Endometriosis: A Functional Medicine Approach

symptoms of endometriosis

Welcome to my blog “Endometriosis: A Functional Medicine Approach”

What Is Endometriosis?

Endometriosis is a chronic, estrogen-dependent gynecological condition affecting approximately 10% of reproductive age women.

Its prevalence rises to approximately 20% to 50% in women with pelvic pain or infertility.

The most widely accepted current theory is that of retrograde menstruation.

Recent reports suggest the uterus is not sterile. Thus, the refluxed menstrual effluent may carry bacteria, and contribute to inflammation, the establishment, and growth of endometriotic lesions.

Other factors (anatomical, genetic, environmental, lifestyle, menstrual cycle dynamics, aberrant immune responses, etc.) are likely involved as 90% of women experience retrograde menstruation, but only about 10% develop endometriosis.

Signs And Symptoms

  • Painful menstruation
  • Pain in lower abdomen
  • Nausea
  • Chronic fatigue
  • Heavy or irregular periods
  • Bloating
  • Constipation
  • Diarrhoea
  • Fainting
  • Painful intercourse
  • Spotting or bleeding between periods
  • Lethargy
  • Infertility

Approximately 20–25% of women present clinically as asymptomatic.

Risk Factors

Among intrauterine and early neonatal exposures, prematurity, birthweight, formula feeding and DES (1940 and 1971) were risk factors for the development of endometriosis in adult life.

Despite multiple theories explaining endometriosis pathogenesis, every concept suggests that endometriosis is a complex multifactorial and heterogeneous disease of uncertain etiology; its development and progression are influenced by genetic, immunological, hormonal, microbial and environmental factors.

Circadian health

Circadian disruption is associated with lower levels of melatonin and a higher risk of endometriosis.

Gut health

Up to 90% of patients with endometriosis experience gastrointestinal symptoms.

Common gastrointestinal symptoms include bloating, nausea, constipation, diarrhea, and vomiting.

In addition to gynecological manifestations, many endometriosis patients experience gastrointestinal symptoms, indicating a potential association between gut health and the disease. Recent studies have revealed alterations in the gut microbiota of individuals with endometriosis, including reduced diversity, microbial composition imbalances, and pathogenic bacteria. These changes can disrupt immune function, increase inflammation, and contribute to the chronic inflammatory state observed in endometriosis. (source)

The gut microbiota can secrete enzymes such as β-glucuronidase and β-glucosidase, which can deconjugate estrogens and increase the reabsorption of free estrogen, leading to higher estrogen levels in the bloodstream.

The collection of genes encoding estrogen-metabolising enzymes in the gut microbiota is commonly known as the “estrobolome”.

Analysis of the microbial genome has revealed that several bacterial genera in the gut microbiota, including Bacteroides, Bifidobacterium, Escherichia coli, and Lactobacillus, can produce β-glucuronidase. (source)

Interestingly, research has shown a significant increase in Escherichia coli levels in the feces of endometriosis patients. These findings suggest that the gut microbiota may contribute to elevated estrogen levels, creating an environment that promotes the progression of endometriosis. (source)

Finally, in a study published in 2023, it seems that gut microbial β-glucuronidase (gmGUS) can become a potential biomarker for the early diagnosis of estrogen-induced diseases. (source)

Imbalances in the composition of gut microbiota, known as dysbiosis, can disturb regular immune function, resulting in increased levels of proinflammatory cytokines, compromised immunosurveillance, and changes in immune cell profiles. These immune dysregulations are implicated in the chronic inflammatory state observed in endometriosis. The chronic inflammation associated with endometriosis creates an environment that promotes increased adhesions and angiogenesis, critical disease features. Adhesions can cause organs and tissues to stick together, leading to pain, functional impairment, and the development of new blood vessels that can provide oxygen and nutrients to the endometrial lesions, allowing them to grow and spread. (source)

A study by Huang et al., which compared the microbiome of peritoneal fluid, stool, and cervical mucus in endometriosis patients and healthy controls, observed an increased abundance of Gram-negative bacteria in the endometriosis group, including Pseudomonas and Prevotella, with the potential to release lipopolysaccharide (LPS). In the context of endometriosis, LPS can stimulate the activation of macrophages, leading to the production of inflammatory cytokines and chemokines. These inflammatory mediators can further promote the proliferation of endometriotic stromal cells, contributing to the growth and progression of endometriotic lesions. (source)

Leaky Gut

Leaky gut may further exacerbate gastrointestinal symptoms in affected individuals. Understanding the role of the gut microbiota and intestinal permeability in endometriosis can provide valuable insights into disease pathogenesis, aid in non-invasive diagnostic approaches, and open new avenues for therapeutic interventions. (source)

Autoimmune mechanisms

The observed associations between endometriosis and autoimmune diseases suggest that clinicians need to be aware of the potential coexistence of endometriosis and autoimmune diseases when either is diagnosed.

