How Endometriosis, Methylation Issues, and Heart Health Are Connected

Prepared by: Nicoletta Rasizzi, BSN, RN

 

Introduction

Endometriosis is a chronic, systemic inflammatory disease that affects approximately 1 in 10 women of reproductive age. Beyond its hallmark symptoms of pelvic pain and infertility, growing evidence indicates that endometriosis increases the risk of cardiovascular disease (CVD) due to systemic inflammation, oxidative stress, and hormonal imbalances.

Methylation dysfunction, often associated with genetic polymorphisms (e.g., MTHFR mutations), further exacerbates this risk by impairing detoxification pathways, raising homocysteine levels, and promoting vascular inflammation. This explanation explores the interconnected pathophysiology of endometriosis, methylation dysfunction, and cardiovascular disease, highlighting the clinical implications and management considerations.

 

1. Endometriosis and Systemic Inflammation

While endometriosis was traditionally viewed as a localized gynecological disorder, it is now recognized as a systemic inflammatory condition.

·         Chronic inflammation leads to increased oxidative stress, triggering endothelial dysfunction—a key contributor to CVD.

·         Studies show that women with endometriosis have:

o    2-3 times higher risk of myocardial infarction and stroke.

o    Increased arterial stiffness and subclinical atherosclerosis.

o    Elevated levels of C-reactive protein (CRP) and pro-inflammatory cytokines, both linked to cardiovascular pathology.

·         Hormonal dysregulation: Estrogen dominance in endometriosis patients can alter lipid metabolism, contributing to dyslipidemia and hypertension—both risk factors for CVD.

 

2. Methylation and Its Role in Endometriosis Progression

Methylation is a biochemical process responsible for:

·         DNA repair and gene expression regulation.

·         Estrogen metabolism and detoxification.

·         Homocysteine clearance to prevent vascular damage.

In endometriosis patients, methylation is often impaired due to:

·         MTHFR gene polymorphisms (C677T and A1298C), which reduce the conversion of folate into its active form, 5-methyltetrahydrofolate (5-MTHF).

·         Impaired estrogen metabolism, leading to estrogen dominance, which exacerbates endometrial growth and systemic inflammation.

·         Reduced detoxification capacity, resulting in a buildup of inflammatory by-products.

 

3. Methylation Dysfunction and Cardiovascular Disease

Defective methylation pathways in women with endometriosis directly impact cardiovascular health through:

·         Elevated homocysteine levels:

o    Poor methylation leads to the accumulation of homocysteine, which promotes:

§  Endothelial cell damage.

§  Increased oxidative stress and vascular inflammation.

§  Atherosclerotic plaque formation.

·         Increased thrombotic risk:

o    Women with endometriosis already have a higher baseline risk of clotting. Methylation defects further raise the risk by promoting hypercoagulability, leading to venous thromboembolism (VTE) and arterial thrombosis.

·         Oxidative stress and reduced antioxidant defense:

o    Methylation dysfunction reduces the production of glutathione, the body’s main antioxidant, increasing susceptibility to oxidative damage in vascular tissues.

 

4. Clinical Evidence: Endometriosis, Methylation, and CVD Risk

·         A 2016 study published in Circulation Journal found that women with endometriosis had a 1.52 times higher risk of myocardial infarction compared to women without the condition.

·         A 2020 study in Frontiers in Endocrinology highlighted that MTHFR polymorphisms were more common in women with endometriosis, contributing to impaired estrogen detoxification and increased homocysteine levels.

·         A 2019 meta-analysis confirmed that elevated homocysteine in women with endometriosis is associated with higher CVD risk, including hypertension, stroke, and heart attack.

 

5. Functional Medicine Approach for Management

To reduce cardiovascular risk in endometriosis patients, it is essential to address both methylation dysfunction and systemic inflammation.

A. Genetic and Biomarker Testing

·         MTHFR, COMT, and CBS genetic screening to identify methylation polymorphisms.

·         Bloodwork to monitor:

o    Homocysteine: Elevated levels indicate methylation issues and increased CVD risk.

o    CRP and ESR: Markers of systemic inflammation.

o    Lipid panel: To monitor for dyslipidemia.

o    Folate, B12, and B6: Essential cofactors in the methylation pathway.

B. Nutritional and Supplementation Support

·         Methylated B-vitamins:

o    5-MTHF (methylfolate) → Supports proper homocysteine metabolism.

o    Methylcobalamin (B12) → Enhances methylation capacity.

o    Pyridoxal-5-phosphate (B6) → Reduces homocysteine accumulation.

·         Glutathione and NAC (N-acetylcysteine) → To combat oxidative stress and support detoxification pathways.

·         Omega-3 fatty acids → Reduce systemic inflammation and protect cardiovascular health.

C. IV Nutrient Therapy for Cardiovascular and Endo Support

·         Glutathione IV → Reduces oxidative stress and protects vascular endothelium.

·         NAC IV → Decreases systemic inflammation and supports methylation pathways.

·         Alpha-lipoic acid (ALA) → Enhances antioxidant capacity and reduces homocysteine.

·         Magnesium and B-complex IV → Supports vasodilation and methylation processes.

D. Hormonal and Inflammation Management

·         Bioidentical hormone replacement therapy (BHRT) → Balances estrogen and progesterone, preventing estrogen dominance.

·         LDN (low-dose naltrexone) → Reduces chronic inflammation associated with endometriosis.

·         Anti-inflammatory diet → Mediterranean-based nutrition to reduce oxidative stress and systemic inflammation.

 

Conclusion

The interplay between endometriosis, methylation dysfunction, and cardiovascular disease highlights the need for a holistic, multi-disciplinary approach.

·         Methylation dysfunction worsens systemic inflammation and oxidative stress in endometriosis patients, significantly increasing CVD risk.

·         Targeted therapies, including IV nutrient support, methylation optimization, and inflammation management, are essential to protect cardiovascular health in this high-risk population.

Recommendations for Further Evaluation:

1.      Genetic screening for MTHFR and COMT mutations.

2.      Homocysteine, CRP, and ESR testing to assess inflammation and CVD risk.

3.      Cardiovascular screening (carotid ultrasound, echocardiogram) for at-risk patients.

4.      Functional medicine consultation for personalized methylation support and cardiovascular protection strategies.