Sexual Health · Sexual Pain
Abstract
Objective
This scoping review aims to evaluate recent studies that examine the relationship between dyspareunia and neurophysiologic factors, and to synthesize their results as it pertains to the development and treatment of introital/vulvar dyspareunia and deep dyspareunia
Data Sources
A comprehensive search was conducted in PubMed (NLM), Embase (Elsevier), CINAHL (EBSCOhost), Web of Science (Clarivate), Psycinfo (ProQuest), and Cochrane Library (Wiley) to find peer reviewed studies written in English published in 2000 or later that discussed how neurophysiology is related to dyspareunia.
Search Strategy
dyspareunia; painful intercourse; genito-pelvic pain; penetration disorder; neuropsychology; central nervous system sensitization; neur; central sensitization.
Methods of Study Selection
A total of 1101 studies were screened and 108 were included in the review. Abstract and full text screening were performed by 4 authors. Articles were also excluded if they did not include an objective diagnostic tool or objective treatment outcome of dyspareunia. We included original peer-reviewed published research in the form of randomized control trials, cohort studies, case control studies, case series of greater than 20 participants, and systematic reviews.
Integration and Results
Multiple study types were noted: 22 randomized control trials, 9 prospective cohort studies, 3 retrospective cohort studies, 30 case control, 16 case series, 17 cross-sectional, and 11 systematic reviews. Of these articles, 72 focused on introital/superficial dyspareunia, 23 focused on deep dyspareunia, and 13 on both. Data was synthesized in text and table format, separated by type of dyspareunia (introital vs deep) and either etiology/diagnosis or treatment.
Conclusion
There are complex neurophysiologic mechanisms that influence both introital and deep dyspareunia, highlighting the roles of peripheral and central sensitization, nerve fiber density, and neuroplasticity in this condition. There are several promising treatments, including TENS, botulinum toxin A, physical therapy, and various multimodal approaches; but further research is needed to establish standardized therapeutic guidelines.
Topics
By this author
Pelvic Pain · Chronic Pelvic Pain
Endometriosis, symptoms, and risk for depression and/or anxiety: a population-based retrospective study
Goodwin E et al., 2025 · BMC women's health · Free full text on PubMed Central
Endometriosis is a chronic and inflammatory condition that often presents with chronic pelvic pain, dysmenorrhea, and dyspareunia, thus having important effects on quality of life. There are two proposed hypotheses to describe the known association between endometriosis and depression and anxiety: (1) the disease hypothesis, where the inflammatory nature of endometriosis is driving increased risk for depression and anxiety; and (2) the pain hypothesis, where it is the painful symptoms underlying the increased risk. We aimed to shed further light on these two hypotheses by assessing the risk for depression and/or anxiety in three groups of patients pathologically assessed for endometriosis: symptomatic endometriosis patients (Symp Endo), symptomatic patients with no pathological endometriosis diagnosis (Symp No Endo), and asymptomatic endometriosis patients (Asymp Endo). This study included pathologically-confirmed endometriosis patients identified from the pathology records of Vancouver Coastal Health Authority between 2000 and 2008. These data were linked with population-based administrative health data for follow-up to 2017. Depression and anxiety were identified through diagnostics codes from health services use data and prescriptions for antidepressants. Bivariate analyses were performed to assess differences between groups. Cox proportional hazards models were run to generate hazard ratios for incident depression and/or anxiety between the groups. There were 2729 people in Symp Endo, 585 in Symp No Endo, and 326 in Asymp Endo. Symp No Endo was more likely than Symp Endo to be visiting a physician for pelvic pain and to be taking prescription-level pain medications (p < 0.001). After adjusting for several covariates, Symp No Endo had a significantly higher risk of incident depression and/or anxiety (adjusted HR: 1.23, 95% CI: 1.06-1.41) compared to Symp Endo. There was no statistically significant difference in risk of depression and/or anxiety between Symp Endo and Asymp Endo (adjusted HR: 0.94, 95% CI: 0.76-1.17). These results point toward the pain focused hypotheses as Symp No Endo patients were at higher risk for depression/anxiety than the Symp Endo group. However, the results also suggest the disease hypothesis is at play, because the Symp Endo and Asymp Endo groups were at the same level of risk for depression/anxiety.
