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Dorsal genital nerve neuromodulation in persistent genital arousal disorder: a pilot study

Year: 2025

Type: article

Abstract: Persistent Genital Arousal Disorder (PGAD), also referred to as Restless Genital Syndrome, Persistent Sexual Arousal Syndrome, or Genito-Pelvic Dysesthesia, is a rare and often distressing condition marked by spontaneous and persistent genital arousal in the absence of sexual desire or stimulation. While predominantly reported in females, PGAD can also affect males. Symptoms such as genital tingling, throbbing, and pressure may persist for extended periods, significantly impairing quality of life and contributing to emotional distress, including embarrassment, guilt, and depression.1 PGAD’s impact on quality of life can be profound, often leading to feelings of embarrassment, guilt, and depression. The prevalence is estimated between 0.6% and 3.0%, which is believed to be an underestimation.2 Current treatment options are limited and primarily based on case reports or clinical experience, with pharmacological and psychological interventions yielding inconsistent results. This underscores the urgent need for innovative therapeutic approaches. The underlying pathophysiology of PGAD remains poorly understood, complicating the development of effective treatments. Emerging hypotheses suggest involvement of peripheral neuralgia, particularly of the dorsal genital nerve (DGN), and central sensitization mechanisms. In this context, neuromodulation has shown promise in treating conditions involving dysregulated neural pathways and sensory disturbances, such as detrusor overactivity in urinary urge incontinence. It may therefore offer therapeutic potential in PGAD by targeting both peripheral and central neural circuits.3 This pilot intervention study was conducted at Radboud University Medical Centre, the Netherlands, between April 2023 and June 2024, and was approved by the local ethics committee (Ref. 2023-16221). Twelve women diagnosed with PGAD were recruited based on established diagnostic criteria, including persistent physical sensations of arousal without desire, symptoms lasting hours or days, lack of relief after orgasm, and significant distress. Written informed consent was obtained from all participants. Following a demonstration of the neuromodulator device (UCon, InnoCon Medical ApS, Denmark),4 eligible participants were enrolled and baseline characteristics were recorded. Prior to intervention, participants completed a 1-week symptom diary and a set of questionnaires assessing quality of life, catastrophizing, anxiety, and depression. The intervention consisted of daily use of the UCon device for three weeks. UCon delivers electrical stimulation to the DGN via surface electrodes placed on the clitoris and inner thigh or abdomen, using a frequency of 20 Hz and pulse duration of 200 μs, for 30 min per session. Stimulation amplitude was individually adjusted based on tolerability, and participants could perform an additional session if desired. Device usage data, including timestamps and stimulation parameters, were logged automatically. Throughout the intervention, participants continued daily symptom tracking and completed the same questionnaires at the end of the 3-week period, along with a user satisfaction survey. A follow-up phase 3 weeks post-intervention included another week of symptom tracking and final questionnaire assessments. Participants were also asked to evaluate the general effect of stimulation, categorized as “no change,” “(temporarily) masking of symptoms,” or “symptom relief” and to indicate whether they would consider using UCon as a treatment. Their global impression of improvement was also recorded (see Supplementary Figure S1). Primary outcomes included changes in symptom severity (5-point Likert scale), perceived effect of stimulation, and willingness to adopt UCon as a treatment. Secondary outcomes encompassed quality of life (EQ-5D-3L and EQ VAS), pain catastrophizing (PCS), anxiety and depression (HADS), satisfaction with the device (D-QUEST), and global improvement (PGI-I). All data were collected using Castor EDC and analyzed descriptively, with results presented as medians and interquartile ranges or percentages due to the small sample size and non-normal data distribution. The cross-sectional or longitudinal outcomes are statistically assessed using the Wilcoxon signed rank test to compare pared data across timepoints (intervention vs. baseline and post-intervention vs. baseline). Statistical analysis were performed in IBM SPSS Statistics (version 29.0.0, IBM Corp., Armonk, NY, USA). Details of the methodology and outcome measures are summarized in Supplementary Table S1. Of the 12 women enrolled, nine completed the study and were included in the final analysis (see Supplementary Figure S2). Most participants reported a modest reduction in PGAD symptom severity during and after the intervention, with an average decrease of 0.3 points on a 5-point Likert scale. Statistical significant reductions in symptom severity were found during week 2 (3.20 ± 1.08) and week 3 (2.98 ± 1.00) of the intervention compared to baseline (3.46 ± 0.89; P = .027 and .018, respectively). Three participants experienced symptom relief during stimulation, with effects lasting up to 60 min in some cases. Two participants showed no change, and one reported worsening symptoms. Six participants expressed willingness to continue using the neuromodulator as part of their treatment. Quality of life scores improved slightly in five participants, while anxiety, depression, and pain catastrophizing scores remained largely stable. No statistically significant differences were observed between baseline and intervention, nor between baseline and post-intervention. Global impression of improvement varied, with most participants reporting mild benefit. Satisfaction with the device was moderate overall. Device adherence was generally good, with an average of 29 sessions per participant in the three week period. No device-related adverse events occurred. Full results and data tables are available in the supplemental materials (Supplementary Tables S2–S4 and Supplementary Figure S1). These findings, while preliminary, offer valuable insights into the potential role of neuromodulation in managing PGAD symptoms. The observed symptom relief in several participants, even if temporary, suggests that targeted stimulation of the DGN may modulate sensory input in a way that interrupts the persistent arousal signals characteristic of PGAD. This aligns with existing theories that PGAD may involve peripheral nerve dysfunction or central sensitization, and supports the hypothesis that neuromodulation could influence both peripheral and central neural circuits. The variability in individual responses highlights the complexity of PGAD as a clinical entity. Some participants experienced clear symptom relief, while others reported no change or even worsening symptoms. This heterogeneity may reflect differences in underlying pathophysiology or psychological comorbidities. Future studies should consider stratifying participants based on symptom profiles to better identify candidates most likely to benefit from neuromodulation. The moderate satisfaction scores and willingness of two-thirds of participants to continue using the device suggest that, despite limitations, the intervention was feasible. Feedback collected during follow-up indicated that most participants preferred the flexibility of using the neuromodulator on demand, with a non-limited duration, rather than adhering to a fixed schedule. Future studies could explore a tailored use stimulation protocol, as it may better reflect variable symptom patterns in PGAD and improve satisfaction with neuromodulation treatment. The small sample size limits statistical power and generalizability. Nonetheless, the descriptive data provide a foundation for hypothesis generation and protocol refinement. In conclusion, this pilot study demonstrates that DGN neuromodulation is a promising intervention for PGAD, with potential to alleviate symptoms in select individuals. While further research is needed to confirm efficacy and optimize treatment protocols, these initial findings contribute to a growing body of evidence supporting neuromodulation as a viable therapeutic avenue in a highly distressing and understudied condition in women’s sexual health. We would like to thank F. Kersten for support during the data collection and K. Kluivers for her work in the methodology. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. N.J.M.R. works as a consultant for InnoCon Medical Denmark. The remaining authors report no conflict of interest.

Source: The Journal of Sexual Medicine

DOI: 10.1093/jsxmed/qdaf348