Oxidative Stress

The phenomenon of oxidative stress, characterised by an imbalance between reactive oxygen species (ROS) and antioxidants, has been proposed as a potential factor contributing to the pathophysiology of endometriosis. Previous research has demonstrated that the presence of oxidative stress within the peritoneal cavity can induce inflammation, hence playing a significant role in the initiation and advancement of endometriotic diseases

Infections

Endometriosis is associated with more upper genital tract and peritoneal infections. These infections might be co-factors causing genetic-epigenetic incidents and influencing endometriosis growth.

Hormonal imbalances

In endometriosis, when endometrial tissue grows outside the uterine cavity, progesterone and estrogen signaling are disrupted, commonly resulting in progesterone resistance and estrogen dominance.

Environmental toxins

Growing evidence suggests that endocrine disrupting chemicals (EDCs) may be etiologically involved in the development and severity of disease.

Diet

Nutritional interventions may be helpful in the prevention and treatment of endometriosis and associated pain. Reducing dietary fat and increasing dietary fiber have been shown to reduce circulating estrogen concentrations, suggesting a potential benefit for individuals with endometriosis, as it is an estrogen-dependent disease. Meat consumption is associated with greater risk of developing endometriosis. Anti-inflammatory properties of plant-based diets may benefit women with endometriosis.

Additionally, seaweed holds estrogen-modulating properties that have benefitted postmenopausal women and offers potential to reduce estradiol concentrations in pre-menopausal women. Furthermore, consumption of vitamin D has been shown to reduce endometrial pain via increased antioxidant capacity and supplementation with vitamins C and E significantly reduced endometriosis symptoms, compared with placebo. (source)

Conventional Treatment

The main therapeutic approach includes surgery, pharmacotherapy, and long-term comprehensive individual treatment.

High recurrence rates of up to 50% within five years of surgery are reported.

Supplements

In regards to quercetin, resveratrol, and curcumin a systematic review concluded:

By acting on mechanisms of inflammation, oxidative stress, cell proliferation, invasion and adhesion, apoptosis, angiogenesis and glucose and lipid metabolism, curcumin, quercetin, and resveratrol showed to have beneficial effects, evidencing their potential application in endometriosis treatment.”

Quercetin

71BNL4cuVqL. AC UF8941000 QL80 e1708068816678While the search for the best endometriosis treatment continues, the focus is being paid to the assistance provided by polyphenols, notably quercetin. A broad spectrum of health-improving benefits of quercetin includes interactions with endometriosis-related molecular targets such as cell proliferation, apoptosis, invasiveness, inflammation, and oxidative stress. According to already-known research, medicines that mimic the physiological effects of quercetin are good candidates for creating novel endometriosis therapies. (source)

Recommended Product: Quercetin: 200mg for 3 months.

EGCG

Recommended Product: ECGC: 400mg twice/day for 3 months.

Curcumin

71emnVw9zTLCurcumin has potent anti-inflammatory, antioxidant, antiangiogenic, anti-neoplastic properties and is used as a therapeutic agent in Indian and Chinese medicine. Extensive in vitro and in vivo data have paved the way for curcumin to become the subject of clinical trials. Early-phase trials have ascertained pharmacological properties and consistently demonstrate it to be safe and well tolerated.

In this study the authors found that curcumin was able to suppress the proliferation of endometrial cells by reducing the oestrogen.

In a review paper published in 2020 the authors concluded that “curcumin can downregulate inflammation and OS in endometriosis. Moreover, curcumin can direct act on invasion, adhesion, apoptosis and angiogenesis in endometrial lesions. The use of curcumin could be interesting in dietary prevention and disease management for women.”

Recommended product: Curcumin: 42 mg of curcumin twice a day for four months.

