Prevalence of Periodontitis in Erectile Dysfunction Patients

ORIGINAL ARTICLE Volume 17 Supp 1 2022 ARTICLE INFO Prevalence of Periodontitis in Erectile Dysfunction Patients Submitted: 17/01/2022 Accepted: 01/03/2022 Online: 03/08/2022 Hirzi Kamaludina*, Jamie Chin Kok Kwongb, Lili Zuryani Marmujic, Khamiza Zainol Abidina DOI: 10.21315/aos2022.17S1.OA05 a Periodontic Specialty Clinic, Gunung Rapat Dental Clinic, Ministry of Health Malaysia, 31350 Ipoh, Perak, Malaysia b Urology Clinic, Department of Surgery, Raja Permaisuri Bainun Hospital, 30450 Ipoh, Perak, Malaysia c Family Medicine Specialty Clinic, Gunung Rapat Health Clinic, Ministry of Health Malaysia, 31350 Ipoh, Perak, Malaysia * Corresponding author: [email protected] To cite this article: Kamaludin H, Kwong JCK, Marmuji LZ, Zainol Abidin K (2022). Prevalence of periodontitis in erectile dysfunction patients. Arch Orofac Sci, 17(Supp.1): 73–84. https://doi.org/10 .21315/aos2022.17S1.OA05 To link to this article: https://doi.org/10.21315/aos2022.17S1.OA05 ABSTRACT Erectile dysfunction (ED) and periodontitis have common risk factors, such as diabetes mellitus and tobacco smoking. Multiple reports are available in regard to the association between ED and chronic periodontitis (CP). The study aimed to determine the association of ED and CP in selected Malaysian population. In this study, 74 patients (mean age = 52.4 ± 10.9 years old) diagnosed with ED, from scores via the International Index of Erectile Function (IIEF-5) questionnaire, were included. ED severity was classified as mild, mild to moderate, moderate, and severe. Periodontal condition was recorded using basic periodontal examination (BPE) method, of which scores of 0, 1, 2, and 3 were associated with having no periodontitis while a score of 4 was considered to have periodontitis. There are 40 (54.1%) subjects found to have periodontitis and the association of ED and periodontitis showed a moderate positive degree of correlation, ρ = 0.487 (p < 0.001). The percentage of subjects having periodontitis indicated an increasing trend with the severity of ED; from 19.0% (mild ED), 54.2% (mild to moderate ED), 75.0% (moderate ED), to 84.6% (severe ED). A greater degree of correlation was noted between dental scaling experience and ED, ρ = 0.635 (p < 0.001). Binomial logistic regression had shown no other co-morbidities and factors were affecting this relation. There seemed to be an association between ED and periodontitis existing in these selected Malaysian populations. Keywords: Basic periodontal examination (BPE); chronic periodontitis; dental scaling; erectile dysfunction; International Index of Erectile Function (IIEF-5) INTRODUCTION Periodontitis is defined as the inflammation of the gingiva extending to the adjacent attachment apparatus, which can be described by the destruction of both the periodontal ligaments and the supporting alveolar bone and may cause the loss of functioning dentition if left untreated. Oral health-related quality of life (OHRQoL) in patients suffering from periodontitis are low when compared to periodontally healthy subjects (Durham et al., 2013). In Malaysia, the burden of periodontal diseases is high, as 94% of adults are experiencing some form of the disease while 18.2% of the population Archives of Orofacial Sciences. 2022; 17(Supp.1): 73–84 http://aos.usm.my/  Penerbit Universiti Sains Malaysia. 2022 This work is licensed under the terms of the Creative Commons Attribution (CC BY) (http://creativecommons.org/licenses/by/4.0/). 73 Archives of Orofacial Sciences 2022; 17(Supp.1): 73–84 is suffering from severe form of chronic periodontitis (CP) (Mohd Dom et al., 2016). Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance. ED patients are having significantly diminished health-related quality of life (HRQoL) (Litwin et al., 1998). Most men who develop ED have underlying vascular changes usually from complications of atherosclerosis, giving rise to vasculogenic ED due to impairment of smooth muscle relaxation, occlusion of cavernosal arteries, or both (Carneiro et al., 2010). CP is proposed to contribute to the aetiology of ED via an increase of serum C-reactive protein (CRP) and tumour necrosis factor-α (TNF-α) (Zuo et al., 2011). CRP and TNF-α inhibit the expression of endothelial nitric oxide synthase (eNOS) in endothelial cells and reducing its biological activity (Venugopal et al., 2002; Carneiro et al., 2010) sequentially decreasing the production of nitric oxide (NO) and in turn decreasing cyclic guanosine monophosphate (cGMP) levels, resulting in the inhibition of endothelial dependent corpus cavernosum smooth muscle relaxation (Burnett, 2006). There are studies done all over the world positively linking CP as the causal factor for ED, either done as a population-based study or as a more focused single centre study (Kellesarian et al., 2018). Thus, the prevalence of CP in severe ED subjects varies but can be up to 81.8% (Sharma et al., 2011). Other related research showed that subjects with ED are more likely to have CP, with an OR of up to 2.28 (Liu et al., 2017). To the best of our knowledge, no study had been done in Malaysia which relates the link of periodontitis to ED. Thus, the aim of this study was to find out whether the positive association between ED and periodontitis applies to the Malaysian population. Meanwhile, the objectives were to quantify the prevalence of periodontitis in patients diagnosed with ED, and to assess the correlation between the severities of periodontitis with the severity of ED. 74 http://aos.usm.my/ MATERIALS AND METHODS Study Population This study was designed as a cross-sectional observational study, measuring the number of patients having periodontitis while having ED at the same point of time without any future review. In this study, 74 male patients were included; 36 subjects were obtained from the outpatient of the Urology Clinic, Department of Surgery in a government hospital and 38 subjects were acquired from screenings done at the Family Medicine Specialty Clinic in a government health clinic. Both centres are located in Malaysia. Ethical approval was attained from the Medical Research and Ethics Committee (MREC), Ministry of Health (MOH), Malaysia [Reference no.: KKM/NIHSEC/ P20-406(12)] and the study was registered with the National Medical Research Register (NMRR), Malaysia (Registration no.: NMRR-19-3936-52463). The study was conducted from July 2020 to December 2020. Each subject was ensured to be informed verbally, and consequently written informed consent was taken for participation in this study. The inclusion criteria were ED-diagnosed patients presenting to the Urology Unit and Family Medicine Specialty Clinic, aged between 30 years old to 70 years old, and had 10 teeth or more in the mouth. Whereas the exclusion criteria were patients currently taking nitroglycerin for myocardial infarction, taking calcium channel blockers medications for hypertension, taking systemic antibiotics within the last six months, as well as having undergone non-invasive and invasive periodontal therapy within the last 12 months. Sample Size Calculation The sample size calculation using the Cochran formula when the finite population size and the estimated population proportion were known had determined that 74 subjects ORIGINAL ARTICLE | Periodontitis in Erectile Dysfunction Patients were required to estimate a large population with a 95% confidence interval (α = 0.05) based on the accumulative annual attendance of ED patients in the primary and tertiary settings, of which only 99 patients had attended both units annually complaining of ED symptoms (Uakarn et al., 2021). Meanwhile, the population proportion of 74% of ED patients suffering from periodontitis was shown by the latest casecontrol study in a European population (Martín et al., 2018). Afterwards, patients were selected by consecutive sampling method to allow for some refusal in participation. International Index of Erectile Function (IIEF-5) Questionnaire International Index of Erectile Function (IIEF-5) questionnaire was chosen because it was easy to administer, simple and short while requiring only 10 min to 15 min to be filled by respondents. It contained five questions rated on a 5-point scale from 1 to 5. The total score was calculated by adding all the answer scores together, and patients would be categorised as having ED if their IIEF-5 score was 21 points and below. Patients would not have ED if their IIEF-5 score was 22 points and above (Rosen et al., 2002). Patients that scored between 22 and 25 points would be excluded from this study. The scores are represented in Table 1. Table 1 IIEF-5 questionnaire scores in relation to ED severity IIEF-5 scores ED severity ≥ 22 No 17 to 21 Mild 12 to 16 Mild to moderate 8 to 11 Moderate 1 to 7 Severe The IIEF-5 questionnaire had been validated for the local Malaysian population (Quek et al., 2002). This questionnaire is useful to evaluate ED symptoms, and to examine prevalence and incidence as well. It is also useful as an initial screening