Treatment in persistent genital arousal disorder: a scoping review

Abstract

Background

Persistent genital arousal disorder (PGAD) is a rare condition characterized by unwanted and distressing symptoms of arousal and dysesthesia. The aim of this scoping review was to map the current state of PGAD management, identify gaps in the literature, and understand patient perspectives.

Methods

We completed a scoping review following guidelines from the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta Analyses Scoping Reviews extension. A systematic literature search for articles pertaining to PGAD/genito-pelvic dysesthesia (GPD) was conducted in August 2023 via Medline, Embase, Scopus, and Web of Science. The search returns were deduplicated and the remaining titles and abstracts were screened for inclusion. General publication characteristics and treatment data were extracted from the included publications via a pilot-tested Google form. All screening and extraction were completed in a masked, duplicate fashion.

Results

Findings from our scoping review revealed a scarcity of systematic research, limited evidence-based data, and the importance of addressing both physical and psychiatric concerns. Our sample included 46 publications from an initial pool of 636 returns. Case studies were the most common study design. Thirty-three studies examined medication, either alone or as part of a treatment regimen. Selective serotonin reuptake inhibitors were the most used medication, followed by pramipexole and carbamazepine. Seven studies used a surgical or procedural intervention. Treatment with pelvic floor Botox was the most common procedure. Patient perspectives in the included case studies highlighted themes of shame, suicidal ideation, social isolation, decreased sleep, and overall decline in quality of life.

Conclusion

The findings from our study emphasize patients’ distressing and psychiatric symptoms, indicating a need to improve treatment regimens, using both evidence-based research outcomes and patient-reported outcomes. Management for PGAD/GPD lacks a standardized framework, indicating a need for further research and the development of clinical practice guidelines to improve patient care.

Persistent genital arousal disorder (PGAD) is a rare, complex condition affecting approximately 1% of women.¹ Patients with PGAD experience persistent and unwanted physical symptoms of arousal including pressure in the genitalia, tingling, throbbing, or being on the verge of an orgasm without sexual stimuli or sexual desire. Patients may experience these symptoms originating from end organs (clitoris, vagina, vulva), the pelvic floor, the cauda equina/sacrum, the spinal cord, or the brain.² In addition to the distressing physical symptoms from various body regions, patients with PGAD may also experience high rates of depression, anxiety, or suicidal ideation.³ Although this constellation of physical and psychosocial symptoms for patients with PGAD is concerning, there is a lack of systematically reviewed research on individualized management and patient outcomes.

The prevalence, symptom profile, and standardized treatment modalities of PGAD have not been fully demonstrated. Further, there are significant variations in reported cases of PGAD,^4,5 eliciting challenges for developing a more standardized approach to assessment and management. This is in contrast to other rare diseases with complex presentations. For example, Ehlers-Danlos syndrome is a group of rare conditions caused by genetic defects in collagen seen in <1% of patients. Additionally, symptoms of Ehlers-Danlos may mimic other conditions, making it difficult to diagnose.⁶ Despite its complexity, there is a wide range of research available for Ehlers-Danlos, with nearly 4500 search returns on PubMed. Efforts have been made to more accurately classify PGAD with aims to drive management. In the first consensus expert review on PGAD, the International Society for the Study of Women’s Sexual Health (ISSWSH) adopted the term persistent genital arousal disorder/genito-pelvic dysesthesia to more fully encompass patients’ complex symptoms.²

Given the complexity of PGAD, its distressing effects on patients, and the lack of systematic research available, a scoping review was needed to explore the extent to which PGAD management has been examined in the current literature. To our knowledge, no such scoping review has been performed. The purpose of this review was to identify gaps in the literature regarding PGAD management, enhance awareness for physicians and patients, and guide future systematic review research. Additionally, we aimed to highlight any barriers patients may face when seeking treatment.

Methods

Reproducibility and study design

Prior to the start of the study, search strategies, criteria for inclusion and exclusion, and data extraction materials were pilot tested. To promote reliability and transparency and ensure that methodology was strictly followed, a protocol was uploaded to Open Science Framework (OSF) before the study began.⁷ Further, the institutional review board determined that our study did not meet qualifications for human subjects status. This scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews (PRISMA-ScR) checklist.^8,9

Literature search

A search of MEDLINE (via PubMed), Ovid Embase, Scopus, and Web of Science databases was performed in August 2023 to locate published articles on PGAD. These databases were chosen in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, which recommends the inclusion of these databases for a sufficient study sample.¹⁰ The search strategy was developed in accordance with the JBI manual.