Resveratrol

51cp3Q0AOkS. AC UF8941000 QL80 e1708068619442Resveratrol is a phytoestrogen, a natural polyphenolic compound with antiproliferative and anti-inflammatory actions, found in many dietary sources such as grapes, wine, peanuts, soy, berries, and stilbenes. Resveratrol possesses a significant anti-inflammatory effect via inhibition of prostaglandin synthesis and it has been proved that resveratrol can exhibit apoptosis-inducing activities.

In a review the authors concluded that “it is clear that the anti-inflammatory effect of this natural compound can contribute to the prevention of endometriosis, this phenolic compound now being considered a new innovative drug in the prevention and treatment of this disease.” (source)

 

Recommended Product: Resveratrol: 400 mg resveratrol twice daily for 12–14 weeks.

Vitamin D

In a systematic review the authors concluded that the data strongly supported a correlation between low vitamin D levels and endometriosis in most studies. Studies suggesting the role of vitamin D in the regulation of important cellular and signaling pathways involving gene expressions and cytokines in endometriosis have been consistent. (source)

Recommended Product: Vitamin D

Probiotics

In another study, the impact of Lactobacillus acidophilus on peripheral blood mononuclear cells (PBMCs) in women with endometriosis was investigated. Endometriosis patients displayed increased production of pro-inflammatory cytokines IL-1 and IL-6 by PBMCs compared to those without endometriosis. L. acidophilus supplementation further heightened cytokine levels; however, after 48 h, bacterial cells exhibited modulatory properties, leading to a reduction in cytokine production. The findings suggest that probiotics, particularly L. acidophilus, might have potential therapeutic benefits for endometriosis. (source)

In a randomized pilot placebo-controlled trial involving women diagnosed with stage 3 and 4 endometriosis, LactoFem® (a formulation containing Lactobacillus) was administered orally once a day for 8 weeks. The study included 37 participants without hormonal treatment in the last three months. The participants were assessed for pain severity using Visual Analogue Scale (VAS) scores for dysmenorrhea, dyspareunia, and chronic pelvic pain at baseline, 8 weeks, and 12 weeks post-intervention. The study showed that Lactobacilli had beneficial effects on endo-associated pain, specifically dysmenorrhea, and chronic pelvic pain. The most significant improvement in dysmenorrhea was observed after 8 weeks of Lactobacilli consumption.

In addition, Lactobacilli significantly reduced overall discomfort during the study. These findings suggest that the administration of Lactobacilli may positively impact endometriosis-related pain symptoms. However, it is important to note that this was a pilot study with a relatively small sample size, and further randomized trials with larger participant groups are needed to better evaluate the effectiveness and long-term effects of lactobacilli in endo management. (source)

Recommended Product: Every Day Extra.

Stress Management

A great option is Sensate. Use code Healthpath20 for £20 off at: www.getsensate.com

Omega 3 Fatty Acids

A cohort of patients was given various supplements including omega 3, and visual analog scale (VAS) scores were improved compared to controls. Fish oil supplemented adolescents with endometriosis were reported to have a 50% drop in VAS scores. Women with higher circulating levels of EPA are less likely to have endometriosis (source)

An in vitro study by Gazvani et al have shown that survival of endometrial cells from women with and without endo was significantly reduced in the presence of high omega-3:omega-6 PUFA ratios compared with cells incubated in the absence of fatty acids, in balanced omega-3:omega-6 PUFA ratios, and in high omega-6:omega-3 PUFA ratios. Animal studies have reported decreased endometriosis-associated pain after omega 3 supplementation. Besides symptom relief, PUFAs have a role in preventing disease pathogenesis. Also, adding fish oils to the diet of endo models, decreased the size of the lesions caused by endometriosis. (source)

Recommended Product: Omega 3

Consider supporting detox: dietary fibre intake, sulphurous vegetables, pre- and probiotic foods, and supplements such as sulforaphane, indole-3-carbinol (I3C), and DIM.

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References

  1. Intricate Connections between the Microbiota and Endo (click here)
  2. The role of gut and genital microbiota and the estrobolome in endo, infertility and chronic pelvic pain (click here)
  3. The association between endo and autoimmune diseases: a systematic review and meta-analysis (click here)
  4. Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms (click here)
  5. Occupational risk factors for endo in a cohort of flight attendants (click here)
  6. Influence of diet on the risk of developing endo (click here)
  7. Diet and Nutrition in Gynecological Disorders: A Focus on Clinical Studies (click here)
  8. Dietary supplements for treatment of endo: A review (click here)
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