By Rebecca Allen, MD, MPH
Synopsis: In this meta-analysis of 563 patients from five randomized controlled trials, objective assessment of acne improvement was higher in the spironolactone group compared to the placebo group (odds ratio, 6.59; 95% confidence interval, 3.50-12.43).
Source: Ghanem L, Kirmani N, De Leon Fernandez N, et al. Efficacy and safety of oral spironolactone for women with acne vulgaris: A systematic review and meta-analysis of randomized placebo-controlled trials with trial sequential analysis. J Cosmet Dermatol. 2025;24(8):e70411.
The authors of this study sought to estimate, with a meta-analysis, the effectiveness of spironolactone for the treatment of acne vulgaris in females. The American Academy of Dermatology includes spironolactone as a possible systemic treatment for those with moderate to severe acne.1
This was a systematic review that included studies that were randomized controlled trials comparing oral spironolactone and placebo and reported results in females with at least one clinical outcome of interest. The authors searched Embase, Cochrane Central, and PubMed databases from inception until December 2024. The primary endpoint was improvement in acne through an objective assessment, such as a validated clinical scale (e.g., Investigator’s Global Assessment or Adult Female Acne Scoring System). Secondary endpoints were subjective assessment and adverse effects, such as breast enlargement and menstrual irregularities. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and studies were assessed for quality.
A total of five randomized controlled trials were included from an initial search yielding 1,071 results. The studies included 563 patients, of whom 251 (44.6%) female patients took spironolactone. Two studies allowed concurrent topical benzoyl peroxide 2.5% gel. Objective assessment of acne improvement was higher in the spironolactone group compared to the placebo group (OR, 6.59; 95% CI, 3.50-12.43). However, there was no difference in the subjective assessment (OR, 5.22; 95% CI, 0.62-44.24). The rate of menstrual irregularities (18.1% vs. 20.4%; P = 0.88) and breast enlargement (14.9% vs. 11.3%; P = 0.26) was not significantly different between the two groups.
Commentary
The authors of this study sought to conduct a meta-analysis of the effectiveness of spironolactone for the treatment of acne vulgaris in females. Acne is a common condition in adolescents and young adults. The authors thought that the lack of difference in the subjective assessment was the result of the inclusion of some older studies that lacked the rigor of more modern trials.
Overall, their conclusion was that spironolactone is an effective option for female patients, although they were not able to perform a subanalysis based on dosage. The meta-analysis also was limited by the inability to adjust the ORs for baseline characteristics, such as concomitant hormonal or topical treatment, age, or polycystic ovarian syndrome status.
Spironolactone is an aldosterone receptor antagonist that inhibits testosterone and dihydrotestosterone binding to androgen receptors in the skin.1 The effect of decreasing androgens is to decrease sebum production in the skin. Increased sebum production by sebaceous glands contributes to the development of acne. Spironolactone is U.S. Food and Drug Administration-approved for the treatment of heart failure, hypertension, edema, and primary hyperaldosteronism. For acne treatment, spironolactone is used off-label. Spironolactone is contraindicated in pregnancy since it may cause feminization of a male fetus. Therefore, it is important that females of reproductive age are using a reliable contraceptive method while taking spironolactone.
Spironolactone is one option in a large armamentarium of treatments for acne, which include topical (benzoyl peroxide, retinoids, salicylic acid, and antibiotics) and systemic (oral contraceptives, spironolactone, antibiotics, and isotretinoin) medications. The starting dose of spironolactone typically is 50 mg to 100 mg daily. Since spironolactone is a potassium-sparing diuretic, hyperkalemia could occur. However, among young healthy patients, this risk is low.
The American Academy of Dermatology does not recommend potassium monitoring if the patient does not have other comorbid conditions or medication use that could raise their potassium levels.1 Given that gynecologists use spironolactone for the treatment of hirsutism in patients with polycystic ovarian syndrome, their familiarity with the medication would allow them to also offer this as a treatment for acne to select patients.
Rebecca H. Allen, MD, MPH, is Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women & Infants Hospital, Providence, RI.
Reference
1. Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90(5):1006.e1-1006.e30.
