Results of the literature search

The literature search yielded 108 results in PubMed, 91 results in PsycInfo, 134 results in Scopus and 8 additional results via Google Scholar and personal contacts (total results = 341). The total number of literatures found after removing duplicates was 159; one paper full-text could not be found. After excluding book chapters, dissertations and conference papers, the titles and abstracts of 145 studies were screened for inclusion criteria. Excluded were editorials, commentaries, and letters, and publications whose publication language was not German or English, or PGAD/GPD was not the content of the study.

Finally, a total of 103 studies were subsequently included in the present review (see flow chart presented in Fig. 1).

Fig. 1

PRISMA flow chart documenting the literature search and inclusion of studies

Study situation and clinical picture of PGAD/GPDCharacteristics and quality of papers found

The 103 included papers comprised 52 case reports (N ≤ 2 cases), 10 case series (n > 2 cases), 20 cross-sectional studies and 21 reviews. For a detailed description of included studies see Addtional file 1: Tables S3–S6.

Data for the 52 case reports and 10 case series were collected primarily through face-to-face interviews and examinations. A total of 123 cases with PGA symptomatology were described. Eighty-one participants (66%) met all five criteria for PGAD/GPD according to Leiblum and Nathan [1]. The remaining participants met at least one PGAD/GPD criterion. For some patients, the exact number of PGAD/GPD criteria remained unclear / were not reported.

Of 20 cross-sectional studies, 14 studies were questionnaire studies or online surveys. Face-to-face interviews and examinations took place in six studies. Of all included cross-sectional studies, 2,078 cases were described as having PGA symptomatology. Of these, 892 cases met all five PGAD/GPD core criteria, and 1,186 cases met at least one PGAD/GPD criterion.

In three cross-sectional studies, patients with PGAD/GPD were compared with healthy controls [8, 26, 27]. There were four cross-sectional studies that allowed the calculation of a prevalence estimate of PGAD/GPD based on their design [28,29,30,31]. The quality ratings for the cross-sectional studies are shown in the Addtional file 1: Table S7. As most studies used a convenience sample or used online recruitment, self-selection of participants in many studies is likely which may question the representativeness of the samples. Moreover, no study so far has provided data on non-responders and only few studies were able to calculate a response rate. Some studies disclosed that non-validated measures to assess PGAD/GPD symptoms were used as such measures were simply not available. However, survey questions were often piloted prior to their use.

Epidemiology of PGAD/GPD

Until 2020, there were few meaningful studies on the epidemiology of PGAD/GPD [28, 29]. In 2020, two epidemiologic studies by Dèttore and Pagnini [30] and Jackowich and Pukall [31] separately assessed symptom expression using the five PGAD/GPD core criteria and associated distress.

Dèttore and Pagnini [30] studied a population of 679 female undergraduates in Florence, Italy. Eleven women (1.62%) reported the presence of all five PGAD/GPD core criteria two women (0.29%) met all five PGAD/GPD core criteria and reported maximum distress scores.

Jackowich and Pukall [31] examined two different populations. In a cohort of 1,634 undergraduates in Canada, 1.1% of males and 0.6% of females reported the presence of all five PGAD/GPD core criteria with moderate-to-high frequency. 4.5% of the participants reported moderate-to-severe distress for one or more symptoms according to the PGAD/GPD core criteria.

In a representative cohort of United States residents, of 1,026 respondents, 4.3% of men and 2.7% of women reported all five PGAD/GPD core criteria with moderate-to-high frequency. A total of 68 study participants (6.6%) reported moderate-to-severe distress for one or more symptoms according to the PGAD/GPD core criteria. In the same sample, 32.9% of respondents reported symptoms related to the first PGAD/GPD core criterion (persistent physiological sexual arousal), highlighting the high prevalence of PGA, which was consistent with the data from other studies [28, 30].

Sociodemographic characteristics of individuals with PGAD/GPD

Among all 2,201 PGAD/GPD cases described in case studies, case series and cross-sectional studies and who met at least one PGAD/GPD criterion, 2,167 were women and 34 were men. However, in some studies, men were excluded from participation [30].

The mean age of all described cases of PGA symptomatology in case reports and case series was 48 years (range: 16–81 years). The mean age at symptom onset in these publications was 42.5 years (range: 6–75 years).

There are few data on PGAD/GPD in adolescence. In some cross-sectional studies, adolescents were explicitly excluded from participation, and in no cross-sectional study were adolescent data separately collected. In an online survey of women with PGA symptoms, 25.2% retrospectively reported disease onset before age 18 [7]. In the case reports, there was only one description of an adolescent case (female, aged 16 years) [32]. There are other case reports in which the affected adults reported symptom onset of PGAD/GPD during adolescence [33, 34], including two women who reported onset of PGAD/GPD, at the time of menarche.

Characteristics of race and ethnicity were collected in very few papers. We, therefore, also evaluated local origin (Asia, Australia, Europe, North and South America), study location, and cross-regional recruitment, if applicable. Finance information was only collected in a few studies. Educational attainment was surveyed much more frequently in the studies, but had a wide variation in survey methods.

In a representative sample of United States residents, Jackowich and Pukall [31] found significantly higher numbers among more highly educated participants and in the non-Hispanic Black and Hispanic/Latina groups when examining the number of PGAD/GPD symptoms.

