Endometriosis

Endometriosis: A Nutrition and Natural-Health Reference

1. Definition and Overview

Endometriosis is classically defined by the presence of endometrial glands and stroma in extrauterine locations. More precisely, it is a chronic, inflammatory, gynecologic disease marked by the presence of endometrial-like tissue outside the uterus, which in many patients is associated with debilitating painful symptoms.

Endometriosis affects approximately 190 million women and people assigned female at birth worldwide. It affects approximately 5–10% of women of reproductive age, and it is associated with pelvic pain and infertility. Patients with endometriosis are also at greater risk of infertility, emergence of fatigue, multisite pain, and other comorbidities. Thus, endometriosis is best understood as a condition with variable presentation and effects at multiple life stages.

A long diagnostic delay after symptom onset is common, and persistence and recurrence of symptoms despite treatment is common. Symptoms do not correlate well with disease severity. Significant dysfunction can be present with minimal gross disease, whereas severe endometriosis is sometimes asymptomatic.

2. Clinical Presentation

Clinical signs are numerous. Among them, dysmenorrhea, dyspareunia, chronic pelvic pain, irregular uterine bleeding and/or infertility are frequently found. This ectopic endometrium is functional and undergoes periodic revisions, explaining the cyclical nature of symptoms and the chronic inflammatory process associated with estrogens.

Its main locations are the pelvic peritoneum, uterosacral ligaments, cul-de-sac of Douglas, rectovaginal septum, and ovaries. Symptoms are related to the site of endometriotic implants and the organ system involved. Cases have been reported of extrapelvic involvement in virtually every other organ system including the central nervous system (CNS), lungs, pleura, kidney, and bladder. The gastrointestinal (GI) tract is the most common extrapelvic site of endometriosis, and symptoms include bowel obstruction, rectal bleeding, and constipation.

3. Body Systems Involved

The pathophysiology of endometriosis involves complicated immune, hormonal, and inflammatory interactions that disrupt normal tissue dynamics. The causes of endometriosis may be complex and may involve endocrine, immune, inflammatory, and angiogenic factors.

The pathological processes underlying endometriosis may also be involved in a spectrum of chronic comorbidities, including cardiovascular disease, gynecological cancer, respiratory disorders and even psychiatric disorders.

3.1 Reproductive System

The reproductive system is the primary site of disease. The ectopic tissue most commonly implants on the pelvic peritoneum, ovaries, and rectovaginal septum. Endometriosis is an inflammatory, fibrotic and estrogen-dependent gynecological disorder characterized by endometrial-like tissue outside the uterus, mainly in the pelvic peritoneum, ovaries, and rectovaginal septum. In rare cases, this endometrial-like tissue can be found in other areas, such as the pericardium, pleura, diaphragm or even the brain.

3.2 Immune System

Meta-analysis has revealed gut microbiota dysbiosis in women with endometriosis. Imbalances in the gut microbiome disrupt immune function, triggering inflammatory responses that elevate pro-inflammatory cytokines, impair immune surveillance, and alter immune cell profiles. These disruptions lead to chronic inflammation, fostering an environment conducive to cellular adhesion, angiogenesis, and fibrosis, which can perpetuate the progression of endometriosis.

3.3 Endocrine System

Endometriosis is an inflammatory, estrogen-dependent condition associated with pelvic pain and infertility. Reports linking endocrine disrupting chemicals (EDCs) with endometriosis suggest these, and endogenous/exogenous estrogens, as potential transforming/inductive/stimulant candidates in theories of endometriosis pathogenesis.

3.4 Epigenetic and Oxidative Stress Pathways

Studies have shown widespread epigenetic abnormalities in endometriotic stromal cells, including changes in deoxyribonucleic acid (DNA) methylation, histone modifications and microRNA (miRNA) expression. Concurrently, oxidative stress also plays a more evident role in the pathologic process of endometriosis. High levels of oxidative stress are widely regarded as a key factor in initiating inflammatory responses, extracellular matrix remodeling, angiogenesis and cell proliferation.

