Introduction The prevalence of acne among adult women is increasing, and androgens play an important role in its pathogenesis. This study aimed to evaluate the short‐term efficacy and safety of low‐dose isotretinoin combined with spironolactone, diammonium glycyrrhizinate, or both in the treatment of women with moderate‐to‐severe acne and hyperandrogenism. Methods This was a single‐center, randomized, open‐label, assessor‐blinded clinical trial. The study protocol was approved by the hospital’s Medical Ethics Committee (Approval No. 2023‐054) and was retrospectively registered with the Chinese Clinical Trial Registry (ChiCTR2500099023) on March 17, 2025, after completion of participant enrollment. A total of 112 participants were randomly assigned to four groups ( n = 28 per group): Group A (isotretinoin 0.2 mg/kg/day), Group B (isotretinoin 0.2 mg/kg/day plus spironolactone 40 mg/day), Group C (isotretinoin 0.2 mg/kg/day plus diammonium glycyrrhizinate 150 mg/day), and Group D (triple therapy). Treatment duration was 8 weeks. The prespecified primary efficacy endpoint was the lesion clearance rate at Week 8, defined as the percentage reduction in total lesion count from baseline. Secondary outcomes included changes in lesion counts, Global Acne Grading System (GAGS) scores, VISIA red area percentiles, quality of life and psychological measures (Dermatology Life Quality Index DLQI, Generalized Anxiety Disorder‐7 GAD‐7, and Patient Health Questionnaire‐9 PHQ‐9), and serum hormone levels. Results All treatment regimens were associated with clinical improvement after 8 weeks. The triple therapy group (Group D) achieved the greatest reduction in total lesion count, with a mean lesion clearance rate of 90.59% (95% CI, 88.25–92.92), compared with 73.94% (95% CI, 67.70–80.17) in Group A, 80.10% (95% CI, 75.06–85.14) in Group B, and 81.70% (95% CI, 77.52–85.88) in Group C. Reductions in lesion counts and GAGS scores were observed across all groups, and VISIA red area percentiles increased, indicating improvement in facial erythema‐related metrics. Quality of life and psychological measures improved in all treatment arms. Exploratory analyses showed changes in selected serum hormone parameters during treatment. Conclusion In this short‐term, single‐center, open‐label, assessor‐blinded trial, low‐dose isotretinoin combined with spironolactone and diammonium glycyrrhizinate demonstrated greater short‐term clinical improvement with acceptable tolerability in women with moderate‐to‐severe acne and hyperandrogenism. Larger, multicenter, randomized studies—preferably double‐blind—with longer follow‐up are warranted to confirm these findings and to evaluate long‐term efficacy and safety.
Jing et al. (2026) studied this question.