Systems pharmacology identifies dermal papilla–specific transcriptomic reversal of androgenetic alopecia by lithium–zinc pathway convergence

The lithium–zinc combination showed statistically significant transcriptomic rescue across all three datasets (GSE90594 z = 3.43, p = 0.0095; GSE36169 z = 3.99, p = 0.017; GSE66663 z = 9.79, p < 0.001). Z-scores reflect standardized displacement from permutation-derived null distributions; p-values are empirical permutation p-values rather than parametric Gaussian tail probabilities. Random-compound benchmarking placed lithium–zinc at the 99.5th percentile in the DP-specific dataset (empirical p = 0.010). Cross-dataset meta-analysis of permutation z-scores confirmed consistency (I² = 0%, Stouffer Z = 9.93, Fisher p < 10⁻⁵). The signal was strongest in the DP-enriched model (z = 9.79), consistent with the biological hypothesis that rescue targets DP-specific pathways. Leave-10%-out and bootstrap analyses confirmed a distributed, non-fragile rescue signal.