Sexual Health · Sexual Pain
Abstract
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.
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Executive Summary of the Vulvodynia Therapeutic Research Summit
Krapf JM et al., 2026 · Obstetrics and gynecology
The current treatment of provoked vestibulodynia involving neuroproliferation is often complete vestibulectomy; however, less invasive treatments are biologically plausible, yet lack study. The International Society for the Study of Women's Sexual Health, the National Vulvodynia Association, the Gynecologic Cancers Research Foundation, and Tight Lipped, a grassroots nonprofit organization that supports people with chronic vulvovaginal and pelvic pain, collectively sponsored a conference, the Vulvodynia Therapeutic Research Summit, held in April 2024. The primary objective of the Vulvodynia Therapeutic Research Summit was to identify options for further research of the treatment of provoked vestibulodynia through expert consensus. After the conference, attendees scored the presented therapeutics in rank order, leading to a hierarchy of merit. Fifteen therapeutic options were presented and ranked in order of most promising to least promising for further study on treating the neuroinflammation of provoked vestibulodynia. The top identified therapeutics for further research were: 1) ketotifen fumarate (mast cell stabilizer with potential to prevent mast cell activation), 2) resiniferatoxin (transient receptor vanilloid 1 agonist causing chemo-inactivation of nerve terminals), 3) specialized pro-resolving mediators or strategies to boost their levels (eg, maresin 1 and 1-trifluoromethoxy-phenyl-3-[1-propionylpiperidin-4-yl] urea), 4) luteolin (flavonoid with potent anti-inflammatory, antioxidant, and neuroprotective properties), 5) alpha-lipoic acid (antioxidant with nerve-specific anti-inflammatory and mast cell stabilizing qualities), and 6) NGFR121W -SNAP IR700 trimer exposed to near-infared light (photoablation targeting nociceptors and sparing surrounding tissue). This executive summary describes the rationale for identifying specific pharmacologic agents and medical devices as targets for research directed toward treatment of the neuroinflammatory process found in the vestibular mucosa of provoked vestibulodynia.
Negative Sliding Sign during Dynamic Ultrasonography Predicts Low Endometriosis Fertility Index at Laparoscopy
Alfaraj S et al., 2021 · Journal of minimally invasive gynecology
Endometriosis fertility index (EFI) is a robust tool to predict the pregnancy rate in patients with endometriosis who are attempting non-in vitro fertilization conception. However, EFI calculation requires laparoscopy. Newly established imaging techniques such as sliding sign, which is used to diagnose pouch of Douglas obliteration, could provide a promising alternative. The objective of this study was to investigate the practicality of using ultrasound data to predict a low EFI (score ≤6). Observational study from a prospective registry (Endometriosis Pelvic Pain Interdisciplinary Cohort, clinicaltrials.gov #NCT02911090). Analyzed data were captured from December 2013 to June 2017. Tertiary referral center at British Columbia Women's Hospital. We analyzed data for 2583 participants from the Endometriosis Pelvic Pain Interdisciplinary Cohort. In this cross-sectional study, we included 86 women aged <40 years. Dynamic ultrasonography for the sliding sign testing and EFI calculation during laparoscopic surgery. Logistic regression was used to obtain receiver operating characteristic area under the curve (AUC) for the prediction models. Significance was p <.05. Patients with a negative sliding sign were older and had severe endometriosis and longer duration of infertility. Patients with a negative sliding sign had significantly lower total EFI scores and lower surgical factors scores than patients with a positive sliding sign. Logistic regression showed that a negative sliding sign and EFI historic factors score can predict an EFI score ≤6 (sensitivity = 87.9%, specificity = 81.1%, AUC = 0.93 [95% confidence interval, 0.88-0.98]). Adding the diagnosis of endometrioma to the previous prediction model resulted in AUC = 0.95 (95% confidence interval, 0.90-0.995), sensitivity = 84.8%, and specificity = 92.5%. The sliding sign could be a potential alternative to the EFI surgical factors, and it could be used in combination with EFI historic factors and the diagnosis of endometrioma to predict an EFI score ≤6 for patients who are not scheduled for immediate surgery.