instrument in general practice settings, and in epidemiological studies where many people are assessed (Rhoden et al., 2002). Study Procedure ED-diagnosed subjects were screened for their periodontal health on site using the basic periodontal examination (BPE), following the community periodontal index (CPI) protocol (Cutress et al., 1987). BPE is a method for periodontal screening and recording, using Ivoclar Vivadent Community Periodontal Index of Treatment Needs C (CPITN C) round handle probe (product number #718283) that has a 0.5 mm ball tip and is colour-coded black from 3.5 mm to 5.5 mm and 7.5 mm to 9.5 mm. The patient’s mouth was divided into six sextants (maxillary right, anterior and left; mandibular left, anterior and right). Each tooth was probed by moving the CPITN C probe inside the gingiva around the entire circumference of the tooth to examine at least six sites (mesiolabial, midlabial, distolabial, and the corresponding lingual or palatal areas). The highest score was then recorded in each sextant, and out of the six readings, only the single highest score was considered as the BPE score, as shown in Table 2. Measures of gingival recession, tooth mobility, the intensity of inflammation, and precise identification of pocket depths or differentiation between supra- and subgingival calculus were not included in this procedure. BPE scores of 0, 1, 2, and 3 were considered as having no periodontitis and 4 was considered as having periodontitis, as defined by the Global Burden of Disease (GBD) 2010 Study (Marcenes et al., 2013). Statistical Analysis The results were analysed using a statistical programme (IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY, USA). A descriptive analysis was conducted for the gathered data. Shapiro-Wilk tests http://aos.usm.my/ 75 Archives of Orofacial Sciences 2022; 17(Supp.1): 73–84 Table 2 The BPE coding Code Findings 0 In the deepest sulcus of the sextant, the probe’s coloured band remains completely visible. Gingival tissue is healthy and does not bleed on gentle probing. No calculus or defective margins are found. 1 The coloured band of the probe remains completely visible in the deepest sulcus of the sextant. No calculus or defective margins are found, but some bleeding after gentle probing is detected. 2 The probe’s coloured band is still completely visible, but there is bleeding on probing, and supragingival and subgingival calculus and/or defective margins are found. 3 The coloured band is partially submerged. 4 The coloured band completely disappears in the pocket, indicating a depth of greater than 5.5 mm. were performed to assess whether they were distributed normally. As it was found that the variables were not normally distributed, a non-parametric test (Fisher’s exact test) was used with a p-value of < 0.05 considered to be statistically significant. Ordinal or nominal variables were analysed for frequency and percentage. The association between the severity of periodontitis and the severity of ED was presented as percentages in a bar chart, to allow greater appreciation of its trend. Correlations were tested using Spearman’s rho (ρ). Logistic regression tests were also performed on the dependent variable against all the other independent variables collected in this study. RESULTS Demographic Data The demographic characteristics are presented in Table 3. There were 74 male subjects with a mean age of 52.4 ± 10.9 years old, ranging from 30 years old to 70 years old, selected from 85 patients that were approached. Six subjects were excluded due to the exclusion criteria, while the remaining were edentulous. The largest number of subjects belong to the 51 years old to 60 years old group of Malay ethnicities, suffering from hypertension, and smoke 1 pack or less cigarette. Majority of the subjects had never done dental scaling before in their life and out of these, some did not know anything in regard to the nature of dental scaling. Meanwhile, the highest 76 http://aos.usm.my/ percentage of ED subjects belong to the mild to moderate ED group. The percentage of subjects having periodontitis against their ED severity are presented in Table 4 and Fig. 1. The percentage of subjects having periodontitis indicated an increasing trend with the severity of ED; from 19.0% (mild ED), 54.2% (mild to moderate ED), 75.0% (moderate ED), to 84.6% (severe ED). Fisher’s exact test was p < 0.001 and Spearman’s correlation (ρ) was 0.487 (p < 0.001) indicating that there is a positive and moderate correlation. This signifies that