Endometriosis-Associated Periodontal Disease: A Large Cohort Perspective Study

Maria Teresa Agneta: conceptualization, investigation, writing – original draft, methodology, validation, visualization, writing – review and editing, supervision, project administration. Giuseppe D'Albis: conceptualization, investigation, writing – original draft, methodology, visualization, writing – review and editing, formal analysis, data curation, resources, validation. Letizia Lorusso: formal analysis, data curation, resources, software, writing – review and editing. Nicola Bartolomeo: software, formal analysis, data curation, writing – review and editing, supervision. Antonia Abbinante: investigation, methodology, writing – original draft. Anna Antonacci: investigation. Pietro Signorile: investigation, conceptualization, methodology, validation, visualization. Francesco D'Aiuto: conceptualization, investigation, methodology, validation, writing – review and editing, visualization. Elisa Mazza: conceptualization, investigation, writing – original draft, methodology, validation, visualization, writing – review and editing. Massimo Corsalini: supervision, project administration, resources. Saverio Capodiferro: conceptualization, investigation, writing – original draft, methodology, validation, visualization, writing – review and editing, formal analysis, project administration, supervision.

A total of 4072 responses were collected and investigated. 961 women (23.6%) self‐reported stage I of the endometriosis; 771 women (19.0%) reported stage II; 829 women (20.4%) reported stage III; and 1511 women (37.1%) reported stage IV. The severity of endometriosis increased significantly with age. Women over 35 years old, who represented only 40.7% at stage I, accounted for 73.0% at stage IV. Educational levels reported by women were significantly different across endometriosis stages. In stages III and IV, the percentage of women with a high school diploma was higher (52.1%) compared to stage I, where women with a university degree prevailed (55.1%). Diagnostic delay was also correlated with the stage of the disease. At stage IV, 47.6% of women reported a diagnostic delay of over 6 years, compared to 28.0% at stage I. Additionally, 18.6% of women at stage IV reported autoimmune diseases, a rate that was significantly higher than the 14.3% at stage I. Only 23.8% of women at stage I reported that their dentist or dental hygienist was aware of their condition. This percentage increased as the disease progressed: 27.8% at stage II, 35.0% at stage III, and 42.0% at stage IV. A high percentage of participants indicated that their symptoms were often minimized or dismissed by family members and close acquaintances, particularly at stages II and III. Meanwhile, the majority of women across all stages felt that the disease influenced their quality of life, with rates increasing significantly from 80.0% at stage I to 93.6% at stage IV (Table  2 ). Comparison of responses to questions on demographics, endometriosis, and medical history characteristics by stage of endometriosis. Note: In bold p ‐values < 0.05. Adjusted by multiple comparison. At stage I, 15.3% of women reported noticing changes in their oral health after taking medication, a percentage that increased in later stages (25.2% at stage II to 30.3% at stage IV). There was no correlation between general gum bleeding and the stage of the disease. However, when gum bleeding was linked to the use of endometriosis medications, a higher percentage of women reported this symptom at stage IV (9.2%) compared to stages I (4.1%) and II (6.1%). At stage III, 53.1% of women reported sore gums, compared to 45.4% at stage I. The differences between stage I and later stages became statistically significant when the survey question linked sore gums to medication use for endometriosis. When asked, “Did you think you had periodontitis?” 13.3% of women at stage III responded affirmatively, compared to 8.3% at stage I. Perceptions of dental and gum health were also significantly different. At stage I, 14.4% of women considered their oral health to be “poor,” compared to 22.1% at stage III and 19.2% at stage IV. Women at stage I reported a significantly lower frequency of non‐trauma‐related tooth mobility and bone loss around teeth compared to those at stage IV. At stage III, 55.6% of women believed their teeth needed treatment, compared to 46.5% at stage I. Additionally, 43.8% of women at stages III and IV reported dental sensitivity, compared to 36.9% at stage I. Statistically significant differences emerged between stages I and III regarding higher frequencies of dry mouth (51.5% vs. 42.2%) and burning sensations in the tongue or oral cavity (21.5% vs. 16.4%). Women at stage IV more