Repercussions of the Anti-inflammatory Diet on Endometriosis Control

Endometriosis is an in fl ammatory pathology characterized by the growth of endometrial tissue outside the uterus, resulting in chronic pelvic pain and infertility. As a result, it has been observed that diet can in fl uence the pathophysiology of this disease by attenuating the in fl ammatory environment. In this context, this study aims to summarize the infl uence of diet as a complementary therapy for endometriosis. To this end, a narrative review was carried out using the BVS, Emb ase, and Cochrane databases, including articles available in full in Portuguese, English, and Spanish published in the last 5 years. According to the literature, a diet can have pro-infl ammatory properties in patients with endometriosis, such as a diet rich in saturated fatty acids, and anti-in fl ammatory properties, involving polyunsaturated fatty acids, in order to infl uence the metabolism of prostaglandins. It is concluded that endometriosis is a chronic in fl ammatory disease that can be modulated with the adoption of anti- infl ammatory dietary habits that can impact women’s quality of life in the long term. Research Article Repercussions of the Anti- infl ammatory Diet on Endometriosis Control Sandriny Maria de Almeida Oliveira¹, Bianca Braga Gomes¹, Cainã Araújo Saraiva¹, Luana Azevedo Dourado¹, Jeremias Aguiar Azevedo¹ and Sávio Benvindo Ferreira²* 1Medical Student, Academic Unit of Life Sciences (UACV), Teacher Training Center (CFP), Federal University of Campina Grande (UFCG), 58900-000, Cajazeiras, Paraíba, Brazil 2PhD in Pharmacology, Academic Unit of Life Sciences (UACV), Teacher Training Center (CFP), Federal University of Campina Grande (UFCG), 58900-000, Cajazeiras, Paraíba, Brazil Sandriny Maria de Almeida Oliveira: ORCiD: https://orcid.org/0000-0001-8681-255X Bianca Braga Gomes: ORCiD: https://orcid.org/0009-0008-7234-8328 Cainã Araújo Saraiva: ORCiD: https://orcid.org/0009-0009-4222-4276 Luana Azevedo Dourado: ORC iD: https://orcid.org/0009-0002-7505-7741 Jeremias Aguiar Azevedo: ORCiD: https://orcid.org/0009-0003-9568-6710 *Sávio Benvindo Ferreira: ORCiD: https://orcid.org/0000-0001-8838-4755 Received: 11 July, 2024 Accepted: 03 August, 2024 Published: 05 August, 2024 *Corresponding author: Sávio Benvindo Ferreira, PhD in Pharmacology, Academic Unit of Life Sciences (UACV), Teacher Training Center (CFP), Federal Univer- sity of Campina Grande (UFCG), 58900-000, Cajazeiras, Paraíba, Brazil, E-mail: [email protected]

Food; diet; Chronic disease; Endometriosis; Infl ammation Copyright License: © 2024 De Almeida Oliveira SM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://www.clinsurggroup.us

Endometriosis is an infl ammatory pathology characterized by the growth of functional and hormone-dependent endometrial tissue outside the uterus, which can result in menstrual changes, chronic pelvic pain, and infertility [1]. It is therefore believed that this clinical condition affects between 6% and 10% of menopausal women and between 50 and 60% of adolescent and adult women with pelvic pain, as well as being responsible for around 50% of the causes of infertility. According to the National Health Surveillance Agency (ANVISA), endometriosis affects 1 in 10 women between the ages of 25 and 35, who come down with pelvic pain that coincides with the menstrual period, a fact that is normalized, resulting in late diagnosis and treatment in around 7 years [2]. The clinical picture of endometriosis varies widely and is confused with other pathologies, such as pelvic in fl ammatory disease and irritable bowel, and is characterized as a benign disease that presents with a lesion in the ovary or endometrioma and foci of endometrial growth (Figure 1) that can reach the intestine, peritoneum, bladder and adjacent organs, resulting in non-speci fi c symptoms [3]. In women 018 https://www.clinsurggroup.us/journals/journal-of-gynecological-research-and-obstetrics Citation: De Almeida Oliveira SM, Gomes BB, Saraiva CA, Dourado LA, Azevedo JA, Ferreira SB. Repercussions of the Anti-inflammatory Diet on Endometriosis Control. J Gynecol Res Obstet. 