(002) Neuroproliferative Vestibulodynia as a Cause of Persistent Genital Arousal Disorder: A First-Ever Case Series
Authors: Uloko M , Hartzell-Cushanick R , Goldstein S , Goldstein I 
Published: June 2023

Abstract

Introduction
Persistent Genital Arousal Disorder (PGAD), a condition of unwanted, unremitting feelings of genital arousal, is associated with significant morbidity including catastrophizing, depression, anxiety, and/or suicidal ideation. There are multiple diverse triggers of PGAD that may originate in one or more of five regions in a patient: end organ, pelvis/perineum, cauda equina, spinal cord, and/or brain. Regarding the contributions to PGAD in the end-organ region, it is hypothesized that vestibulodynia may be a trigger for PGAD. The vestibule has unique sensory qualities, as this region receives sensory innervation from branches of both the somatic pudendal and visceral pelvic nerves.

Objectives
Neuroproliferative vestibulodynia is a disorder of excess deposition of mast cells with resultant excess c-afferent nociceptors in the vestibule. To the best of our knowledge, vestibulodynia, specifically neuroproliferative vestibulodynia, has not been reported in the literature as a cause of PGAD. The purpose of this study was to report on four women with lifelong PGAD suspected of having neuroproliferative vestibulodynia.

Methods
These women underwent: i) a detailed biopsychosocial assessment including sex therapy and diagnostic testing, evaluation of baseline PGAD intensity, vulvoscopy, cotton swab testing of the vestibule, PGAD intensity post-cotton swab test, and vestibular anesthesia testing (VAT); ii) treatment by complete vestibulectomy with vaginal advancement flap reconstruction; iii) staining of vestibular tissue with CD 117 (for mast cells) (Figure 1) and PGP 9.5 (for nerves) (Figure 2) and iv) measurement of clinical outcome with patient global impression of improvement. The VAT was performed with a topical anesthetic carefully applied to the vestibule between Hart’s line and the hymen. Complete anesthesia was assessed by cotton swab testing. Pre- and post-VAT intensity levels were compared.

Results
These patients had lifelong PGAD with a history of frequent masturbation at a very young age and feelings of catastrophizing, depression, anxiety, and/or suicidal ideation. Three patients had experienced sexual trauma, eating disorders, and had stressful relationships with family members. All four used various SSRI medications for depression/anxiety disorders and PGAD management from a young age. The youngest patient presented at 13 years with a presumptive diagnosis, primarily based on VAT, of neuroproliferative vestibulodynia. Surgery was delayed until she stopped growing at age 18. The other three presented at ages 20, 24, and 24. All four had full, although temporary, resolution of PGAD symptoms post-VAT. Each underwent a complete vestibulectomy with vaginal advancement flap procedure; the mean age at time of surgery was 22 +/− 3 years. Stained vestibular tissues showed in excess of 20 mast cells and nerves per high power field, consistent with neuroproliferative vestibulodynia. Curiously, post-operatively, none of the patients required the usual post-op opioid pain medications typical of patients undergoing vestibulectomy. While all four still experience mild PGAD symptoms when stressed, their PGAD symptoms are very much improved post-op with significant symptom resolution, with a mean follow-up of 11 months, range 4 – 26.

Conclusions
This is the first case series to document that neuroproliferative vestibulodynia is a treatable cause of PGAD, although more research is needed.

Disclosure
No.