Oral contraceptive pill (OCP) treatment alters the gene expression of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) in polycystic ovary syndrome (PCOS) women compared to drug-naive PCOS women

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 resistance, 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 thromboembolic 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), monocyte 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-estradiol and 0.15 mg-levonorgestrel for at least six months (cases) were estimated using real-time qPCR. The statistical 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 correlated with (BMI) (p = 0.002). Conclusion OCPs helped reduce clinical hyperandrogenism and regularise menstrual cycles in women with PCOS. However, OCP use was associated with increased fold expression of inflammatory markers which positively correlated with metabolic abnormalities.

Usefulness of the Sympto-Thermal Method with Standardized Cervical Mucus Assessment (InVivo Method) for Evaluating the Monthly Cycle in Women with Polycystic Ovary Syndrome (PCOS)

“…Cervical mucus produced and stored by the cervical crypts accepts, filters, prepares and stores male sperm deposited in the woman’s vaginal vault during sexual intercourse. In addition, cervical mucus is a barrier preventing pathogens from entering the endometrium through its content of immune factors such as IgA, IgG, cytokines, and antimicrobial proteins [ 30 , 37 , 38 , 39 ]. Changes in the composition, quality, and quantity of cervical mucus due to either urogenital microbial carriage or systemic disorders affecting the function of cervical crypts, can result in abnormal functioning of the cervix as an immune and anti-infective valve for the upper floors of the reproductive system [ 40 ].…”

Androgen excess: a hallmark of polycystic ovary syndrome

“…Estrogen reduces the bioactivity of androgen by increasing SHBG contents. One study pointed out that the 6 months of OCP treatments worsened the IR state and hepatic lipid accumulation, which is closely associated with exacerbated inflammation ( 119 , 120 ). A combined OCP, including estrogen and progestin components, provides greater benefits for HA, but increased thrombotic risk limits its use ( 121 ).…”

Exploration on the Role and Mechanism of Chronic Inflammation on Polycystic Ovary Syndrome Based on Blood-Water Homoeopathy in Chinese Medicine

“…Inflammatory factors can increase endothelial permeability and promote leukocyte aggregation and adhesion on the endothelium, which have the effect of enhancing thrombus formation and delaying thrombus dissolution. In patients with hyperglycaemia and hyperinsulinism, vascular endothelial cells are damaged, platelet reactivity and adhesion are increased, coagulation factor expression is promoted, and the concentration of PAI-1, the main physiological inhibitor of fibrinogen activator, is increased, resulting in the upstream stage of thrombus formation [14] . The presence of viscous, running blood in obese PCOS patients is also a high risk factor for the prethrombotic state.…”