4. Theories of Origin and Pathogenesis

There exist many theories on the initiation and propagation of different types of endometriotic lesions, of which the most common is Sampson's theory according to which the retrograde flow of menstrual blood is linked to the development of endometriosis. The body's inability to remove endometriosis implants into the peritoneal fluid may be aggravated by anatomical features. Some elements increase menstrual reflux, hypertension of the utero-tubal junction, waves of retrograde tubular contractions of the myometrium, and uterine malformations. Moreover, in patients suffering from endometriosis, menstruation is often longer and more abundant, and menstrual cycles are shorter.

The theory of benign metastasis holds that ectopic endometrial implants are the result of lymphatic or hematogenous dissemination of endometrial cells. Microvascular studies demonstrated flow of lymph from the uterine body into the ovary, rendering possible a role for the lymphatic system in the etiology of ovarian endometriosis.

A more recent proposal suggests extra-uterine stem/progenitor cells originating from bone marrow may differentiate into endometriotic tissue. Candidate cell lineages include bone marrow mesenchymal stem progenitors and endothelial progenitors, and this represents an active area of investigation.

Another theory states that remnant Müllerian cells may remain in the pelvic tissues during development of the Müllerian system. Under situations of estrogen stimulation, they may be induced to differentiate into functioning endometrial glands and stroma.

5. Contributing and Associated Factors

5.1 Genetic and Familial Factors

Some women may have a genetic predisposition to endometriosis. Studies have shown that first-degree relatives of women with this disease are more likely to develop it as well. The etiology of endometriosis is complex and multifactorial. The risk factors associated with the development of endometriosis include family history, menstrual and reproductive cycle, low body mass index (BMI), diet, alcohol use, smoking, environmental factors, immune system, genetic factors and intrinsic abnormalities in the endometrium.

5.2 Hormonal Factors

Excessive intake of red meat is associated with increased levels of estrogen sulfate, leading to higher levels of steroids and inflammatory factors that influence the progression of endometriosis. Dietary factors can be related to endometriosis etiology due to their role in regulating steroid hormone metabolism, the effect on muscle contraction, regulating inflammation, oxidative stress, and the menstrual cycle. Some observational studies showed that a plant-based diet leads to a decrease in the bioavailability of estrogen; estrogen plays a role in inducing extra-uterine endometrial tissue proliferation.

5.3 Environmental and Endocrine Disruptors

Data focused primarily on endocrine disruptors, such as dioxins and polychlorinated biphenyls, that appear to have the strongest effect. Intriguing data suggest a link with night work, sun exposure, and red meat consumption. For other risk factors studied, particularly those related to lifestyle (tobacco consumption, alcohol, coffee, soy, physical exercise), the data are not sufficient to draw conclusions.

5.4 Early-Life and Perinatal Factors

The majority of studies found that women born with low birthweight (<2.5 kg or <5.5 lb) were more likely to be diagnosed with endometriosis. For other early life factors, the evidence is mixed or limited. Exposures during early life, including in utero, are thought to play an important role in the subsequent onset of the condition.

5.5 Gut Microbiome Dysbiosis

Microbial dysbiosis plays a pivotal role in the initiation and progression of endometriosis. Imbalances in the microbiome lead to elevated proinflammatory factors and compromised immune function, contributing to the onset of endometriosis. Gut microbiota can modulate estrogen metabolism via the estrobolome, influence systemic and local immune responses, and shape low-grade chronic inflammation, all of which are relevant to endometriosis and infertility. Research suggests that the gut microbiota may enhance central sensitization associated with chronic pain in endometriosis by modulating the activities of microglia, astrocytes, and immune cells, thereby intensifying patients' pain perception.

