Mediterranean diet adherence and healthy diet indicator might decrease odds of endometriosis

This study was conducted in accordance with the Declaration of Helsinki 23 . Ethical approval was obtained from the Medical Ethics Committee of the National Nutrition and Food Technology Research Institute at Shahid Beheshti University of Medical Sciences, Iran. All participants provided written informed consent, and confidentiality of personal data was ensured. Some baseline data from this study have been previously reported in related publications using the same dataset 20 – 22 . The study design, participant demographics, and assessment of exposures and outcomes were previously described in detail 22 , In brief, a case–control study was conducted in hospitals in Tehran, Iran, between February and September 2021, involving 115 women diagnosed with endometriosis and 230 control subjects 22 . Some of the analysis on the other dietary patterns reported in our previous study lasted until January 2022 22 . Eligible participants were women aged 18 to 49 years who were not pregnant, breastfeeding, or menopausal at the time of recruitment. Individuals with chronic diet-related conditions such as diabetes, cardiovascular disease, kidney failure, or cancer were not included. The case group included women diagnosed with endometriosis, confirmed either macroscopically during surgery or through histopathological examination. Controls met the same eligibility criteria but had no clinical evidence of endometriosis or pelvic pain syndrome. All diagnoses were verified by an experienced gynecologist who was blinded to the study objectives. Dietary intake was assessed using a validated 168-item Food Frequency Questionnaire (FFQ) 24 and a validated food album 25 featuring household measurement illustrations, as previously described 22 . Daily energy and macronutrient intake were calculated using the USDA Food Composition Table 26 or the Iranian food composition Table 27 . Interviews and questionnaires were administered by trained interviewers blinded to participants’ group assignments to minimize information bias. Anthropometric data were collected by the investigator 22 , and physical activity levels were evaluated using a validated questionnaire developed by Aadahl et al. 28 . Adherence to the Mediterranean dietary pattern was assessed using the validated Medi-Lite score 29 . Food groups typical of the Mediterranean diet (e.g., fruits and nuts, fish, vegetables, legumes, whole grains, and the MUFA/SFA ratio) were scored based on tertile distribution: 2 points for the highest tertile, 1 for the middle tertile, and 0 for the lowest tertile. Conversely, food groups not aligned with the Mediterranean diet (e.g., meat and dairy products) were reverse-scored. Due to insufficient data, alcohol consumption was excluded from the scoring. The total score ranged from 0 (indicating poor adherence) to 16 (indicating high adherence) 29 . We assessed overall diet quality using the HDI, originally developed by Huijbregts et al. 30 and operationalized in our previous study 31 . The HDI is grounded in world health organization (WHO) dietary guidelines and comprises nine components reflecting balanced nutritional intake: Saturated fatty acids, unsaturated fatty acids, protein, carbohydrates, fiber, fruits and vegetables, pulses, nuts and seeds, cholesterol. Using data from FFQ, we calculated intake for each component. A participant received 1 point per component when meeting the recommended threshold (i.e., adequacy for protective components or limits for harmful components), resulting in a total HDI score range from 0 to 9 31 . For statistical analysis, SPSS (Statistical Package for the Social Sciences program; version 27; Chicago, IL, USA) was used. Two-tailed analyses were performed, with P-values < 0.05 considered statistically significant. Continuous variables were assessed for normal distribution using skewness, histogram, Q-Q plots, and the Kolmogorov-Smirnov test. Quantitative characteristics were presented as mean (SD) for normally distributed variables and median (interquartile range, IQR) for non-normally distributed ones. Categorical demographic features were displayed as frequency and percentages. Chi-square test was employed for qualitative data comparison between endometriosis patients and controls. The Independent Samples T-test or Mann-Whitney test was used for comparing normally and non-normally distributed quantitative variables, respectively. Medi-Lite and HDI scores were categorized into two groups—high adherence versus low adherence—based on the study sample’s median value. Logistic regression models were then performed to estimate adjusted odds ratios (OR) with 95% confidence intervals (CI), controlling for age, BMI, energy intake, age at menarche, menstruation duration, smoking, occupation, regular menstruation and familial history of endometriosis.

