Fertility and Sterility
Volume 95, Issue 1 , Pages 320-323, January 2011

Periodontal disease in polycystic ovary syndrome

  • Erhan Dursun, D.D.S.

      Affiliations

    • Department of Periodontology, School of Dentistry, Hacettepe University, Ankara, Turkey
    • ,
  • Ferda Alev Akalın, D.D.S., Ph.D.

      Affiliations

    • Department of Periodontology, School of Dentistry, Hacettepe University, Ankara, Turkey
    • ,
  • Güliz Nigar Güncü, D.D.S., Ph.D.

      Affiliations

    • Department of Periodontology, School of Dentistry, Hacettepe University, Ankara, Turkey
    • ,
  • Nese Çınar, M.D.

      Affiliations

    • Endocrinology and Metabolism Unit, Department of Internal Medicine, School of Medicine, Hacettepe University, Ankara, Turkey
    • ,
  • Duygu Yazgan Aksoy, M.D.

      Affiliations

    • Endocrinology and Metabolism Unit, Department of Internal Medicine, School of Medicine, Hacettepe University, Ankara, Turkey
    • ,
  • Tolga Fikret Tözüm, D.D.S., Ph.D.

      Affiliations

    • Department of Periodontology, School of Dentistry, Hacettepe University, Ankara, Turkey
    • ,
  • Kamer Kılınc, M.D.

      Affiliations

    • Department of Biochemistry, School of Medicine, Hacettepe University, Ankara, Turkey
    • ,
  • Bülent Okan Yıldız, M.D.

      Affiliations

    • Endocrinology and Metabolism Unit, Department of Internal Medicine, School of Medicine, Hacettepe University, Ankara, Turkey
    • Corresponding Author InformationReprint requests: Bülent Okan Yıldız, M.D., Endocrinology and Metabolism Unit, Department of Internal Medicine, Hacettepe University School of Medicine, 06100, Sıhhiye, Ankara, Turkey (FAX: 90-312-2322518).

Received 8 May 2010; received in revised form 19 June 2010; accepted 8 July 2010. published online 31 August 2010.

Article Outline

Polycystic ovary syndrome (PCOS) and periodontal disease (inflammatory diseases of the tissues around teeth) are common disorders associated with diabetes and cardiometabolic risk. Comprehensively examining the periodontal status in PCOS, this study suggests that the susceptibility for periodontal disease may significantly increase in patients with PCOS compared with healthy young women, and that local/periodontal oxidant status appears to be affected in PCOS.

Key Words: Periodontal disease, gingivitis, oxidative stress, androgen excess, insulin resistance

 

Polycystic ovary syndrome (PCOS) is a common disorder affecting 6%–8% of women of reproductive age (1). Women with PCOS have an adverse cardiometabolic risk profile, including insulin resistance (IR), central obesity, dyslipidemia, and increased prevalence of cardiovascular risk factors. Accordingly, PCOS might be viewed as a gender-specific form of the metabolic syndrome (2).

Periodontitis is a common chronic infection characterized by an exaggerated gingival inflammatory response against pathogenic bacterial microflora, resulting in alveolar bone and eventually tooth loss (3). Several lines of evidence established the association between periodontitis and systemic disorders, including metabolic syndrome, diabetes, and cardiovascular disease (CVD) 4, 5. Because both periodontitis and metabolic syndrome are associated with systemic inflammation and IR, these two disorders may be linked through a common pathophysiologic pathway (4).

Available evidence suggests that oxidative stress may be a common link for the association between periodontitis and components of the metabolic syndrome, diabetes, and CVD (6). Both nitrites and nitrates, which appear in nitric oxide (NO) metabolism, and myeloperoxidase (MPO) are considered to reflect the strength of oxidative stress (7).

Gingival crevicular fluid (GCF) is a complex mixture of substances derived from serum, leukocytes, and structural cells of periodontium and oral bacteria (8). GCF is the most appropriate fluid to sample when investigating periodontal status. Because it passes through the tissues and accumulates biomarkers of tissue events (7). GCF analysis has been an object of investigations for early detection of periodontitis (9).