Deep Dyspareunia in Endometriosis: Role of the Bladder and Pelvic Floor
Orr NL et al., 2018 · The journal of sexual medicine
The etiology of endometriosis-associated deep dyspareunia may include direct endometriosis-specific factors (eg, stage or invasiveness of disease) and/or indirect contributors such as bladder/pelvic floor dysfunction (eg, related to myofascial mechanisms or nervous system sensitization). This study aimed to determine whether bladder/pelvic floor tenderness and painful bladder syndrome were associated with severity of deep dyspareunia in women with endometriosis, regardless of Stage (I/II vs III/IV) or other endometriosis-specific factors. Observational study from a prospective patient registry (January 2014 to December 2016) at a tertiary centre for endometriosis. Included were women aged 18 to 49 years who had surgical removal and histopathologic confirmation of endometriosis at the centre. Cases with Stage I/II vs Stage III/IV endometriosis were analyzed separately. Bivariate associations with the primary outcome (severity of deep dyspareunia) were tested for bladder/pelvic floor tenderness, painful bladder syndrome, as well as endometriosis-specific factors identified at the time of laparoscopic surgery (eg, deep infiltrating endometriosis) and demographic factors (eg, age). Multivariable ordinal logistic regression was carried out to adjust for factors associated with the primary outcome. Primary outcome was severity of deep dyspareunia on an 11-point numeric rating scale, categorized as none/mild (0-3), moderate (4-6), and severe (7-10), from a preoperative self-reported questionnaire. Overall, 411 women had surgically confirmed endometriosis: 263 had Stage I/II and 148 had Stage III/IV endometriosis. Among women with Stage I/II endometriosis, severity of deep dyspareunia was associated with both bladder/pelvic floor tenderness and painful bladder syndrome (AOR = 1.94, 95% CI: 1.11-3.38, P = .019 and AOR = 1.99, 95% CI: 1.15-3.44, P = .013, respectively), independent of endometriosis-specific factors or other factors associated with deep dyspareunia severity. Similar associations were found in women with Stage III/IV endometriosis (bladder/pelvic floor tenderness AOR =2.51, 95% CI: 1.25-5.02, P = .01, painful bladder syndrome: AOR = 1.90, 95% CI: 1.01-3.57, P = .048). Myofascial or nervous system mechanisms may be important for deep dyspareunia in women with endometriosis, even in those with moderate-to-severe disease (Stage III/IV). Strengths include the prospective registry, and histological confirmation of endometriosis and staging by experienced endometriosis surgeons. Limitations include assessment of only one pelvic floor muscle (levator ani). In women with Stage I/II or Stage III/IV endometriosis, severity of deep dyspareunia was strongly associated with bladder/pelvic floor tenderness and painful bladder syndrome, independent of endometriosis-specific factors, which suggests the role of myofascial or sensitization pain mechanisms in some women with deep dyspareunia. Orr NL, Noga H, Williams C, et al. Deep Dyspareunia in Endometriosis: Role of the Bladder and Pelvic Floor. J Sex Med 2018;15:1158-1166.
Clinical predictors of endometriosis in the infertility population: is there a better way to determine who needs a laparoscopy?
Whitehill K et al., 2012 · Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
Endometriosis is a known contributor to infertility, but the gold standard for its diagnosis is surgical. Therefore, it is important for clinicians to be able to predict which women with infertility are at high risk for endometriosis and thus should be offered laparoscopy. We sought to identify the clinical predictors of endometriosis in the infertility population. We conducted a retrospective review of patients at an academic infertility centre. The primary outcome was identification of endometriosis at laparoscopy, and we used logistic regression to test clinical variables for their ability to predict endometriosis. Primary infertility, dysmenorrhea, and uterosacral/cul-de-sac nodularity were significant independent predictors of finding endometriosis at laparoscopy. Other clinical variables (including hysterosalpingogram findings) were not independent predictors of endometriosis, and physicians with an endometriosis-focused practice were more likely to diagnose endometriosis at laparoscopy. Key predictors of endometriosis in the infertility population are primary infertility, dysmenorrhea, and uterosacral/cul-de-sac nodularity. These results will be used to develop and validate a formal clinical prediction model for endometriosis in infertile women.
Related research
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.