The general characteristics of the participants were delineated in a previous publication 22 . A total of 317 participants were involved, with 107 having endometriosis, while 4 were eliminated due to discrepancies in energy intake. A total of 313 women (105 endometriosis cases and 208 healthy controls) were included in the final analysis. Among healthy controls, individuals with higher adherence to the Mediterranean diet (as assessed by the Medi-Lite score) were slightly older, more physically active, had a higher BMI, and were more likely to be married compared to those with lower adherence (all P < 0.05). No significant differences were observed between the adherence groups in terms of age at menarche, familial history of endometriosis, education level, smoking status, employment, or menstrual regularity. Among participants with endometriosis, no statistically significant differences were found between low and high adherence groups for most characteristics (Table 1 ). Table 1 General characteristics of participants with endometriosis and healthy controls, separated according to mediterranean diet adherence (Medi-Lite score). Healthy controls N  = 208 Participants with endometriosis N  = 105 Low adherence N  = 81 High adherence N  = 127 P -value* Low adherence N  = 91 High adherence N  = 14 P -value* Median Q1–Q3 Median Q1–Q3 Median Q1–Q3 Median Q1–Q3 Age, year 30.00 27.00–33.00 31.00 28.00–36.00 0.027 36.00 30.00–40 35.50 30-38.50 0.966 Age at menarche, year 13.00 12.00–14.00 13.00 12.00–14.00 0.474 13.00 11.00–15.00 12.00 11.00–13.00 0.379 Physical activity, Minutes/week 5.00 0.00–30.00 20.00 1.00-100.00 0.009 30.00 0–75 37.50 15.00–70.00 0.779 Body Mass Index, kg/m 2 23.15 20.66–25.87 24.22 22.31–27.06 0.021 27.99 23.84–30.10 25.88 21.96–28.42 0.051 Number Percentage Number Percentage P -value** Number Percentage Number Percentage P -value** Married 41 50.6 92 72.4 0.001 53 58.2 9 64.3 0.669 Having familial history of Endometriosis 2 2.5 4 3.1 0.775 44 48.4 8 57.1 0.540 Education 0.210 0.412  Primary/secondary school 5 6.2 15 11.8 12 13.2 1 7.1  Diploma 16 19.8 33 26 22 24.2 1 7.1  Bachelor’s degree 41 50.6 60 47.2 42 46.2 9 64.3  Master’s/Doctoral degree 19 23.5 19 15 15 16.5 3 21.4 Never smokers 63 77.8 103 81.1 0.841 49 53.8 7 50 0.928 Employed 53 65.4 80 63 0.778 37 40.7 8 57.1 0.467 Regular menstruation, yes 59 72.8 90 70.9 0.758 76 83.5 12 85.7 0.835 Significant values are in bold. *Using Mann Whitney test. **Using χ 2 test, or Fisher’s excact test as appropriate. General characteristics of participants with endometriosis and healthy controls, separated according to mediterranean diet adherence (Medi-Lite score). Significant values are in bold. *Using Mann Whitney test. **Using χ 2 test, or Fisher’s excact test as appropriate. Healthy controls had a significantly higher MEDI-Lite score than women with endometriosis (9.21 ± 2.50 vs. 5.63 ± 2.56; p  < 0.001). The intakes of fruits and nuts, vegetables, fish, and legumes were significantly greater among