Pelvic Pain · Chronic Pelvic Pain
Pain sensitivity questionnaire in endometriosis
Gentles AJ et al., 2025 · The journal of pain · Free to read
There is increasing recognition that nociplastic pain and central sensitization may play a role in endometriosis-associated pain. The Pain Sensitivity Questionnaire Minor (PSQ-M) evaluates subjective widespread pain sensitivity, and is linked to pain outcomes in chronic pain populations. However, evidence connecting the PSQ-M to central sensitization in endometriosis is limited. Using the Central Sensitization Inventory (CSI) as a comparison, this study compared the PSQ-M as a clinical proxy for central sensitization in endometriosis individuals. Data collected from 983 endometriosis participants (mean age of 34 years), between January 2020 and December 2022, were analyzed from a prospective registry. A significant but weak positive correlation was observed between PSQ-M and CSI scores (r=0.099, p<0.001). A significant but weak correlation was found between the number of central sensitivity syndromes and pelvic pain-related comorbidities with the PSQ-M (r=0.093, p<0.001), compared to a stronger correlation with the CSI (r=0.687, p<0.05). PSQ-M scores were not significantly associated with baseline (r=0.013, p=0.797) or post-operative (r=-0.046, p=0.801) quality-of-life. There was no change in the PSQ-M and a small change in CSI after endometriosis surgery, suggesting that surgical treatment of endometriosis does not directly address central sensitization. In conclusion, the PSQ-M may not be the optimal clinical proxy for central sensitization in endometriosis. This study evaluates the Pain Sensitivity Questionnaire - Minor (PSQ-M) as a proxy for central sensitization in endometriosis. The PSQ-M showed weak correlations with central sensitivity syndromes and pain scores and was not associated with post-surgical quality-of-life, suggesting it may not be the optimal tool for assessing central sensitization in endometriosis.
Uterine Surgery · Myomectomy
Outcomes Post-Laparoscopic Intervention for Accessory and Cavitated Uterine Masses: A Review and a Molecular Insight
Bedaiwy MA et al., 2025 · Gynecologic and obstetric investigation
Accessory and cavitated uterine masses (ACUM) are rare Mullerian anomalies, defined as an isolated accessory cavitated mass lined with endometrial epithelium. This article explores ACUM lesions from two aspects and integrates a case report of a successful laparoscopic-assisted intervention for ACUM in a 24-year-old woman with refractory dysmenorrhea with a review of current literature on laparoscopic surgical techniques. Unique to this case was the process of undergoing targeted genetic sequencing via the Find ITTM Panel Version 3.4 on the ACUM, looking for mutations in KRAS, PIK3CA, and FGFR2. A process that was inspired by recent reports that indicate that even normal endometrium can harbor cancer-associated mutations. A comprehensive search of Ovid MEDLINE and Embase was performed. Studies were selected if they explored laparoscopic surgery's impact on ACUM patients' outcomes related to fertility, menorrhagia, or dysmenorrhea. Risk of bias assessment was performed using the JBI Critical Appraisal Checklist. From 160 articles identified, 25 full-text articles were analyzed with a total of 75 unique patients discussed. Dysmenorrhea was present in 100% of cases (n = 75/75), and laparoscopic resection improved patient symptoms in 84% (n = 63/75) of cases. The mass excised in the case was positive for somatic missense mutations in RET (R813W) and HRAS (G12S) genes, identified at low variant allele frequencies. These results demonstrated that laparoscopic surgical approaches are effective and frequently the first surgical approach chosen for the treatment of ACUM, but that techniques to treat these conditions are not standardized. This case is the first to demonstrate mutations in ACUM, suggesting a potential role for cancer-associated somatic mutations in their genesis. Future developments in this area may include sending more of these samples for genetic analysis, improving our understanding of how these lesions are formed, while also working to standardize how they are removed.