5.6 Comorbidities and Long-Term Disease Associations

Endometriosis-affected women have a higher risk than the general female population for ovarian cancer, coronary heart disease (CHD), and other long-term disease risks as well as for autoimmune and atopic disorders.

6. Dietary Factors

The association between nutrition and endometriosis is controversial. The certainty of the relationship between endometriosis and outcomes of nutritional factors was rated "very low" to "low," which limits current literature from being applied for conclusive interpretations. Further large-scale randomised trials and consequent meta-analyses are recommended for high-level evidence.

6.1 Red Meat

The analysis of available literature supports the idea that processed and unprocessed red meat increases the risk of endometriosis, while no conclusive evidence exists about the effects of other protein sources on the disease. This is one of the more consistently reported dietary associations across multiple systematic reviews.

6.2 Vegetables and Fruits

An umbrella review found a mild (class IV, lowest strength on evidence quartile) protective effect for vegetables (RR 0.590; 95% CI 0.49–0.71), though this was at the lowest strength on the evidence quartile. Green leafy vegetables and fresh fruit consumption may reduce the risk of endometriosis. Higher consumption of fruits and green vegetables may be protective because it can decrease inflammatory markers such as interleukin-6 (IL-6) that are elevated among women diagnosed with endometriosis.

6.3 Dairy Products

A higher intake of total dairy [all low-fat and high-fat dairy foods] was associated with decreased risk of endometriosis (RR 0.90; 95% CI, 0.85 to 0.95; P < 0.001), but these associations were not observed with intakes of low or high-fat dairy, cheese or milk separately. Dairy products contain anti-inflammatory and anti-oxidative agents, vitamin D, and calcium that may induce a protective effect in endometriosis.

6.4 Dietary Fats

Studies on total fat consumption, including monounsaturated, polyunsaturated, saturated, and trans-unsaturated fats, do not suggest a definitive association with endometriosis. The composition of fatty acids in the diet may be related to the risk of endometriosis. Fish oil consumption may lead to a decreased risk of endometriosis due to its anti-inflammatory effects, while high trans-fat intake leads to an increased risk.

6.5 Caffeine

Caffeine, one of the most widely used pharmacologically active substances worldwide, has been studied as a potential contributing factor linked with the development of hormone-dependent conditions. This theory stems from the fact that caffeine affects the levels of steroid hormones, the production of the sex hormone-binding globulin in the liver, and the conversion of androgens to estrogens by altering aromatase function. Some analyses suggest that high caffeine intake may increase the risk of endometriosis, though the overall evidence base for this association remains limited.

6.6 Overall Dietary Patterns

A healthy diet, primarily focusing on plant-based diets low in animal products, includes vegetables, fruits, legumes, nuts, fish, whole grains, and low-fat dairy, and moderate consumption of red meat, alcoholic beverages, salt, and saturated fatty acids. However, it is unclear if a healthy diet alleviates endometriosis symptoms in women. Although dietary modifications are considered the third most successful self-management measure, no specific diet appears to yield higher self-reported advantages.

7. Nutrients Studied in Relation to Endometriosis

7.1 Omega-3 Polyunsaturated Fatty Acids (PUFAs)

Scientific Evidence: Endometriosis is a chronic inflammatory gynecologic disorder associated with pelvic pain and impaired health-related quality of life. Omega-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory potential and may confer adjunctive benefit when combined with conventional therapy.

Animal and in vitro data are consistent: animal studies demonstrated that omega-3 reduced the volume and weight of endometriosis lesions, reduced inflammatory cytokines (TNF, IL-1β, IL-6), and reduced total oxidant status and oxidative stress index levels. However, omega-3 has no significant effect on pain severity and quality of life of endometriosis patients in clinical trials. Nonetheless, omega-3 fatty acids possess anti-inflammatory properties and have been suggested as a potential therapeutic option for endometriosis.

