BMC Women's Health, 2023
Abstract
Background Polycystic ovary syndrome (PCOS) presents clinical symptoms of menstrual abnormalities, excessive hair growth (hirsutism), scalp hair loss, acne and infertility. Metabolic abnormalities such as obesity, insulin resist‑ ance, glucose intolerance and cardiovascular problems constitute an essential part of PCOS, all of which can have significant long-term health consequences. Low-grade chronic inflammation demonstrated by persistent moderately elevated serum levels of inflammatory and coagulatory markers plays a critical role in the pathogenesis of PCOS. Oral contraceptive pills (OCPs) constitute the mainstay of pharmacologic therapy for women with PCOS to regularize cyclicity and ameliorate androgen excess. On the other hand, OCP use is associated with various venous thromboem‑ bolic and proinflammatory events in the general population. PCOS women always carriers the increased lifetime risk of these events. The studies on the effect of OCPs on inflammatory, coagulation and metabolic parameters in PCOS are less robust. Therefore in this study, we investigated and compared the messenger RNA (mRNA) expression profiles of genes implicated in inflammatory and coagulation pathways between drug-naive and OCP-treated PCOS women. The selected genes include intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), mono‑ cyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1). Furthermore, the correlation between the selected markers and various metabolic indices in the OCP group has also been explored. Method The relative amounts of ICAM-1, TNF-α, MCP-1 and PAI-1 mRNA in peripheral blood mononuclear cells from 25 drug-naive PCOS subjects (controls) and 25 PCOS subjects who received OCPs containing 0.03 mg-ethinyl-estra‑ diol and 0.15 mg-levonorgestrel for at least six months (cases) were estimated using real-time qPCR. The statistical Open Access Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases, involving 6–20% percent of women of reproductive age [ 1 ], with an even greater incidence among Kashmiri women [ 2 ]. Apart from the symptoms of hyperandrogenism and infertility, PCOS is associated with several metabolic abnormalities, including obesity, insulin resistance (IR), hyperlipidemia, systemic inflammation and functional atherosclerosis [ 3 – 5 ]. Elevated inflammatory and coagulatory markers characterize this low-grade inflammation and endothelial dysfunction. Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) are potent biological markers for the development of inflammatory and metabolic diseases which may include PCOS [ 6 – 8 ]. ICAM-1 belongs to the super immunoglobulin family and is produced mainly on cell surfaces of endothelial cells, smooth muscle cells, macrophages and activated lymphocytes. It is required for the adhesion of freely moving leukocytes to blood vessel walls and trans-endothelial migration to the vascular intima. This action is crucial in the evolution of atheroma from early to advanced stages. Cleavage of membranebound ICAM-1 results in circulating soluble ICAM-1 (sICAM-1) [ 9 , 10 ]. In prospective epidemiologic investigations, its levels in serum have been linked to abdominal obesity, insulin resistance and cardiovascular disease (CVD) [ 11 ]. TNF-α, a cytokine released by adipose tissue, instigates insulin resistance. In the endothelium, the TNF-α signaling pathway, which is regulated by nuclear factor kappa B (NF-KB), governs the expression of adhesion molecules such as sICAM-1 [ 12 ]. Many studies have found that women with PCOS have significantly higher ICAM-1, MCP-1 and TNF-α than women without PCOS [ 13 , 14 ]. interpretation was conducted using SPSS version 20.0 (SPSS, Inc, Chicago, IL), Epi Info version 2002 (Disease Control and Prevention Centres, Atlanta, GA) and GraphPad Prism 5 (GraphPad Software, La Jolla, CA) software. Result Six months of OCP therapy enhanced the expression of inflammatory genes viz ICAM-1, TNF-α and MCP-1 mRNA in PCOS women by 2.54, 2.05 and 1.74 folds, respectively, in this study. However, PAI-1 mRNA in the OCP group showed no significant increase. Furthermore, in cases, ICAM-1 mRNA expression positively correlated with body mass index (BMI) (p = 0.01), fasting insulin (p = 0.01), insulin 2 h p = 0.02), glucose 2 h (p = 0.01) and triglycerides (p = 0.01). TNF-α mRNA expression positively correlated with fasting insulin (p = 0.0007). MCP-1 mRNA expression positively cor‑ related with (BMI) (p = 0.002). Conclusion OCPs helped reduce clinical hyperandrogenism and regularise menstrual cycles in women with PCOS. [truncated]