controls, whereas meat and dairy intake were significantly higher in cases ( p  < 0.001 for all). Notably, whole grain intake was also higher among women with endometriosis compared to controls (23.43 vs. 4.15 g/day; p  = 0.022; Table  2 ). Table 2 The mediterranean diet components separated by participants with endometriosis and healthy controls. Variables Patients with endometriosis ( n = 105) Healthy controls ( n = 208) P -value MEDI-LITE score 1 5.63 ± 2.56 9.21 ± 2.50 < 0.001 Fruits and Nuts intake (g/day) 2 161.15 (107.76–234.87) 312.67 (165.14–576.58) < 0.001 Vegetables intake (g/day) 2 140.40 (83.55–207.21) 314.28 (168.48–469.59) < 0.001 Fish intake (g/day) 2 0.30 (0.00–15.71) 16.02 (9.83–31.79) < 0.001 Whole grains intake (g/day) 2 23.43 (0.00–92.00) 4.15 (0.32–13.14) 0.022 Legumes intake (g/day) 2 15.35 (5.66–30.79) 28.30 (14.70–55.02) < 0.001 Monounsaturated fatty acids to saturated fatty acids ratio 2 1.14 (0.85–1.43) 0.97 (0.80–1.47) 0.152 Meat intake (g/day) 2 92.32 (62.17–141.29) 32.13 (17.49–51.64) < 0.001 Dairy intake (g/day) 2 359.29 (198.65–590.06) 240.63 (124.88–414.81) < 0.001 g gram. Significant values are in bold. 1 Using independent samples T-test for parametric variables and values are mean ± SD. 2 Using Mann–Whitney U-test for non-parametric variables and values are median (25th–75th). Some of baseline data are reported involved in other dietary patterns previously 21 . The mediterranean diet components separated by participants with endometriosis and healthy controls. g gram. Significant values are in bold. 1 Using independent samples T-test for parametric variables and values are mean ± SD. 2 Using Mann–Whitney U-test for non-parametric variables and values are median (25th–75th). Some of baseline data are reported involved in other dietary patterns previously 21 . The mean HDI score was significantly lower in cases than controls (2.80 ± 1.84 vs. 5.54 ± 1.57; p  < 0.001). Cases consumed significantly fewer total fruits and vegetables, pulses, nuts, seeds, fiber, and carbohydrates, while their intake of saturated fat, monounsaturated fat, and cholesterol was significantly higher compared to controls ( p  < 0.001 for most components, Table  3 ). Table 3 The healthy diet indicator components separated by participants with endometriosis and healthy controls. Variables Patients with endometriosis ( n  = 105) Healthy controls ( n  = 208) P -value Healthy diet indicator 1 2.80 ± 1.84 5.54 ± 1.57 < 0.001 Fruits and vegetables (g/day) 2 343.54 (236.37–440.94) 643.49 (410.69–1107.06) < 0.001 Pulses and nuts and seeds (g/day) 2 18.25 (8.87–33.41) 38.17 (20.11–66.88) < 0.001 Protein intake (energy %) 1 14.12 ± 2.83 13.81 ± 3.50 0.432 Carbohydrate intake (energy %) 1 48.91 ± 7.78 60.78 ± 8.12 < 0.001 Fiber intake (g/day) 1 15.24 ± 6.04 27.20 ± 14.51 < 0.001 SFA intake (energy %) 1 13.57 ± 4.10 8.52 ± 2.85 < 0.001 MUFA intake (energy %) 1 15.93 ± 5.96 9.86 ± 5.15 < 0.001 PUFA intake (energy %) 1 8.39 ± 2.61 9.09 ± 3.72 0.053 Cholesterol intake (mg/day) 2 314.49 (194.40–488.96) 228.39 (160.56–488.96) < 0.001 g gram, mg milligram. Significant values are in bold. 1 Using independent samples T-test for parametric variables and values are mean ± SD. 2 Using Mann–Whitney U-test for non-parametric variables and values are median (25th–75th). The healthy diet indicator components separated by participants with endometriosis and healthy controls. g gram, mg milligram. Significant values are in bold. 1 Using independent samples T-test for parametric variables and values are mean ± SD. 2 Using Mann–Whitney U-test for non-parametric variables and values are median (25th–75th). Higher adherence to the Mediterranean diet was associated with a markedly reduced odds of endometriosis. Women with a MEDI-Lite score above the mean had 94% lower odds of endometriosis compared to those with lower scores (adjusted OR = 0.06; 95% CI: 0.02–0.17; p  < 0.001). For individual components, higher intake of fruits and nuts (adjusted OR = 0.21; 95% CI: 0.09–0.48; p  < 0.001), vegetables (adjusted OR = 0.17; 95% CI: 0.08–0.39; p  < 0.001), fish (adjusted OR = 0.15; 95% CI: 0.07–0.34; p  < 0.001), and legumes (adjusted OR = 0.31; 95% CI: 0.14–0.65; p  = 0.002) were significantly associated with reduced odds of endometriosis. Conversely, higher meat (adjusted OR = 10.36; 95% CI: 4.31–24.87; p  < 0.001) and dairy intake (adjusted OR = 4.58; 95% CI: 2.04–10.26; p  < 0.001) were linked to increased odds of endometriosis. Interestingly, higher whole grain consumption was also associated with higher odds (adjusted OR = 2.30; 95% CI: 1.10–4.82; p  = 0.027; Table  4 ). Table 4 The association between MEDI-LITE score and its components with odds of endometriosis. Variables Patients with endometriosis/healthy controls Crude model Adjusted model OR (CI 95%) P -value OR (CI 95%) P -value MEDI-LITE score  Total score 105/208 0.57 (0.50–0.65) < 0.001 0.60 (0.50–0.70) < 0.001  Lower than mean 91/81 Ref. Ref. Ref. Ref.  Higher than mean 14/127 0.09 (0.05–0.18) < 0.001 0.06 (0.02–0.17) < 0.001 Fruits and nuts intake (g/day)  Total intake 105/208 0.99 (0.99–0.99) < 0.001 0.99 (0.99–0.99) < 0.001  Lower than mean 77/79 Ref. Ref. Ref. Ref.  Higher than mean 28/129 0.22 (0.13–0.37) < 0.001 0.21 (0.09–0.48) < 0.001 Vegetables intake (g/day)  Total intake 105/208 0.99 (0.98–0.99) < 0.001 0.99 (0.98–0.99) < 0.001  Lower than mean 83/73 Ref. Ref. Ref. Ref.  Higher than mean 22/135 0.14 (0.08–0.24) < 0.001 0.17 (0.08–0.39) < 0.001 Fish intake (g/day)  Total intake 105/208 0.97 (0.95–0.98) < 0.001 0.97 (0.96–0.99) 0.008  Lower than mean 75/71 Ref. Ref. Ref. Ref.  Higher than mean 30/137 0.20 (0.12–0.34) < 0.001 0.15 (0.07–0.34) < 0.001 Whole grains intake (g/day)  Total intake 105/208 1.01 (1.00-1.01) < 0.001 1.01 (1.00-1.02) < 0.001  Lower than mean 44/112 Ref. Ref. Ref. Ref.  Higher than mean 61/96 1.61 (1.00-2.59) 0.047 2.30 (1.10–4.82) 0.027 Legumes intake (g/day)  Total intake 105/208 0.97 (0.95–0.98) < 0.001 0.96 (0.95–0.98) < 0.001  Lower than mean 71/85 Ref. Ref. Ref. Ref.  