2024;10(2):017-022. DOI: https://dx.doi.org/10.17352/jgro.000126 who are oligosymptomatic, infertile, or in the early stages of the disease, diagnosis can be late, which results in thousands of underdiagnosed cases that become chronic and compromise quality of life [4]. The spectrum of signs and symptoms of this infl ammatory disease, the non-correspondence of symptoms with the stage of the disease, and the limitation of the use of imaging tests due to cost-effectiveness mean that the diagnosis of endometriosis is postponed for years, as well as resulting in 5 or more consultations until the start of speci fi c treatment or the referral of women to specialized centers [5]. Thus, the choice of drug therapies for endometriosis takes into account the in fl ammatory pathophysiology of the disease and the responsiveness to hormones, in addition to the fact that the physiological conditions of the pregnancy and menopause period are associated with the resolution of the resulting chronic pain [6]. In other words, the prescription of progestogen analogs and Combined Oral Contraceptives (COCs), which simulate hormonal conditions similar to those of pregnancy, and GnRH agonists, which promote the suppression of endogenous estrogen and resemble menopause [4]. On the other hand, the literature shows that aspects related to lifestyle changes, especially in relation to an anti-infl ammatory diet, are important as a complement to pharmacological therapy, with the aim of approaching the disease through different therapies. That said, it has been observed that a selective diet can in fl uence the course of endometriosis pathophysiology, such as in fl ammation and prostaglandin metabolism [7]. This diet is related to the consumption of oral omega-3 polyunsaturated fatty acids, a dietary supplement approved by the Food and Drug Administration (FDA) that has a suppressive action on endometrial cells [8]. It is worth mentioning that studies have analyzed the correlation of nutrition on the pathogenesis of endometriosis and on the in fl ammatory state of the disease, such as a diet based on antioxidants, as they minimize free oxygen radicals and, consequently, infl ammation [6]. On the other hand, a diet rich in carbohydrates is associated with a pro-in fl ammatory state, which can aggravate the main symptom of the disease, which is chronic pain [9]. With this in mind, considering the infl uence of diet on the progression of endometriosis and as a potential complementary therapy to pharmacological therapy, this study aims to summarize the repercussions of an anti- infl ammatory diet on the control of endometriosis. Methodology Characterization of the research This is a narrative, qualitative, and descriptive review, in which bibliographic studies on a particular subject are analyzed and synthesized in order to provide a relevant and current theoretical reference, as well as gather new perspectives on a speci fi c topic [10]. In order to construct the research question, the PICO strategy (Population, Intervention, Control, and Outcomes/Outcome) was used, resulting in the research question: “What are the repercussions of an anti-infl ammatory diet on the control of endometriosis?” Conducting the research The review was carried out during the months of November and December 2023, in the electronic databases Embase, Cochrane, and VHL aimed at indexing scienti fi c journals and articles. The keywords provided by the Health Sciences Descriptors (DeCS) and the Boolean operators used in the search were: endometriosis AND diet OR nutrition AND infl ammation, with the search languages being Portuguese and English, involving articles from the last 5 years. The papers were then selected by title, followed by reading the abstract and then the full text, original articles that dealt with endometriosis in the dietary context, as well as the in fl uence of food as an anti- infl ammatory therapy, were selected. The exclusion criteria were duplicate studies, review articles, and articles involving animals which, after full reading, did not answer the research question. Summary of results Based on the search criteria, 123 articles were found and, at fi rst, reviews and studies involving animals were excluded, followed by other articles excluded by title and abstract and, fi nally, after a thorough reading, 8 articles were selected to make up the state of the art. This was followed by an analysis of the theoretical basis of each study, as well as an observation of the general characteristics of the articles, highlighting the most relevant points to be synthesized in the current narrative review. As this is a review article, it was not necessary to submit the study to an ethics and research committee, as the analysis was based on secondary data already published in other articles. Theoretical background Understanding Endometriosis Endometriosis is a chronic, in fl ammatory gynecological disease in which endometrial tissue grows outside the uterine cavity, resulting in local in fl ammation, compression, and Figure 1: Possible foci of endometriosis. Source: Adapted from [13]. 