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ORIGINAL ARTICLE  
Year : 2018  |  Volume : 11  |  Issue : 3  |  Page : 269-273
 

Towards a common etiopathogenesis: Periodontal disease and endometriosis


1 Department of Periodontology, Manipal College of Dental Sciences, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Obstetrics and Gynecology, Kasturba Medical College and Hospitals, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India

Date of Web Publication20-Nov-2018

Correspondence Address:
Dr. Swati Pralhad
Department of Periodontology, Manipal College of Dental Sciences, Mangalore, Manipal Academy of Higher Education, Manipal - 576 104, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jhrs.JHRS_8_18

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   Abstract 


Context: Periodontal disease and endometriosis are seen to share a common pathogenesis. There is only one report suggesting the possible association between the two conditions. Aims: To study the association between endometriosis and periodontal disease. Settings and Design: This was a case–control study. Subjects and Methods: Periodontal screening was carried out in 25 women with endometriosis and 25 women without endometriosis. Severity of periodontal disease was classified based on the extent of loss of attachment. Statistical Analysis Used: Student's t-test, Mann–Whitney U test, and Karl Pearson correlation coefficient tests were used for statistical analysis. Results: The proportion of women with severe periodontitis was seen to be higher among women with endometriosis (70%). Conclusions: The results of the present study indicate the existence of a relationship between endometriosis and periodontal disease. However, further studies among larger cohorts of endometriosis may provide evidence about the association.


Keywords: Endometriosis, inflammatory burden, periodontal disease


How to cite this article:
Thomas V, Uppoor AS, Pralhad S, Naik DG, Kushtagi P. Towards a common etiopathogenesis: Periodontal disease and endometriosis. J Hum Reprod Sci 2018;11:269-73

How to cite this URL:
Thomas V, Uppoor AS, Pralhad S, Naik DG, Kushtagi P. Towards a common etiopathogenesis: Periodontal disease and endometriosis. J Hum Reprod Sci [serial online] 2018 [cited 2018 Dec 10];11:269-73. Available from: http://www.jhrsonline.org/text.asp?2018/11/3/269/245879





   Introduction Top


Endometriosis is a common and important health problem of women. It is estimated to be present in 3%–10% of the women in the reproductive age group and also in 25%–35% of infertile women.[1] Endometriosis is many a times without symptoms. However, when present, they may include abdominal cramps or back pain during menstruation, painful urination or bowel movements especially during menstruation, and/or abnormal or heavy bleeding during menstruation. It is a disorder in which functional endometrium is present in locations other than the uterine inner lining; the cause of it however remains unknown. Retrograde menstruation with transport of endometrial cells, hematogenous or lymphatic spread, or direct transplantation of endometrial cells accounts for the leading theories of endometriosis. Another possible explanation is an alteration in the cellular local and humoral immune response which may affect the body's natural ability to recognize and destroy any misdirected growth of endometrial tissue.[2]

Periodontitis, a chronic inflammatory disease of the supporting structures of tooth, which is seen to occur in >85% of the general population, is also considered to manifest in individuals with altered host immunomodulatory response.[3] This may explain the variation in susceptibility to periodontal disease among individuals despite considerable accumulation of bacterial plaque including the presence of putative pathogens. Periodontal disease is usually painless, with occasional sensitivity to heat and/or cold on exposed root surfaces, localized dull pain radiating deep into the jaw, and/or gingival tenderness or “itchiness” maybe experienced by few patients.

Periodontal disease is linked to a chronic systemic inflammatory burden secondary to the systemic dissemination of periodontal pathogenic bacteria, their products (e.g., lipopolysaccharides), and locally produced inflammatory mediators (i.e., interleukin [IL]-1 β, IL-6, tumor necrosis factor [TNF]-α, prostaglandin E2, and thromboxane B2). As is the case for endometriosis, autoimmunity has been implicated in the pathogenesis of periodontal disease.[4]

Commonality with altered levels of immune modulators in patients with endometriosis and periodontal disease prompted us to explore the association between the two.


   Subjects and Methods Top


This was a case–control study carried out among women attending the gynecology care facility of the Department of Obstetrics and Gynaecology at a Government District Hospital affiliated to Medical College. The study was initiated after approval from the Institution Ethics Committee. The sample size for the study was 50, of which 25 were women with endometriosis taken as cases and 25 were those without endometriosis taken as controls. The control were age and socioeconomic status matched.

Women in the age group of 18–45 years willing to participate in the study were recruited, following written informed consent process. Pregnant women, smokers, those who had received systemic antibiotics in the last 3 months, those who had undergone periodontal treatment in the last 6 months, and those who had <20 teeth were not recruited in the study.

The recruitment of cases and controls was made by the gynecology team. The diagnosis of endometriosis was made based on the examination at laparoscopy or laparotomy whenever the patient had undergone the procedure. The patient records during the period of study of those women who had undergone laparoscopy for interval tubal sterilization, tubal evaluation for fertility workup, and those getting operated for ovarian endometrioma were screened. Their clinical and sonographic findings were noted.