To our knowledge, there are no studies evaluating the relationship between periodontal disease and PCOS. We aimed to investigate periodontal status in women with PCOS and to evaluate potential interrelationship between periodontal clinical and oxidant status in the syndrome.

We studied 25 nonobese PCOS patients and 27 age- and weight-matched healthy control women. The PCOS diagnosis was based on the 2003 Rotterdam criteria (10). All patients had clinical and/or biochemical hyperandrogenism and chronic oligoanovulation, and 17/25 (68%) had polycystic ovaries (PCO) on ultrasound. Hyperandrogenism and chronic oligoanovulation were defined as previously described (11). PCO was defined as the presence of ≥12 follicles in each ovary each measuring 2–9 mm in diameter and/or increased ovarian volume (>10 mL). Cushing syndrome, nonclassic congenital adrenal hyperplasia, hyperprolactinemia, thyroid dysfunction, and androgen-secreting tumors were excluded, as suggested by the criteria (10).

The control group consisted of healthy women who had regular menstrual cycles without clinical or biochemical hyperandrogenism or PCO. All subjects included in the study were never smokers, and had no history of systemic disease or any drug use, including oral contraceptives, for ≥3 months, and all had normal glucose tolerance.

The study protocol was approved by Institutional Review Board of Hacettepe University Medical School, and written informed consent was obtained from each of the participants. Anthropometric measurements, including height, weight, body mass index (BMI), waist circumference, and waist-to-hip ratio (WHR), were determined. After overnight fasting, periodontal examinations, GCF sampling, and standard 2-hour 75 g oral glucose tolerance test (OGTT) were obtained. All blood and GCF samplings and periodontal examinations were performed at the same day in early follicular phase (days 2–5).

All of the participants were clinically and radiographically evaluated. Clinical periodontal parameters including probing depth (PD) (12), clinical attachment level (CAL) (12), gingival index (GI) (13), bleeding on probing (BOP%) (12), and plaque index (PI) were recorded (14). Panoramic radiographs were taken from all subjects.

Three single-rooted teeth in the maxillary anterior region having the most prominent gingival inflammation were chosen for GCF sampling. The samples were obtained according to the method described by Rudin et al. (9) using standardized paper strips (Periopaper, no. 593525; Ora Flow, Amityville, NY, USA).

Hormonal and biochemical parameters, including fasting glucose and insulin, and glucose-120 during OGTT, total testosterone (tT), DHEAS, SHBG, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were measured as previously described (15).

For the evaluation of oxidant status, MPO and NO in GCF and NO in serum were measured (7). MPO activity of GCF was measured using the spectrophometric MPO assay that is a modification of the method reported by Suzuki et al. (16). GCF and serum NO levels were determined as previously described (17).

All data were analyzed using SSPS version 13.0. Continuous variables were analyzed using a two-tailed Student t test. For nonparametric variables (BOP%, Ferriman-Galwey score), data were compared using Mann-Whitney U test. Pearson/Spearman coefficient was used to examine the correlations. Stastistical significance was defined as P<.05.

The clinical, hormonal, and metabolic features of the subjects are presented in Table 1. Although the groups were weight matched, the mean BMI was higher in the PCOS group (P=.01). Nevertheless, none of the participants in any group had a BMI of ≥27 kg/m2. PCOS group had higher tT, lower SHBG, and higher free androgen index (FAI) levels (P<.001 for all). Fasting glucose levels were similar between the groups, whereas fasting insulin, homeostasis model assessment of IR and glucose-120 were higher in women with PCOS (P=.003, P=.009, P<.001, respectively). Among lipid parameters, TC and HDL-C levels did not show a difference between the groups, whereas TG levels were higher among women with PCOS (P=.02).

