Oral spironolactone was supported by stronger evidence than topical formulations for adult female acne, while topical treatment showed potential as a locally acting option with minimal systemic exposure.
Investigators searched PubMed and Google Scholar on September 1, 2025, for studies evaluating oral or topical spironolactone in female patients with acne. Eligible evidence included randomized controlled trials, nonrandomized comparative studies, observational studies, and case series, with clinical studies published from 1984 through 2024. Because evidence specifically evaluating topical spironolactone in adult women was scarce, they included relevant studies conducted in mixed-sex or male populations.
The review compared 25 to 200 mg/day of oral and 2% to 5% topical spironolactone across efficacy outcomes, dosing regimens, comparator treatments, adverse effects, quality-of-life outcomes, systemic exposure, monitoring requirements, and practical clinical use.
The strongest evidence for oral spironolactone came from the phase 3 SAFA trial, which randomly assigned 410 adult women with facial acne warranting oral antibioticsto receivespironolactone, 50 mg/day for 6 weeks and 100 mg/day if tolerated thereafter for a total of 24 weeks, or placebo. Mean acne-specific quality-of-life symptom scores favored spironolactone at 12 weeks and showed a larger difference at 24 weeks, reaching 21.2 with spironolactone vs. 17.4 with placebo. Investigator-assessed treatment success at 12 weeks occurred in 19% of patients receiving spironolactone vs. 6% receiving placebo. However, the difference in the primary outcome at 12 weeks did not reach the 2-point difference the trial was powered to detect.
Other trials provided supporting evidence for oral treatment. Among 63 women aged 25 to 45 years with moderate adult female acne, 75% of those receiving spironolactone 50 mg/day plus topical benzoyl peroxide were rated clear or almost clear at 12 weeks vs. 30% receiving placebo plus benzoyl peroxide. In another randomized trial of 133 women with moderate acne, spironolactone 150 mg/day plus topical benzoyl peroxide was more effective at 6 months than doxycycline 100 mg/day plus benzoyl peroxide, with improvements in acne severity measures and quality of life.
Evidence for topical spironolactone was more limited but showed reductions in acne lesions. In a randomized study of 78 patients, 5% spironolactone gel reduced total lesion counts vs. placebo over 6 weeks, although the difference in acne severity index was not statistically significant. Another study found that 2% spironolactone solution reduced mean comedone counts from 91 to 57, papules from 5.7 to about 0, and pustules from 4.2 to 0 over 12 weeks. Several topical studies involved healthy male volunteers or mixed-sex cohorts rather than specifically adult women, making their applicability to adult female acne indirect.
Oral spironolactone was welltolerated, but adverse effects included menstrual irregularities and breast tenderness, with hyperkalemia a concern among older patients or those with relevant comorbidities. In a retrospective study of 618 women, hyperkalemia occurred in 17% of those aged 46 to 65 years vs. less than 1% of those aged 18 to 45 years.
Topical spironolactone showed minimal systemic exposure in the available evidence. In a crossover study of healthy male volunteers, topical 5% spironolactone did not alter measured testosterone-related parameters, and canrenone was undetectable in plasma. In another study, 6% of patients experienced pruritus and 11% reported burning with 2% spironolactone solution. No treatment discontinuations were attributed to these reactions.
Relative efficacy could not be established from comparisons across studies. The topical evidence was particularly limited: studies enrolled no more than 80 patients, follow-up was generally short, formulations varied from 2% to 5%, outcome measures were not standardized, and some evidence came from populations other than adult women. Oral studies also varied in dose, outcome measures, and follow-up duration.
The narrative review had additional limitations. The investigators searched 2 databases, largely restricted eligibility to English-language publications, conducted no formal risk-of-bias assessment, and did not perform a meta-analysis. They acknowledged that selection bias could not be excluded.
“The two routes appear complementary rather than competing,” wrote lead study author Magdalena Łyko, of the University Centre of General Dermatology and Oncodermatology atWroclaw Medical University in Poland, and colleagues.
Full disclosures of the study authors can be found in the study.