019 https://www.clinsurggroup.us/journals/journal-of-gynecological-research-and-obstetrics Citation: De Almeida Oliveira SM, Gomes BB, Saraiva CA, Dourado LA, Azevedo JA, Ferreira SB. Repercussions of the Anti-inflammatory Diet on Endometriosis Control. J Gynecol Res Obstet. 2024;10(2):017-022. DOI: https://dx.doi.org/10.17352/jgro.000126 obstruction of other organs, generating chronic pain and, in advanced cases, infertility [4]. In other words, it corresponds to ectopic endometrial tissue outside the uterine cavity and myometrium and can be found in the pelvic and abdominal cavities, adhered to the peritoneum, ovary, bladder and/or intestines [1]. In a study [3] that worked with a sample of 153 women with endometriosis, the most prevalent symptoms were: dyspareunia (65.4%), dysmenorrhea (88.2%), and infertility (52.9%) and, when endometrial tissue appears in non- reproductive organs, the associated complaints are: dyschezia, hematochezia and dysuria. The causes that explain endometriosis have not yet been fully elucidated and may vary in terms of the manifestations and bodily responses to ectopic endometrial implants, whose progression is not restricted to a single pathway and may regress, progress, or stabilize [11]. The symptoms associated with endometriosis usually appear in adolescence or early adulthood, and they also manifest cyclically with the hormonal variations of the menstrual cycle, as the growth of endometrial tissue is estrogen-dependent [12]. With regard to treatment, the choice of method should take into account the expression of each symptom and the site affected by the disease, as well as including the desire to become pregnant or not, the patient’s age, and possible surgical complications. Treatment with combined contraceptives aims to slow down the progression of the disease and is used as the fi rst choice for women who want contraceptive protection associated with mild symptoms of endometriosis, as it reduces dysmenorrhea and helps to reduce endometriomas [4]. Thus, the hormonal drugs cited in the literature - such as isolated progestogens, combined oral contraceptives, gestrinone, danazol, and GnRH - have similar effects in relieving pelvic pain. In addition, there is surgical treatment to remove endometrial foci in the case of women who have not responded to drug treatment and suffer from progressive pelvic pain [1]. Pathophysiology of endometriosis In principle, endometriosis is a common, in fl ammatory, and debilitating gynaecological disease that can lead to the occurrence of many chronic pathologies, such as pelvic pain, dysmenorrhoea, and infertility, characterized by the presence of endometrial tissue outside the uterus, affecting the ovaries, fallopian tubes, bladder, and more distant tissues [14] (Figure 2). Despite being recognized as an in fl ammatory disease, the pathogenesis of endometriosis and the origin of chronic pain and other symptoms remain poorly understood. However, it is known that some hormonal, neurological, and systemic infl ammatory factors may be related to the pathophysiology of this condition [15]. In this sense, it is clear that chronic in fl ammation has been proposed in several studies as an enhancer of the pathophysiological mechanism of endometriosis [16]. This is because the pro-in fl ammatory condition of endometriosis triggers an increase in cytokine and growth factor concentrations, as well as leading to a decrease in cell apoptosis and an increase in angiogenesis [17]. As evidence of this, in recent decades, researchers have Figure 2: Pathophysiology of endometriosis. Source: Adapted from [21]. 020 https://www.clinsurggroup.us/journals/journal-of-gynecological-research-and-obstetrics Citation: De Almeida Oliveira SM, Gomes BB, Saraiva CA, Dourado LA, Azevedo JA, Ferreira SB. Repercussions of the Anti-inflammatory Diet on Endometriosis Control. J Gynecol Res Obstet. 