Higher than mean 34/123 0.33 (0.20–0.54) < 0.001 0.31 (0.14–0.65) 0.002 Monounsaturated fatty acids to saturated fatty acids ratio  Total intake 105/208 1.08 (0.72–1.62) 0.684 1.05 (0.58–1.93) 0.851  Lower than mean 40/116 Ref. Ref. Ref. Ref.  Higher than mean 65/92 2.04 (1.26–3.31) 0.003 2.20 (1.08–4.48) 0.029 Meat intake (g/day)  Total intake 105/208 1.03 (1.02–1.04) < 0.001 1.03 (1.02–1.04) < 0.001  Lower than mean 15/141 Ref. Ref. Ref. Ref.  Higher than mean 90/67 12.62 (6.79–23.45) < 0.001 10.36 (4.31–24.87) < 0.001 Dairy intake (g/day)  Total intake 105/208 1.00 (1.00–1.00) < 0.001 1.00 (1.00–1.00) < 0.001  Lower than mean 37/119 Ref. Ref. Ref. Ref.  Higher than mean 68/89 2.45 (1.51–3.99) < 0.001 4.58 (2.04–10.26) < 0.001 OR odds ratio, CI confidence interval. Significant values are shown in bold. These values are odds ratio (95% CIs) and obtained from logistic regression. Adjusted Model: adjusted based on age, BMI, energy intake, age at menarche, menstruation duration, smoking, occupation, regular menstruation and familial history of endometriosis. The association between MEDI-LITE score and its components with odds of endometriosis. OR odds ratio, CI confidence interval. Significant values are shown in bold. These values are odds ratio (95% CIs) and obtained from logistic regression. Adjusted Model: adjusted based on age, BMI, energy intake, age at menarche, menstruation duration, smoking, occupation, regular menstruation and familial history of endometriosis. Women with higher HDI scores had 95% lower odds of endometriosis (adjusted OR = 0.05; 95% CI: 0.02–0.12; p  < 0.001). Among HDI components, greater intake of fruits and vegetables (adjusted OR = 0.09; 95% CI: 0.04–0.23; p  < 0.001), pulses, nuts, and seeds (adjusted OR = 0.35; 95% CI: 0.17–0.75; p  = 0.006), and higher fiber intake (adjusted OR = 0.12; 95% CI: 0.05–0.30; p  < 0.001) were associated with significantly lower odds of endometriosis. On the other hand, higher saturated fat (adjusted OR = 9.88; 95% CI: 4.22–23.10; p  < 0.001) and MUFA intake (adjusted OR = 7.91; 95% CI: 3.48–17.97; p  < 0.001) were associated with increased odds (Table  5 ). Table 5 The association between healthy diet indicator and its components with odds of endometriosis. Variables Case/control Crude model Adjusted model OR (CI 95%) P -value OR (CI 95%) P -value Healthy diet indicator  Total score 105/208 0.42 (0.35–0.51) < 0.001 0.46 (0.36–0.59) < 0.001  Lower than mean 90/47 Ref. Ref. Ref. Ref.  Higher than mean 15/161 0.04 (0.02–0.09) < 0.001 0.05 (0.02–0.12) < 0.001 Fruits and vegetables (g/day)  Total intake 105/208 0.99 (0.99–0.99) < 0.001 0.99 (0.99–0.99) < 0.001  Lower than mean 86/70 Ref. Ref. Ref. Ref.  Higher than mean 19/138 0.11 (0.06–0.19) < 0.001 0.09 (0.04–0.23) < 0.001 Pulses and nuts and seeds (g/day)  Total intake 105/208 0.97 (0.96–0.98) < 0.001 0.96 (0.95–0.98) < 0.001  Lower than mean 69/87 Ref. Ref. Ref. Ref.  