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INTRODUCTION
Endometriosis is characterized by the presence of ectopic endometrial tissue and severe pain. Often, affected women turn to non-medical interventions, such as dietary modifications. This study aims to assess the impact of endometriosis on dietary habits and quality of life.
METHODOLOGY
An online survey of Italian women with endometriosis was conducted to collect demographic, clinical, dietary and daily life data following diagnosis.
RESULTS
Of the 4,078 participants, 66% reported changes in their eating habits, and 92% saw a deterioration in their daily lives. Diets included gluten-free (15%), anti-inflammatory (8%), Mediterranean (7.1%) and ketogenic (4%). The study revealed an increase in the consumption of vegetables, fruit (10%), cereals, legumes (6.6%) and fish (4.5%), and a reduction in dairy products (18.4%), soy-containing foods (6.7%) and saturated fats (8%). Changes in dietary habits were correlated with stages of endometriosis and deterioration in daily life. Level of education, stages of endometriosis, duration of symptoms and changes in dietary habits were related to changes in daily life.
CONCLUSION
Our findings highlight the importance of monitoring dietary behaviors to prevent unhealthy habits and malnutrition in women with endometriosis. Further studies are needed to assess how different diets influence symptoms and improve the daily lives of these women.
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1-Introduction
Endometriosis is a prevalent condition among non-malignant gynecological disorders, affecting around 10% of women of childbearing age. It is one of the main anatomical factors contributing to persistent pelvic pain (1). Endometriosis is commonly characterized as a chronic estrogen-dependent inflammatory condition, involving the presence of endometrial-like tissue outside the uterus. Because of these characteristics, it is now recognized as a systemic disease rather than one confined solely to the pelvic region (1).
Endometriosis often coexists with various other conditions such as fibromyalgia, migraines, irritable bowel syndrome, mental health disorders, and immunological conditions such as rheumatoid arthritis (2). It is characterized by a variety of symptoms including chronic pain, dysmenorrhea, dyschesia, dyspareunia, dysuria, fatigue, and reduced fertility. However, the precise causes and mechanisms underlying the development of endometriosis have yet to be fully elucidated. The pathogenesis and pathophysiology of this condition remain areas of active research, and further investigations are needed to achieve a complete understanding of the disease (2, 3).
The presence of endometriosis can have a profound impact on women's physical and social well-being, resulting in a significant burden of disease, both in terms of economic implications and effect on quality of life (4). In addition, endometriosis leads to increased absenteeism from work or school (6). The condition exerts a significant influence on women's mental and emotional well-being (7), as well as on their social activities (8) and sexual relationships (9). Studies have indicated that endometriosis can diminish physical quality of life to a degree similar to that of cancer patients (8).
A recent systematic review and meta-analysis demonstrated that endometriosis has a detrimental effect on health-related quality of life, comparable to that of chronic pain (10-12). As a result, many women with endometriosis turn to non-medical methods to manage symptoms and improve their daily lives (13). Thus, women with endometriosis often resort to lifestyle interventions such as rest, heat therapy, meditation, exercise and dietary modifications to manage their symptoms (3).
Dietary interventions, in particular, have shown promising results in improving endometriosis-related symptoms. Studies have indicated that a significant proportion of women with endometriosis (76%) use self-management strategies, with almost half (44%) opting for dietary modifications (14). Another recent study found that 55.5% of participants reported that diet influenced their endometriosis symptoms, and that modifying their diet brought symptom relief (15). Dietary factors may play a role in the progression and development of endometriosis by influencing steroid hormone metabolism, the menstrual cycle, inflammation regulation, oxidative stress and muscle contraction (16).
As a result, the diets and dietary modifications adopted by women with endometriosis have attracted increasing interest from researchers. The question of whether and how specific diets and lifestyles can influence the pathogenesis and progression of endometriosis continues to be investigated (16, 17).
The link between dietary factors and endometriosis has attracted interest due to the recognition that diet can impact both physiological and pathological processes. Some authors suggest that dietary modifications may have therapeutic potential to attenuate chronic inflammatory processes and reduce the perception of visceral pain (18, 19). Some natural anti-inflammatory agents, such as Omega-3 polyunsaturated fatty acids (PUFAs) and squalene, a biofunctional lipid compound, have shown beneficial effects on chronic diseases (20-22).
