Nature’s estrogen: Dioscorea and the emerging potential of β-selective estrogen receptor modulation in menopause

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Objectives To evaluate Dioscorea species (wild yam) as a phyto-estrogenic alternative for managing menopause-associated metabolic and neurocognitive disturbances, with particular emphasis on estrogen receptor-β (ERβ)–mediated mechanisms and their relevance to safety and efficacy in menopause management. Methods This review synthesizes evidence from preclinical studies, mechanistic investigations, and emerging translational research to examine the estrogenic, metabolic, and neuroprotective effects of Dioscorea-derived compounds, particularly diosgenin and related saponins. The analysis focuses on ERβ activation and its downstream interactions with metabolic and neurobiological signalling pathways. Results Evidence indicates that Dioscorea-derived phyto-estrogens selectively activate ERβ and modulate pathways involved in glucose homeostasis, lipid metabolism, mitochondrial function, and neuronal resilience. Notably, ERβ interaction with peroxisome proliferator-activated receptor-γ (PPAR-γ) appears to integrate estrogenic and metabolic signaling, resulting in improved insulin sensitivity, adipokine regulation, and reduced systemic inflammation in ovariectomized animal models. Additionally, Dioscorea compounds enhance neuroprotection by increasing hippocampal brain-derived neurotrophic factor (BDNF) levels, preserving synaptic integrity, and improving cognitive function. Discussion The reviewed findings suggest that ERβ-selective phyto-estrogens from Dioscorea may address both metabolic and neurocognitive components of menopause metabolic syndrome while potentially avoiding safety concerns associated with prolonged hormone replacement therapy. The convergence of estrogenic and metabolic pathways via ERβ–PPAR-γ crosstalk provides a mechanistic basis for the observed benefits. Conclusion Dioscorea species represent a promising mechanism-based phyto-estrogenic strategy for menopause management, offering potential metabolic and neuroprotective benefits with improved safety profiles. However, the therapeutic applicability of Dioscorea requires standardized extract formulations and well-designed clinical trials to fully establish its clinical efficacy and safety.