2024;10(2):017-022. DOI: https://dx.doi.org/10.17352/jgro.000126 been able to fi nd the presence of in fl ammatory mediators such as interleukin (IL)-1 beta, IL-6, and Tumor Necrosis Factor-alpha (TNF- ) in the endometrial tissue of women with endometriosis, demonstrating that in fl ammation plays a crucial role in the pathogenesis of endometriosis, as these cytokines positively regulate the production of human endometrial haptoglobin in women with endometriosis [14]. In addition, the macrophages that in fi ltrate the ectopic lesions through chemokine-induced recruitment express typical markers of alternative activation, promoting neoangiogenesis and facilitating the growth of endometriosis by increasing the levels of vascular endothelial growth factor in the peritoneal fl uid [18]. Furthermore, the chronic in fl ammatory state of endometriosis activates nociceptors, resulting in central and peripheral sensitization [7]. Consequently, the altered in fl ammatory microenvironment characteristic of endometriotic tissue may be related to hyperalgesia and the persistence of chronic pain [19]. In addition, women with endometriosis have been reported to have signifi cant changes in oxidative stress parameters [20]. This factor induces a cytotoxic effect, increased cell membrane permeability, enzyme activation, DNA damage, and cell death, so pain in women with endometriosis is related to the response to tissue injury, the resulting in fl ammatory process, and oxidative stress [7]. Finally, in addition to these factors, high serum estrogen levels can contribute to the production of prostaglandins and the development of cell proliferation, favoring in fl ammation and the intensifi cation of endometriosis [7]. As a result, because it is a chronic in fl ammatory disease dependent on oestrogen, the greatest risk of endometriosis occurs between the ages of 25 and 35, given that the density of serum hormone levels, especially oestrogen, normally decreases at the age of 35 [19]. The role of nutrition as a complementary therapy Pro-infl ammatory diet: Some factors associated with the diet may have properties considered to be pro-in fl ammatory in patients with endometriosis, for example, a diet with high amounts of saturated fatty acids and carbohydrates, and low amounts of polyunsaturated fatty acids (especially omega-3 fatty acids), fl avonoids, and antioxidants [18]. As a starting point, we can cite the results of the Nurses’ Health Study II, which shows that the consumption of red meat possibly increases painful symptoms, as it reduces estrogen transporters resulting in greater availability of this hormone in circulation, which stimulates the progression of endometriotic foci that are hormone-dependent [7]. In a study of thirty-one women diagnosed with endometriosis and suffering from gastrointestinal disorders, twenty-eight of them (90.3%) had nickel (Ni) in their oral mucosa and were diagnosed with allergic contact mucositis due to Ni, while three of the thirty-one (9.7%) patients did not have nickel in their oral mucosa. After three months on a low-nickel diet, all gastrointestinal, extraintestinal, and gynecological symptoms decreased signifi cantly [15]. In this context, nickel (Ni) in high concentrations can be toxic, inducing in fl ammatory and allergic disorders, for humans the main source of the element is in foods such as tomatoes, cocoa, beans, mushrooms, green leafy vegetables, whole wheat fl our, soybeans, corn, onions, garlic, shell fi sh, nuts, canned foods [15]. Furthermore, a study carried out using data from the National Health and Nutrition Examination Survey with participants from the general US population concluded that those with the highest Dietary Infl ammatory Index (DII) scores had a 57% higher risk of endometriosis than those with the lowest DII scores [16]. This is due to the high levels of systemic infl ammation caused by the pro-infl ammatory diet, which can affect the markers C-reactive protein, IL-6, IL-8, and TNF- , collaborating for the implantation of endometrial cells, growth, invasion, and angiogenic properties of ectopic lesions [18]. Anti-infl ammatory diet: The main treatments for endometriosis are based on hormonal medication and surgical removal of lesions [7]. However, around 75% of