Other diets, such as the Mediterranean diet, the low FODMAP (fermentable oligo-, di-, monosaccharides and polyols) diet, and the gluten-free diet, have also been studied in relation to chronic inflammatory diseases (23, 24). A recent systematic review focusing on the impact of dietary modifications on pain perception in relation to endometriosis demonstrated that diet had a positive influence on pain perception in women with endometriosis. In particular, a high intake of PUFAs, a gluten-free diet and a low-nickel diet were associated with better pain management in endometriosis (25).
In addition, the addition of nutrients with anti-inflammatory and antiestrogenic properties, such as antioxidants (curcumin, epigallocatechin gallate, quercetin, resveratrol and inositol), found in fruits, vegetables and oily fish, while eliminating pro-inflammatory substances such as lactose, saturated fats and soy, has been suggested to relieve the pain of endometriosis (15, 26-29).
Moreover, initial investigations into the efficacy of probiotics in the management of endometriosis in women have shown promising results in terms of pain relief (30). In addition, studies have reported that the administration of Lactobacillus-type probiotics can improve pain associated with endometriosis in women (31). Therefore, existing data imply the significant impact of dietary supplements in inducing favorable changes in the gut microbiota, which may play a role in promoting human health and reducing the risk of inflammatory conditions, including endometriosis.
Consequently, dietary choices can have an impact on disease progression and pain perception in endometriosis.
However, it's important to note that solid evidence regarding the relationship between nutrition, a healthy diet and the treatment of endometriosis is limited, as are studies exploring the effect of the disease on food choices.
Thus, the aim of this study was to investigate the potential effects of the disease on the dietary habits and daily activities of women following a diagnosis of endometriosis.
2-Methods
The Italian Association of Dental Hygienists (AIDI) and the Technical Scientific Association of Food, Nutrition and Dietetics (ASAND), in collaboration with the Clinical Nutrition Unit of the "Magna Graecia" University of Catanzaro, conducted an online survey to explore various aspects of the daily lives of women with endometriosis. This cross-sectional study collected data between April 9 and June 27, 2021. An anonymous nationwide survey was administered via Google Forms, targeting women over the age of 18 residing in Italy who had self-reported a diagnosis of endometriosis. Recruitment was carried out via direct links to the survey and invitations distributed via social networks such as Facebook, WhatsApp, Twitter and Instagram, specifically through AIDI, ASAND and the Italian Endometriosis Association. The latter serves as a network to foster discussion, community and support among women with endometriosis. The study received ethical approval from the Local Ethics Committee of the Central Region of Calabria (code 355/2021/CE).
2.1. Questionnaire
We developed a semi-structured online questionnaire aimed at collecting self-reported sociodemographic data (age, education level, professional status), the perceived impact of endometriosis symptoms on daily life, disease-related information (years since diagnosis, stage, symptoms, time to diagnosis, pharmacological treatment, associated autoimmune diseases), and self-reported changes in dietary habits after a diagnosis of endometriosis (see Supplementary Table S1).
In our study, dietary change was defined as a self-reported modification of the previous diet (15, 32-34). The impact of endometriosis symptoms on daily life was examined through questions related to chronic fatigue, depression and anxiety, sleep disturbance, reduced fertility or subfertility, reduced sexual satisfaction, reduced work capacity, reduced social interactions, difficulties in planning and performing daily activities, and pain management challenges (7-12, 35-38). Our questionnaire was developed by adapting previously validated tools (7-12, 35-38). Participants provided informed consent via an anonymous online form at the start of the questionnaire. Participants were asked to self-report the stage of their endometriosis diagnosis, if known, according to the American Society of Reproductive Medicine (ASRM) classification system, which includes four stages: Stage I (Minimal), Stage II (Mild), Stage III (Moderate), and Stage IV (Severe) (39). The questionnaire consisted of 31 questions, using mainly closed questions with predefined response options. Five questions allowed participants to provide open-ended answers and share their personal opinions. The survey took an average of 15 to 20 minutes to complete.