Higher than mean 36/121 0.37 (0.23–0.61) < 0.001 0.35 (0.17–0.75) 0.006 Protein intake (energy %)  Total intake 105/208 1.02 (0.95–1.10) 0.433 1.04 (0.94–1.16) 0.361  Lower than mean 43/113 Ref. Ref. Ref. Ref.  Higher than mean 62/95 1.71 (1.06–2.75) 0.026 1.42 (0.71–2.85) 0.317 Carbohydrate intake (energy %)  Total intake 105/208 0.83 (0.79–0.86) < 0.001 0.85 (0.81–0.90) < 0.001  Lower than mean 90/66 Ref. Ref. Ref. Ref.  Higher than mean 15/142 0.07 (0.04–0.14) < 0.001 0.13 (0.06–0.30) < 0.001 Fiber intake (g/day)  Total intake 105/208 0.88 (0.85–0.91) < 0.001 0.81 (0.76–0.87) < 0.001  Lower than mean 80/76 Ref. Ref. Ref. Ref.  Higher than mean 25/132 0.18 (0.10–0.30) < 0.001 0.12 (0.05–0.30) < 0.001 SFA intake (energy %)  Total intake 105/208 1.53 (1.38–1.69) < 0.001 1.43 (1.26–1.62) < 0.001  Lower than mean 15/141 Ref. Ref. Ref. Ref.  Higher than mean 90/67 12.62 (6.79–23.45) < 0.001 9.88 (4.22–23.10) < 0.001 MUFA intake (energy %)  Total intake 105/208 1.21 (1.15–1.28) < 0.001 1.16 (1.09–1.24) < 0.001  Lower than mean 17/139 Ref. Ref. Ref. Ref.  Higher than mean 88/69 10.42 (5.75–18.88) < 0.001 7.91 (3.48–17.97) < 0.001 PUFA intake (energy %)  Total intake 105/208 0.93 (0.87-1.00) 0.084 0.95 (0.86–1.05) 0.379  Lower than mean 58/98 Ref. Ref. Ref. Ref.  Higher than mean 47/110 0.72 (0.45–1.15) 0.175 0.95 (0.47–1.91) 0.899 Cholesterol intake (mg/day)  Total intake 105/208 1.00 (1.00–1.00) < 0.001 1.00 (1.00–1.00) 0.003  Lower than mean 42/114 Ref. Ref. Ref. Ref.  Higher than mean 63/94 1.81 (1.13–2.92) 0.014 0.81 (0.37–1.77) 0.601 OR odds ratio, CI confidence interval. Significant values are shown in bold. These values are odds ratio (95% CIs) and obtained from logistic regression. Adjusted Model: adjusted based on age, BMI, energy intake, age at menarche, menstruation duration, smoking, occupation, regular menstruation and familial history of endometriosis. The association between healthy diet indicator and its components with odds of endometriosis. OR odds ratio, CI confidence interval. Significant values are shown in bold. These values are odds ratio (95% CIs) and obtained from logistic regression. Adjusted Model: adjusted based on age, BMI, energy intake, age at menarche, menstruation duration, smoking, occupation, regular menstruation and familial history of endometriosis.

Our findings suggest that greater adherence to the Mediterranean diet and higher overall diet quality, as measured by the Medi-Lite and HDI scores, are strongly associated with reduced odds of endometriosis. Diets rich in fruits, vegetables, legumes, fish, fiber, and plant-based foods were protective, while higher consumption of meat, dairy, and saturated fats was linked to increased odds. These results highlight the potential role of dietary patterns in the prevention or management of endometriosis and support the promotion of healthy, plant-based dietary habits among women of reproductive age. However, generalization of the results should be done with caution. Further longitudinal and interventional studies are warranted to confirm these associations and to explore underlying mechanisms.