symptoms recur after surgery, and ovarian suppressant drugs have several side effects similar to those of menopause and/or are contraceptives, which generates the need for alternatives to promote patients’ quality of life [8]. Studies are progressively analyzing the importance of therapy strategies that address all demands, including aspects related to quality of life. This trend is demonstrated in the analysis of the impact of changes in dietary patterns on controlling the symptoms of chronic diseases such as endometriosis. Over the last decade, it has been observed that diet can infl uence various mechanisms involved in endometriosis, such as infl ammation, prostaglandin metabolism, and estrogen regulation [7]. In this sense, it is important to consider that an ideal therapy for endometriosis includes reducing painful symptoms, reducing the size of the lesion, and limiting side effects. These criteria are met by oral omega-3 polyunsaturated fatty acids, a dietary supplement approved by the Food and Drug Administration (FDA), which participate in the regulation of prostaglandin metabolism and cytokine physiology, potentially producing anti-infl ammatory lipid mediators [8]. In this sense, quantitative and qualitative analysis of dietary intake is valid, since infl ammatory processes play a signifi cant role in the pathogenesis and progression of endometriosis [20]. In addition, in vitro studies have shown that oral omega-3 polyunsaturated fatty acids have a suppressive effect on endometrial cell survival [22]. Among the dietary habits analyzed, a prospective study included 35 women with endometriosis to analyze the role of the Mediterranean Diet (MD) on the perception of pain in endometriosis and on oxidative stress. This dietary pattern is based on a daily intake of fruit, vegetables, whole grains, and vegetable fats, and a weekly intake of fi sh, poultry, legumes, 021 https://www.clinsurggroup.us/journals/journal-of-gynecological-research-and-obstetrics Citation: De Almeida Oliveira SM, Gomes BB, Saraiva CA, Dourado LA, Azevedo JA, Ferreira SB. Repercussions of the Anti-inflammatory Diet on Endometriosis Control. J Gynecol Res Obstet. 2024;10(2):017-022. DOI: https://dx.doi.org/10.17352/jgro.000126 and eggs, as well as moderate portions of dairy products and limiting red meat and foods with added sugar. Thus, the results of the study showed a trend toward a relationship between adherence to DM and minimization of chronic non-menstrual pelvic pain ( p = 0.06), dyspareunia ( p = 0.04), dysuria ( p = 0.04) and dyskinesia ( p < 0.001) in the fi rst three months of the diet [7]. It is therefore understood that dietary therapies can be effective in promoting the quality of life of patients with endometriosis, considering, for example, that omega-3 polyunsaturated fatty acids have the potential to reduce the painful symptoms associated with endometriosis, reduce the size of the lesion, preserve the patient’s ability to conceive and have minimal side effects [22]. The Mediterranean Diet mainly recommends fi sh rich in omega-3 fatty acids and extra virgin olive oils, which have an anti-in fl ammatory effect. In addition, in the study, the daily fi ber intake of women with endometriosis was below the recommended levels. Therefore, an increase in fi ber intake was promoted through the consumption of fruits, vegetables, and whole grains, in order to regulate the fecal excretion of excess estrogen. This approach was based on the understanding that high serum estrogen levels related to endometriosis lead to the production of prostaglandins, favoring in fl ammation and the proliferation of the disease. Thus, adopting a Mediterranean dietary pattern, rich in fruit, vegetables, legumes, whole grains, and fi sh, is a possible non-pharmacological therapeutic intervention for endometriosis [7]. In addition, a prospective cohort study showed an inverse relationship between magnesium intake and the risk of endometriosis (RR = 0.86, 95% CI: 0.73 - 1.01; p = 0.007), which indicates the potential therapeutic use of magnesium. In addition, vitamin C was highlighted for its antioxidant and anti- infl ammatory effects, benefi ts associated with minimizing the oxidative stress characteristic of endometriosis. Therefore, the intake of vitamins and minerals can play an important role in the therapeutic strategy [20].

