Association between periodontal disease and polycystic ovary syndrome : A scoping review

ISSN Online 0719-2479 www.joralres.com © 2018 70 Abstract: Background: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in women. It is believed that sex hormones play a role in the maintenance of bone mass and directly or indirectly influence several cell types, including periodontal cells. Objective: To evaluate the association between periodontal disease and PCOS according to the evidence reported in the last decade. Material and Method: A search was made in the biomedical databases: Pubmed, Embase, Scopus, SciELO, Science Direct and SIGLE for the 2007-2017 period. Selection criteria: prospective and retrospective studies reporting the relationship between periodontal disease and PCOS. The methodological quality of the studies was analyzed using the Critical Appraisal Skills Program scale. Results: 10 articles were found: 1 clinical trial and 9 case-control studies. The number of patients ranged from 48 to 196, mean age between 23.3 and 28.1 years, age range between 15 and 45 years. Studies were conducted in Turkey, India and Iran. All the studies presented good methodological quality and a positive association between PCOS and periodontal disease. Conclusion: PCOS shows a positive and significant association with the clinical and molecular parameters of periodontal diseases.

It has been recently shown that women with PCOS have high levels of TNF-α due to insulin resistance (IR) and hyperandrogenism (HA); 3,11, 26 and high levels of MMPs 6,9 and proinflammatory ILs. 11Therefore, it is plausible to assert that the severity of periodontal disease may be associated with that of PCOS.][8][9][10][11][12][13][14][15][16][17] The aim of this scoping review is to evaluate the association between periodontal disease and PCOS according to the evidence reported in the last decade.

MATERIALS AND METHODS.
This review was carried out in accordance with a previously prepared research protocol based on PRISMA statement. 27earch A comprehensive search was carried out in the biomedical databases Pubmed, Embase, Scopus, SciELO, Science Direct, SIGLE (System of Information on Gray Literature in Europe) and a manual search was also conducted from January 2, 2007 to December 1, 2017, in the journals of periodontology with the greatest impact factor, such as: Periodontology 2000, Journal of Clinical Periodontology, Journal of Periodontology.

Selection criteria
Articles reporting the relationship between periodontal disease and PCOS, without language restriction, were included in the study.Case reports, case series and systematic reviews were excluded.

Process of selection and extraction of data
The titles and abstracts of each of the studies obtained were reviewed.The full texts of the studies that met these parameters were obtained in order to determine their risk of bias.
To assess the studies, a checklist was made in duplicate, in order to extract the information of interest.Two reviewers (LG and EI) independently carried out the evaluation of the articles regarding name, author, year of publication, type of study, number of patients, age of the patients, country where the study was carried out, groups of study and conclusions.For the resolution of any discrepancy between the reviewers, they met and discussed with a third reviewer (SR) until consensus was reached.