frequently reported noticing changes in the tongue surface after their endometriosis diagnosis (19.5% vs. 13.4% at stage I). Overall, the frequency of women noticing worsening oral health problems (gingivitis, periodontitis, gum bleeding, mouth ulcers, dry mouth) or unresolved issues post‐treatment increased from 19.75% at stage I to 26.69% at stage IV (Table  3 ). Comparison of responses to questions on oral cavity disorders by stage of endometriosis. Q9B Note: In bold p ‐values < 0.05. Adjusted by multiple comparison. Women at stages II, III, and IV more frequently reported changing their diet after being diagnosed with endometriosis. They were also more frequently aware of the indirect link between the condition and pelvic floor muscle disorders. Finally, women at stages II, III, and IV reported higher rates of deep vaginal pain and changes in vaginal pain during intercourse following surgical intervention. Awareness of the positive effects of physiotherapy and rehabilitation for pelvic floor dysfunction symptoms also increased significantly, from 59.0% at stage I to 74.9% at stage IV (Table  4 ). Comparison of responses to questions on health, wellness, and lifestyle characteristics by stage of endometriosis. Note: In bold p ‐values < 0.05. Adjusted by multiple comparison. Multiple Correspondence Analysis (MCA) applied to explore relationships between answers to the questionnaire revealed that the first dimension explains 86% of the total variance, while the first and second dimensions together account for 89% of the total variability. These two dimensions were used as coordinates to construct a plot (Figure  1 ), where proximity indicates similarity between categories. The k‐means cluster analysis identified four distinct clusters, represented by different colors in the figure. Clusters of responses based on the two dimensions of multiple correspondence analysis. Notably, Dimension 1 discriminated between two major response categories: Those indicative of a negative perception of oral health (clusters 1 and 2) and those suggesting a non‐negative perception (cluster 3). For this reason, weights corresponding to the values of the first dimension were assigned to the responses of everyone. Since cluster 4 primarily included responses where patients answered, “I don't know,” these responses were assigned a weight of 0 in the score calculation (Figure  S1 ). Based on these findings, the PDP score was computed for each patient by summing the assigned weights. Multivariate general linear model was performed to examine the relationship between the PDP score and the endometriosis stage, adjusted by age class and delays in receiving the diagnosis. Endometriosis stage was a statistically significant predictor, with Stage II, III, and IV showing the largest coefficient ( β  = 0.76, p  < 0.0001; β  = 0.96, p  < 0.0001; β  = 0.66, p  < 0.0001), indicating that patients in these stages reported higher PDP scores compared to those in Stage I. The class of age had a statistically significant effect on the PDP score: women over 45 years of age showed the largest coefficient compared to women aged between 15 and 25 years ( β  = 0.76, p  < 0.0001) meaning that older women tended to report a higher score of perception of periodontal diseases, which is consistent with the well‐established evidence that both the prevalence and severity of periodontal disease increase with age. Prominent forms of periodontal disease are, in fact, very rare in individuals under the age of 25. Years passed before receiving the endometriosis diagnosis was found to be positively associated with the PDP score, suggesting that longer delays in receiving the diagnosis were associated with higher scores of the perception of periodontal diseases (Table  5 ). Results of the multivariate general linear model performed to examine the relationship between the PDP score and the endometriosis stage, adjusted by age class and delays in receiving the diagnosis. Note: In bold p ‐values < 0.05. Abbreviation: SE, standard error. Patients diagnosed after more than 6 years had a significantly higher PDP score compared to those diagnosed within 1 year (Δ = 1.71, 95% CI: 1.26–2.16) (Figure  2 ). Similarly, a diagnostic delay of 4–6 years was associated with a higher PDP score compared to < 1 year (Δ = 1.33, 95% CI: 0.76–1.89). Regarding disease severity, patients with stage III and IV endometriosis showed a higher PDP score compared to stage I (Δ = 0.96, 95% CI: 0.44–1.49 for stage III; Δ = 0.66, 95% CI: 0.19–1.14 for stage IV). Differences among age groups were less pronounced, with no significant variations in PDP scores between most comparisons. Forest plot of the differences of the PDP scores estimates from the multivariate general linear model.