Research question

The primary research questions for this scoping review were as follows: (1) What treatment approaches have been investigated for PGAD? (2) What is the evidence of treatment effectiveness? (3) What barriers do patients face when seeking treatment? The objective of this scoping review was to identify and map the existing literature on treatment approaches to PGAD and highlight steps for future research.

Selection process

Prior to study investigation, all authors were trained on the purpose and methodology of a scoping review using the 2020 JBI Reviewers Manual.⁹ Identified returns from the comprehensive database search were uploaded into the title and abstract screening platform Rayyan.¹¹ The title and abstract of each citation were screened in a masked, duplicate fashion for inclusion in the study. Any disagreements between investigators were reconciled via discussion, with a third party available if needed. Following screening of title and abstract, full-text screening was performed and the reason for exclusion was documented.

Inclusion and exclusion criteria

Inclusion criteria for the scoping review were developed using the population, concept, and context framework provided by the JBI manual.⁹ The population of this review included the following study designs: clinical trials, retrospective database reviews, systematic reviews, meta-analyses, cross-sectional analyses, cohort studies, case-control studies, and case reports. We excluded commentaries, correspondence, and letters to journals due to their inconsistency. The concept consisted of studies with one or more treatment options for PGAD. Any study unrelated to PGAD, examining PGAD in men only, written in a language other than English, or failing to report a treatment intervention for PGAD was excluded from the study. Discrepancies in inclusion/exclusion were resolved through discussion with a third investigator if needed. Reasons for exclusion were reported and presented in a PRISMA flow diagram.

Data charting

Data were charted using a Google form. The following characteristics were extracted from each study: study title, author name, PubMed identifier, year of publication, years analyzed, study design, and number of subjects enrolled. Additionally, intervention, efficacy outcomes, and barriers or facilitators to care were extracted from each study. Prior to data extraction, investigators independently extracted the first five articles within the sample and resolved any discrepancy through discussion. A third party was available for arbitration if needed. Following this training exercise, investigators extracted data from the remaining studies in a masked, duplicate manner.

Synthesis

We summarized data using descriptive statistics for studies investigating PGAD interventions, the types of interventions for management of PGAD, and the type of study designs included in our scoping review. We also extracted statements on patient perspectives from included case studies and analyzed the data using a qualitative approach. All raw data, final reconciled data, and statistical analysis methods were uploaded to OSF.

Results

General characteristics of included studies

Our literature search yielded 636 returns, of which 387 were duplicates and removed. The remaining 249 titles and abstracts were screened. An additional 138 articles did not meet inclusion criteria, and 111 were retained for full-text review. Sixty-five studies were excluded during full-text review, yielding 46 publications in our final sample. The PRISMA flow diagram demonstrates the study selection process (Figure 1). The most common study designs in our sample were case studies (34/46, 73.9%), followed by literature reviews (6/46, 13.0%). Table 1 outlines the general study characteristics examined in our final sample. A total of 13 studies in our sample did not mention a specific PGAD symptomatic region (13/46, 28.3%). However, when described, the most common regions involved in symptom presentation were end organs (9/46, 19.6%) or multiple regions (9/46, 19.6%). Most included studies examined multiple interventions for PGAD treatment (19/46, 41.3%) and medications (16/46, 34.8%), whereas the least common interventions included manual physiotherapy, hypnotherapy, and electroconvulsive therapy (all 1/46, 2.2%). Supplemental Table 1 summarizes the findings of each included study with respect to interventions. Four of the included studies mentioned barriers to seeking care (4/46, 8.7%).

Figure 1.

PRISMA flow diagram.

Table 1.