Although its pathogenesis is poorly understood, it is known that endometriosis is a multifactorial chronic disease infl uenced by genetic, pro-in fl ammatory, hormonal, immunological, systemic, and environmental factors. Risk factors include family history, long menstrual cycle, low parity, and low physical activity [15]. In addition, studies show that endometriosis is intrinsically related to an in fl ammatory process, tissue damage, oxidative stress, and high estrogen levels [7]. These factors are responsible for causing the symptoms of endometriosis, such as chronic non-speci fi c pain, dysmenorrhea, dyspareunia, dysuria, and the risk of infertility [16]. At this juncture, after analyzing various studies, it was observed that because endometriosis is a multifactorial disease with a concomitant infl ammatory pattern, the dietary intake of patients has an infl uence on some of the symptoms presented, so a complementary approach to treatment would be conducted focused on minimizing in fl ammatory processes in general, in order to reduce uncomfortable symptoms [9]. In this way, pro-in fl ammatory foods should be avoided, since changing some dietary patterns can reduce infl ammatory markers by mitigating the chemical signals of prostaglandins that are responsible for painful stimuli [23]. Furthermore, it is necessary to continue researching diets as part of therapeutic strategies, as dietary patterns have shown important benefi ts in reducing the symptoms of chronic diseases, such as endometriosis [7]. Of particular note at this juncture is the intake of oral omega-3 polyunsaturated fatty acids and the consumption of foods rich in fi ber, vitamins, and minerals. This is mainly due to the regulation of prostaglandins and antioxidant Properties [20]. However, studies are still needed to defi ne the appropriate levels of supplementation for controlling endometriosis symptoms [22].

It is clear that the prevalence of endometriosis is high, as it is a disease that is still underdiagnosed and thought of as a diagnosis of exclusion, especially in patients with infertility and chronic pelvic pain who often do not respond to the recommended pharmacological therapy. As such, treatment should always be individualized, taking into account studies and protocols that show the effectiveness of different therapeutic regimes and patients’ quality of life. Regarding the role of diet as a complementary therapy, it was observed that the consumption of antioxidant nutrients, additional fatty acids, and a combination of vitamins and minerals, in addition to reducing the consumption of red meat, has in fl uenced the modulation of endometriosis. That is, the consumption of foods with anti-in fl ammatory properties interferes with the pathophysiology of this chronic disease in the long term. On the other hand, studies have shown that a pro-in fl ammatory diet contributes to the production of infl ammatory cytokines and prostaglandins that enhance the disease’s unwanted symptoms, such as chronic pain. Therefore, the inclusion of anti-in fl ammatory dietary habits, such as the consumption of omega-3 fatty acids, fruits, vegetables, legumes, whole grains, fi sh, and fi ber, as well as the exclusion of ultra-processed foods containing saturated fatty acids and carbohydrates, is a non-pharmacological therapeutic intervention with important repercussions in modulating the infl ammatory state of the disease and promoting the quality of life of patients with endometriosis. In this context, there is a consensus in the literature that endometriosis is a multifactorial chronic disease, and its pathophysiology is still complex and poorly understood, which makes diagnosis and treatment dif fi cult, especially when it comes to the infl uence of diet on the progression or prevention of this disease. Furthermore, despite the studies and theories 022 https://www.clinsurggroup.us/journals/journal-of-gynecological-research-and-obstetrics Citation: De Almeida Oliveira SM, Gomes BB, Saraiva CA, Dourado LA, Azevedo JA, Ferreira SB. Repercussions of the Anti-inflammatory Diet on Endometriosis Control. J Gynecol Res Obstet. 2024;10(2):017-022. DOI: https://dx.doi.org/10.17352/jgro.000126 linking biological mechanisms and the effect of dietary profi les on the improvement or worsening of endometriosis symptoms, these studies still lack robust epidemiological evidence. Authors’ contribution SO, BG, CS, LD, JA: Conception, organization, writing of the work, critical review, and approval of the fi nal manuscript. SF: Conception, critical review and approval of the fi nal manuscript. Financing source This work did not receive any type of fi nancial support or subsidy from any entity in the public or private domain.