A 2025 systematic review and meta-analysis of five RCTs (total n=424) found that there were no statistically significant effects of omega-3 PUFAs on pain (MD = −0.387; 95% CI −1.742 to 0.967; I² = 93.3%; p = 0.575). However, a 2026 retrospective cohort study (patients treated at a single center, January 2021–December 2024) reported that compared with controls, the omega-3 group experienced greater reductions in overall pain, larger decreases in IL-6, TNF-α, and CRP, and greater improvements in health-related quality of life scores. The authors concluded that adjunctive omega-3 PUFA intake was associated with improved pain, reduced inflammatory biomarkers, and better health-related quality of life in endometriosis, warranting confirmation in future prospective randomized studies. The overall clinical evidence remains preliminary and inconsistent, and high-quality confirmatory RCTs are lacking.

7.2 Vitamin D

Scientific Evidence: Women with endometriosis have shown reduced serum vitamin D levels compared to those without or those mildly affected. The biological mechanism through which vitamin D may affect endometriosis risk is not yet fully understood, though it is hypothesized to involve immune system regulation, since there is strong circumstantial evidence that endometriosis is dependent not only on circulating steroid hormones.

The clinical evidence for vitamin D supplementation in endometriosis presents mixed results, with some trials demonstrating benefits in pain reduction and inflammatory markers while others show no significant advantage over placebo. High-dose vitamin D (50,000 IU) supplementation has shown the most consistent benefits in clinical trials. A systematic review found that vitamin D supplementation exhibits efficacy in alleviating dysmenorrhea associated with endometriosis, as evidenced by a meta-analysis showing a significant reduction in dysmenorrhea (mean difference −1.41, 95% CI −2.61 to −0.22, P = 0.02). In contrast, another systematic review of RCTs showed no significant effect of vitamin D intake for dysmenorrhea (2 studies, 44 vitamin D vs. 44 placebo, mean −0.71, 95% CI −1.94 to 0.51) and non-cyclic pelvic pain. Although in vitro and animal studies seem to suggest regression of the endometriotic implants and decrease of invasion and proliferation after vitamin D supplementation, this was not reflected in the results of included human studies. Evidence is mixed and preliminary.

7.3 Antioxidant Vitamins (Vitamins C and E)

Scientific Evidence: A meta-analysis of RCTs found that antioxidants significantly reduced dysmenorrhea (SMD, −0.48; 95% CI, −0.82 to −0.13; I²=75.14%). Meta-analysis results also suggested that antioxidant supplementation significantly improved pelvic pain (SMD, −1.51; 95% CI, −2.74 to −0.29; I²=93.96%), although antioxidants seem not to have a significant beneficial impact on the severity of dyspareunia. Dietary antioxidant supplementation seems to beneficially impact the severity of endometriosis-related dysmenorrhea and pelvic pain. The high heterogeneity (I²>75%) in these meta-analyses limits interpretability, and evidence is considered preliminary.

7.4 Magnesium

Scientific Evidence: The stronger protective association for milk and magnesium intakes in women who have never reported infertility may be due to these factors' influence on chronic pelvic pain symptoms or due to differing endometriosis etiologies. Formal interventional data on magnesium supplementation specifically for endometriosis are limited, and available evidence is largely observational and weak.

8. Natural Compounds and Herbal Ingredients

8.1 N-Acetylcysteine (NAC)

Scientific Evidence (human studies): NAC is the acetylated form of the amino acid cysteine, functioning as an antioxidant and glutathione precursor. NAC is an antioxidant compound known for its anti-inflammatory and antiproliferative effects on endometriotic cells and tissue. Recent studies have shown that NAC alters the expression of proliferative, differentiation-related, and inflammatory proteins and genes in endometriotic cells.

