Overlooked Systemic Contributors to Sexual Dysfunction: Emerging Roles of POTS, Ehlers-Danlos Syndrome, and Mast Cell Activation Syndrome
Poster #: 028
Session/Time: A
Author:
Janvi Agrawal, MS
Mentor:
Rachel Rubin, MD
Research Type: Review Article
Abstract
INTRODUCTION:
Unexplained sexual dysfunction is a frequently reported concern in urology, gynecology, and sexual medicine clinics. While psychosocial, hormonal, and local genitourinary factors are commonly investigated, systemic contributors are often overlooked. Dysautonomia, hypermobile Ehlers-Danlos syndrome (hEDS), and mast cell activation syndrome (MCAS) are chronic disorders associated with urogynecologic complaints and may plausibly increase the risk of sexual dysfunction through overlapping pathophysiological mechanisms. Each affects key domains relevant to sexual health, including autonomic regulation, connective tissue integrity, vascular dynamics, and inflammatory signaling. Understanding these associations is essential to improving comprehensive evaluation and care for patients presenting with sexual concerns.
MAIN BODY:
Ehlers-Danlos syndromes (EDS) frequently manifest with pelvic floor symptoms such as incontinence, pelvic organ prolapse, vulvodynia, and chronic pelvic pain, many of which impair sexual function. In a community-based case-control study, women with hEDS or hypermobility spectrum disorders demonstrated significantly lower Female Sexual Function Index (FSFI) scores across desire, arousal, lubrication, orgasm, and satisfaction domains compared to controls, independent of depressive or autonomic symptoms. These findings highlight the intrinsic impact of connective tissue disorders on sexual health. MCAS has been implicated in sexual dysfunction through mast cell-mediated neuroimmune pathways. Mast cell-related vestibular neuroproliferation has been linked to vestibulodynia and dyspareunia, even without increased mast cell density. In mastocytosis, an MCAS-related disorder, nearly one-quarter of patients reported sexual dysfunction. Non-clonal MCAS has similarly been associated with genitourinary pain syndromes. Furthermore, case reports suggest that mast cell-directed therapy may alleviate neuropsychiatric symptoms in patients with comorbid POTS or EDS, underscoring mast cell mediators as contributors to dysautonomia, neuroinflammation, and potentially sexual dysfunction. Postural orthostatic tachycardia syndrome (POTS), a disorder of autonomic dysregulation, is frequently comorbid with EDS and MCAS and has been independently linked to sexual dysfunction. In a cross-sectional study of 189 patients with POTS, women exhibited significantly reduced sexual desire, arousal, and satisfaction, while men demonstrated impaired erectile function, orgasm, and overall satisfaction. Autonomic symptom severity predicted dysfunction in women, while age was a key determinant in men. Together, these findings emphasize that autonomic disturbances have a measurable impact on sexual outcomes.
CONCLUSION:
Although preliminary evidence links hEDS, MCAS, and POTS to sexual dysfunction, systematic study of their collective impact is lacking. These conditions often co-occur, suggesting shared pathophysiological pathways that may exacerbate sexual symptoms. Recognition of these associations highlights a gap in sexual medicine research and clinical practice. Greater awareness could enable earlier identification of systemic contributors to sexual dysfunction, promote interdisciplinary collaboration, and support the development of more holistic diagnostic and therapeutic strategies. Future investigations should define prevalence, predictors, and mechanistic underpinnings of these conditions in sexual medicine populations to improve patient care and quality of life.
Unexplained sexual dysfunction is a frequently reported concern in urology, gynecology, and sexual medicine clinics. While psychosocial, hormonal, and local genitourinary factors are commonly investigated, systemic contributors are often overlooked. Dysautonomia, hypermobile Ehlers-Danlos syndrome (hEDS), and mast cell activation syndrome (MCAS) are chronic disorders associated with urogynecologic complaints and may plausibly increase the risk of sexual dysfunction through overlapping pathophysiological mechanisms. Each affects key domains relevant to sexual health, including autonomic regulation, connective tissue integrity, vascular dynamics, and inflammatory signaling. Understanding these associations is essential to improving comprehensive evaluation and care for patients presenting with sexual concerns.
MAIN BODY:
Ehlers-Danlos syndromes (EDS) frequently manifest with pelvic floor symptoms such as incontinence, pelvic organ prolapse, vulvodynia, and chronic pelvic pain, many of which impair sexual function. In a community-based case-control study, women with hEDS or hypermobility spectrum disorders demonstrated significantly lower Female Sexual Function Index (FSFI) scores across desire, arousal, lubrication, orgasm, and satisfaction domains compared to controls, independent of depressive or autonomic symptoms. These findings highlight the intrinsic impact of connective tissue disorders on sexual health. MCAS has been implicated in sexual dysfunction through mast cell-mediated neuroimmune pathways. Mast cell-related vestibular neuroproliferation has been linked to vestibulodynia and dyspareunia, even without increased mast cell density. In mastocytosis, an MCAS-related disorder, nearly one-quarter of patients reported sexual dysfunction. Non-clonal MCAS has similarly been associated with genitourinary pain syndromes. Furthermore, case reports suggest that mast cell-directed therapy may alleviate neuropsychiatric symptoms in patients with comorbid POTS or EDS, underscoring mast cell mediators as contributors to dysautonomia, neuroinflammation, and potentially sexual dysfunction. Postural orthostatic tachycardia syndrome (POTS), a disorder of autonomic dysregulation, is frequently comorbid with EDS and MCAS and has been independently linked to sexual dysfunction. In a cross-sectional study of 189 patients with POTS, women exhibited significantly reduced sexual desire, arousal, and satisfaction, while men demonstrated impaired erectile function, orgasm, and overall satisfaction. Autonomic symptom severity predicted dysfunction in women, while age was a key determinant in men. Together, these findings emphasize that autonomic disturbances have a measurable impact on sexual outcomes.
CONCLUSION:
Although preliminary evidence links hEDS, MCAS, and POTS to sexual dysfunction, systematic study of their collective impact is lacking. These conditions often co-occur, suggesting shared pathophysiological pathways that may exacerbate sexual symptoms. Recognition of these associations highlights a gap in sexual medicine research and clinical practice. Greater awareness could enable earlier identification of systemic contributors to sexual dysfunction, promote interdisciplinary collaboration, and support the development of more holistic diagnostic and therapeutic strategies. Future investigations should define prevalence, predictors, and mechanistic underpinnings of these conditions in sexual medicine populations to improve patient care and quality of life.