Oral and Topical Spironolactone in Adult Female Acne: A Narrative Review Comparing Systemic and Local Approaches.

Background: Adult female acne (AFA) affects 12-45% of women over 25 years of age and is frequently resistant to conventional therapies. The antiandrogenic properties of spironolactone have positioned it as a promising non-antibiotic alternative. While oral spironolactone has been increasingly studied, its topical formulation remains comparatively underexplored, and recent evidence syntheses have generally pooled both routes of administration rather than comparing them within a framework specific to AFA. Objective: This narrative review synthesizes and critically compares the available evidence on the efficacy, safety, and practical considerations of oral versus topical spironolactone in AFA. Methods: A literature search was conducted in PubMed and Google Scholar on 1 September 2025, using search terms combining adult female acne with spironolactone. Original clinical studies-randomized controlled trials, observational studies, and case series-were included. Preclinical studies, non-English-language articles, and non-original data were excluded. Results: Oral spironolactone (50-200 mg/day) consistently demonstrates significant reductions in inflammatory and non-inflammatory lesion counts and improves acne-specific quality of life. Head-to-head trials indicate comparable or superior efficacy relative to doxycycline, with longer treatment persistence than oral antibiotics. Topical spironolactone (2-5%) reduces comedones, papules, and pustules with minimal systemic absorption, suggesting a potential option for patients who are not candidates for systemic therapy. However, the evidence base for topical formulations remains limited by small sample sizes and heterogeneous study designs, and is derived largely from small mixed-sex or non-AFA cohorts and from pharmacokinetic studies in healthy volunteers; its applicability to AFA is therefore currently indirect and extrapolated. Conclusion: Oral spironolactone is supported by robust evidence as an effective non-antibiotic option for AFA and is suitable for moderate-to-severe disease, whereas topical spironolactone appears promising but remains supported by limited and partly indirect evidence, derived largely from small and heterogeneous studies, and may be appropriate for mild-to-moderate acne or when systemic therapy is contraindicated. Because no head-to-head trial has compared the two routes, the comparison presented here is necessarily indirect. Future research should prioritize head-to-head comparisons of both routes and standardization of topical formulations.