Assessment of methodological quality
The Critical Appraisal Skills Program scale (CASP) was used for the assessment of the methodological quality of each study. 16,28This tool is based on 11 criteria and there are several versions to be used according to study type, such as randomized controlled trials or case-control studies.
Articles identified in electronic search (databases) and journals n=16 Articles selected for reading the abstracts n=12 Articles included in the systematic review n=10 Articles excluded because they were duplicates n=1 Articles selected for reading the titles n=15 Articles excluded after assessing their titles n=3 Articles excluded after assessing their abstract n = 2 Systematic review (n = 1) Case report (n = 1)  The increase in MMP-8 levels in et al. 9 35 with PCOS and gingivitis 26.4 were significantly higher in women with PCOS, who also saliva and serum seems to be more 25 systemically and periodontally healthy 25.84 exhibited more gingivitis than systemically healthy pronounced in women with PCOS 20 systemically healthy and with gingivitis 26.4 women.No significant changes were observed in salivary and is potentiated in the presence TIMP-1 levels with respect to PCOS.The serum levels of of gingival inflammation.Alterations MMP-8 and the MMP-8/TIMP-1 ratio were significantly in the MPM/TIMP system triggered higher in women with PCOS, regardless of the presence by local and systemic inflammation of gingivitis, while there were no differences in TIMP-1 may be involved in the pathogenesis levels.A positive correlation was indicated between of PCOS or in the worsening of its probing depth, bleeding on probing, plaque index and clinical presentation.salivary or serum MMP-8 levels or the MMP-8/TIMP-1 ratio in the case of PCOS, while a negative correlation for TIMP-1 was found in systemically healthy women.(18 -45) 98 systemically healthy 28.6 with bleeding on probing were significantly higher in disease is higher in women with women with PCOS (p<0.05).However, no significant PCOS.This is related to the role difference was observed in the rate of tooth loss among of chronic systemic inflammation women with and without PCOS (p=0.384).In the PCOS in the pathophysiology of both group, 92 women (93.9%) were affected by mild perio-PCOS and periodontal diseases.dontitis and 6 (6.1%) were diagnosed with moderate periodontitis.Mild periodontitis was observed in 97 women (99%) in the control group, while only one (1%) had moderate periodontitis.There was no significant difference between these groups in terms of periodontitis severity (p=0.118).The average BMI was higher in the PCOS group (p=0.01).In conclusion, susceptibility et al. 15 27 systemically healthy

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The PCOS group had a higher tT, a lower SHBG and higher to periodontitis can increase levels of FAI (p<0.001 for all).The evaluation of the significantly in patients with homeostasis model of IR and glucose-120 were higher PCOS, and gingivitis is a comin women with PCOS (p=0.003,p=0.009, respectively).mon finding; the local/perio-The levels of TC and HDL-C were not different between dontal oxidation state seems the groups, while TG levels were higher among women to be affected in PCOS.with PCOS (p=0.02).In women with PCOS, the clinical periodontal parameters and the volume of crevicular fluid (subclinical sign of gingival inflammation) were higher than in the control group.There were no significant differences between the groups with respect to gingival index (p=0.14)and plaque index (p=0.86).MPO and NO levels were higher in the PCOS group (p=0.019 and p=0.02, respectively), while the difference in NO levels between the groups was not significant (p=0.71).There were significant positive correlations between clinical periodontal parameters, MPO and NO levels and serum parameters.Fasting insulin and glucose-120 levels correlated with the parameters of gingival inflammation: fasting gingival-insulin index (r=0.

RESULTS.
The selection process of the articles is shown in Figure 1.After that, ten articles were selected for a thorough review of their content.
The number of patients ranged from 48 to 196 in the included studies, 6-15 mean age ranged from 23.3 to 28.85 years, and the age range was between 15 and 45 years.The 10 selected studies were conducted in: Turkey, 6,8,9,11,13-15 India, 7,12 and Iran. 10 Nine studies 6,8-15 were cases-controls and one study 7 was a randomized controlled trial.Characteristics, results and conclusions of the included studies are shown in Table 1.
In one study, 7 PCOS was diagnosed according to the criteria of the Androgen Excess and PCOS Society (AES-PCOS) published in 2006, which include the presence of HA (necessary condition) in combination with ovarian dysfunction (i.e.OA or ultrasound with PO), with the exclusion of other causes. 1,3,6,18Diagnostic methods, confounding factors and altered clinical parameters of the analyzed studies are shown in Table 2.
All the studies reached 10 out of a maximum of 11 points on the CASP scale.