An observational cohort study (n=92 consecutive Italian women with ultrasound-confirmed ovarian endometriosis) found that after 3 months, within NAC-treated patients the cyst mean diameter was slightly reduced (−1.5 mm) versus a significant increase (+6.6 mm) in untreated patients (P = 0.001). More cysts reduced and fewer cysts increased their size during NAC treatment. A 2023 prospective single-cohort follow-up study at Sapienza University Hospital confirmed this, enrolling patients aged 18–45 years with a clinical/histological diagnosis of endometriosis who received oral NAC 600 mg, 3 tablets/day for 3 consecutive days per week for 3 months. At baseline and after 3 months, dysmenorrhea, dyspareunia, and chronic pelvic pain were assessed using the Visual Analog Scale, while endometrioma size was estimated through transvaginal ultrasound. These studies are uncontrolled or non-randomized; evidence is promising but preliminary. Adequately powered RCTs are needed.

8.2 Resveratrol

Scientific Evidence: Resveratrol, a plant-derived polyphenolic phytoalexin, demonstrates broad-spectrum health beneficial effects, including anti-proliferative, anti-inflammatory, antineoplastic and antioxidant properties. Because of these properties and its wide distribution in plants, resveratrol is proposed as having great potential to treat endometriosis.

In animal models of endometriosis, resveratrol supplementation decreased the number and volume of endometrial implants, suppressed proliferation, vascularization, inflammation, cell survival and increased apoptosis. In in-vitro studies, resveratrol treatment reduced invasiveness of endometriotic stromal cells (ESCs) and suppressed their inflammatory responses.

In a human RCT, a randomized clinical trial found that the intake of resveratrol in a dose of 40 mg/day with the monophasic contraceptive pill reduced the pain scores in women with a diagnosis of endometriosis. While these early signals are noteworthy, among the 30 articles reviewed in one systematic review covering curcumin, quercetin, and resveratrol, only a single clinical trial was included, demonstrating that human evidence is very limited and most data derive from in vitro and animal studies.

8.3 Curcumin

Scientific Evidence: Curcumin can reduce inflammation in endometrial cells by inhibiting SREBP-1 expression. An in vitro study showed that curcumin downregulated the expression of Vascular Endothelial Growth Factor (VEGF), a key angiogenic factor that promotes the growth of new blood vessels, in endometriosis cells. The inhibitory effect of curcumin on endometriosis cell survival was mediated, at least in part, through the downregulation of VEGF expression.

Human clinical trial data for curcumin in endometriosis are extremely sparse; the evidence base is currently limited to in vitro and animal studies with only preliminary human data.

8.4 Quercetin

Scientific Evidence: Quercetin is a flavonoid found in many plant foods (e.g., onions, apples, capers). Research has aimed to provide evidence of how quercetin can act as a natural intervention to control endometriosis pathophysiology. Available evidence is primarily derived from in vitro and animal experiments. Human RCT data specific to quercetin and endometriosis are absent, and evidence is very preliminary (pre-clinical only).

8.5 Chinese Herbal Medicine (CHM) — Traditional Use and Scientific Evidence

Traditional Use: Chinese herbal medicine (CHM) is a system of medicine with an unbroken written tradition stretching back over two thousand years. Although endometriosis as a distinct entity did not exist in the classical tradition, the symptoms of dysmenorrhoea, dysuria, dyschezia, and menorrhagia were systematically differentiated and apparently well treated. Endometriosis is recorded as Zheng Jia in traditional Chinese medicine books. Guizhi Fuling Pills (GFPs), a classic prescription for promoting blood circulation and removing blood stasis, are widely used for women's blood stasis diseases represented by Zheng Jia.

In traditional Chinese medicine diagnosis, participants in clinical trials have been described as having Qi and blood stagnation with an underlying kidney deficiency. A population-based survey from Taiwan found that overall, 90.8% of reproductive age women with endometriosis utilized TCM, and 25.2% of them sought TCM with the intention of treating their endometriosis-related symptoms.