The analysis of the gathered data provides a thorough understanding of the relationship between endometriosis and the perception of oral health, revealing how different stages of the disease affect both the quality of life and the dental health of individuals (Yalçın Bahat et al.  2022 ; Capezzuoli et al.  2022 ). Findings emphasize the significant relationship between the advancement of endometriosis and increased negative perceptions about oral health, which were measured by the Periodontal Diseases Perception (PDP) score. Notably, the analysis revealed that women diagnosed with advanced stages of endometriosis (II, III, and IV) exhibited a heightened perception of periodontal diseases, suggesting potential oral health implications of this chronic condition (Sobstyl et al.  2023 ; Grandi et al.  2019 ). A particularly significant finding is the progressive increase in the PDP score in relation to the endometriosis severity, further emphasizing the systemic impact of the disease on oral health. Women classified in stages II, III, and IV exhibited significantly higher periodontal disease perception (PDP) scores than those in stage I, with no substantial difference observed among the advanced stages. This suggests a strong relation between endometriosis progression and the perceived deterioration of periodontal health. Although the underlying mechanisms are still incompletely defined, they likely involve systemic effects of the disease and its treatments, encompassing chronic inflammation, hormonal dysregulation, and potential pharmacological impacts on oral tissues. As endometriosis advances, exacerbation of oral health‐related symptoms, such as gingival bleeding, xerostomia, and dentin hypersensitivity, may arise due to immune alterations, endocrine disturbances, and prolonged medication exposure (Shigesi et al.  2019 ; Zervou et al.  2024 ; Chao et al.  2022 ). Moreover, multivariate general linear modeling found age and diagnostic delay as significant contributors to PDP scores. Older women and those experiencing prolonged diagnostic latency reported a more pronounced decline in perceived oral health, underscoring the multifaceted burden of advanced endometriosis (van Stein et al.  2023 ). These findings highlight the interplay between disease chronicity and heightened awareness of oral health complications, further emphasizing the need for an integrated, multidisciplinary approach in the management of patients with advanced endometriosis (McGrath et al.  2023 ). The observed relation between delayed diagnosis and deteriorating oral health perception is particularly concerning, as prolonged diagnostic latency may extend exposure to both disease‐related and treatment‐induced factors, including stress, that negatively impact periodontal integrity (Macrì et al.  2024 ). The study revealed a progressive escalation of oral complications—manifesting as gingival pain, bleeding, and alterations in tongue morphology—parallel to disease advancement. Notably, pharmacological management of endometriosis, particularly in stage IV, was strongly associated with increased gingival bleeding, a finding corroborated by existing literature, which attributes this phenomenon to the effects of hormonal therapies on periodontal tissues. Additionally, other oral manifestations, including dental hypersensitivity, xerostomia, and a burning sensation of the tongue, exhibited greater prevalence in the later stages of the disease (Hartner et al.  2023 ; Tourny et al.  2023 ). These findings suggest an intricate interplay between systemic inflammatory responses, endocrine dysregulation, and long‐term pharmacological exposure, all of which could contribute to the exacerbation of oral health disturbances in patients with advanced endometriosis (Gajbhiye  2023 ). The findings of this study highlight a growing awareness among women regarding the potential link between endometriosis and poor oral health (Teal and Edelman  2021 ). However, this awareness is not yet mirrored among dental professionals, whose knowledge of the condition remains relatively limited. In the early stages of the disease, only 23.8% of women reported that their dentist or dental hygienist was aware of their diagnosis, with this percentage increasing as the disease progressed. This disparity highlights the urgent need for enhanced interdisciplinary communication between patients, dental practitioners, and dental hygienists, particularly for those in advanced stages of endometriosis. Dental professionals should adopt a more proactive role in recognizing and managing the complex oral health challenges that these patients face, as their condition necessitates specialized and tailored care (Fiorillo  2019 ; Gaffar et al.  2022 ; Schmalz et al.  2023 ). Beyond oral health, women with more severe endometriosis exhibited significant lifestyle adaptations, including dietary modifications and heightened awareness of pelvic floor dysfunction, suggesting a more comprehensive perception of the disease's systemic impact (Gutke et al.  2021 ). A similar pattern of heightened awareness may extend to oral health concerns. However, the elevated prevalence of dental hypersensitivity and periodontal diseases in advanced stages indicates a pressing need for more vigilant and preventive dental care in this population (Clavagnier  2015 ). These findings emphasize the need for early diagnosis and multidisciplinary management of endometriosis, advocating for integrative approaches that incorporate both gynecological and dental expertise. Periodontal health maintenance should be regarded as a crucial component of patient management, particularly in advanced disease stages, where oral manifestations become more pronounced (Wu et al.  2024 ; Crump et al.  2024 ). Furthermore, the increased recognition and documentation of oral health complications among women with endometriosis should prompt further investigation into the intricate