In reply to ertan yetkin MD. Non-pelvic co-morbid symptoms of 45 patients with pain of pelvic origin,before and after treatment

We thank Dr Yetkin for his insightful comments regarding our study of comorbid symptoms associated with pelvic venous disorders. Our work, and three related publications, highlight consistent associations between pelvic vein dysfunction and a range of conditions marked by orthostatic intolerance (OI).^1–3 A prospective multicenter study with one-year follow-up, presented at CIRSE 2024 by Knuttinen et al., further expands on these findings. ⁴

We agree that migraine is an important and revealing symptom. In our cohort, 69% of patients experienced migraines, with an average 54% reduction in severity after treatment. Similar or greater improvements were reported by Rosenberg et al. (2020) following pelvic vein intervention. ⁵ We hypothesize that impaired venous return to the heart and brain, a hallmark of OI, contributes to cerebral hypoperfusion and migraine. Alternatively, abnormal signaling from pelvic veins may play a role: distressed pelvic veins release CGRP and Substance P, both potent neuropeptides involved in migraine pathogenesis. ⁶ Reduction of these mediators after pelvic vein treatment could explain the observed clinical benefit.

While Dr Yetkin suggests a unifying “dilating venous disease” model, we believe a pathophysiologic rather than morphologic framework better integrates these findings. We propose the concept of an “Orthostatic Flow Syndrome,” encompassing impaired venous return, vascular obstruction, and dysautonomia as shared mechanisms. Historical pathology studies and recent data suggest both venous dilation and fibrosis may coexist, often in the context of abnormal collagen and healing, such as in Ehlers–Danlos syndrome (present in 56% of our cohort).^7,8

Finally, the improvement of migraine, fibromyalgia-type pain, and other systemic symptoms underscores the need to study how pelvic venous pathology and vasoactive signaling intersect with systemic circulatory and neurovascular function. ⁹ We appreciate Dr Yetkin’s thoughtful engagement and agree that further mechanistic and translational research is warranted.