We would like to thank the Júlio Bandeira Hospital (HUJB) and our supervisor for the opportunity to develop the scientifi c initiation project on endometriosis that inspired this article.

1. Torres JI, Araújo JL, Vieira JA, Souza CD, Passos IN, Rocha LD. Endometriosis, diffi culties in early diagnosis and female infertility: A review. Res Soc Dev. 2021;10(6). Available from: https://doi.org/10.33448/rsd-v10i6.15661 2. Alex R. Endometriosis may affect 10% of Brazilian women. Agência Brasil. 2021. Available from: https://agenciabrasil.ebc.com.br/saude/ noticia/2021-03/endometriose-pode-afetar-10-das-mulheres 3. Pannain GD, Ramos BSD, Souza LC de, Salomão LRN, Coutinho LM. Epidemiological profi le and clinical assistance of women with endometriosis in a Brazilian public university hospital. Femina. 2022;178–83. Available from: https://pesquisa.bvsalud.org/portal/resource/pt/biblio-1367572 4. Rosa e Silva JC, Valerio FP , Herren H, Troncon JK, Garcia R, Poli Neto OB. Endometriosis – Clinical aspects from diagnosis to treatment. Femina. 2021;49(3):134-41. Available from: https://docs.bvsalud.org/ biblioref/2021/05/1224073/femina-2021-493-p134-141-endometriose- aspectos-clinicos-do-dia_CFa8LoS.pdf 5. Fauconnier A, Drioueche H, Huchon C, Du Cheyron J, Indersie E, Candau Y, et al. Early identifi cation of women with endometriosis by means of a simple patient-completed questionnaire screening tool: a diagnostic study. Fertil Steril. 2021;116(6):1580–9. Available from: https://doi.org/10.1016/j.fertnstert.2021.07.1205 6. Helbig M, Vesper AS, Beyer I, Fehm T. Does nutrition affect endometriosis? Obstet Gynecol. 2021;81(2):191–9. Available from: https://pubmed.ncbi.nlm.nih.gov/33574623/ 7. Cirillo M, Argento FR, Becatti M, Fiorillo C, Coccia ME, Fatini C. Mediterranean diet and oxidative stress: A relationship with pain perception in endometriosis. Int J Mol Sci. 2023;24(19):14601. Available from: https://www.mdpi.com/1422-0067/24/19/14601 8. Abokhrais IM, Saunders PTK, Denison FC, Doust A, Williams L, Horne AW. A pilot randomised double blind controlled trial of the effi cacy of purifi ed fatty acids for the treatment of women with endometriosis-associated pain (PurFECT): study protocol. Pilot Feasibility Stud. 2018;4:83. Available from: https://doi.org/10.1186/s40814-018-0274-8 9. Habib N, Buzzaccarini G, Centini G, Moawad GN, Ceccaldi PF, Gitas G, et al. Impact of lifestyle and diet on endometriosis: a fresh look to a busy corner. Menopause Rev. 2022;21(2):124–32. Available from: https://doi.org/10.5114/pm.2022.116437 10. Vosgerau DSR, Romanowski JP . Review studies: conceptual and methodological implications. Rev Educational Dialogue. 2014;14(41):165– 90. Available from: http://educa.fcc.org.br/scielo.php?script=sci_ arttext&pid=S1981-416x2014000100009 11. Moretto EE, Souza JPF, Farenzena LP , Crippa LG, Pedrotti MT, Bellan LM, et al. Endometriose. lumeufrgsbr. 