Comorbidity

Waldinger and Schweitzer [35] found increased comorbidity with restless leg syndrome and overactive bladder in their patients with PGAD/GPD symptoms and defined a separate clinical syndrome to be distinguished from PGAD/GPD called restless genital syndrome. Increased comorbidity with restless leg syndrome (RLS) has also been documented in other studies [7, 8, 36, 37]. Also, genital symptoms are commonly reported [7]. The frequency of clitoral and vulvar pain was reported as 35.4% and 44.3%, respectively, in two studies [7, 20]. Pukall et al. [20] grouped PGAD/GPD together with vulvodynia in a common disease category of genito-pelvic dysesthesia.

Many studies and case reports [34, 36, 38] described a high degree of psychological comorbidity in PGAD/GPD; for example, in one study, 45% of respondents reported comorbid depressive symptoms, 35% reported anxiety, and 16% reported obsessions [2]. In two studies using standardized questionnaires, patients with PGAD/GPD showed significantly more anxiety and depressive symptoms compared to a control group without PGAD/GPD symptoms [8, 27]. In this context, anxiety and depressive symptoms can occur both before and after the onset of PGAD/GPD symptomatology [7, 24]. The prevalence of suicidal ideation is strikingly common in women with PGAD/GPD [8].

Two studies have described an increased incidence of childhood sexual abuse [24, 36].

Relationship between ED and PGAD/GPD

Two cross-sectional studies [2, 24] investigated ED in women who met all five PGAD/GPD original criteria. In one study [24], 19.7% of respondents reported a history of an ED diagnosis. In the other study [2], 8% of respondents reported a positive history. These results were not further commented on by the authors.

In two case reports [23, 39], there were descriptions of patients with PGAD/GPD who reported a history of an ED (AN, as well as AN and BN).

No study was included that drew a connection between ED and PGAD/GPD. There was a single case report describing a current comorbid ED (BN) [40].

A few other case reports exist that describe episodes of binge eating that may be regarded as a symptom of an ED [32, 41, 42]. In the work of Zwerling et al. [42], episodes of binge eating were attributed to Kleine-Levin Syndrome.

Etiology of PGAD/GPD

The ideas regarding the genesis of the disease are various, and specifically, neurological, pharmacological, hormonal, vascular and psychological causes have been discussed. It has also been suspected that there are patients with PGAD/GPD for which several underlying causative factors may be simultaneously active [4, 38].

Peripheral nerve irritation is often described as a neurological cause of PGAD/GPD. Nerve irritation can be caused by small fiber sensory neuropathy [35] or triggered by mechanical compression of the peripheral nerves [43]. Meningeal cysts (Tarlov cysts), which are thought to irritate spinal nerve roots, are most commonly reported as a mechanical cause [34, 44, 45]. CNS disorders have also been described as a neurological cause of PGAD/GPD [46, 47].

The initiation or discontinuation of selective serotonin reuptake inhibitors (SSRI) or other psychotropic drugs has been cited as pharmacological causes of PGAD/GPD [29, 40, 48,49,50,51,52]. In an online survey, Jackowich et al. [7] found SSRI use to be the most commonly cited possible trigger for PGA symptoms. When SSRIs are discontinued, increased sensitivity of peripheral nerves [40, 49] or altered processing of sensory stimuli could occur as a rebound phenomenon [49]. Both SSRI use and SSRI discontinuation could increase genital blood flow in a hormonally mediated manner [40, 49]. However, the exact pharmacological mechanisms of action are still unknown.

The genesis of PGAD/GPD is thought to involve sex hormones. Some case reports describe the discontinuation of estrogens [32] or an estrogen-rich diet [53] as triggers for PGAD/GPD. Alteration of hormone receptors of the genital organs is suspected [53]. A change in progesterone and estradiol concentrations in the blood after menopause was considered a risk factor for PGAD/GPD by Waldinger and Schweitzer [23].

Vascular causes of PGAD/GPD have been described as pelvic varices or genital vascular changes, which can lead to peripheral nerve irritation [54,55,56].

Psychological causes of PGAD/GPD are discussed due to the frequent comorbidity of PGAD/GPD with mental disorders (see 3.2.4) [57]. In this context, a psychic concomitant causation is assumed; however, studies assuming a purely psychic causation of PGAD/GPD are rare. Pernot-Masson [58] describes PGAD/GPD as a form of dissociative disorder, there is one case report [59] with the same consideration.

A bio-psychosocial approach is also helpful in PGAD/GPD, since biological, psychological, and social factors influence each other in the development and maintenance of the disorder [57, 60]. How the experience of unwanted genital arousal is evaluated by the affected person seems to be particularly important. Therefore, dysfunctional attitudes toward sexuality correlate with distress from PGAD/GPD symptoms [27, 57, 61]. In addition to the cognitive and emotional appraisal of symptoms, another mechanism is likely maintaining the condition; for example, anxiety and distress can directly stimulate sexual arousal [7, 57].

Heritability of PGAD/GPD has rarely been discussed [62].

Treatment of PGAD/GPD

Currently, there are no Food and Drug Administration (FDA)-approved or evidence-based treatments for PGAD/GPD. All evidence regarding the treatment of PGAD/GPD derives from case reports and case series [43].

Consistent with the unclear and most likely multifact