options include cyproterone acetate 2 mg/ethinylestradiol 35 μg or drospirenone 3 mg/ethinylestradiol 20 μg. 1
• The OCP provides additional benefits: suppresses ovarian androgen secretion, increases sex hormone-binding globulin (reducing free testosterone), regulates menses, and protects the endometrium. 1
• Combining spironolactone with OCPs also helps manage the menstrual irregularities that spironolactone alone can cause. 2

Mechanism of Action

• Spironolactone decreases testosterone production, competitively inhibits binding of testosterone and dihydrotestosterone to androgen receptors in the skin, and may inhibit 5α-reductase. 3, 1
• It increases sex hormone-binding globulin levels, further reducing free testosterone. 3

Expected Efficacy

Clinical Improvement

• Improvement in hirsutism takes 6-12 months due to hair growth cycles, so set realistic patient expectations from the outset. 1
• In idiopathic hirsutism, spironolactone 200 mg/day reduces hirsutism scores by approximately 54% after one year. 4
• For PCOS patients, spironolactone 100-150 mg daily achieves improvement in 85% of patients, with complete remission in 55%, though patients with severe disease respond less favorably. 3
• A retrospective study of 85 patients showed 66% were clear or markedly improved with spironolactone 50-100 mg daily. 3

Comparison to Other Antiandrogens

• Spironolactone as monotherapy is as effective as cyproterone acetate combined with estradiol for idiopathic hirsutism. 5
• In PCOS patients, cyproterone acetate may produce slightly better hirsutism scores, but spironolactone remains highly effective. 5
• Flutamide and spironolactone plus CPA/EE show similar efficacy in reducing hirsutism scores. 6

Critical Safety Monitoring

Potassium Monitoring

• Routine potassium monitoring is NOT required in young, healthy women with normal renal, hepatic, and adrenal function. 3
• Only 0.75% of potassium measurements exceed 5.0 mmol/L in women aged 18-45 taking spironolactone 50-200 mg daily for acne. 3
• DO monitor potassium in: older patients, those with hypertension, diabetes, chronic kidney disease, or those taking ACE inhibitors, ARBs, NSAIDs, or digoxin. 1, 3
• Educate patients to avoid high-potassium foods (low-sodium processed foods, coconut water). 3

Contraception Requirements

• Never prescribe spironolactone without concurrent reliable contraception in women of reproductive potential. 1
• This is a critical safety measure due to the risk of feminization of male fetuses. 1

Common Side Effects

Dose-Related Effects

• Menstrual irregularities (22%), particularly metrorrhagia with shortened cycles, are the most intolerable side effect at higher doses. 2, 3
• Diuresis (29%) is common but usually well-tolerated. 3
• Breast tenderness (17%) and breast enlargement may occur. 3, 1
• Fatigue, headache, and dizziness are reported. 3
• Rare cases of urticaria and scalp hair loss have been documented. 2

Essential Adjunctive Therapies

Mechanical Hair Removal

• Medical management must be combined with mechanical hair removal methods (electrolysis, laser) because drugs only partially affect terminalized hairs already present. 1
• Multiple laser treatments are typically needed for optimal results. 7

Lifestyle Modification

• Weight loss of just 5% of initial body weight significantly improves androgen levels and hirsutism in PCOS. 1
• Prescribe an energy deficit of 500-750 kcal/day and recommend at least 150 minutes/week of moderate-intensity exercise. 1

Topical Therapy

• Eflornithine hydrochloride cream is the only FDA-approved topical treatment for hirsutism and should be used as adjunctive therapy, not sole treatment. 1

Long-Term Management

Duration of Therapy

• Hirsutism treatment is palliative, not curative, and medical therapy must continue long-term to maintain androgen suppression. 1
• Discontinuation typically results in recurrence of symptoms. 1

Critical Pitfalls to Avoid

1. Do not use antiandrogens without concurrent contraception in women of reproductive potential. 1
2. Do not expect rapid results—visible improvement requires 6-12 months. 1
3. Do not start at 200 mg daily—begin at 100 mg daily (50 mg twice daily) to minimize menstrual side effects. 2
4. Do not use spironolactone as monotherapy—combine with OCPs for optimal efficacy and safety. 1