Targeting the Female Endocannabinoid System, Hormonal Changes, Iron Metabolism, and Bone Health in Menopause: A Scoping Systematic Review

Menopause is a universal milestone in women’s reproductive aging characterized by permanent cessation of menstruation following ovarian follicular depletion. This transition precipitates a progressive decline in estrogen and progesterone, triggering a spectrum of vasomotor, psychological, cognitive, genitourinary, musculoskeletal, and metabolic symptoms that impair quality of life, mental well-being, sexual health, and social participation. While hormone replacement therapy (HRT) remains effective, its use is limited by cardiovascular, thromboembolic, oncological, and metabolic risks, prompting interest in non-hormonal and integrative approaches. Emerging evidence implicates dysregulation of the female endocannabinoid system (FECS), mineral deficiencies—particularly iron deficiency—and accelerated skeletal remodeling as interconnected contributors to menopausal symptom burden and long-term morbidity. This scoping systematic review synthesizes peer-reviewed literature published between 2010 and 2025 to examine interactions among hormonal decline, iron metabolism, mineral homeostasis, FECS signaling, and bone health, while evaluating the biological plausibility and clinical evidence supporting phytocannabinoid-based interventions. Estrogen withdrawal disrupts bone remodeling, alters iron homeostasis, exacerbates mineral deficiencies, and modifies ECS activity across central, immune, and skeletal tissues [7–10]. FECS modulation, particularly via cannabidiol (CBD), may influence vasomotor stability, mood, sleep, pain, inflammation, and bone turnover; however, human clinical evidence in menopause remains limited. The review supports an integrated, systems-based framework for menopause management beyond hormone replacement alone.