Pelvic Pain · Chronic Pelvic Pain
Nociplastic Pain in Endometriosis: A Scoping Review
Gentles A et al., 2024 · Journal of clinical medicine · Free full text on PubMed Central
Endometriosis is an inflammatory chronic condition associated with nociceptive, neuropathic, and nociplastic pain. Central sensitization (CS) is the primary nociplastic pain mechanism. However, there are currently no standardized methods for detecting CS or nociplastic pain. This review aims to identify available tools for characterizing CS/nociplastic pain in endometriosis-related chronic pelvic pain. Following the PRISMA-P protocol, MEDLINE, Embase, Scopus, and PsychINFO databases were searched on 23 April 2024, for the terms "endometriosis", "central sensitization", "nociplastic pain", "widespread pain", and "assessment tools". Publications were selected if they mentioned tool(s) for detecting nociplastic pain or CS in endometriosis patients. Information was extracted on study demographics, assessment types, and the tools used for detection. Of the 379 citations retrieved, 30 papers met the inclusion criteria. When working to identify CS and nociplastic pain, fourteen studies exclusively used patient-reported questionnaires, six used quantitative sensory testing (QST), two used clinical assessments, and eight used multiple approaches combining patient-reported questionnaires and clinical assessment. This review illustrates the diversity of tools currently used to identify CS and nociplastic pain in endometriosis patients. Further research is needed to evaluate their validity and to standardize methods in order to improve the accuracy of nociplastic pain identification and guide treatment.
Related research
Sexual Pain · Dyspareunia
Deep Dyspareunia: Review of Pathophysiology and Proposed Future Research Priorities
Orr N et al., 2020 · Sexual medicine reviews
Dyspareunia has been traditionally divided into superficial (introital) dyspareunia and deep dyspareunia (pain with deep penetration). While deep dyspareunia can coexist with a variety of conditions, recent work in endometriosis has demonstrated that coexistence does not necessarily imply causation. Therefore, a reconsideration of the literature is required to clarify the pathophysiology of deep dyspareunia. To review the pathophysiology of deep dyspareunia, and to propose future research priorities. A narrative review after appraisal of published frameworks and literature search with the terms (dyspareunia AND endometriosis), (dyspareunia AND deep), (dyspareunia AND (pathophysiology OR etiology)). Deep dyspareunia (present/absent or along a pain severity scale). The narrative review demonstrates potential etiologies for deep dyspareunia, including gynecologic-, urologic-, gastrointestinal-, nervous system-, psychological-, and musculoskeletal system-related disorders. These etiologies can be classified according to anatomic mechanism, such as contact with a tender pouch of Douglas, uterus-cervix, bladder, or pelvic floor, with deep penetration. Etiologies of deep dyspareunia can also be stratified into 4 categories, as previously proposed for endometriosis specifically, to personalize management: type I (primarily gynecologic), type II (nongynecologic comorbid conditions), type III (central sensitization and genito-pelvic pain/penetration disorder), and type IV (mixed). We also identified gaps in the literature, such as lack of a validated patient-reported questionnaire or an objective measurement tool for deep dyspareunia and clinical trials not powered for sexual outcomes. We propose the following research priorities for deep dyspareunia: deep dyspareunia measurement tools, inclusion of the population avoiding intercourse due to deep dyspareunia, nongynecologic conditions in the generation of deep dyspareunia, exploration of sociocultural factors, clinical trials with adequate power for deep dyspareunia outcomes, partner variables, female sexual response, pathways between psychological factors and deep dyspareunia, and personalized approaches to deep dyspareunia. Orr N, Wahl K, Joannou A, et al. Deep Dyspareunia: Review of Pathophysiology and Proposed Future Research Priorities. Sex Med Rev 2020;8:3-17.