relation between endometriosis and periodontal disease (Jin et al.  2024 ; Thomas et al.  2018 ; Kavoussi et al.  2009 ). This calls for the development of evidence‐based guidelines specifically addressing the oral healthcare needs of women with this chronic condition (Machado et al.  2020 ). Ultimately, this study underscores the necessity for continued research into the underlying pathophysiological mechanisms linking endometriosis and periodontal disease. Raising awareness among healthcare providers and patients about the potential oral health ramifications of endometriosis is imperative to ensure that affected women receive comprehensive care, encompassing both their reproductive and oral health needs. Future research should prioritize elucidating these mechanistic pathways and evaluating targeted interventions aimed at mitigating the oral health consequences associated with endometriosis (Halawani et al.  2024 ). The results support an association between endometriosis severity and patient age, with a higher prevalence of women over 35 in advanced disease stages (Comptour et al.  2024 ). This observation suggests that endometriosis progression may be driven by cumulative factors over time, including persistent hormonal dysregulation, chronic inflammation, and delayed diagnosis. Furthermore, the elevated incidence of comorbidities such as irritable bowel syndrome and autoimmune disorders in these patients highlights the systemic nature of endometriosis, reinforcing its multifaceted pathophysiology and the necessity for an integrative therapeutic approach. A particularly striking aspect of this study is the profound, multidimensional impact of endometriosis on patients' quality of life (Nnoaham et al.  2011 ). Across all disease stages, participants reported substantial pain and fatigue, with symptom severity escalating in advanced cases. The intricate interplay between chronic pain and psychological distress was evident, as many individuals exhibited symptoms of anxiety and depression, further exacerbating the burden of daily functioning. These findings reinforce the biopsychosocial complexity of endometriosis, aligning with existing literature that underscores its far‐reaching systemic implications. These findings highlight a largely overlooked aspect of endometriosis: its impact on oral health. Patients across all stages reported an increased prevalence of dental hypersensitivity, gingival bleeding, and orofacial pain compared to the general population. Notably, those in advanced stages exhibited a higher incidence of temporomandibular joint (TMJ) dysfunction, suggesting a potential association between chronic systemic inflammation and musculoskeletal involvement. This aligns with emerging research indicating that the inflammatory burden of endometriosis may extend beyond the reproductive system, contributing to oral and temporomandibular disorders. These insights underscore the importance of an interdisciplinary approach to patient care, integrating dentistry into the broader management of endometriosis (Kaushik et al.  2020 ). Multiple pathophysiological mechanisms may underlie the association between endometriosis and oral health disturbances. Chronic systemic inflammation, a defining feature of endometriosis, likely exacerbates periodontal disease and other oral pathologies by promoting a pro‐inflammatory microenvironment. Additionally, hormonal dysregulation—particularly estrogenic imbalance—may influence oral tissue homeostasis, given the presence of estrogen receptors in gingival and mucosal tissues, which modulate their response to injury and infection (Marquardt et al.  2023 ; Boyapati et al.  2021 ). Furthermore, the psychological burden of a chronic illness, including heightened stress levels, may contribute to oral health deterioration, as stress is a well‐documented risk factor for conditions such as bruxism, periodontal inflammation, and immune dysregulation within the oral cavity. This study highlights the imperative for a multidisciplinary approach in the management of endometriosis, emphasizing the integration of gynecologists, dental specialists, and mental health professionals to comprehensively address the heterogeneous symptomatology of affected individuals (Mazza et al.  2023 ). Routine oral health assessments and individualized therapeutic strategies may play a pivotal role in mitigating the oral manifestations frequently observed in this patient population, ultimately enhancing their overall quality of life. Furthermore, heightened awareness among healthcare providers regarding the systemic and multifactorial nature of endometriosis could facilitate earlier detection and the implementation of a more holistic and patient‐centered treatment paradigm. This study presents limitations that should be acknowledged when interpreting the findings. First, the cross‐sectional design, based on self‐reported data from an online questionnaire, does not allow for causal inferences or the establishment of temporal relationships between endometriosis and periodontal disease. The use of self‐reported periodontal conditions, while practical for large‐scale data collection, may be subject to recall bias and does not replace objective clinical assessments. Moreover, participants were recruited through Facebook support groups for women with endometriosis, which, although useful for reaching a large and engaged population, may introduce selection bias, as it may not fully represent the broader demographic and clinical variability of all women affected by the condition. In particular, individuals with more severe symptoms or greater disease awareness may have been more inclined to participate. Finally, although the questionnaire was developed in collaboration with a multidisciplinary team and validated by experts, it was not previously standardized or psychometrically validated in similar studies, which may affect the reproducibility of the results.

