Efficacy and Safety of Spironolactone for Adolescent Acne Vulgaris

Acne vulgaris (AV) is a common inflammatory skin disease in adolescents, frequently driven by androgen-mediated sebum production and associated with significant psychosocial burden [1, 2]. Spironolactone, an aldosterone receptor antagonist with anti-androgenic properties, is prescribed off-label for adult female acne (AFA) [3]. However, limited data exist on its efficacy and safety in adolescents. We conducted a systematic review exploring spironolactone in adolescent AV. Ovid MEDLINE and Embase were searched (inception to November 20, 2024) following PRISMA guidelines (Mendeley table 1 available at: https://data.mendeley.com/datasets/6wdzr6b4m4/1). Five studies met the inclusion criteria, reflecting 247 patients (mean age 17 years; Mendeley figure 1 available at: https://data.mendeley.com/datasets/6wdzr6b4m4/1). Two routes of spironolactone were used: topical (33.6%, n = 83) and oral (66.4%, n = 164) (Table 1). Among 83 patients who received topical spironolactone at concentrations of 5% gel twice a day (BID) (n = 48) and 2% solution BID (n = 35), 40 (48.2%) achieved complete resolution (CR), while 43 (51.8%) showed partial resolution (PR). The average time from treatment initiation with topical spironolactone to clinical improvement was 113.5 days. One study reported hydrogen peroxide as a concurrent topical treatment, and one study found topical spironolactone to be significantly more effective than topical clindamycin. For those who received oral spironolactone (n = 164), 28 (17.1%) achieved CR, 95 (57.9%) showed PR, and 39 (23.8%) experienced no resolution. One patient (0.6%) had a worse outcome. The oral spironolactone dose ranged from 100 to 125 mg daily (Mendeley table 2 available at: https://data.mendeley.com/datasets/6wdzr6b4m4/1). The average time to clinical improvement was 219 days. Concurrent systemic treatment included oral contraceptive pill (n = 49), antibiotics (n = 20), isotretinoin (n = 7), and corticosteroids (n = 2). Safety data were consistently favorable (Table 2). Topical spironolactone resulted in local itching (n = 2) and burning (n = 4). For oral spironolactone, the reported side effects included headaches (n = 3), rash (n = 1), diarrhea (n = 1), and dysmenorrhea (n = 1). Additionally, menstrual irregularities, breast tenderness, and syncope were also noted (n = NR). Fifteen patients discontinued treatment, seven of whom did so due to the aforementioned side effects. The remaining eight discontinued treatment due to switching to oral contraceptive pills (n = 5), inadequate clinical response (n = 2), or personal decision to stop (n = 1). Overall, patient adherence was high with 93.9% (n = 232) completing treatment courses. Our findings suggest that although some studies appeared to favor topical over oral formulations, these were not direct comparisons and may reflect differences in study design and population. AFA is driven by peripheral androgen receptor hypersensitivity and local intracrine androgen production, making receptor blockade by oral spironolactone particularly effective [4]. In adolescents, acne is influenced more by pubertal hormonal surges, sebum production, and other factors such as IGF-1, potentially limiting oral spironolactone's relative efficacy [2]. Topical spironolactone nonetheless exhibited promising efficacy with fewer systemic side effects and a shorter time to improvement, indicating a potential option for adolescents, though findings should be interpreted cautiously given the need for direct comparative trials. These observed effects of topical treatment may relate to its direct inhibition of sebaceous gland androgen receptors, thereby reducing local sebum production. However, the efficacy data are not conclusive, as patients selected for topical therapy may have had milder acne at baseline, making them more likely to respond favorably. Furthermore, in terms of safety and prescribing patterns, oral spironolactone has been associated with gynecomastia in males, making it less frequently prescribed in this population [5]. This review is limited by the small number of studies, which were open-label and lacked control groups, and by some that reported outcomes or patient characteristics incompletely, underscoring the poor quality and heterogeneity of the data. The concurrent use of therapies also complicates the assessment of spironolactone's independent efficacy. Current evidence suggests that spironolactone, particularly topical formulations, may be a well-tolerated option for selected adolescents with acne vulgaris, although controlled trials are needed to define its role more clearly. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.