Descriptive statistics

Variable	Frequency (n = 46)	%
Treatment examined
Multiple	19	41.3
Medication	16	34.8
Other	7	15.2
Surgery	2	4.3
Therapy/counseling	2	4.3
Study design
Case study	34	73.9
Literature review	6	13.0
Retrospective database review	2	4.3
Scoping review	1	2.2
Systematic review	1	2.2
Cross-sectional analysis	1	2.2
Cohort study	1	2.2

Interventions and efficacy

Thirty-three studies examined medications either alone or as part of a treatment regimen for PGAD. Ten of these studies—eight case reports and two literature reviews—examined selective serotonin reuptake inhibitors (SSRIs), which were determined to be effective in five studies. Both literature reviews reported reduction in symptoms with SSRIs for patients, and three of the case studies reported that SSRIs were effective in reducing symptoms. The most commonly prescribed SSRI was sertraline. Pramipexole was examined as a medication intervention in five cases and was effective in all five cases. Carbamazepine was used in four included studies and was “somewhat effective.” Other medications prescribed include pregabalin, clomipramine, and topical anesthetics.

Seven included studies monitored effectiveness using a surgical/procedural intervention. Surgeries included pelvic floor Botox (4/46, 8.7%), spinal cyst decompression (3/46, 6.5%), and periclitoral mass excision (1/46, 2.2%). Treatment regimens involving a surgical intervention ranged from “somewhat effective” to “effective.” Botox was examined in four articles, including three case studies and one literature review. Two of the case studies demonstrated resolution of PGAD symptoms; however, one case study demonstrated initial resolution with a gradual return of symptoms. In a case series of 11 patients, cyst decompression resulted in improvement of symptoms for 10/11 of the patients (91%). The other two studies documenting cyst decompression were one literature review and one retrospective data review, and both demonstrated improvement in results. The case study in which a patient underwent periclitoral mass excision resulted in a gradual resolution of pain and arousal symptoms.

Patient perspectives

Thirty-four studies in our included sample were case reports or case series. Shame was a recurring theme experienced by many patients and was expressed in six case studies. For example, a case study by Ahmad et al reported a patient in Pakistan who experienced intense shame following the onset of her PGAD/genito-pelvic dysesthesia (GPD) symptoms, which was compounded by her cultural and religious environment.¹² Waldinger et al described a patient who did not admit her symptoms to her practitioner for 3 years because of associated shame and guilt.¹³ Another theme seen across case reports was suicidal ideation or suicidal thoughts. In 11 included case studies, patients expressed concerns with suicidal thoughts because of their PGAD/GPD symptoms. A case study by Yildirim et al described a patient who had intense feelings of guilt and developed suicidal thoughts after an episode of spontaneous orgasm in the same room as her son.¹⁴ Korda et al described a patient who previously had a history of depression but only started having suicidal thoughts after the onset of PGAD.¹⁵ Other common themes in the case studies included social isolation,^15–17 interference with sleep,^2,12 and overall decline in quality of life.^12,18

Discussion

Literature relating to PGAD/GPD and its management remains scarce, with the majority of studies presented as case reports or series. Recent trends, however, indicate an emergence of comprehensive and systematic evaluations of PGAD/GPD management. Despite the growing amount of research, the literature is predominantly observational, and management lacks an overall structured framework.

Treatment algorithm

In 2021, ISSWSH developed a consensus expert review that included a novel management algorithm based on the five regions: end organ, pelvis, cauda equina/sacrum, spinal cord, and brain.² The expert panel recommends identifying the region of symptom provocation and focusing treatment specifically on the identified region.² Studies using this algorithm remain scarce, and only 25% of studies included in our sample were published after its development. Additionally, the ISSWSH algorithm is a consensus-based algorithm consisting largely of expert opinion. Consensus statements synthesize existing research, expert opinions, and case studies with the aim to support clinical decision making for a specific process.¹⁹ Such statements may be particularly useful in a rare disease such as PGAD/GPD because of the significant variation in patient presentations and the need for an individualized treatment approach. However, in the evidence hierarchy, expert opinion is considered the lowest level of evidence-based research,^20,21 because it is often driven by the authors’ experience and there is no control for confounding bias.²² In contrast, clinical practice guidelines are formalized statements that define diagnosis and management, provide recommendations for clinical decision making, and serve as best practice for patient care.^19,23 Clinical practice guidelines are developed through a rigorous synthesis of systematic reviews, which are considered the highest level of evidence-based research.²² Though a consensus-based algorithm is a promising start, especially given the distressing nature of PGAD/GPD, a move toward development of a clinical practice guideline for PGAD/GPD should be the ultimate goal. To do so, however, would require more longitudinal studies in the form of randomized controlled trials, presenting even more challenges, because both self-reporting patients and funding are limited.