2021; Available from: https://lume.ufrgs.br/handle/10183/223088 12. Vieira GCD, Silva JAC da, Padilha RT, Padilha D de MM. Endometriosis: causes, implications and treatment of female infertility through assisted reproduction techniques. Res Soc Dev. 2020;9(10). Available from: http://dx.doi.org/10.33448/rsd-v9i10.9128 13. Endometriosis. Germany: Institute for Quality and Effi ciency in Health Care (IQWiG); 2024 Mar 24. Available from: https://www.informedhealth.org/ endometriosis.html#Further-information 14. Demézio da Silva CV, Felipe VL, Shivappa N. Dietary Infl ammatory Index score and risk of developing endometriosis: A case–control study. J Endometriosis Pelvic Pain Disord. 2021;13(1):32-39. Available from: https://doi.org/10.1177/2284026520967599 15. Borghini R, Porpora MG, Casale R, Marino M, Palmieri E, Greco N, et al. Irritable bowel syndrome-like disorders in endometriosis: prevalence of nickel sensitivity and effects of a low-nickel diet. An open-label pilot study. Nutrients. 2020;12(2):341. Available from: https://doi.org/10.3390/nu12020341 16. Liu P , Maharjan R, Wang Y, Zhang Y, Zhang Y, Xu C, et al. Association between dietary infl ammatory index and risk of endometriosis: A population-based analysis. Front Nutr. 2023;10:1077915. Available from: https://doi.org/10.3389/fnut.2023.1077915 17. Nodler JL, DiVasta AD, Vitonis AF, Karevicius S, Malsch M, Sarda V, et al. Supplementation with vitamin D or ω-3 fatty acids in adolescent girls and young women with endometriosis (SAGE): a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2020;112(1):229-36. Available from: https://doi.org/10.1093/ajcn/nqaa096 18. Yousefl u S, Sadatmahalleh SJ, Mottaghi A, Nasiri M. Association between dietary infl ammatory index and endometriosis risk in a case-control study. J Endometriosis Pelvic Pain Disord. 2021;13(2):77-82. Available from: https://doi.org/10.1177/2284026520984415 19. Hu PW, Yang BR, Zhang XL, Yan XT, Ma JJ, Qi C, et al. The association between dietary infl ammatory index with endometriosis: NHANES 2001- 2006. PLoS One. 2023;18(4). Available from: https://doi.org/10.1371/journal.pone.0283216 20. Schink M, Konturek PC, Herbert SL, Renner SP , Burghaus S, Blum S, et al. Different nutrient intake and prevalence of gastrointestinal comorbidities in women with endometriosis. J Physiol Pharmacol. 2019;70(2). Available from: https://doi.org/10.26402/jpp.2019.2.09 21. Jiang I, Yong PJ, Allaire C, Bedaiwy MA. Intricate connections between the microbiota and endometriosis. Int J Mol Sci. 2021;22(11):5644. Available from: https://doi.org/10.3390/ijms22115644 22. Abokhrais IM, Denison FC, Whitaker LHR, Saunders PTK, Doust A, Williams LJ, et al. A two-arm parallel double-blind randomised controlled pilot trial of the effi cacy of Omega-3 polyunsaturated fatty acids for the treatment of women with endometriosis-associated pain (PurFECT1). PLoS One. 2020;15(1):e0227695. https://doi.org/10.1371/journal.pone.0227695 23. Golabek A, Kowalska K, Olejnik A. Polyphenols as a diet therapy concept for endometriosis—current opinion and future perspectives. Nutrients. 2021;13(4):1347. Available from: https://doi.org/10.3390/nu13041347