To validate our questionnaire, as reported in other studies (40), we performed a factor analysis using Horn's parallel analysis for principal components, with varimax rotation (32, 33, 40). An eigenvalue of 1 was used as a threshold to determine the number of factors. In total, the explained variance represented 64.4% of the variance. To assess internal consistency, reflecting the degree to which instrument items measure the same concept, we used Cronbach's α test. A Cronbach α value greater than 0.70 indicates good internal consistency, and our questionnaire achieved a Cronbach α value of 0.72.
2.2. Statistical analysis
To find a correlation between changes in dietary habits and endometriosis stage with an r-value of 0.05, study power of 80% and one-sided alpha of 0.05, a sample size of 3,134 women with endometriosis was required. On closure of the online survey and cessation of data collection, the final database was downloaded as a Microsoft Excel sheet and subjected to data analysis. Open-ended questions were carefully reviewed, condensed and coded for statistical analysis. Missing data were not imputed in the statistical analysis. Results are presented as absolute (n) and relative (%) frequencies for categorical variables. Pearson's correlation coefficient was used to identify confounding variables associated with changes in dietary habits and daily life, assuming a normal distribution for continuous variables.
De plus, un test du Chi-carré a été réalisé pour examiner les changements d'habitudes alimentaires et la vie quotidienne parmi les participantes après le diagnostic d'endométriose, stratifiés par stade de la maladie. Le même test a été employé pour évaluer les schémas alimentaires et les choix alimentaires parmi les femmes atteintes d'endométriose ayant rapporté une détérioration de leur qualité de vie. La signification statistique a été fixée à p < 0,05 (bilatéral). Toutes les analyses statistiques ont été réalisées à l'aide du logiciel SPSS 25.0 pour Windows (IBM Corporation, New York, NY, États-Unis).
3-Results
During the survey, a total of 4,078 responses were collected and analyzed. Table 1 shows the demographic and clinical characteristics of women withendometriosis. The largest proportion of participants (45%) were between 36 and 45 years of age, and 37% of women were in the severe stage of the disease. Of the participants, 1,333 were on hormonal treatment at the time of interview, with 1,331 using oral contraceptive pills or vaginal contraceptive rings (see Table 1). Respondents' level of education varied, encompassing bothhigh school anduniversity education (see Table 1). A delay in diagnosis exceeding 7 years was reported by 39% of participants (see Table 1). Approximately 17% of women reported autoimmune diseases, including Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid disorders, and others (data not shown). Celiac disease was reported by 1.2% of participants.
3.1 Changes in eating habits after diagnosis of endometriosis
Following the diagnosis ofendometriosis, eating habits changed in 66. 4% of respondents (Figure 1).
Figure 3 - Food choices of women with endometriosis
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3.2 Impact of endometriosis symptoms on daily life
Family and friends tend to minimize endometriosis symptoms for 46% (n = 1,872) of respondents (data not shown). In addition, daily life worsened for 92% (n = 3,767) of women surveyed as a result of the disease. In particular, women with endometriosis reported difficulties managing pain and planning or carrying out daily activities (22%), reduced work capacity (12%), and reduced social interactions (10%) (Figure 4). In addition, chronic fatigue and depression-anxiety were reported by 22% and 13% of women with endometriosis, respectively (Figure 4).
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3.3. Predictors of changes in eating habits and worsening of daily life
Chez les femmes atteintes d'endométriose, la corrélation de Pearson a montré que les changements d'habitudes alimentaires étaient corrélés aux stades de l'endométriose (r = 0,10, p < 0,001), aux années de symptômes (r = 0,37, p = 0,018) et aux changements de la vie quotidienne (r = 0,14, p < 0,001) (données non montrées). De plus, dans cette population, l'aggravation de la vie quotidienne était corrélée au niveau d'éducation (r = -0,04, p = 0,002), aux stades de l'endométriose (r = 0,15, p < 0,001), aux années de symptômes (r = 0,13, p < 0,001) et aux changements d'habitudes alimentaires (r = 0,14, p < 0,001) (données non montrées).
In logistic regression analysis, changes in dietary habits were associated with endometriosis stages and deterioration in daily life (Table 2). In addition, changes in daily life were significantly associated with all variables, including education level, endometriosis stages, years of symptoms and changes in dietary habits (Table 2).
