The Hidden Burden: Connective Tissue, Mast Cell, and Autoimmune Comorbidities Cluster in POTS with Endometriosis

Purpose To characterize and compare the prevalence of autoimmune, connective tissue, neurological, and psychiatric comorbidities between POTS patients with and without endometriosis, and to compare these rates to published general population estimates. Methods In a retrospective cohort analysis, we reviewed medical records for 458 patients with POTS who presented to our autonomic center from 2018 to 2024. POTS was defined by symptoms of orthostatic intolerance accompanied by a heart rate increase of ≥ 30 beats per minute within the first 10 minutes of head-up tilt table testing. A clinical or surgical diagnosis of endometriosis was defined by a gynecologic specialist. Results 458 female patients with POTS were included in the analysis. When compared to POTS patients without endometriosis, POTS patients with endometriosis had statistically significantly higher rates of Ehlers-Danlos syndrome (EDS) (33.6% vs. 12.7%, p < 0.001), Mast cell activation syndrome (MCAS) (19.2% vs. 3.5%, p < 0.001), chronic migraines (55.9% vs. 39.3%, p < 0.001), fibromyalgia (23.1% vs. 11.4%, p = 0.001) and Raynaud’s phenomenon (15.7% vs. 6.6%, p = 0.003). Compared to the general population, POTS patients demonstrated higher rates of EDS, chronic migraines, and fibromyalgia. POTS patients with endometriosis also demonstrated higher rates of MCAS and Raynaud’s phenomenon compared to the general population. Conclusions POTS patients with endometriosis exhibit significantly higher rates of connective tissue disorders, mast cell-mediated disease, autoimmune conditions, and chronic pain syndromes, with prevalence rates far exceeding general population estimates. These findings suggest shared pathophysiological mechanisms between POTS and endometriosis and support the need for comprehensive screening and multidisciplinary management in this population.