Endometriosis was considered as present if on laparoscopy/laparotomy if any of the following were present:

  • “Powder-burn” or “gunshot” lesions on the serosal surfaces of the peritoneum (black, dark brown, or bluish nodules or small cysts containing old hemorrhage surrounded by a variable degree of fibrosis) or
  • “Chocolate cysts” containing a thick, viscous dark brown fluid.


Histopathological confirmation was available for only those who had surgery for endometrioma of larger than 4 cm.

The periodontal screening was carried out by a periodontist soon after recruitment. The periodontal parameters recorded were plaque index, gingival index, probing pocket depth, and loss of attachment (LOA). Periodontal disease was considered to be present if any of the following were present: if plaque index score of 1 or greater, gingival index score of ≥1.1, probing depth ≥4 mm, and LOA >3 mm.[5]

Instruments used for the periodontal screening were mouth mirror, Williams's periodontal probe (Hu-Friedy, Chicago, IL, USA), dry gauze piece or cotton, and torch for illumination.

All surfaces of all the teeth present were examined in the plaque index and gingival index and the mean was recorded.[6],[7]

Periodontal pockets were measured as the distance from the gingival margin to the location of the tip of Williams's periodontal probe inserted in to the pocket. Pocket depth was measured on each tooth, on six sites, i.e., mesiobuccal, buccal, distobuccal, mesiolingual, lingual, distolingual, and the mean was obtained.

LOA was measured as the distance from a fixed point, i.e., the cementoenamel junction to the base of the probable pocket using Williams probe. Based on the mean scores of LOA, the severity of periodontal disease was classified.[8]

Student's t-test, Mann–Whitney U-test, and Karl Pearson correlation coefficient tests were done to evaluate the association between endometriosis and periodontal disease. For all statistical calculations, the Statistical Package for the Social Sciences (Version 20, SPSS, IBM, USA) was used.


   Results Top


The mean age of women with endometriosis was 29.72 ± 6.11 years and that of women without endometriosis was 29.48 ± 5.87 years.

Scores for plaque index were similar among cases and controls (1.26 ± 0.47 and 1.26 ± 0.3 for cases and controls, respectively; P = 0.662). The measures for probing pocket depth (3.73 ± 1.12 and 3.79 ± 0.66 in cases and controls, respectively) and LOA (4.75 ± 1.35 and 4.50 ± 0.63 in cases and controls, respectively) also did not show any statistical difference, irrespective of the presence or absence of endometriosis.

However, the gingival index was seen to be significantly higher in patients with endometriosis (1.55 ± 0.53 and 1.12 ± 0.25 in cases and controls, respectively; P = 0.001).

When severity was assessed, proportion of women with moderate-to-severe periodontitis was seen to be higher among women with endometriosis [Table 1].
Table 1: Relationship between severity of periodontal disease and endometriosis

Click here to view


When the individual parameters were assessed for their inter-influence using Karl Pearson correlation, it was found that a good correlation existed on the effect of gingival index and plaque index on the remaining variables. A linear relationship was found between plaque index [Graph 1], gingival index [Graph 2], probing pocket depth [Graph 3], and LOA [Graph 4] among subjects with endometriosis.




   Discussion Top


The main finding of this study is that severe periodontal disease was seen to be associated with endometriosis. The question arises if the two be related. Since there are oxidative stress and increased reactive oxygen species (ROS) production even in periodontal disease, can this oxidative stress augment the stress for endometriosis? Similarly, the immune dysregulation seen in periodontal disease can account for the local immune deficiency propagating endometriosis. Endometriosis is an estrogen-dependent inflammatory disease that is defined histologically by the presence of endometrial gland and stroma-like tissue outside the uterus. Many theories, viz., retrograde menstruation, metaplasia, hormones, oxidative stress and inflammation, immune dysfunction, apoptosis suppression, and genetic and stem cells, have been proposed to explain the pathogenesis of endometriosis, and to date, they all remain to be conclusively confirmed.[9] However, of interest are the theories of oxidative stress and immune dysfunction. It is well described that in periodontal diseases, there is oxidative stress and the immune function is altered.

The peritoneal fluid in patients with endometriosis is seen to harbor ROS.[10] These ROS cause lipid peroxidation which leads to deoxyribonucleic acid (DNA) damage in the endometrial cells. Furthermore, the oxidative stress signals generated from ROS cause inflammation which leads to the recruitment of lymphocytes and activated macrophages which produce cytokines and induce oxidation of enzymes that promote endothelial growth.[11] The resultant accumulation of ROS propagates endometriosis. The findings that autoimmune diseases are common in women with endometriosis suggest the involvement of a defective immune response in these patients.[12] A higher concentration of activated macrophages, decreased cellular immunity, and repressed natural killer cell function is seen in women with endometriosis.[13],[14] The growth of endometrial cells in ectopic sites could be due to an inflammatory response that is triggered during the regurgitation of endometrial cells.[15] It could also be due to the secretion of cytokines and growth factors by the immune and endometrial cells, which induce cell proliferation and promote implantation and growth of ectopic lesions.[16]

