Palmitoylethanolamide in Postmenopausal Metabolic Syndrome: Current Evidence and Clinical Perspectives

Menopause leads to a decline in estrogen levels, resulting in significant metabolic alterations that increase the risk of developing metabolic syndrome-a cluster of conditions including central obesity, insulin resistance, dyslipidemia, and hypertension. Traditional interventions such as hormone replacement therapy carry potential adverse effects, and lifestyle modifications alone may not suffice for all women. This review explores the potential role of palmitoylethanolamide (PEA), an endogenous fatty acid amide, in managing metabolic syndrome during the postmenopausal period. PEA primarily acts by activating peroxisome proliferator-activated receptor-alpha (PPAR-α), influencing lipid metabolism, energy homeostasis, and inflammation. Evidence indicates that PEA may promote the browning of white adipocytes, enhancing energy expenditure and reducing adiposity. It also improves lipid profiles by boosting fatty acid oxidation and decreasing lipid synthesis, potentially lowering low-density lipoprotein cholesterol and triglyceride levels while increasing high-density lipoprotein cholesterol. Additionally, the anti-inflammatory properties of PEA enhance insulin sensitivity by reducing pro-inflammatory cytokines that interfere with insulin signaling. PEA may aid in weight management by influencing appetite regulation and improving leptin sensitivity. Furthermore, its neuroprotective effects may address the mood disturbances and cognitive decline associated with menopause. Given these multifaceted biological activities and a favorable safety profile, PEA may represent a promising non-pharmacological supplement for managing metabolic syndrome in postmenopausal women. However, further large-scale clinical studies are necessary to establish its efficacy, optimal dosing, and long-term safety. If validated, PEA could become an integral part of strategies to improve metabolic and neuropsychological health outcomes in this population.