Deep Dyspareunia and Sexual Quality of Life in Women With Endometriosis
Shum LK et al., 2018 · Sexual medicine · Free full text on PubMed Central
Deep dyspareunia occurs in half of women with endometriosis, a condition present in 10% of reproductive-age women and associated with negative effects on sexual quality of life (SQoL). However, women with endometriosis can have other clinical factors (eg, superficial dyspareunia, other pelvic pains, and psychological or pain conditions) possibly affecting SQoL. To determine whether deep dyspareunia is associated with SQoL in women with endometriosis, independent of potential confounders. This study involved a prospective patient registry of women at a tertiary-level referral center for endometriosis and pelvic pain. Inclusion criteria were (i) referrals to the center recruited into the registry from January 2014 through December 2016 and (ii) subsequent surgery at the center with histologic confirmation of endometriosis. Exclusion criteria included menopausal status, age at least 50 years, never sexually active, or did not answer dyspareunia or SQoL questions. Bi-variable tests and multiple linear regression analysis were performed. SQoL measured by the 5-item sexual intercourse subscale of the Endometriosis Health Profile-30 (EHP-30) modular questionnaire (0-100%, with higher scores indicating worse SQoL). Consent rate for the prospective registry was 87%; 277 women met the study criteria (mean age = 34.2 ± 7.1 years). Most women had stage I to II endometriosis at time of surgery (64%), with the remaining having stage III to IV endometriosis. Through regression analysis, worse SQoL (higher EHP-30 sexual intercourse subscale score) was independently associated with: more severe deep dyspareunia (P < .0001), more severe superficial dyspareunia (P < .0001), increased depression (P < .001), higher pain catastrophizing (P = .04), bladder pain syndrome (P = .02), heterosexual orientation (P < .001), and new referral status (P = .02). In women with endometriosis at a tertiary referral center, more severe deep dyspareunia was associated with worse SQoL, independent of superficial dyspareunia, psychological comorbidities, and other potential confounders. Shum LK, Bedaiwy MA, Allaire C, et al. Deep Dyspareunia and Sexual Quality of Life in Women With Endometriosis. Sex Med 2018;6:224-233.
Anatomic Sites and Associated Clinical Factors for Deep Dyspareunia
Yong PJ et al., 2017 · Sexual medicine · Free full text on PubMed Central
Deep dyspareunia negatively affects women's sexual function. There is a known association between deep dyspareunia and endometriosis of the cul-de-sac or uterosacral ligaments in reproductive-age women; however, other factors are less clear in this population. To identify anatomic sites and associated clinical factors for deep dyspareunia in reproductive-age women at a referral center. This study involved the analysis of cross-sectional baseline data from a prospective database of 548 women (87% consent rate) recruited from December 2013 through April 2015 at a tertiary referral center for endometriosis and/or pelvic pain. Exclusion criteria included menopausal status, age at least 50 years, previous hysterectomy or oophorectomy, and not sexually active. We performed a standardized endovaginal ultrasound-assisted pelvic examination to palpate anatomic structures for tenderness and reproduce deep dyspareunia. Multivariable regression was used to determine which tender anatomic structures were independently associated with deep dyspareunia severity and to identify clinical factors independently associated with each tender anatomic site. Severity of deep dyspareunia on a numeric pain rating scale of 0 to 10. Severity of deep dyspareunia (scale = 0-10) was independently associated with tenderness of the bladder (b = 0.88, P = .018), pelvic floor (levator ani) (b = 0.66, P = .038), cervix and uterus (b = 0.88, P = .008), and cul-de-sac or uterosacral ligaments (b = 1.39, P < .001), but not with the adnexa (b = -0.16, P = 0.87). The number of tender anatomic sites was significantly correlated with more severe deep dyspareunia (Spearman r = 0.34, P < .001). For associated clinical factors, greater depression symptom severity was specifically associated with tenderness of the bladder (b = 1.05, P = .008) and pelvic floor (b = 1.07, P < .001). A history of miscarriage was specifically associated with tenderness of the cervix and uterus (b = 2.24, P = .001). Endometriosis was specifically associated with tenderness of the cul-de-sac or uterosacral ligaments (b = 3.54, P < .001). In reproductive-age women at a tertiary referral center, deep dyspareunia was independently associated not only with tenderness of the cul-de-sac and uterosacral ligaments but also with tenderness of the bladder, pelvic floor, and cervix and uterus. Yong PJ, Williams C, Yosef A, et al. Anatomic Sites and Associated Clinical Factors for Deep Dyspareunia. Sex Med 2017;5:e184-e195.
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.