Sexual Pain · Dyspareunia
Deep Dyspareunia in Endometriosis: A Proposed Framework Based on Pain Mechanisms and Genito-Pelvic Pain Penetration Disorder
Yong PJ, 2017 · Sexual medicine reviews
Endometriosis is a common chronic disease affecting 1 in 10 women of reproductive age, with half of women with endometriosis experiencing deep dyspareunia. A review of research studies on endometriosis indicates a need for a validated question or questionnaire for deep dyspareunia. Moreover, placebo-controlled randomized trials have yet to demonstrate a clear benefit for traditional treatments of endometriosis for the outcome of deep dyspareunia. The reason some patients might not respond to traditional treatments is the multifactorial nature of deep dyspareunia in endometriosis, which can include comorbid conditions (eg, interstitial cystitis and bladder pain syndrome) and central sensitization underlying genito-pelvic pain penetration disorder. In general, there is a lack of a framework that integrates these multifactorial causes to provide a standardized approach to deep dyspareunia in endometriosis. To propose a clinical framework for deep dyspareunia based on a synthesis of pain mechanisms with genito-pelvic pain penetration disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Narrative review after literature search with the terms (endometriosis AND dyspareunia) OR (dyspareunia AND deep) and after analysis of placebo-controlled randomized trials. Deep dyspareunia presence or absence or deep dyspareunia severity on a numeric rating scale or visual analog scale. Four types of deep dyspareunia are proposed in women with endometriosis: type I that is directly due to endometriosis; type II that is related to a comorbid condition; type III in which genito-pelvic pain penetration disorder is primary; and type IV that is secondary to a combination of types I to III. Four types of deep dyspareunia in endometriosis are proposed, which can be used as a framework in research studies and in clinical practice. Research trials could phenotype or stratify patients by each type. The framework also could give rise to more personalized care for patients by targeting appropriate treatments to each deep dyspareunia type. Yong PJ. Deep Dyspareunia in Endometriosis: A Proposed Framework Based on Pain Mechanisms and Genito-Pelvic Pain Penetration Disorder. Sex Med Rev 2017;5:495-507.
Sexual Pain · Dyspareunia
Phenotyping Sexual Pain in Endometriosis Using the Central Sensitization Inventory
Orr NL et al., 2020 · The journal of sexual medicine
Deep dyspareunia, a common symptom in endometriosis, has previously been associated with bladder and/or pelvic floor tenderness (BPFT), which suggests a role for central nervous system sensitization. The Central Sensitization Inventory (CSI, 0-100) is a validated self-reported scale for patients with central sensitization. The objective of this study was to phenotype deep dyspareunia using BPFT and the CSI. The methods included cross-sectional analysis from a prospective registry from January 2018 to June 2018 at a tertiary center for endometriosis (ClinicalTrials.gov #NCT02911090). Included were women aged 18-50 years with endometriosis (previously surgically diagnosed, current visualized endometrioma on ultrasound, or current palpable or visualized nodule on ultrasound), who were newly or re-referred to the center. Severity of deep dyspareunia was self-reported using an 11-point numeric rating scale (0 = no pain; 10 = worst pain imaginable), categorized as no or low deep dyspareunia (0-4) and high deep dyspareunia (5-10). We identified the subgroup with high deep dyspareunia and presence of BPFT, where we hypothesized a central component of the sexual pain. This subgroup was compared with 2 other subgroups: no or low deep dyspareunia and high deep dyspareunia but no BPFT. The CSI was compared between the groups using analysis of variance, followed by post hoc testing (P < .05). The main outcome measure was the CSI score ranging from 0 to 100. Data from 163 women with endometriosis were analyzed. The mean age of this cohort was 36.4 ± 6.8 years, and the mean CSI score was 41.0 ± 18.6. 