COPPER DEFICIENCY IN POSTMENOPAUSAL WOMEN: A SYSTEMATIC REVIEW OF PREVALENCE, CLINICAL IMPACT, DIAGNOSTIC CHALLENGES, AND MANAGEMENT STRATEGIES

Background: Menopause marks a critical physiological transition characterized by declining estrogen levels, increasedoxidative stress, and heightened risk of chronic conditions including osteoporosis, cardiovascular disease, and immunedysfunction. Copper (Cu), an essential trace element, serves as a cofactor for enzymes involved in energy metabolism,connective tissue integrity, antioxidant defense (superoxide dismutase), and iron homeostasis. Postmenopausal women maybe particularly susceptible to copper deficiency due to age-related metabolic shifts, dietary inadequacies, and hormonalchanges. Despite its clinical relevance, comprehensive systematic synthesis of evidence on copper deficiency in this populationremains limited. The objective is to systematically review the prevalence, clinical manifestations, diagnostic approaches, andmanagement strategies of copper deficiency in postmenopausal women, and to synthesize available evidence on itsassociations with bone health, cardiovascular outcomes, hematological parameters, and immune function. Materials andMethods: A systematic literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and Embasefrom inception to September 2025. Search terms included combinations of “copper deficiency,” “copper status,”“postmenopausal,” “menopause,” “osteoporosis,” “bone mineral density,” “cardiovascular,” and related keywords. Studiesreporting copper status, deficiency prevalence, clinical outcomes, or interventions in postmenopausal women were eligible.Study selection followed PRISMA guidelines. Data on prevalence, biomarkers, clinical associations, and interventions wereextracted and synthesized narratively; quantitative pooling was performed where homogeneous data permitted. Results:Evidence indicates that copper status declines with age and may be lower in postmenopausal compared with premenopausalwomen in some populations, although findings are heterogeneous. Low dietary copper intake and serum copper levels areassociated with reduced bone mineral density (BMD), particularly at the lumbar spine (modest mean difference ~0.02 g/cm²in recent meta-analysis). Copper deficiency contributes to anemia (often with neutropenia), impaired antioxidant capacity,altered lipid metabolism, and potential cardiovascular risk. Diagnostic accuracy of conventional biomarkers (serum Cu,ceruloplasmin) is limited; functional markers (erythrocyte SOD, platelet cytochrome c oxidase, CCS) show greater sensitivity.Dietary sources and targeted supplementation can restore status, but recovery from depletion may require sustainedintervention beyond short-term repletion. Conclusion: Copper deficiency represents an under-recognized contributor tomorbidity in postmenopausal women. Improved awareness, refined diagnostic biomarkers, routine nutritional assessment, andevidence-based dietary or supplemental strategies are warranted to mitigate risks of osteoporosis, hematologic disorders, andcardiovascular complications. Future research should prioritize standardized prevalence studies across diverse populations,validation of novel biomarkers, and randomized trials of copper supplementation on hard clinical endpoints.