This study highlights the intricate interplay between endometriosis, oral health, and overall quality of life, emphasizing the need for a multidisciplinary and integrative approach to patient care. Recognizing these interconnections allows healthcare professionals to implement more comprehensive strategies, ultimately improving clinical outcomes and patient well‐being. Future research should focus on elucidating the underlying pathophysiological mechanisms linking endometriosis to oral health and developing targeted therapeutic interventions that address both systemic and localized manifestations of the disease.

According to United Nations data, endometriosis affects an estimated 3 million women in Italy, 14 million in Europe, and 150 million globally (Somigliana et al.  2023 ). Endometriosis is a chronic, estrogen‐dependent, and benign gynecological disease with a complex, multifactorial pathogenesis. It is characterized by the ectopic implantation and proliferation of functional endometrial tissue outside the uterine cavity. The precise pathophysiological mechanisms remain poorly understood; however, exposure to environmental estrogens is implicated as a significant risk factor, potentially triggering the pathological cascade in individuals with a genetic or epigenetic predisposition (Vannuccini et al.  2022 ). Despite advances in medical research, diagnostic and therapeutic strategies for endometriosis remain inadequate. A definitive diagnosis still relies exclusively on surgical intervention, complicating efforts to estimate the true prevalence of the disease. Endometriosis affects approximately 10%–20% of women of reproductive age, spanning from adolescence to menopause, with peak incidence occurring between 30 and 40 years. This prevalence is independent of ethnicity and socioeconomic status. Notably, 20%–25% of cases remain asymptomatic and undiagnosed for years, whereas 75%–80% of affected individuals experience debilitating symptoms, including severe pelvic pain, heavy menstrual bleeding, intermenstrual spotting, dysuria, dyschezia, chronic lower back pain, gastrointestinal disturbances, dyspareunia, and infertility affecting 30%–40% of women with endometriosis (Zondervan et al.  2018 ). Beyond the systemic burden of the disease, emerging evidence suggests a correlation between endometriosis and periodontal diseases, highlighting a potential link between systemic inflammatory disorders and oral health. This association may be driven by shared immunopathological mechanisms, including dysregulated cytokine profiles (such as elevated IL‐6, IL‐1β, and TNF‐α), chronic low‐grade inflammation, and impaired immune regulation (Koninckx et al.  2019 ). From a microbiological perspective, both conditions have been associated with alterations in the local microbiome composition. In periodontitis, the overgrowth of pathogenic species such as Porphyromonas gingivalis , Treponema denticola , and Tannerella forsythia disrupts the microbial homeostasis of the gingival sulcus, contributing to tissue destruction and systemic inflammatory responses. Similarly, recent studies have identified microbial dysbiosis in the peritoneal fluid and reproductive tract of women with endometriosis, suggesting a possible role for microbial translocation and immune activation in disease progression (Amro et al.  2022 ; Garcia Garcia et al.  2023 ). Moreover, hormonal therapies and immunomodulatory drugs used in the management of endometriosis may exacerbate oral conditions by altering salivary flow and mucosal immunity, thereby increasing the risk of xerostomia, oral candidiasis, and mucosal inflammation, and potentially aggravating periodontal tissue breakdown (Culley et al.  2013 ; Van Niekerk et al.  2019 ). Based on emerging evidence of shared inflammatory and immunological pathways, it is hypothesized that women with endometriosis may exhibit a higher prevalence of periodontal diseases, potentially contributing to a reduced quality of life (Evans et al.  2019 ). Oral health is increasingly recognized as an integral component of systemic well‐being. This study aimed to assess, through a structured cognitive questionnaire, potential associations between endometriosis and self‐reported periodontal diseases, evaluating their collective impact on quality of life.