Table 1. Clinical, metabolic, and periodontal parameters of the polycystic ovary syndrome (PCOS) and control groups.
ParameterPCOSControlP value
Age22.7 ± 3.624.2 ± 2.5.087
Height (cm)162.2 ± 5.5164.8 ± 6.1.12
Weight (kg)59 ± 8.256.1 ± 7.7.18
BMI (kg/m2)22.4 ± 2.520.6 ± 1.9.01
WHR0.7 ± 0.060.7 ± 0.05.13
FG score11.2 ± 4.90.2 ± 0.5<.001
tT (ng/dL)82.5 ± 4039 ± 17.2<.001
DHEAS (ng/mL)285.1 ± 127215.6 ± 123.7.06
SHBG (nmol/L)36.0 ± 21.864.7 ± 23.8<.001
FAI11.7 ± 8.62.4 ± 1.5<.001
Fasting Glucose (mg/dL)84.2 ± 10.685.1 ± 10.4.76
Glucose-120 (mg/dL)105.8 ± 24.583 ± 15.8<.001
Fasting Insulin (μU/mL)11.5 ± 4.68.0 ± 2.5.003
HOMA-IR2.4 ± 11.7 ± 0.6.009
TC (mg/dL)162.3 ± 31.9161.4 ± 29.7.91
TG (mg/dL)97.9 ± 74.259.9 ± 18.2.02
HDL-C (mg/dL)58 ± 14.663.7 ± 13.9.17
PD1.8 ± 0.31.5 ± 0.3.013
CAL1.8 ± 0.31.7 ± 0.4.14
GI1.5 ± 0.441.0 ± 0.64.002
BOP%77.7 ± 34.833.5 ± 40.4.001
PI0.8 ± 0.20.6 ± 0.3.014
GCF Volume (μL)0.25 ± 0.190.10 ± 0.09.002
GCF MPO (U)0.99 ± 0.730.53 ± 0.64.019
GCF NO μmol/L12.97 ± 1.2312.24 ± 0.90.02
Serum NO μmol/L29.13 ± 3.4528.77 ± 3.54.71

Note: All data are given as mean ± SD (P<.05 statistically significant). To convert to the international system of units, multiply by the following conversion factors: tT (3.467 nmol/L), DHEAS (0.002714 μmol/L), glucose (0.0551 nmol/L), insulin (7.175 pmol/L), HDL-C (0.0259 mmol/L), TG (0.0113 mmol/L). BMI = body mass index; BOP% = percentage of bleeding on probing; CAL = clinical attachment level; FAI = free androgen index (tT × 100/SHBG); FG = Ferriman-Gallwey; GCF = gingival crevicular fluid; GI = gingival index; glucose-120 = plasma glucose level at 120 minutes during oral glucose tolerance test; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostasis model assessment of insulin resistance [fasting insulin (μU/mL) × fasting glucose (mmol)/22.5]; MPO = myeloperoxidase; NO = nitric oxide; PI = plaque index; PD = probing depth; TC = total cholesterol; TG = triglycerides; tT = total testosterone; WHR = waist-to-hip ratio.

In women with PCOS, clinical periodontal parameters (PD, GI, BOP%, PI) and GCF volume (subclinical sign of gingival inflammation) were higher than in the control group (P=.013, P=.002, P=.001, P=.014, and P=.002, respectively). For sampling teeth, there were no significant differences between groups regarding GI (P=.14) and PI (P=.86). GCF MPO and NO levels were higher in the PCOS group (P=.019 and P=0.02, respectively), whereas the difference in serum NO levels between groups was not significant (P=.71). In panaromic radiographs, no periodontal bone loss was detected.

There were significant positive correlations among the clinical periodontal parameters, GCF MPO and NO levels, and serum parameters. Fasting insulin and glucose-120 levels correlated with the parameters of gingival inflammation: GI–fasting insulin (r = 0.29; P=.04), GI–glucose-120 (r = 0.29; P=.04), BOP%–glucose-120 (r = 0.36; P=.009), and GCF volume–glucose-120 (r = 0.37; P=.007). GCF volume correlated with tT (r = 0.28; P=.04) and FAI (r = 0.30; P=.03).