Scientific Evidence: In China, treatment of endometriosis using Chinese herbal medicine is routine and considerable research into the role of CHM in alleviating pain, promoting fertility, and preventing relapse has taken place. A 2025 meta-analysis of 11 RCTs (n=1401 participants) found that CHM significantly reduced VAS scores for dysmenorrhea (SMD=−2.04, P=0.0484) and dyspareunia (SMD=−2.42, P=0.0031), although heterogeneity was high. However, most existing studies are small-sample, single-center clinical trials with inconsistent conclusions, and systematic evaluation of TCM efficacy and safety remains lacking. Evidence is therefore considered preliminary, with moderate-to-high heterogeneity limiting conclusions.

The Shaofu Zhuyu Decoction (SZD) is one such formula. SZD is a traditional Chinese herbal formula commonly used for gynecological disorders involving "blood stasis" and lower abdominal pain. Although applied clinically for endometriosis, evidence regarding its efficacy and safety remains fragmented.

8.6 Other Supplements Under Investigation

The literature has reviewed effects of a wide range of supplements including zinc, magnesium, omega-3, propolis, quercetin, curcumin, N-acetylcysteine, probiotics, resveratrol, alpha-lipoic acid, vitamin C, vitamin E, selenium, and epigallocatechin-3-gallate (EGCG) in the context of endometriosis. Based on results of in vitro, animal, and human studies, it might be said that dietary supplements can be used as a complementary treatment for endometriosis, though for most individual agents, human RCT data are sparse or absent, and available evidence is largely pre-clinical.

Melatonin is another compound with emerging interest. In subgroup analysis of a meta-analysis, a significant reduction of dysmenorrhea was observed in a subset of trials that administered melatonin (SMD, −1.40; 95% CI, −2.47 to −0.32; I²=79.15%), though again, high heterogeneity and small trial sizes limit conclusions.

9. Lifestyle Factors

9.1 Physical Activity and Exercise

Results from systematic review indicate that physical activity and exercise have a beneficial impact on quality of life, pain intensity, mental health, pelvic floor dysfunction, and bone density. A meta-analysis demonstrated that physical activity and exercise have a significant impact on the improvement of quality of life, particularly in the context of pain (P<0.0001), control and powerlessness (P<0.00001), and emotional well-being (P=0.006). However, randomized controlled trials are currently scarce, and the quality of evidence derived from these studies is relatively low.

A narrative review found that body awareness exercises such as Hatha yoga, progressive muscle relaxation, and the Jacobson method reduced pain and stress and improved the quality of life associated with endometriosis.

9.2 Body Weight

Risk factors associated with endometriosis include low body mass index (BMI) as a recognized associated factor in the epidemiological literature. The relationship between body composition and endometriosis risk is considered multifactorial and is the subject of ongoing research.

9.3 Alcohol and Tobacco

For risk factors related to tobacco consumption and alcohol, the data are not sufficient to draw conclusions regarding their role in endometriosis development or progression.

10. Evidence Summary and Strength of Evidence

• Consistent observational evidence: Red meat consumption (increased risk); vegetable and fruit consumption (possible decreased risk); total dairy consumption (possible decreased risk).
• Mixed or preliminary clinical trial evidence: Vitamin D (some RCT benefit for dysmenorrhea, other RCTs null), antioxidants broadly (meta-analysis signal for dysmenorrhea, high heterogeneity), N-acetylcysteine (promising uncontrolled cohort data), resveratrol (single small RCT).
• Pre-clinical (in vitro / animal) evidence only: Curcumin, quercetin, and many individual supplements reviewed in the literature. These findings have not yet been confirmed in adequately powered human RCTs.
• Traditional use, limited modern RCT evidence: Chinese herbal medicine formulas. Studies exist but are generally small, single-center, and of high heterogeneity.
• Physical activity: Consistent signals of benefit for pain and quality of life, but RCT evidence is scarce and low quality.

Currently, there are no specific dietary recommendations for endometriosis patients endorsed by major health authorities, and overall nutritional science in this area is an active and evolving field.

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