37 percent (61/163) had high deep dyspareunia and BPFT; 29% (47/163) had high deep dyspareunia and no BPFT; and 34% (55/163) had no or low deep dyspareunia. The CSI significantly differed between the 3 groups (analysis of variance: F = 22.4, P < .001). In post hoc testing, the CSI was higher in women with high deep dyspareunia and BPFT (51.3 ± 16.9), compared with women with no or low deep dyspareunia (30.9 ± 15.4, P < .001) and compared with women with high deep dyspareunia but no BPFT (39.4 ± 17.2, P = .001). The CSI could be used to classify and phenotype patients with endometriosis-associated sexual pain. Strengths include a prospective registry with integrated pain scores, validated questionnaires, and physical examination findings. Limitations include the lack of quantitative sensory testing for central sensitization. In women with endometriosis, the subgroup with high deep dyspareunia and bladder and/or pelvic floor tenderness had a significantly higher score on the CSI than other subgroups, suggesting that this group may have a central component to their sexual pain. Orr NL, Wahl KJ,Noga H, et al. Phenotyping Sexual Pain in Endometriosis Using the Central Sensitization Inventory. J Sex Med 2020;17:761-770.
Sexual Pain · Dyspareunia
Dyspareunia in Their Own Words: A Qualitative Description of Endometriosis-Associated Sexual Pain
Wahl KJ et al., 2021 · Sexual medicine · Free full text on PubMed Central
Dyspareunia has been called the neglected symptom of endometriosis and is underexplored in clinical and research contexts. Understanding the physical experience and patient-important aspects of endometriosis-associated sexual pain can help advance valid measurement of this symptom. The goal of this research was to characterize the physical experience of endometriosis-associated dyspareunia in the words of people affected by this condition. This was a qualitative descriptive study that included participants with current or previous endometriosis-associated dyspareunia recruited from a data registry. Data collection involved semistructured interviews that began with an open-ended question about dyspareunia followed by prompts related to the nature of sexual pain. Interviews transcripts were subjected to qualitative content analysis using a priori (pain site, onset, character, radiation, associations, time course, and exacerbating/relieving factors) and emergent themes. A total of 17 participants completed interviews. Mean participant age was 33.3 years and most were identified as white, college-educated, heterosexual, and partnered. Location, onset, and character were important; interrelated features of endometriosis-associated dyspareunia were: (i) introital pain began with initial penetration and had pulling, burning, and stinging qualities and (ii) pelvic pain was experienced with deep penetration or in certain positions and was described as sharp, stabbing, and cramping. Dyspareunia ranged from mild to severe, had a marked psychosocial impact for some participants, and was managed using a variety of treatments and strategies. The endometriosis-associated dyspareunia experienced by participants was heterogenous in presentation, severity, and impact. Our findings have implications for the development of valid patient-reported outcome measures of this symptom. Wahl KJ, Imtiaz S, Lisonek M, et al. Dyspareunia in Their Own Words: A Qualitative Description of Endometriosis-Associated Sexual Pain. Sex Med 2021;9:100274.
Sexual Health › Sexual Pain › Dyspareunia · General Gynecology › Pelvic Pain › Chronic Pelvic Pain · Research Methods › Evidence Synthesis › Systematic Reviews
Elizabeth Cook, Amanda Yunker, Rachel Lane Walden, Ella Barrett-Chan, Hargun Dhillon, Avonae Gentles, Mahfuza Sreya, William Zhu, Sawsan As-Sanie
Liz Cook, Beth Cook, Betsy Cook, E Cook, A Yunker, R Walden, E Barrett-Chan, H Dhillon, A Gentles, M Sreya, Bill Zhu, Will Zhu, Billy Zhu, W Zhu, S As-Sanie
PMID 40846214 40846214 DOI 10.1016/j.jmig.2025.07.018 10.1016/j.jmig.2025.07.018 Cook et al. 2026, Cook 2026