Periodontal Status and Endothelial Dysfunction in Patients With Polycystic Ovary Syndrome

NCT06184412 | Completed

• 1 other identifier: PI19/00437B
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Emerging research indicates a link between polycystic ovary syndrome (PCOS) and periodontal diseases, revealing the intricate relationship between oral health and systemic conditions. PCOS, a hormonal disorder in women of reproductive age, often associates with obesity, dyslipidemia, and insulin resistance, heightening the risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). The pathogenesis of PCOS involves an inflammatory response marked by increased CRP, inflammatory cytokines, elevated blood leukocytes, adhesion molecule expression, and oxidative stress markers like myeloperoxidase (MPO). Periodontal diseases, bacterial infections affecting gums, ligaments, cement, and bone, include gingivitis (gum inflammation) and periodontitis (irreversible tissue destruction). Evidence suggests a link between periodontitis and increased CVD risk, while such association with gingivitis is limited. Potential mechanisms linking periodontal diseases and CVD involve cytokine release, oral bacteria toxin production, and direct bloodstream transfer. Recognition of lipopolysaccharide (LPS) and TNFα triggers innate immune cells via TLR4 and TNFR, activating NF-κB and JNK expression. JNK amplifies inflammatory responses, inducing proinflammatory genes, and TNFα, IL-1, IL-6, and IL-8 can invade endothelial layers, promoting adhesion molecule expression. Enhanced leukocyte ROS production, especially in periodontitis, contributes to endothelial dysfunction and heightened cardiovascular risk. The activation of multiple inflammatory pathways likely links PCOS, periodontal disease, and increased cardiovascular risk. Thus, the researchers aim to investigate if the presence of periodontal diseases, particularly gingivitis, exacerbates oxidative stress, inflammation and atherosclerosis surrogate markers in women with PCOS, and explore the underlying molecular mechanisms.

Conditions

Periodontal Diseases

Keywords

inflammation; atherosclerosis; gingivitis; oxidative stress

Outcome Measures

Primary Outcomes (3)

• Evaluate subclinical atherosclerotic markers in the study population

  Determine leukocyte-endothelial cell interactions and cellular adhesion molecules in serum (ICAM, VCAM and p-Selectin)

  At recruitment

• Evaluate inflammatory markers in the study population

  Determine proinflammatory cytokines in serum (TNF-alpha, IL6) and expression of inflammatory mediators in leukocytes by Western blot (JNK, NFkB, MCP1)

  At recruitment

• Evaluate oxidative stress markers in the study population

  Determine serum oxidative stress markers (MPO, glutathione), expression of GPX-1 by Western blot and total ROS, mitochondrial ROS and superoxide by flow cytometry in leukocytes.

  At recruitment

Secondary Outcomes (4)

• Evaluate inflammasome complex activation in the study population

  At recruitment

• Evaluate markers of autophagy in the study population

  At recruitment

• Evaluate markers of ER stress in the study population

  At recruitment

• Evaluate markers of mitochondrial biogenesis and complexes in the study population

  At recruitment

Study Arms (2)

Control group without periodontal disease

Women without periodontal disease neither PCOS

PCOS group with or without periodontal disease

Women with PCOS with or without periodontal disease

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: According to presence of polycystic ovary syndrome
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Primary care clinic

You may qualify if:

• Women with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria:
• Irregular ovulation (cycles longer than 35 days or less than 26 days)
• Elevated levels of free testosterone (\>0.5 ng/dl)
• Hirsutism and the presence of polycystic ovaries
• Healthy women without periodontal diseases matched in BMI and age to the PCOS group.

You may not qualify if:

• Other systemic inflammatory conditions
• Recent antibiotic use
• Chronic anti-inflammatory use
• Cancerous or bone-affecting pathologies
• Diabetes or autoimmune diseases
• Use of any medication during the previous semester

Sponsors & Collaborators

• Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

Location

Related Publications (7)

• Marquez-Arrico CF, Silvestre-Rangil J, Gutierrez-Castillo L, Martinez-Herrera M, Silvestre FJ, Rocha M. Association between Periodontal Diseases and Polycystic Ovary Syndrome: A Systematic Review. J Clin Med. 2020 May 23;9(5):1586. doi: 10.3390/jcm9051586.

  PMID: 32456146 BACKGROUND

• Romandini M, Baima G, Antonoglou G, Bueno J, Figuero E, Sanz M. Periodontitis, Edentulism, and Risk of Mortality: A Systematic Review with Meta-analyses. J Dent Res. 2021 Jan;100(1):37-49. doi: 10.1177/0022034520952401. Epub 2020 Aug 31.

  PMID: 32866427 BACKGROUND

• Porwal S, Tewari S, Sharma RK, Singhal SR, Narula SC. Periodontal status and high-sensitivity C-reactive protein levels in polycystic ovary syndrome with and without medical treatment. J Periodontol. 2014 Oct;85(10):1380-9. doi: 10.1902/jop.2014.130756. Epub 2014 Mar 4.

  PMID: 24592911 BACKGROUND

• Schenkein HA, Loos BG. Inflammatory mechanisms linking periodontal diseases to cardiovascular diseases. J Clin Periodontol. 2013 Apr;40 Suppl 14(0 14):S51-69. doi: 10.1111/jcpe.12060.

  PMID: 23627334 BACKGROUND

• Greabu M, Giampieri F, Imre MM, Mohora M, Totan A, Pituru SM, Ionescu E. Autophagy, One of the Main Steps in Periodontitis Pathogenesis and Evolution. Molecules. 2020 Sep 22;25(18):4338. doi: 10.3390/molecules25184338.

  PMID: 32971808 BACKGROUND

• Domon H, Takahashi N, Honda T, Nakajima T, Tabeta K, Abiko Y, Yamazaki K. Up-regulation of the endoplasmic reticulum stress-response in periodontal disease. Clin Chim Acta. 2009 Mar;401(1-2):134-40. doi: 10.1016/j.cca.2008.12.007. Epub 2008 Dec 13.

  PMID: 19109937 BACKGROUND

• Paladines N, Dawson S, Ryan W, Serrano-Lopez R, Messer R, Huo Y, Cutler CW, Ramos-Junior ES, Morandini AC. Metabolic reprogramming through mitochondrial biogenesis drives adenosine anti-inflammatory effects: new mechanism controlling gingival fibroblast hyper-inflammatory state. Front Immunol. 2023 Jun 7;14:1148216. doi: 10.3389/fimmu.2023.1148216. eCollection 2023.

  PMID: 37350964 BACKGROUND

MeSH Terms

Conditions

Periodontal Diseases; Inflammation; Atherosclerosis; Gingivitis

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Infections; Gingival Diseases

Study Officials

• Milagros Rocha, PhD

  FISABIO-HOSPITAL DR PESET

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Postdoctoral Researcher

Study Record Dates

• First Submitted: December 14, 2023
• First Posted: December 28, 2023
• Study Start: February 1, 2020
• Primary Completion: June 1, 2022
• Study Completion: September 1, 2022
• Last Updated: January 9, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)