J Bagh College Dentistry Vol. 29(1), March 2017 Salivary Free Pedodontics, Orthodontics and Preventive Dentistry 165 Salivary Free Testosterone and Gingival Health Condition among a Group of Women with Polycystic Ovary Syndrome AndalusAbid HassanTahir, B.D.S. (1) Baydaa Hussien,B.D.S, M.Sc. (2) ABSTRACT Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women in their reproductive age.It is characterized by anovulation or oligo-ovulation and hyperandrogensim.Androgen excess is the central defect in polycystic ovary syndrome. It is a complex disorder affects general health in addition to oral health.This study aimed to assess the gingival health status among a group of women with polycystic ovary syndrome as well as to estimate the levels of salivaryfree testosterone in unstimulated saliva in relation to gingival health condition. Materials and methods: Sixty two women with an age range 20-25 years old and with a body mass index range18.5-24.9 (normal weight) were included in this study. They were divided into two groups; the study group which included thirty one women with polycystic ovary syndrome, those women. nattended Babylon Teaching Hospital/ Infertility Center and the control group which included thirty one women with regular menstrual cycles,without clinical or biochemical features of hyperandrogenism and ultrasound exclusion of polycystic ovary (without polycystic ovary syndrome). Collection of unstimulated salivary samples was carried out under standardrizedconditions, salivary free testosterone levels were estimated. Plaque index of Silness and Lӧe (1964) was used to assess dental plaque. While gingival index of Lӧe and Silness (1963) was used to assess gingival inflammation. Data analysis was conducted through the application of the (SPSS version 18). The analysis of data included: Mean, Standard deviation, t-test, Pearson Correlation (r), Receiver Operative Characteristics Curve (ROC curve). Results:Results showed that the mean value of plaque index was found to be higher in the control group (1.18±0.03) than that in the study group (1.00±0.08) with statistically highly significant difference (p<0.01).While the mean value of gingival indexwas higher among the study group (1.52±0.06)than that in the control group (1.31±0.05)with statistically highly significant difference (p<0.01).Salivary levels of free testosterone among women with polycystic ovary syndrome (44.12±1.37 pg/ml) were found to be higher than that of control (18.50±0.87) with statistically highly significant difference (p<0.01).The results in this study showed that the correlations between salivary free testosterone with the oral variables (plaque index, gingival index) were statistically not significant (P>0.05). In order to assess the specificity and sensitivity of the use of salivary free testosterone as a diagnostic tool, statistical analysis of Receiver Operative Characteristics Curve (ROC) was used and predictive Value Measurmentswere done in this study. The results showed that the area under the curve for salivary free testosterone test was (1.000) with highly significant p-value (p<0.01). The best optimal cut off point for salivary free testosterone was (30.86) with (100%) sensitivity and specificity, indicating a very good predictive capacity for using salivary free testosterone as a marker for the diagnosis of polycystic ovary syndrome. Conclusions : It was concluded that gingival inflammation was high among women with polycystic ovary syndrome. Furthermore, salivary levels of free testosterone were found to be high among women with polycystic ovary syndrome. Key words: polycystic ovary syndrome, salivary free testosterone, plaque index, gingival index. (J Bagh Coll Dentistry 2017; 29(1):165-169) INTRODUCTION Polycystic ovary syndrome (PCOS) is now recognized as a common, heterogenous, heritable disorder affecting women throughout lifetime(1) and it is the leading cause of female anovulatory infertility (2) .The exact cause of PCOS is unknown, however, it results from a combination of genetic and environmental factors(3). The precise prevalence of PCOS is unknown as the syndrome depends on the diagnostic criteria used, however, World Health Organization (WHO) estimates that it affected 116 million women worldwide in 2012 (3.4% of women)(4).PCOS is chronic condition of anovulation or oligovulation with clinical or biochemical hyperandrogenism which occurs in the absence of other underlying condition(5). (1) Master student , Department of Pedodontic and Preventive Dentistry, College of Dentistry, University Baghdad. (2) Assistant Professor, Department of Pedodontic and Preventive Dentistry, College of Dentistry, University Baghdad. It was found that the majority of women with PCOS demonstrated elevated circulating androgen levels(6). Serum level of free testosterone, and not total testosterone, are more frequently elevated in women with PCOS (7). It has become evident