Overview of the Efficacy and Safety of Topical Hormonal Therapies for the Treatment of Acne Vulgaris: A Narrative Review.

OBJECTIVE

Although systemic hormonal therapies (spironolactone, oral contraceptives) are clinically effective for the treatment of acne vulgaris (AV) in female patients, perceived safety concerns have contributed to the growing interest in topical hormonal AV therapies.

METHODS

We searched PubMed using the terms "topical," "antiandrogen," "hormonal," "clascoterone," "spironolactone," and "acne vulgaris."

RESULTS

The majority of articles identified related to clascoterone and topical spironolactone. Clascoterone cream 1% was approved in 2020 by the US Food and Drug Administration (FDA) for patients with AV aged 12 years or older based on two Phase III randomized controlled trials (RCTs) in 1440 patients (722 randomized to clascoterone) and an open-label extension study; other evaluations included a Phase IIa pharmacokinetic study and a Phase IIb RCT. Six clinical studies-mostly small, randomized trials-reported 193 patients treated with topical spironolactone as 5% cream, 5% gel, 2% solution, and 1% nanogel, and 1 RCT evaluated topical flutamide gel in 27 patients. The efficacy and safety of topical spironolactone and flutamide are supported by limited data with some conflicting results; neither agent is approved by the FDA and both must be compounded extemporaneously with no supporting pharmacokinetic data.

LIMITATIONS: Clinical studies of topical spironolactone are limited by the small number of patients and wide range of formulations evaluated.

CONCLUSION

Available evidence supports the use of clascoterone cream 1% and suggests potential benefits and limitations of topical spironolactone in patients with AV; however, for topical spironolactone, pharmacokinetic studies and large-scale RCTs are needed to better characterize both efficacy and safety profiles.