4. Discussion
The aim of this study was to investigate the potential effects of the disease on women's eating habits and daily activities following a diagnosis ofendometriosis. The large cohort of 4,078 participants provides a solid basis for data analysis. The majority of women being between 36 and 45 years of age may reflect the typical age of diagnosis or the time when women actively seek medical assistance (4, 5). The 37% prevalence of women with a severe stage(stage IV) represents a significant proportion of those facing the greatest challenges associated with endometriosis (4, 5, 10-12). The delay in diagnosis exceeding 7 years for 39% of participants is worrying, and underlines the importance of accurate and rapid diagnosis. Several studies have reported diagnosis delays similar to those observed in our population, with mean times ranging from 4.4 years in the USA to 10.4 years in Germany (41, 42). The main reasons for these delays include intermittent use of contraceptives, self-medication of pain with over-the-counter analgesics and diagnostic errors.
The fact that 66.4% of women reported changing their dietary habits after a diagnosis of endometriosis suggests a significant impact of the disease on women's perceptions of nutrition and health (14). Reported food choices, such as gluten-free, anti-inflammatory, Mediterranean and ketogenic diets, indicate that women are exploring a variety of dietary approaches to treat symptoms and improve their quality of life. Analysis of food choices according to disease stage revealed significant differences. Women with severe endometriosis(stage IV) appear to follow an anti-inflammatory diet more frequently, while eliminating foods high in saturated fats and simple sugars. These findings may indicate an attempt to manage the inflammation associated with severe endometriosis. At the same time, greater adherence to an anti-inflammatory diet could reflect a response to the severity of symptoms and the need to treat inflammatory processes. On the other hand, differences in food choices could also be influenced by women's greater awareness of the effect of nutrition on health. The results of our study are in line with current understanding in this field.
An Italian retrospective study examined the effects of a gluten-free diet on symptoms associated with endometriosis (23). At 12-month follow-up, 52% of patients reported significant improvements in pain compared with baseline (23). Interestingly, around 30% of patients did not adhere to the gluten-free diet (23). A gluten-free diet may be beneficial for patients with gastrointestinal tract-related abdominal pain, constipation, bloating and suspected visceral hypersensitivity. However, adherence to such diets can be compromised by financial constraints and inherent difficulties. Our study revealed that the anti-inflammatory diet was more commonly followed by women with severe-stage disease. Although popular, there is currently insufficient scientific evidence to support the role of this diet in the management of endometriosis.
A single-arm study conducted in Australia examined the effects of the Mediterranean diet on pain associated with endometriosis (43). Patients adhered to a specific diet including fruits, fresh vegetables, oily fish, white meat, soy products, whole-grain products, magnesium-rich foods andextra-virgin olive oil. In addition, the Mediterranean diet includes the consumption of many spices. Significant pain relief, including improvements in general pain, dysmenorrhea, dyschesia, dyspareunia andgeneral condition, has been observed (43). The Mediterranean diet may relieve endometriosis-related pain through synergistic mechanisms. Extra-virgin olive oil and fish have shown anti-inflammatory effects (44, 45). Oleocanthal, present in extra-virgin olive oil, has a molecular structure similar to that of ibuprofen and exerts a cyclooxygenase inhibitory effect via the same mechanism (46).
In addition, the antioxidant effects, abundant fiber content and magnesium present in the Mediterranean diet may have positive effects on pelvic pain and inflammation (47, 48). In addition, certain spices such as onions, rosemary, chillies, ginger, turmeric andgarlic are commonly incorporated into the Mediterranean diet and anti-inflammatory model. Recent preclinical and clinical studies have confirmed the efficacy of these spices and their bioactive compounds in the prevention and reduction of various chronic diseases, including arthritis, asthma, cancer, neurodegenerative disorders and cardiovascular conditions (49, 50). These spices have the potential to alleviate the inflammatory effects associated with endometriosis.
