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Original research and peer-reviewed evidence underpinning the AR(C6) system.
Dr. Rhea Iyer (Weill Cornell Medicine) & Ioannis Hadjithannas (Royal Hampshire County Hospital) – AR(C6) Research Division – 2026
Polycystic ovary syndrome (PCOS) affects 8-13% of reproductive-age women globally and is the leading cause of androgen-driven dermatological disease in this population. Hyperandrogenism stimulates the pilosebaceous unit, producing hirsutism and acne vulgaris as the dominant clinical manifestations — quantified by the modified Ferriman-Gallwey scale and the Global Acne Grading System or Investigator Global Assessment scale respectively. First-line pharmacological treatments, including combined oral contraceptives and spironolactone, are contraindicated in women seeking conception and carry recognized adverse effect profiles. No network meta-analysis has synthesized botanical and nutraceutical agents against dermatological primary endpoints or benchmarked them against pharmacological standard of care within a unified evidence network. This review addresses that gap directly, producing the first ranked comparative hierarchy of interventions for hirsutism and acne in PCOS. Secondary endpoints include free androgen index, testosterone, SHBG, androstenedione and insulin resistance (HOMA-IR). Pharmacological agents are included as active network nodes, enabling direct comparisons not previously available in the literature.
A frequentist random-effects network meta-analysis (NMA) conducted in R using the netmeta package, assuming a common between-study variance (tau-squared) across all comparisons. Primary effect measure: mean difference (MD) for same-scale outcomes; standardized mean difference (SMD) for cross-scale pooling. Intervention ranking expressed as P-scores. A Bayesian NMA conducted as confirmatory analysis using gemtc/JAGS with weakly informative half-normal priors (scale 0.5); SUCRA values estimated for probabilistic ranking. Databases searched: CENTRAL, Embase (Ovid), MEDLINE, PubMed. Screening via Rayyan with independent dual-reviewer blinded assessment; Cohen’s kappa reported at both stages. Risk of bias assessed using Cochrane RoB-2. Evidence certainty graded by Grade-NMA across six domains. Registered on PROSPERO 8 April 2026. Review period: 1 April – 30 June 2026.
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