as the ED progresses in severity, periodontitis also becomes more severe in form. Fig. 2 shows a graph of the percentage of subjects’ dental scaling experience against their ED severity. There is an increasing trend noted in the percentage of subjects that had never done dental scaling with the severity of ED. Spearman’s correlation (ρ) was 0.635 (p < 0.001) indicating that there is a positive and moderate correlation signifying that as the ED progresses in severity, there are increased likelihood that the subjects never had any dental scaling treatment performed on them. Logistics regression tests were conducted on the variables of study site, age groups, race, smoking status as well as pre-existing co-morbidities namely diabetes mellitus, hypertension, ischaemic heart disease, and benign prostatic hyperplasia. Of note, ED subjects in the age group of 51 years ORIGINAL ARTICLE | Periodontitis in Erectile Dysfunction Patients Table 3 Demographic characteristics of subjects Group Total n (100%) Sub-group 74 n Age (years old) 52.4±10.9 30–40 13 (17.6%) 41–50 16 (21.6%) 51–60 25 (33.8%) 61–70 20 (27.0%) Age range (years old) 30–70 Race Malay Medical history Smoking history 41 (55.4%) Chinese 16 (21.6%) Indian 16 (21.6%) Others 1 (1.4%) Diabetes 27 (36.5%) Hypertension 35 (47.3%) IHD 7 (9.5%) BPH 15 (20.3%) Others 10 (13.5%) Never 20 (27.0%) Stopped 22 (29.7%) Smoke ≤ 1 pack 30 (40.5%) Smoke > 1 to 2 packs Last dental visit for scaling ED severity 2 (2.7%) ≤ 1 year 9 (12.2%) > 1 year 30 (40.5%) Never 35 (47.3%) Mild 21 (28.4%) Mild to moderate 24 (32.4%) Moderate 16 (21.6%) Severe 13 (17.6%) Note: IHD = Ischaemic heart disease; BPH = Benign prostatic hyperplasia Table 4 Percentage of subjects having periodontitis against ED severity Presence of CP IIEF-5 severity Yes Total No n % n % n % 4 5.4 17 23.0 21 28.4 Mild to moderate ED 13 17.6 11 14.9 24 32.4 Moderate ED 12 30.0 4 11.8 16 21.6 Severe ED 11 14.9 2 2.7 13 17.6 Total 40 54.1 34 45.9 74 100.0 Mild ED http://aos.usm.my/ 77 Archives of Orofacial Sciences 2022; 17(Supp.1): 73–84 Fig. 1 Percentage of subjects having periodontitis against ED severity. Fig. 2 Percentage of subjects’ dental scaling experience against ED severity. 78 http://aos.usm.my/ ORIGINAL ARTICLE | Periodontitis in Erectile Dysfunction Patients old to 60 years old had an odds ratio of 2.5 of having periodontitis and then the odds ratio declined to 1.5 in the 61 years old to 70 years old ED subjects. Nevertheless, none of these results are statistically significant. It is worthy to note that ED subjects with diabetes mellitus and whom currently smoke in this study have a low odds ratio to suffer periodontitis. DISCUSSION To the best of our knowledge, the present study was the first conducted on the Malaysian population and had presented an apparent link between periodontitis and ED, and between dental scaling experience and ED. The mean age in this study is 52.4 ± 10.9 years old, concurring with a study that found age above 50 years old is the single most significant risk factor for ED (Tan et al., 2003) with its OR for the 50 years old to 60 years old age groups being similar to this study. The percentage distribution of the subjects in this study by race were almost similar to the general population distribution in Malaysia as a whole, according to a 2010 census (DOSM, 2011). There were 20.3% Indians subjects in this study as compared to 7.3% in the general population. This notable increase may be explained by the tendency of the Indian population to have ED, having an adjusted odds ratio of 1.93 as compared to the Malay, Chinese and others in the population (Tan et al., 2003). Furthermore, previous studies have found that the prevalence of ED in the Malaysian population based on race were similar (Nordin et al., 2019), closely resembling the prevalence of ED based on race of the present study. Therefore, the results of this study could be generalised to the whole Malaysian population if there was an increase in the sample size and greater number of sites were recruited. A previous crosssectional study of CP in ED (Sharma et al., 2011) which had similar methodology as ours except that it had verified the ED with penile coloured Doppler ultrasound, also had similar observations. This study had included diabetics, hypertensive, ischaemic heart disease and smoking subjects, plus patients with benign prostatic hyperplasia. In order to detect a difference with a higher precision, which is 95% confidence interval, a larger sample size was required and therefore