The results of this study, which aimed to investigate the association between adherence to the Mediterranean diet and the HDI with the odds of endometriosis among Iranian women, clearly demonstrated that higher adherence to the Mediterranean diet was associated with a 94% reduction in the odds of endometriosis, and a higher HDI score was associated with a 95% lower odds. Furthermore, the adjusted model in this study illustrated that the likelihood of endometriosis decreased with increased consumption of fruits, vegetables, legumes, fiber, plant based foods and fish, while it increased with higher intake of meat, SFA and dairy products, which aligns with other studies conducted in this field 15 , 32 – 34 . Surprisingly, we observed a direct association between consumption of whole grains and MUFA with the odds of endometriosis and an indirect association between consumption of carbohydrate and odds of endometriosis which should be considered by caution. Dietary patterns rich in fruits, vegetables, legumes, fiber, plant based foods and fish may influence the progression and severity of endometriosis through factors such as antioxidants, vitamins D and B, and increased fiber intake 35 . Although plant-based diets are associated with reduced bioavailability of estrogen, increased consumption of green vegetables, fruits, PUFAs, omega-3, and some dairy products may reduce the risk of endometriosis by decreasing inflammatory factors such as IL-6 16 , 32 . Higher magnesium in the Mediterranean diet prevents the rise in intracellular calcium levels, which in turn leads to uterine relaxation and reduced pain 36 . Fish and olive oil, as important components of the Mediterranean diet, possess anti-inflammatory effects. This mechanism is attributed to oleocanthal in olive oil, which has a structure similar to ibuprofen and functions similarly by inhibiting cyclooxygenase, thereby reducing endometriosis-related pain 37 . In our study, increased consumption of dairy products in the Mediterranean diet was associated with increased odds of developing endometriosis, which contradicts the findings of other studies. There is evidence suggesting that the consumption of dairy products in early life is associated with a reduced risk of endometriosis in adulthood. Zemel et al. demonstrated that increased calcium and dairy intake are associated with a reduction in TNF-α and IL-6, as well as oxidative stress markers such as ROS, which are among the most important factors contributing to the development of endometriosis 38 . From another perspective, increased consumption of dairy products, which is associated with increased calcium and vitamin D absorption, can stimulate IL-6 secretion, leading to a decrease in IL-17 concentration and alterations in T-helper function 39 , 40 . Therefore, vitamin D deficiency could be considered a plausible biological risk factor for inflammatory diseases. However, a number of studies have not observed any evidence of the effect of vitamin D deficiency on increasing the risk of endometriosis 41 . We found a counterintuitive pattern: higher total carbohydrate intake (as a percent of energy) was linked to lower odds of endometriosis, while higher whole grains intake (grams per day) was linked to higher odds. While this is surprising, several factors and published literature help contextualize these findings. There was no evidence of the effect of whole grains on the risk of endometriosis in some previous studies 37 , 42 . Large cohort studies in Western populations have not shown a consistent association between total carbohydrate intake and endometriosis risk. In the Nurses’ Health Study II, higher glycemic index (quality of carbs, not the amount) was linked to a slightly increased risk, but neither total carbohydrate nor cereal fiber intake alone showed strong evidence of increasing or decreasing risk 43 . Other studies have focused on different outcomes (e.g., cardiovascular disease, endometrial cancer), which are not directly comparable to endometriosis 44 – 46 . Higher whole grain consumption is usually associated with lower risk for various chronic diseases due to fiber, antioxidants, and anti-inflammatory components. However, evidence specifically on endometriosis is limited. In Nurses’ Health Study II, cereal fiber (mainly from grains) was not associated with endometriosis risk 43 . Dietary patterns, food processing, genetic factors, and environmental exposures in Iran likely differ significantly from Western settings. For example, grains in the Iranian diet may differ in type, preparation, and accompanying foods. Moreover, whole grain consumption remains relatively rare in Iran, where traditional breads like lavash, sangak, and barbari are typically prepared using refined flour 47 . traditional breads incorporate substantial quantities of sodium salt and baking soda, both of which play active roles in the baking process 48 , 49 . We know that sodium contributes to inflammatory processes, which play a pivotal role in both the initiation and advancement of endometriosis 50 , 51 . In addition, not all whole grain products are high in fiber or beneficial compounds. Some may be highly processed (e.g., certain breads), and their role could be very different from minimally processed grains. Whole grain products serve as a primary dietary source of gluten. Given that the symptoms of endometriosis often resemble those of other inflammatory and immune-related conditions like celiac disease 52 , reducing gluten consumption may alleviate pain and improve both physical functioning and mental well-being 18 . It should be noted that higher carbohydrate intake might reflect higher fruit or other food intake (not only grains), this could impact results. It seems somewhat impossible to justify the observed result regarding a direct relationship between MUFA intake and endometriosis. Several comprehensive reviews and meta-analyses indicate that higher intake of saturated fats and trans fats could be associated with a greater risk of endometriosis, but studies on MUFAs generally suggest a different trend. In fact, some research suggests MUFA and omega-3 polyunsaturated fat intake may be associated with a lower or neutral risk of developing endometriosis, not an increased risk, though findings are not entirely consistent across all research 53 . Our observed results may be due to the dietary sources of MUFA in our population, potential displacement of anti-inflammatory PUFAs such as omega-3, or residual confounding from other lifestyle factors. Further research is needed to clarify these associations. This study has several limitations, including not controlling for all of the confounding factors. Controlling for factors such as socioeconomic status is of great importance in this regard. The consumption of a number of items which could impact endometriosis risk was not assessed, including coffee, soy, phytoestrogens, saturated and unsaturated oils, and dietary supplements, which should be considered in future research.