over the past 30 years that PCOS is more than a reproductive disorder(8). PCOS shows a link with oral health in addition to its effect on general health (9).Periodontal diseases and PCOS are the most common disorders in women with significant public health impact(10).This syndrome have an impact on gingival inflammation or vice versa(9).It was found that the salivary free testosterone level was high in gingivitis patients (11). Salivary diagnostic approaches have been developed to monitor oral diseases such as periodontal diseases(12,14).Saliva is said to be a "mirror of the body" because it provides vital clues to systemic health (14); therefore, saliva has become J Bagh College Dentistry Vol. 29(1), March 2017 Salivary Free Pedodontics, Orthodontics and Preventive Dentistry 166 useful as an alternative for blood in medical diagnosis and research(15).Besides, the development of new technologies may promote a wider use of salivary assay in the near future (16). As far as it is known, there was no previous Iraqi study concerning the estimation of the salivary levels of free testosterone and their relation with gingival health condition among women with PCOS. Furthermore, in order to gain knowledge regarding the gingival health status and salivary free testosterone for this target group in which saliva may provide a simple, inexpensive and noninvasive measure, therefore, this study was designed and conducted. MATERIALS AND METHODS The total sample composed of sixty two females aged(20-25) years with normal weight (body mass index range of 18.5-24.9). Those were divided into two groups: thirty one women newly diagnosed with PCOS who referred to Babylon Teaching Hospital/ Infertility Clinic as a study group and thirty one women with regular menses,without clinical or biochemical features of PCOS and ultrasound exclusion of polycystic ovary syndrome from the relatives of those women as a control group. This study was carried out during the period from the end of December (2014) till the end of May (2015). The study group was diagnosed according to Rotterdam criteria(17).Exclusion criteria included: smocking,pregnancy,previous diagnosis of condition with hormonal disturbance,presence of systemic disease(diabetes,hypertention,cardiovascurdisease),m edication affecting periodontium (antiepeliptic,immunosuppresent, antihypertensive, corticosteroid), confounding medications(contraceptive pills, steroid hormone), use of antibiotic and /or inflammatory drugs within the last months,the presence of less than 20 natural teeth (less representive for periodontal condition).Collection of unstimulated salivary samples was carried out under standardrized conditions following the instruction cited by (Navazesh and Kumer,)(18),the salivary samples were collected and stored in -20C until analysis, salivary free testosterone level (pg/dl) was measured by ELISA method using DEMEDITEC ELISA kit(19). Plaque index of Silness and Lӧe(20)was used to assess dental plaque. While gingival inflammation was evaluated using gingival index of Lӧe and Silness (21).Data analysis was conducted through the application of the (SPSS version 18). The analysis of data included:Mean, Standard deviation, t-test, Pearson Correlation (r), Receiver Operative Characteristics Curve (ROC curve). RESULTS Table (1) shows the mean values of plaque index and gingival index among the study and control groups. It was found that the mean value of plaque index was higher in the control group than that in the study group with statistically highly significant difference (p<0.01).While the mean value of gingival index was higher among the study group than the control group with statistically highly significant difference (p<0.01). Table (2) shows the mean values of salivary free testosterone for both the study and control groups. The result revealed that the salivary level of free testosterone was higher among women with PCOS than their level in the control group with statistically highly significant difference (p<0.01). Table (3) shows the correlation between salivary free testosterone with oral variables (PlI and GI). It was found that all correlation between salivary free testosterone and oral variables were statistically not significant(P>0.05). Table (4) shows the best optimal cut off point for salivary free testosterone as a diagnostic tool. It was found that the optimal cut off point for salivary free testosterone was (30.86) with (100%) sensitivity and specificity and the area under the curve was (1.00). Table1: Plaque index and gingival index(mean±SD) among the study andcontrol groups. Variable Group Statistical Difference Study Control Mean ±SD Mean ±SD t-test p-value PlI 1.00 0.08 1.18 0.03 12.30 **0.00 GI 1.52 0.06 1.31 0.05 15.09 **0.00 **=Highly significant ( P<0.01). df=60 Table 2: Salivary free testosterone (mean±SD) among the study and control groups. Variable Group Statistical Difference Study Control