to omit these diseases’ known risk factors would result in the inability of this study to be completed. As there were only 99 ED patients seen annually, the calculated sample size of 74 patients is already a huge sum as it is. Common established risk factors of periodontal disease and ED are diabetes, and tobacco smoking. Poorly controlled diabetes mellitus type 1 or type 2 is a risk factor for periodontal disease, associated with an increase in susceptibility to oral infections including periodontal diseases, as well as its more rapid progression (Meng, 2007). Likewise, diabetic men have an increased risk of developing ED with a high prevalence rate, of up to 90% (Sasaki et al., 2005). However, many well-controlled diabetics can maintain periodontal health and respond well to periodontal therapy (Pucher & Stewart, 2004), which may result in a lower rate of ED prevalence (Wessells et al., 2011). Conversely, tobacco smoking has a destructive effect on periodontal tissues and increases the rate of periodontal disease progression (Zini et al., 2011) via the modification of host response to the challenge of bacterial plaque (Ozçaka et al., 2011). Similarly, smoking causes oxidative stress and is accepted as a risk factor in the development of ED (Peluffo et al., 2009), with smokers being at an increased risk of ED at all points of time compared to those who have never smoked (Bacon et al., 2006). Despite this, improvements in erections after smoking cessation were reported to happen albeit in a different time frame depending on the previous smoking duration (Pourmand et al., 2004). On the other hand, this study did not find any correlation between diabetes and smoking with ED or periodontitis, which http://aos.usm.my/ 79 Archives of Orofacial Sciences 2022; 17(Supp.1): 73–84 may be explained by the small number of subjects participating in this study causing a loss of sensitivity and may be rectified by increasing the number of subjects in future studies. The overall prevalence of ED in this study differs from a previous study which had seen a larger proportion of ED subjects having the severe form of ED (Nordin et al., 2019), whereas the bulk of the subjects in this study were found to have mild and mild to moderate ED. This may be explained by the fact that the previous study was conducted in a larger urban centre with a higher cost of living, thus possibly translating to the higher stress experienced by subjects. Evidence had shown that chronic periodontal disease can be associated with ED (Zadik et al., 2009), via the impairment of nitric oxide (NO) production by vascular endothelium. A study demonstrated this relationship by experimentally inducing periodontitis in rats, which led to impaired penile erection and reduced endothelial nitric oxide synthase (eNOS) expression (Zuo et al., 2011). In essence, C-reactive protein (CRP) and tumour necrosis factor-α (TNF-α) are two important cytokines and inflammatory markers, inhibiting the endothelial cells’ production of eNOS, in turn causing its biological activity to be diminished (Venugopal et al., 2002). Superoxide resulting from the oxidative stress may interact with NO ensuing the reduction of its activity (Jeremy et al., 1999). All of this denotes that there is a chronic and low intensity inflammation arising from systemic response initiated by periodontitis, subsequently causing a deterioration in endothelium-dependent vascular dilatation (Villar et al., 2006). This may explain the stronger degree of correlation between previous scaling experience and IIEF-5 severity (ρ = 0.635) in contrast with the correlation of the severity of CP against the severity of ED (ρ = 0.487). Bacterial load inside the periodontal pockets as a result of failure in obtaining regular 80 http://aos.usm.my/ professional dental treatments such as scaling may have caused the worsening of ED symptoms in a linear progression. Whereas studies had shown that the amount of dental plaque and calculus may not result in periodontal disease progression in a linear fashion, as it also depends on the variability of microbe-induced host immune response (Pan et al., 2019). Proper immune response will dominate if local tissue stimulation and host immune response are balanced (Moutsopoulos & Konkel, 2018). Periodontal tissue destruction is initiated if the pathogenicity of the local microbial population is elevated by the colonisation of keystone pathogens causing over-activation of the host immune response via proinflammatory cytokines, such as interleukins