Psychiatric treatment

The general ISSWSH consensus recommends starting treatment focused on region 1 (end organ) and region 2 (pelvis), because these regions are the most commonly implicated in PGAD/GPD.² However, the expert panel also notes the importance of initiating diagnostic workup and management for region 5 (brain)² due to the distressing psychological symptoms associated with PGAD/GPD, including anxiety, depression, catastrophization, and suicidal ideation.¹ Most studies in our included sample identified at least one distressing psychiatric symptom in patients, and in many cases, patients were admitted to psychiatric facilities as a result of their symptoms.^24,25 Although this was often due to their psychiatric symptoms, some patients were admitted under the care of psychiatry because it was believed their physical symptoms were a manifestation of psychiatric illness. Additionally, though one of the most common treatments used in our included sample was SSRIs, it must be noted that in some instances SSRIs exacerbated arousal symptoms or were the initial etiologic agent for PGAD/GPD.^2,26 Still, of the 10 studies examining SSRIs, SSRIs were effective in five articles. This was especially true when the regimen was individualized to patient needs, such as titrating the medication dosage or adding an additional medication. For example, findings from a case report of an adolescent woman with PGAD demonstrated a complete resolution of spontaneous arousal following treatment with sertraline and hormonal vaginal ring contraception.²⁷ Additionally, treatment that incorporated cognitive behavior therapy, mindfulness, and patient education was effective. For example, a case study by Merwin and Brotto demonstrated a reduction in negative psychological symptoms—catastrophization, rumination, anxiety, and depression—following cognitive behavioral therapy, dialectical behavioral therapy, and mindfulness techniques. Further, the patient reported a decrease in physical arousal symptoms and an increase in quality of life and ability to cope with distressing symptoms related to PGAD.¹⁶ Taken together, these findings highlight the importance of managing the distressing psychological symptoms for patients.

Patient perspectives

In most of the case studies included in our sample, patients were incredibly reluctant to seek care or admit their symptoms during a health care visit due to shame, fear, or previous instances where their experiences were invalidated. Twenty-nine of the 33 case reports demonstrated an example in which the patient was previously dismissed or completely mismanaged. One case discussed a patient who underwent a complete clitoridectomy for her symptoms, which provided partial relief of spontaneous orgasm with no relief of other dysesthesias.¹³ When patients were managed properly with medications, cases often reported a discontinuation of the medication or need to switch the medication due to side effects. For example, one case report discussed a patient who discontinued carbamazepine treatment due to severe dizziness, even though the medication relieved her PGAD/GPD symptoms.⁴ Though the continued development of a more standardized, evidence-based treatment approach is necessary, these findings suggest an additional need to include patient perspectives in the treatment process. The development of a patient-reported outcome measurement set may fill this need and allow for greater patient autonomy and participation in decisions regarding their health.

Strengths and limitations

To promote transparency and reproducibility, the study protocol and raw data were uploaded to OSF.⁷ To reduce the risk of bias, all data extraction was completed in a masked, duplicate fashion. Regarding limitations, our study is cross-sectional in design and thus findings may not be generalizable across time. Language bias is another limitation, because we may have missed other results. Additionally, most included publications in our sample were case studies, which offer limited evidence-based decisions.

Conclusion

Literature relating to PGAD/GPD and its management remains scarce, with the majority of studies presented as case reports or series. Our findings mirror previous statements from research findings demonstrating that efficacy of various treatments for PGAD is difficult to determine because a large portion of the literature consists of anecdotal evidence and nondescriptive studies. Although more systematic research is being conducted for this distressing disorder, a move toward the development of a clinical practice guideline and inclusion of patient-reported outcome measures is necessary. Because nearly 74% of our included articles are case studies, our findings further illustrate this need and may help to promote the development of formal case control studies and clinical trials.

Disclosure statement

No financial or other sources of support were provided during the development of this manuscript. Dr. Vassar reports receipt of funding from the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, the US Office of Research Integrity, Oklahoma Center for Advancement of Science and Technology, and internal grants from Oklahoma State University Center for Health Sciences—all outside of the present work. Dr. Babb is a member of the scientific advisory board for Vella Biosciences, the consumer advisory board for Sprout Pharmaceuticals, and the speaker’s bureau for Astellas Pharmaceuticals and Sprout Pharmaceuticals and has consultant agreements with the Consortium for the Study of Female Sexual Wellness. The other authors report no potential conflicts of interest.