Mean ±SD Mean ±SD t-test p-value Salivary free testosterone (pg/ml) 44.12 1.37 18.50 0.87 88.08 0.00** **=Highly significant at P<0.01 df=60 J Bagh College Dentistry Vol. 29(1), March 2017 Salivary Free Pedodontics, Orthodontics and Preventive Dentistry 167 Table 3: Correlation coffecient between salivary free testosterone with plaque index, gingival index among the study and control groups. Variable Study Control PlI GI PlI GI Free testosterone (pg/ml) r P R P r P r P -0.01 #0.98 -0.08 0.69# -0.11 #0.54 0.15 #0.43 # = not significant at P>0.05 Table 4: Cutoff point, sensitivity, specificity and area under curve of salivary free testosterone. Variable Test Result Variable(s) Cut off Sensitivity % Specificity % Area under curve P- value Salivary free testosterone Optimal 30.86 100 100 1.00 .000** **=Highly significant at P<0.01 DISCUSSION Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women in their reproductive years (22). It affects general health as well as oral health (9). The results of the current study showed that the mean value of the plaque index was found to be higher in the control group compared to that in the study group with statistically highly significant difference (p˂0.01). This may be due to oral health negligence in the control group and this could be attributed to lack of motivation about dental plaque control. This resultwas inconsistent with the result reported by previous studies(9,10,23)which found that the mean value of dental plaque was lower in the control group. The result of present study showed a highly significant increased gingival inflammation represented by higher gingival index among PCOS group. This result was also reported by other researchers(8, 23)who found thatgingivitis was higher in the PCOS group than that in the control group. This could be explained by the fact that gingival inflammation may be linked to systemic inflammation (24).It was reported that PCOS is considered as a state of a low grade chronic inflammation(25).Furthermore, PCOS is one of the endocrine disorder characterized by hormonal imbalance and among these, steroid hormones (26) which have been mostly linked with periodontal pathogenesis (27). It was found that the gingival tissue is one of the targets for steroid hormones which can exacerbate gingivitis during period of hormonal flactuation(28). A previous study reported an increase in the level of estrogen hormone among women with PCOS(26), the gingival tissue respond to increased level of estrogen hormone by undergoing vasodilatation and increased capillary permeability also there is increased migration of fluid and white blood cells out of blood vessels. Cyclic increase in the production of sex steroid hormones often alter the biology of gingival tissue and vasculature, and recognition by effector cells of the local immune system (29,30). The current study revealed that salivary free testosterone level was higher in the study group than that in the control group with statistically highly significant difference (p˂0.01). This result was also reported by previous study(31). The highly significant increase in salivary free testosterone among women with PCOS could be explained by the fact that androgen excess is the central defect in PCOS women and hyperandrogenism is the most common characteristic feature of this syndrome, the level of serum free testosterone is increased in women with PCOS (5) due to decrease sex hormone binding globulin (SHBG) production (7). It was reported that there is a correlation between serum free testosterone and salivary free testosterone (32),so, the increase in the level of free testosterone in serum could explain the increase in salivary free testosterone level among women with PCOS. In this study, it was found that salivary free testosterone is considered as the most specific and sensitive biochemical marker that used as a diagnostic tool for women with PCOS, this is supported by the result of Receiver Operative Characteristics Curve (ROC) that was used to assess the specificity and sensitivity of the use of salivary free testosterone as a biomarker for PCOS. In medicine, the ROC analysis had been extensively used in the evaluation of diagnostic tests (33). It was found that the area under the curve for free salivary testosterone was (1.00) and (100%) sensitivity and (100%) specificity with cut off point of (30.86) indicating very good predictive capacity for the use of salivary free testosterone as a biomarker for the diagnosis of PCOS. In current study, the correlations between salivary free testosterone with oral variables (PlI, GI) were found to be statistically not significant (p˃0.05). The result of this study was inconsistent with previous study(11) which found that GI, PlI were significantly correlated with increased salivary free J Bagh College Dentistry Vol. 29(1), March 2017 Salivary Free Pedodontics, Orthodontics and Preventive Dentistry 168 