families and tumour necrosis factors (Pan et al., 2019), affecting its homeostatic balance. Moreover, periodontal treatment has been suggested to improve endothelial dysfunction (Tonetti et al., 2007), but evidence had suggested that this may be confined to the population with severe CP (Amar et al., 2003). Periodontal bacteria, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, with their lipopolysaccharides (LPS)-mediated effects have been shown to cause endothelial dysfunction (Kebschull et al., 2010) via penetration into the vascular endothelium. On the other hand, it is imperative to note that there is a high number of subjects (47.3%) that had never sought dental treatment, especially routine maintenance such as dental scaling. A substantial number of subjects also did not seek dental scaling treatment annually. It is generally accepted that females displayed lower periodontal disease prevalence and severity than males (Furuta et al., 2011), crediting to the fact that the female gender has a better oral health behaviour and hygiene status, even though dental fear is more prevalent and more severe amongst them. Thus, it was suggested that males’ attitude is to be blamed for their shortfall in dental care ORIGINAL ARTICLE | Periodontitis in Erectile Dysfunction Patients utilisation, as attitude affects behaviour directly (Skaret et al., 2003). Consequently, it can be hypothesised that with routine dental treatment such as scaling, the association between periodontitis and ED would be weakened, as periodontal disease is eliminated. During the duration of this study, there were notable instances of five ED patients that were excluded as they were edentulous, while at the same time were reported to be unresponsive to the prescribed oral phosphodiesterase-5 (PDE-5) inhibitors. All five patients were informed of having extracted all of their teeth due to mobility in a short period of time (within a few years) when they were relatively young (around their late 30s and early 40s). These appeared to be classic signs and symptoms of a severe form of periodontitis. Hence, it can be postulated that some sort of unknown causative pathways is responsible, whether it be their own hosts’ uncontrolled proinflammatory immune responses or because of the virulence characteristics of existing periodontal pathogens present, which had possibly damaged their endothelial cells permanently. A possible link is via genetic predisposition to overexpression of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) enzymes causing excessive reactive oxygen species (ROS) production, consequently initiating endothelial cells damage with fibrosis (Joshipura et al., 2015). Increased NOX can also cause decreased NADPH (reduced NADP+) availability, lessening NO production, as NADPH acts as one of the many co-enzymes in the conversion of L-arginine into NO. method. The preferable method would be a full periodontal charting of each subject as well as radiological examinations. In this study, there was no information regarding subjects’ household income level, educational level, activity level, employment status as well as mental health status being recorded and analysed, as it was suggested that these factors may contribute to the occurrence of ED as well. Thus, it would be ideal if these factors were included in future research so that a holistic analysis may be performed. Future research should be directed to the outcomes of the severity of vasculogenic ED when periodontal therapy is performed in a randomised controlled trial set-up. This can establish a causative link between these two diseases. CONCLUSION There seemed to be an association between periodontitis and ED in the selected Malaysian population, as evident by the high prevalence, the rising trend of periodontitis incidence plus never having dental scaling done, with the severity of ED. Thus, it is advisable to enquire periodontitis patients regarding the possibility of having ED by utilising the validated and simple IIEF-5 questionnaire, and vice versa, and then to refer accordingly for the benefit of patients. ACKNOWLEDGEMENTS We would like to thank the Director General of Health, Malaysia for his permission to publish this article. Study Limitations REFERENCES One of the limitations in this study was the use of BPE scoring to determine the presence of periodontitis. It was done to simplify the method of data collection due to logistics constraints and the limited availability of funds. 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