DISCUSSION.
All the analyzed studies showed a positive association between PCOS and periodontal diseases (gingivitis and/or periodontitis).Therefore, it is possible to assert that patients with PCOS have a higher risk of developing periodontal disease.However, there are factors in all the studies that may have influenced the reported results.
First, there is the complexity and heterogeneity of PCOS, with different definitions. None of these factors alone can explain the spectrum of alterations that characterize the syndrome. 1,3,14,16,29Third, the diagnosis of PCOS is based on the Rotterdam criteria, consisting of a combination of clinical, biological and ultrasound evaluations. 1-3,29,305][46] Given that the clinical presentation of PCOS varies between continents, it is difficult to establish a universal diagnosis using only European or North American guidelines. 16,47A relevant aspect of this review was the finding of a clinical trial 7 that showed that the integral treatment of periodontal disease could also contribute to the treatment of patients with PCOS by reducing the levels of proinflammatory mediators, reactive oxygen species and oxidative stress.Therefore, future evaluation of periodontal disease in patients with PCOS should explore in greater depth the effect of non-surgical periodontal therapy on the improvement of inflammatory parameters and the severity of PCOS.
It should also be noted that eight studies 6,9-15 included strict inclusion and exclusion criteria in order to restrict confounding factors.For example, women with a BMI>25 kg/m 2 were defined as obese and excluded from a study.In addition, Deepti et al., 7 Saglam et al., 8 and Porwal et al., 12 measured the waist circumference and waist-hip ratio of the subjects.However, the selection of BMI as an indicator of obesity has its limitations because it often does not measure adiposity. 16,49In addition, one study 50 reported that Asian young adult women (all studies included in the review were conducted in Asia) tend to have lower BMI and higher percentage of body fat than other ethnic groups, so it was suggested to combine the BMI and the analysis of biometric impedance for the detection of obesity and overweight in young Asian adults.Therefore, it is hypothesized that periodontal clinical parameters and the local and systemic inflammatory profile in the PCOS groups could be associated with higher levels of undiagnosed central adiposity, which lead to chronic lowgrade inflammation. 16rom a statistical perspective, emphasis should be placed on the use of an adequate sample size together with the extraction and collection of high quality data.In addition, all studies were observational and conducted only in three Asian countries.Longitudinal, multicenter, well-designed prospective clinical studies conducted in patients of different ethnicities are suggested.
This will make it possible to generalize these findings to the global population.Nevertheless, the conclusions of the studies included in the present scoping review should be interpreted with caution.

CONCLUSION.
PCOS shows a positive and significant association with the clinical and molecular parameters of periodontal diseases.

Figure 1 .
Figure 1.Flowchart of the selection process of articles.
MMP-9 and MPO were higher in the Pg demonstrated by salivary and group compared to the Ph group (p<0.05).The serum serum levels of neutrophilic levels of MMP-9 were lower in the Hg group than in the enzymes.This interaction may Hh and Pg groups (p<0.05).The groups with PCOS exhi-contribute to the disturbance bited a positive correlation between clinical periodontal of ovarian remodeling that parameters and serum levels of MMP-9 or salivary MPO, characterizes PCOS.

Table 1 .
Characteristics of analyzed studies.Association between periodontal disease and polycystic ovary syndrome: A scoping review.
Arbildo H, Rojas S, Gamarra LG & Infantes ED.J Oral Res 2018; 7(2):70-78.doi:10.17126/joralres.2018.018ISSN Online 0719-2479 -www.joralres.com© 2018 , particularly in the case of ponse to the selective members gingivitis.The levels of Aggregatibacter actinomycetemcomitans of this microbial community, and Treponema denticola were similar between the of playing a role in the resultin gingival groups under study.The presence PCOS also increased inflammation and in periodontal serum antibody levels against P. gingivalis, Prevotella health.The most consistent intermedia and S. oralis, when gingivitis was also present.effect is exerted on Pg.Gingival inflammation correlated positively with the levels of the taxa studied in saliva, particularly in women with PCOS.The presence of P. gingivalis and F. nucleatum in saliva also showed a strong positive correlation with the corresponding serum antibody levels.The two groups of PCOS exhibited significantly TNF-α.Thus, PCOS may have an higher concentrations of TNF-α in saliva than the control impact on gingival inflammation group (p=0.024 and p=0.013, respectively).The FGS index or vice versa.was significantly higher in the PCOS + gingivitis group than in the PCOS+healthy periodontium group (p=0.030).