Why is spironolactone ordered for hair loss in women with androgenetic alopecia, particularly those with polycystic ovary syndrome (PCOS) or a history of cardiovascular disease, such as acute coronary syndrome and atrial fibrillation?

Why Spironolactone is Ordered for Hair Loss

Spironolactone is ordered for hair loss in women because it blocks androgen receptors in hair follicles and reduces testosterone production, making it highly effective for female pattern hair loss (androgenetic alopecia), particularly when combined with topical minoxidil. 1, 2

Mechanism of Action

Spironolactone works through multiple antiandrogen pathways that directly address the hormonal basis of female pattern hair loss:

• Competitively inhibits testosterone and dihydrotestosterone binding to androgen receptors in the skin and hair follicles 1, 3
• Decreases testosterone production by reducing adrenal androgen synthesis 1, 2
• Increases sex hormone-binding globulin (SHBG), which reduces free circulating androgens 1, 3
• May inhibit 5-alpha-reductase, the enzyme that converts testosterone to the more potent dihydrotestosterone 3

Clinical Efficacy

The evidence strongly supports spironolactone's effectiveness for female hair loss:

• 66% of women achieve clear or marked improvement at doses of 50-100 mg daily, either as monotherapy or adjunctive therapy 4, 1
• Overall improvement rate of 56.60% across multiple studies, with combination therapy showing 65.80% improvement versus 43.21% for monotherapy 5
• Arrests hair loss progression with long-term safety, and a significant percentage achieve partial regrowth 2
• Superior to finasteride in women: combination of minoxidil-spironolactone showed significantly better outcomes than minoxidil-finasteride, with 56.7% achieving excellent response versus 0% with finasteride 6

Dosing Strategy

Start with 100 mg daily in the evening, as this is the most commonly effective dose supported by guidelines 4:

• Doses range from 50-200 mg daily, with most patients responding to 100-150 mg daily 4, 1
• Higher doses (up to 200 mg) can be used but increase side effects proportionally 4
• Several months of treatment is required to reach full effectiveness 4
• Combination with topical minoxidil 2-5% provides additive benefit and is recommended for optimal results 6, 7, 8

Special Populations

Women with PCOS

Spironolactone is particularly valuable in PCOS-related hair loss because these women have elevated androgens driving both hirsutism and alopecia 4, 2. The drug addresses the underlying hyperandrogenism while oral contraceptives suppress ovarian androgen production 1, 3.

Women with Cardiovascular Disease

Potassium monitoring is essential in patients with cardiovascular disease, renal impairment, or those taking ACE inhibitors, angiotensin receptor blockers, or digoxin 4:

• Baseline potassium, then at 2-3 days, 7 days, monthly for 3 months, then every 3 months 1
• Hold therapy if potassium >5.5 mEq/L and discontinue if >6.0 mEq/L 1
• However, in young healthy women without these conditions, routine potassium monitoring is unnecessary: only 0.75% of potassium measurements exceeded 5.0 mmol/L in women aged 18-45 taking spironolactone 50-200 mg daily for acne 4

Side Effects and Management

Common side effects are dose-dependent 4:

• Menstrual irregularities (15-30%): most common side effect, with relative risk of 4.12 at 200 mg/day versus lower doses 4
  • Concomitant use of oral contraceptives or hormonal IUD minimizes this side effect 4
• Breast tenderness (3-17%) 4
• Dizziness (3-4%), nausea (2-4%), headache (2%), polyuria (1-2%), fatigue (1-2%) 4

Pregnancy category C: causes feminization of male fetuses in animal studies, so contraception is mandatory 4, 3. Combining with oral contraceptives serves dual purposes of preventing pregnancy and regulating menses 4.

Contraindications and Precautions

Avoid spironolactone in patients:

• Taking potassium supplements or potassium-sparing diuretics 1
• Using potent CYP3A4 inhibitors 4
• Taking combined ACE inhibitor plus angiotensin receptor blocker (increases hyperkalemia risk) 4
• With significant renal, hepatic, or adrenal dysfunction 4, 1

Patients should avoid high-potassium foods (low-sodium processed foods, coconut water) 4.

Combination with Oral Contraceptives

First-line therapy should be combined oral contraceptives to suppress ovarian androgen secretion and increase SHBG 1, 3:

• Add spironolactone 100-150 mg daily if inadequate response after 6-9 months of oral contraceptives alone 1
• Avoid oral contraceptives with androgenic progestins (which worsen hair loss) 3
• Combining spironolactone with drospirenone-containing oral contraceptives is safe: no potassium elevations in 27 patients taking spironolactone 100 mg with ethinyl estradiol/drospirenone 4, 3

Why Not Used in Men

Spironolactone is not used in male androgenetic alopecia due to risk of feminization, including gynecomastia 4, 2. A Japanese study was discontinued prematurely in male patients because all developed gynecomastia 4.

Long-term Safety

Despite a black box warning about carcinogenicity from animal studies, human evidence shows no association with breast cancer: a large retrospective cohort of 1.29 million women with 8.4 million patient-years found no increased breast cancer risk 4.