Endometriosis is a common, benign, estrogen-dependent condition characterized by the presence of endometrium-like tissue outside the uterus, typically affecting the pelvis, peritoneum, ovaries, and rectovaginal septum 1 , 2 . Due to its chronic nature and association with comorbidities such as irritable bowel syndrome, mental health disorders, fibromyalgia, and autoimmune diseases, endometriosis is considered a significant medical challenge 3 , 4 . It affects approximately 10% of women of reproductive age, with 35–50% of those presenting with pelvic pain or infertility being diagnosed with the condition 5 , 6 . Clinical manifestations commonly include chronic pain symptoms such as dysmenorrhea, lower back pain, and non-menstrual pelvic or abdominal pain 7 . Endometriosis is also a major contributor to infertility, primarily due to fallopian tube adhesions, altered pelvic anatomy, and disruptions in the hormonal environment, which can impair oocyte quality and embryo implantation 3 . The etiology of endometriosis involves complex interactions among endocrine, inflammatory, and immune pathways 7 , along with genetic and environmental factors 8 , 9 . Over recent decades, several risk factors for the development and progression of endometriosis have been identified, including lifestyle behaviors, physical activity levels, body mass index (BMI), use of oral contraceptives, smoking, and alcohol consumption 10 , 11 . Among these, diet has emerged as a key modifiable lifestyle factor that may influence the onset and severity of endometriosis through multiple biological mechanisms, including modulation of inflammatory responses, prostaglandin metabolism, oxidative stress, smooth muscle contraction, and hormonal and immune function 12 . The role of dietary patterns in endometriosis has attracted growing interest, particularly due to their impact on underlying pathophysiological processes. Recent studies have reported encouraging results regarding the benefits of nutritional interventions in alleviating endometriosis symptoms, with nearly half of patients adopting dietary modifications and self-management strategies 10 , 13 . Diet-induced changes in chronic inflammation and visceral function have been well documented 14 , 15 . Specifically, dietary patterns may influence endometriosis risk by affecting menstrual cyclicity, inflammation, oxidative stress, smooth muscle activity, and steroid hormone metabolism 16 . Emerging evidence supports the role of dietary patternn rich in fruits, vegetables, legumes, whole grains, and unsaturated fats in reducing systemic inflammation in patients with chronic inflammatory conditions 17 , 18 . Increased intake of polyunsaturated fatty acids (PUFAs), gluten-free, or low-nickel diets, may improve endometriosis-related pain perception 19 . In addition, our previous research has demonstrated the promising association of fertility diets, the MIND diet, and the Alternative Healthy Eating Index (AHEI) with reduced odds of endometriosis 20 – 22 . Despite growing interest, limited research has examined the relationship between adherence to the Mediterranean diet and the Healthy Diet Indicator (HDI) with incidence of endometriosis. Given the known anti-inflammatory and antioxidant properties of these dietary patterns, this study aims to investigate its association with the odds of endometriosis among Iranian women.