Metabolic Determinants of PCSK9 Regulation in Women with Polycystic Ovary Syndrome: The Role of Insulin Resistance, Obesity, and Tobacco Smoke Exposure.

The aim of this study was to examine associations involving serum proprotein convertase subtilisin/kexin type 9 (PCSK9) in metabolic disturbances observed in women with polycystic ovary syndrome (PCOS), with particular emphasis on the potential impact of tobacco smoke exposure. The study included 88 women: 60 with PCOS (23 smokers and 37 non-smokers) and 28 without PCOS. Selected biochemical and molecular biomarkers related to lipid metabolism, oxidative stress, and inflammation were assessed. No significant differences in PCSK9 levels were observed among non-smoking women with PCOS, smoking women with PCOS, and non-smoking women without PCOS. However, in women with PCOS, excess body weight and insulin resistance were associated with increased PCSK9 concentrations. Significant correlations between PCSK9, lipid profile parameters, and the Castelli and triglycerides-glucose indices suggest a potential role of PCSK9 as a biomarker of dyslipidemia and cardiometabolic risk. Elevated PCSK9 levels may contribute not only to increased low-density lipoprotein cholesterol but also to enhanced formation of oxidized low-density lipoprotein, which is particularly detrimental to cardiovascular and metabolic health. Vitamin D levels were more strongly associated with smoking status and insulin resistance than with excess body weight. Overall, these findings indicate that PCSK9 regulation in PCOS may be driven predominantly by metabolic factors rather than PCOS status or smoking per se, and that metabolic status and vitamin D deficiency should be considered when assessing cardiometabolic risk in this population.