This study suggests an increased susceptibility for periodontitis and a local/periodontal prooxidative state in lean and normal glucose-tolerant women with PCOS compared with healthy women. Our finding of higher scores of periodontal indices in PCOS patients compared with age- and weight-matched healthy control women denotes that periodontal health is deteriorated and that gingival inflammation (gingivitis) is a common finding in these patients. This is further supported by the higher GCF volume (9). Radiographic analyses revealed no periodontal bone loss in these patients, indicating that they had the periodontal disease at the gingival level (gingivitis) but not periodontal bone loss level (periodontitis). Prominent gingival inflammation at this young age may establish a ground for future periodontitis in women with PCOS (18).

The three major risk factors for periodontitis are smoking (19), obesity (19), and diabetes (20). In the present study, all participants were never smokers, nonobese, and normally glucose tolerant, excluding smoking, obesity, and diabetes as confounding factors. Nevertheless, it is well known that obesity influences the phenotypic expression of PCOS and might play a significant role in the pathophysiology of hyperandrogenism and chronic anovulation (21). Because of the aforementioned relationship between obesity and periodontitis, for PCOS patients the risk of being obese in the future jeopardizes them to also having periodontitis. Furthermore, significant correlations between the clinical signs of gingivitis and serum insulin, glucose, and androgens indicate a possible interaction between hormonal and metabolic phenotype and the periodontal status in PCOS.

In periodontitis, neutrophils play a central role in the initial host inflammatory response against periodontal pathogens (22). Consequently, oxidative stress is enhanced during periodontitis 23, 24. As an indicator of oxidative stress, increased GCF MPO levels have been shown at sites with gingivitis and chronic periodontitis 25, 26. In the present study, the women with PCOS had increased MPO and NO levels in GCF along with unaltered serum NO levels, suggesting a local/periodontal oxidative stress in these patients. It seems that local/periodontal NO metabolism is more influenced than the systemic one in PCOS. This may be due to the cumulative effects of both PCOS and gingivitis in the periodontal region. Alternatively, we might have failed to detect systemic oxidative stress due to the insensitivity of serum NO as a marker. Indeed, unaltered serum NO levels in patients with PCOS have been reported in earlier studies 27, 28, whereas studies evaluating other oxidative damage products supported the presence of systemic oxidative stress in PCOS 29, 30.

The main limitations of the present study are the relatively small sample size and its cross-sectional design. Additionally, we did not examine the influence of obesity or glucose intolerance on periodontal status in PCOS. Because periodontitis is closely linked to obesity and diabetes, severity and extent of periodontitis might be increased in obese or diabetic women with PCOS 5, 6.

In conclusion, our results suggest that the susceptibility for periodontitis may significantly increase, that gingivitis is a common finding in patients with PCOS, and that local/periodontal oxidant status appears to be affected in PCOS. Future investigations on the interrelationships between PCOS, periodontal disease, and oxidative stress are necessary to increase understanding in this field.

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Acknowledgments 

The authors thank Ayla Harmanci, M.D., Erdem Karabulut, and Murat Ozbek, D.D.S., for help in the initial coordination of the study and Metin Ödevci and Sude Eminzade for technical assistance.

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 E.D. has nothing to disclose. F.A.A. has nothing to disclose. G.N.G. has nothing to disclose. N.C. has nothing to disclose. D.Y.A. has nothing to disclose. T.F.T. has nothing to disclose. K.K. has nothing to disclose. B.O.Y. has nothing to disclose.

 Supported by Hacettepe University grant no. 0701101017.

PII: S0015-0282(10)02158-8

doi:10.1016/j.fertnstert.2010.07.1052

Fertility and Sterility
Volume 95, Issue 1 , Pages 320-323, January 2011

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