The authors declare no conflicts of interest.

A designed 45‐item structured questionnaire was administered to a cohort of 4079 women clinically diagnosed with endometriosis. Participants were recruited via targeted online communities within the social networking platform Facebook, leveraging these specialized groups to access a representative sample. The questionnaire was developed in collaboration with a multidisciplinary team of healthcare professionals from the University of Bari Aldo Moro, including gynecologists of the Italian Endometriosis Foundation in Rome, as well as dentists, dental hygienists, physiotherapists, dieticians, and psychologists. The questionnaire was designed to investigate the following key domains: endometriosis status, types of treatments received, manifestations and symptoms within the oral cavity (including self‐reported oral health and periodontal conditions), oral hygiene practices, dietary habits, physical activity, quality of life, and the presence of comorbidities associated with immune function. The final section of the questionnaire included an open‐ended question, allowing participants to provide personal perspectives and experiences. Data collection was conducted between April and June 2024. The present study was carried out according to the Declaration of Helsinki, and the research protocol was approved and registered in the Local Ethical Committee of Calabria Region Central Area (code 355/2021/CE). The first section of the survey focused on demographic information, endometriosis diagnosis, and the participants' medical history. The second section examined oral disorders potentially linked to both pharmacological and non‐pharmacological treatments, with specific questions addressing whether participants observed oral changes after medication use or experienced symptoms such as oral bleeding. The third section targeted health, wellness, and lifestyle factors. Each question was assigned a unique code (e.g., Q1, Q2, etc.) to streamline data collection and analysis. Open‐ended responses were excluded from the quantitative analysis (Table  1 ). Question list collected in the survey. The descriptive statistical analysis of the survey response was presented using frequencies and percentages. In the comparison between the stages of endometriosis, the chi‐square test or Fisher's exact test was used, as appropriate. To evaluate the possible relationship between endometriosis and the perception of periodontal diseases, a score was created to summarize on a numerical scale the responses to survey questions regarding the perception of oral cavity disorders. This score was obtained using Multiple Correspondence Analysis (MCA), which was applied to explore relationships between answers. Only the questions with a p ‐value < 0.25 in the univariate analysis were included in the MCA to ensure the most relevant variables contributed to the score. The answers to the questions were labeled as “yes,” “no,” and “I don't know” (abbreviated as “idk”). In the case of question Q11, a grade was assigned to the responses as follows: “Idk” (I don't know), “Grd0” (Insufficient), “Grd1” (Average), “Grd2” (Good), “Grd3” (Very Good), and “Grd4” (Perfect). Cluster analysis using the k‐means method was performed to identify distinct response patterns. The first MCA dimension was used to calculate a score (Periodontal Diseases Perception Score—PDP score) that increases as the perception of periodontal diseases becomes stronger. The Kolmogorov–Smirnov test was used to verify the assumption of normality for PDP score and was described using the mean and standard deviation. A multivariate general linear model was used to analyze the relationship between the PDP score and endometriosis stages, considering age and years before receiving the diagnosis of endometriosis as adjustment factors. Both in the comparison of proportions and in the generalized linear model, pairwise multiple comparisons were performed by adjusting the p ‐value using Tukey's method. A two‐tailed p ‐value less than 0.05 was considered statistically significant. All analyses were performed using SAS software version 9.4.

Figure S1. Weights assigned to responses based on the first dimension of multiple correspondence analysis.