Periodontal disease is a chronic inflammatory condition, where neutrophils are the predominant inflammatory cells. These neutrophils are implicated in the disease pathogenesis because of oxidative stress during phagocytosis. Moreover, this interaction leads to increased cytokine expression and immunological activity in the gingival tissues.[17] In addition, plaque being the main etiologic factor for periodontal disease, lipopolysaccharides, and DNA from these bacteria caused the activation of activating protein-1 (AP-1) and nuclear factor-kB (NF-kB) and the production of inflammatory cytokines. This causes the recruitment of hyperresponsive neutrophils, which increase the production of ROS. Activation of AP-1 and NF-kB causes activation of osteoclasts and matrix metalloproteinases which cause tissue damage. Tissue destruction further activates macrophages neutrophils and fibroblasts to generate more ROS. Thus, a vicious circle is formed with the presence of periodontal pathogens, ROS, and tissue destruction.[18]

Periodontal disease is very much remote from the area of endometriosis and trying to relate them may appear hypothetical. However, since they share similar pathogenesis, the association as manifested by higher proportion of severe periodontal disease in patients of endometriosis cannot be ignored. It can be hypothesized that the oxidative stress elsewhere, in this case, the periodontal disease, may augment the stress for endometriosis. Similarly, the immune dysregulation seen in periodontal disease can account for the local immune deficiency propagating endometriosis [Figure 1].
Figure 1: Possible mechanism linking periodontal disease and endometriosis

Click here to view



   Conclusion Top


The number patients studied were less and hence to compare and relate severity of endometriosis based on its stage and association with periodontal disease could not be carried out. Probably, a study designed to evaluate behavior of periodontal disease among larger cohorts of endometriosis at different stages may provide epidemiological evidence about the association.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Giudice LC, Kao LC. Endometriosis. Lancet 2004;364:1789-99.  Back to cited text no. 1
    
2.
Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril 2012;98:511-9.  Back to cited text no. 2
    
3.
Burt B. Research, Science and Therapy Committee of the American Academy of Periodontology. Position paper: Epidemiology of periodontal diseases. J Periodontol 2005;76:1406-19.  Back to cited text no. 3
    
4.
Sharma CG, Pradeep AR. Anti-neutrophil cytoplasmic autoantibodies: A renewed paradigm in periodontal disease pathogenesis? J Periodontol 2006;77:1304-13.  Back to cited text no. 4
    
5.
Pralhad S, Thomas B, Kushtagi P. Periodontal disease and pregnancy hypertension: A clinical correlation. J Periodontol 2013;84:1118-25.  Back to cited text no. 5
    
6.
Silness J, Loe H. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand 1964;22:121-35.  Back to cited text no. 6
    
7.
Loe H, Silness J. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand 1963;21:533-51.  Back to cited text no. 7
    
8.
Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999;4:1-6.  Back to cited text no. 8
    
9.
Sourial S, Tempest N, Hapangama DK. Theories on the pathogenesis of endometriosis. Int J Reprod Med 2014;2014:179515.  Back to cited text no. 9
    
10.
Wang Y, Sharma RK, Falcone T, Goldberg J, Agarwal A. Importance of reactive oxygen species in the peritoneal fluid of women with endometriosis or idiopathic infertility. Fertil Steril 1997;68:826-30.  Back to cited text no. 10
    
11.
Gupta S, Agarwal A, Krajcir N, Alvarez JG. Role of oxidative stress in endometriosis. Reprod Biomed Online 2006;13:126-34.  Back to cited text no. 11
    
12.
Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: A survey analysis. Hum Reprod 2002;17:2715-24.  Back to cited text no. 12
    
13.
Sikora J, Mielczarek-Palacz A, Kondera-Anasz Z. Role of natural killer cell activity in the pathogenesis of endometriosis. Curr Med Chem 2011;18:200-8.  Back to cited text no. 13
    
14.
Osuga Y, Koga K, Hirota Y, Hirata T, Yoshino O, Taketani Y. Lymphocytes in endometriosis. Am J Reprod Immunol 2011;65:1-0.  Back to cited text no. 14
    
15.
Christodoulakos G, Augoulea A, Lambrinoudaki I, Sioulas V, Creatsas G. Pathogenesis of endometriosis: The role of defective 'immunosurveillance'. Eur J Contracept Reprod Health Care 2007;12:194-202.  Back to cited text no. 15
    
16.
Ulukus M, Arici A. Immunology of endometriosis. Minerva Ginecol 2005;57:237-48.  Back to cited text no. 16
    
17.
Garg N, Singh R, Dixit J, Jain A, Tewari V. Levels of lipid peroxides and antioxidants in smokers and nonsmokers. J Periodontal Res 2006;41:405-10.  Back to cited text no. 17
    
18.
Dahiya P, Kamal R, Gupta R, Puri A. Oxidative stress in chronic periodontitis. Chron Young Sci 2011;2:178-81.  Back to cited text no. 18
  [Full text]  


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