Our findings are consistent with previous studies in which participants reported that avoiding or limiting a wide range of nutrients, including dairy, gluten, soy, sugar and coffee, helped relieve their symptoms, while adding fruit or vegetables proved beneficial (51). Several epidemiological studies have associated a high intake of fruit (52),omega-3 fatty acids (15), and dairy products during adolescence (53) with a reduced risk of developing endometriosis. Conversely, high consumption of trans-unsaturated fats (15), red meat (16) andalcohol (54) was associated with increased risk, although it remains to be determined whether these factors also influence symptoms of diagnosed endometriosis. Some participants in our study also adopted a ketogenic diet, high in fat, moderate in protein and very low in carbohydrates. This diet promotes the production of endogenous ketones as an alternative metabolic fuel source (55). Preclinical studies have demonstrated the positive effects of the ketogenic diet on markers of oxidative stress and inflammation, which is relevant to endometriosis (56-59).
However, there is currently insufficient scientific evidence to support the use of this dietary protocol for endometriosis. A prospective controlled study demonstrated the anti-inflammatory effects of a nutraceutical containing vitamin B3, omega-3/6, quercetin, calcium salt, 5-methyltetrahydrofolate, parthenium and turmeric in women with endometriosis (19). This study revealed significant reductions in pain symptoms and serum levels of CA-125, PGE2 and 17β-estradiol in the nutraceutical-treated group (19). A small proportion (5%) of women in our questionnaire reported using this nutraceutical for pain relief. However, due to uncertainty about the long-term safety of dietary antioxidant supplementation beyond 6 months, prolonged use cannot be recommended (60, 61).
Importantly, the correlation between changes in dietary habits, stage of endometriosis and duration of symptoms suggests that some dietary adjustments may be adaptive responses to symptom severity or disease progression. The negative effect of the disease on women's daily lives is evident in the study results and is consistent with the findings of other scientific studies (7, 8, 10, 11, 15). The downplaying of symptoms by family and friends may contribute to an increased emotional burden for women faced with incomprehension. Worsening quality of life, indicated by difficulties in managing pain and planning daily activities, highlights a range of physical and psychological challenges that women face, consistent with observations from other studies (7, 8, 10, 11, 15). The prevalence of 22% for chronic fatigue and 13% for depression-anxiety underlines the importance of a comprehensive, integrated approach to endometriosis management.
The results of our study highlight the need for specific nutritional advice for women with endometriosis. Currently, there are no established nutritional guidelines for this clinical condition, highlighting the need for clinical trials to identify optimal nutritional strategies to alleviate the symptoms of endometriosis.
Our study has several strengths, not least the use of an online survey, which facilitated rapid recruitment of a large sample of women. The participants represented a range of ages, levels of education and stages of endometriosis according to the ASRM classification. However, our study also has limitations. Firstly, it is a cross-sectional study.
Secondly, we relied on self-reported data and did not use food frequency questionnaires or food diaries to assess macro- and micro-nutrient deficiencies or to explore the impact of these conditions using validated questionnaires (38). In addition, we categorized the age of patients; however, we did not set a maximum age limit in this study.
In addition, we did not investigate anthropometric parameters or the effects of endometriosis diagnosis on malnutrition risk. In addition, there may be a selection bias, as survey participants were members of the Italian Endometriosis Association, which may indicate a higher level of health awareness compared with the general population.
Nevertheless, despite these limitations, our study generates hypotheses for future investigations. Currently, there is little research available on the effects of dietary modifications on symptoms associated with endometriosis, with only a small number of studies (19, 27, 41-43) addressing this topic. However, several dietary approaches have been proposed as potential strategies to attenuate endometriosis progression and improve clinical symptoms. Nevertheless, further studies are needed to investigate the efficacy of these dietary interventions.
5. Conclusion
In conclusion, our study shows that dietary changes are commonly used by women withendometriosis as a self-management tool. These women modify various aspects of their diet to alleviate their symptoms. However, it remains unknown which specific dietary interventions are effective for women with different types of endometriosis or specific individual characteristics. The results of our study underline the importance of referring patients for nutritional counseling to prevent nutritional deficiencies. It is crucial to educate women on the aims and rationale of dietary intervention, and to provide advice on which nutrients to include or avoid. Future clinical trials investigating the efficacy of specific diets for women with endometriosis will help tailor individualized dietary approaches for optimal results.
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LES AUTRICES
Ersilia Troiano2 ,4 Santino Mazza3 
Antonia Abbinante5 ,6 Maria Teresa Agneta5 ,6 
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