testosterone. On the other hand, another study(34)found that the level of salivary free testosterone decreased in gingivitis patients. It was reported that testosterone has an anti-inflammatory effect on periodotium(35,36). It has an inhibitory effects in the cyclooxygenasepathway of arachidonic acid metabolism in the gingiva by inhibiting prostaglandin secretion(37),and stimulates bone cell proliferation and differentiation and therefore has a positive effect on bone metabolism (38). One must keep in mind the contrast in the result among studies could be attributed to differences in diagnostic criteria employed,sample size, differences in biochemical procedures, even differences in statistical methods employed and difference in the way of saliva collecting, type of saliva collected (stimulated or unstimulated),in addition to differences in inclusion criteria used for selection of women, in this study, only women with a normal weight were included in the study while in previous studies, there was no restriction in the criteria used for selection of women with PCOS. From the results of this study, it was concluded that women with PCOS had high gingival inflammation, thus, an organized, comprehensive oral health preventive and educational programs in addition to the intense oral hygiene programs are essential to improve the gingivalhealth condition of women with polycystic ovary syndrome.Frthermore, salivary levels of free testosterone were found to be high among women with polycystic ovary syndrome. An interesting result in this study that salivary free testosterone can be used as a marker for diagnosis of women with polycystic ovary syndrome. REFERENCES 1. Sirmans S, Kristen pate A. Epidemiology, Diagnosis and Management of polycysticovary syndrome. J Clin epidemiology 2014;(6): 1-13. 2. Tang T, Glanville J, Orsi N, Balen AH. The use of metformine for women with PCOS undergoing IVF treatment. Hum Reprod 2006;21(6):1416-1425. 3. Goodarzi M O, Dumesic D A, Chazenbalk G, Azziz R. Polycystic ovary syndrome: Etiology, pathogenesis and diagnosis. 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J Bone Miner Res 1997;12:464- 471. الخالصة تتميز متالزمة تكيس المبايض بعدم . تؤثر على النساء في عمر االنجاب خلفية الموضوع :متالزمة تكيس المبايض هي واحدة من اكثر اضطرابات الغدد الصماءشيوعا"التي ان متالزمة تكيس المبايض هي اضطراب .زيادة الهرمون الدكري هو االضطراب االساسي لمتالزمة تكيس المبايض .وزيادة الهرمون الدكري االباضة اواضطراب االباضة تقييملتقييم حدوث امراض اللثة لمجموعة من النساء المصابات بمتالزمة تكيس المبايض ول كانتان اهداف هذا البحث .باالضافه الى صحة الفم معقد تؤثر على الصحة العامة .للثةمحفز وعالقتها بصحة االفي اللعاب غير الحر الهرمون الذكريىمستو وتم تقسيم النساء الى ( 9.02-2.81راوحت بين )ت( سنة وباوزان طبيعية 02-02اعمارهن بين ) راوحتالمواد وطرائق العمل:شملت هده الدراسة اثنان وستون من النساء ت و واحد وثالثون امراة تشتمل على نفس , )مجموعة الدراسة(وحدة العقم/في مستشفى بابل التعليمي وعتين : واحد وثالثون امراة من المصابات بمتالزمة تكيس المبايض ممج على ارتفاع االندروجين اواالصابة بمتالزمة تكيس المبايض تحت االمواج فوق الصوتية )المجموعة المواصفات وبدورة شهرية منتظمة وليس لديهم اي عالمات او اعراض Silnessا لتصنيفتم استخدام مقياس الصفيحة الجرثومية وفق.ي الحر في اللعاب غير المحفزالهرمون الذكرقياس تم موحدةتم جمع اللعاب غير المحفزفي ظروف .الضابطة( and Lӧe(8992 اما )تم قياسها وفقا لمقياس اللثة فقد لتهاباLӧe and Silness(8991 ). مع وجود فرق ( 21.2±22.8)من المجموعة تحت الدراسة(21.2±81.8طة)ية كان اعلى لدى المجموعة الضابالنتائج:اظهرت النتائج ان متوسط قيمة الصفيحة الجرثوم مع وجود ( 22.2 ±18.8)منه لدى المجموعة الضابطة (29.2± 20.8)بينما القيمة المتوسطة اللتهاب اللثة كانت اعلى لدى مجموعة الدراسة .معنوي عالي بين المجموعتين من مستوياتها لدى النساء في المجموعة الضابطة (13.8±80.22)وجد ان مستويات الهرمون الذكري كانت اعلى لدى النساء المصابات بتكيس المبايض .فرق معنوي عالي اظهرت نتائج هذه الدراسة بانه اليوجد فرق معنوي بخصوص ارتباطات الهرمون الذكري مع متغيرات الفم )الصفيحة .مع وجود فرق معنوي عالي( 13.2 22.81±) ائص المستقبل الفاعل الذي يستعمل لتقييم الخصوصية والحساسية الستعمال الهرمون الدكري لقد اظهرت نتائج هذه الدراسة بان اختبار منحني خص.(ةالتهاب اللث ,الجرثومية مشيرا" الى .(خصوصية٪822(حساسية و)٪822( مع )8اللعابي كمؤشر لتشخيص متالزمة تكيس المبايض وجد بان المنطقه تحت المنحني بالنسبه للهرمون الدكري كانت ) .ص متالزمة تكيس المبايضامكانية اعتباره كمؤشر جيد لتشخي عالية في لعاب النساء الحروكانت مستويات الهرمون الذكري .االستنتاجات:لقد تم االستنتاج بان التهاب اللثة كان عاليا" لدى النساء المصابات بمتالزمة تكيس المبايض .لتشخيص متالزمة تكيس المبايضالمصابات بمتالزمة تكيس المبايض مما يقترح امكانية قياسه في اللعاب كمؤشر جيد http://www.ncbi.nlm.nih.gov/pubmed/?term=Laven%20JS%5BAuthor%5D&cauthor=true&cauthor_uid=12447098 http://www.ncbi.nlm.nih.gov/pubmed/?term=Imani%20B%5BAuthor%5D&cauthor=true&cauthor_uid=12447098 http://www.ncbi.nlm.nih.gov/pubmed/?term=Eijkemans%20MJ%5BAuthor%5D&cauthor=true&cauthor_uid=12447098 http://www.ncbi.nlm.nih.gov/pubmed/?term=Fauser%20BC%5BAuthor%5D&cauthor=true&cauthor_uid=12447098