Connected Issues: Understanding Ehlers-Danlos Syndrome and Endometriosis

Connected Issues, Connective Tissues

We met with a team of specialists to discuss the multifactorial, multidisciplinary, and emerging approaches to discuss the little-known relationship between several women’s health disorders.

The group of specialists included:

• Board Certified Cardiologist
• Integrative Board Certified Gastroenterologist
• Board Certified Gynecological Surgeon with a focus on Endometriosis
• Mental Health Counselor, specializing in Chronic Illness
• Pelvic Floor Physical Therapist
• Board Certified Psychiatrist, specializing in Gut Psychiatry
• Board Certified Nurse Practitioner, specializing in Vulvovaginal Tissue

Here are the Core Conditions Discussed: MCAS, POTS, EDS, and Endometriosis

These conditions — mast cell activation syndrome (MCAS), postural orthostatic tachycardia syndrome (POTS), Ehlers-Danlos syndrome (EDS) and Endometriosis — are increasingly recognized as co-occurring!

Let’s Start with Understanding Them:

Mast cells are immune cells that serve as a first line of defense against pathogens and allergens. They are abundant in tissues exposed to the external environment:  skin, gastrointestinal tract, lungs, and vulvar vestibule. When activated, they release histamine, heparin, cytokines, and other pro-inflammatory mediators.

• In Mast Cell Activation Syndrome, mast cells become chronically activated, leading to persistent inflammation and pain that extends beyond acute flares.
• Postural orthostatic tachycardia syndrome (POTS) is a form of dysautonomia characterized by an excessive increase in heart rate. It reflects impaired autonomic regulation of cardiovascular function upon postural change. This can present as lightheadedness, palpitations, fatigue and more!
• Endometriosis is a chronic inflammatory condition in which tissue resembling the endometrial lining grows outside the uterus. It is now understood how it involves both hormonal and immune-mediated mechanisms.
• Ehlers-Danlos syndrome (EDS) is a group of hereditary connective tissue disorders caused by defects in collagen structure/processing, characterized by joint hypermobility, skin hyperextensibility, and tissue fragility.

So how are these things related? Why do they present together?

Here’s what we heard from the providers:

EDS, POTS, MCAS and Endometriosis are chronic, systemic inflammatory conditions linked by an underlying connective tissue disorder and immune responses.

• EDS involves disordered collagen, leading to joint hypermobility, tissue fragility, and vascular laxity.
• POTS in EDS is theorized to result from vascular laxity (“stretchy veins”) and/or peripheral neuropathy, contributing to blood pooling, vasodilation, and tachycardia upon standing.
• MCAS may contribute to vasodilation and tachycardia through mast cell mediator release (e.g., histamine).
• Endometriotic lesions have a higher number of mast cells than normal uterine tissue and endometriosis involves immune system dysregulation.

Additional associations mentioned:

• IBS and gut-brain dysfunction: GI symptoms including IBS are common in hEDS/POTS and may involve gut-brain axis disruption.
• Neuroproliferation in the vulvar vestibule: Provoked vestibulodynia is associated with increased nerve fiber density (neuroproliferation) in the vestibular mucosa.
• Pelvic congestion: mentioned in the context of venous laxity in EDS.
• MCAS and psychiatric conditions: Mast cell mediators can exacerbate anxiety and depression through neuroinflammatory pathways.

What are the things to note? What does this mean for women’ s everyday lives?

• Consider a low-histamine diet: Reducing high-histamine foods (e.g., red meat) is commonly recommended in MCAS management
• “Eat the rainbow”: Emphasizing dietary diversity for phytonutrient intake is a general recommendation.
• Physical therapy:P Addressing postural dysfunctions such as anterior pelvic tilt, knee hyperextension, core weakness, diastasis/doming, sacroiliac joint pain, hypertonic pelvic floor, ligament laxity, and organ prolapse. PT is a cornerstone of EDS management.
• Longer recovery processes: Patients with EDS often have prolonged healing and recovery times due to connective tissue fragility.

While we have learned so much, there is still more to learn. We spoke about new research, emerging findings and ideas in the works:

• Non-invasive diagnosis of endometriosis (blood/saliva biomarkers):
• Characterizing endometriosis clinically and recognizing it as a chronic inflammatory disease with profound immune dysregulation not “just hormones”.
• Vulvodynia Therapeutic Research Summit is working on mast cell stabilizers and antihistamines for further research in treating neuroproliferative provoked vestibulodynia.
• GLP-1 receptor agonists can be microdosed for anti-inflammatory effects in MCAS. A 2025 case series of 47 MCAS patients reported that 89% demonstrated clinical benefit with GLP-1 receptor agonists.
• Several psychiatric medications have antihistaminic properties. Selecting such agents in patients with concurrent MCAS and psychiatric symptoms is a reasonable clinical strategy to be explored.

If you are interested in hearing more or want to listen to this panel of exceptionally educated providers, find it on YouTube: Youtube Video-Connected Issues Webinar