Sleep disorders in patients with endometriosis; a cross-sectional study.

BACKGROUND: Endometriosis affects 10-15% of women of reproductive age and is considered a critical gynecological problem. Endometriosis causes pain and infertility, both of which can impair the patient's quality of life. Sleep disorders account for the most bothersome presentation of impaired quality of life. This study investigated the frequency and severity of sleep disorders in women with endometriosis. METHODS: In this analytical cross-sectional study, 665 women referred to three hospitals in Tehran, Rasool-e-Akram, Pars, and Nikan, were included (463 patients with endometriosis and 202 women without endometriosis). All of them were informed about the study design and the aim of the research, and then they were asked to sign the consent form and complete the Pittsburgh Sleep Quality Index (PSQI). After data gathering and entering, they were analyzed by SPSS version 22 and were considered significant with P < 0.05. RESULTS: The study population's mean age was 35.4 ± 7.9 years. The mean global PSQI score in the case group (endometriosis patients) was higher than in the control group (non-endometriosis patients) (10.6 vs. 7.1; P < 0.001). Patients with dyspareunia, dysuria, pelvic pain, and dyschezia had a significantly higher PSQI score (P < 0.05). CONCLUSION: According to the findings of the present study, the sleep quality in endometriosis patients is low, and there is a need to pay greater attention to these patients. This may result in some changes in the therapeutic strategies for this disease.

Female Sexual Health: Screening and Evaluation.

Female sexual dysfunction is highly prevalent, affecting 30% to 50% of cisgender women globally. Low sexual desire, sexual arousal disorder, and orgasm disorder affect 10% to 20%, 6% to 20%, and 4% to 14% of women, respectively. Dyspareunia or pain with intercourse affects 8% to 22% of women. Universal screening is recommended; and a thorough medical history and physical examination are the foundations of evaluation and assessment. Laboratory tests and imaging are sometimes warranted, but referral to a sexual medicine expert is suggested if the practitioner is unfamiliar or uncomfortable with treatment.

Comparison of promestriene with vaginal fractional CO2 laser and radiofrequency treatments of genitourinary syndrome of menopause.

OBJECTIVE: To compare the effects of fractional CO2 laser and microablative fractional radiofrequency treatment with promestriene topical estrogen on sexual function and genitourinary syndrome of menopause symptoms. METHODS: This was a prospective randomized open-label clinical trial conducted with 62 postmenopausal women assigned to three intervention groups: a) topical promestriene for 90 days (n = 17); b) fractional CO2 laser treatment (n = 24); and c) microablative fractional radiofrequency treatment (n = 21). Each of the latter two groups underwent three treatment sessions at 4-week intervals. At baseline and at the end of the study, all participants had a gynecological examination that included vaginal pH measurement, and the completion of the Vaginal Symptom Score, the Vaginal Health Index, and the Female Sexual Function Index. For the energy treatment groups, adverse effects were evaluated after each session. Group homogeneity was assessed at baseline, and results were evaluated over time (from baseline to the end of treatment) and between groups over time. RESULTS: All baseline parameters were similar among studied groups. At the end of the study, all 3 treatments had produced similar effects: a reduction of vaginal pH, and an improvement of vulvovaginal symptoms (Vaginal Symptom Score and Vaginal Health Index scores) as well as sexual function (higher total Female Sexual Function Index scores, and in the desire, arousal, lubrication and pain domain scores), with no differences observed between groups. Side-effects were slight for both energy treatment groups, mainly represented by vaginal discharge. CONCLUSION: The present study suggests that the two energy treatments were efficient along with promestriene at improving postmenopausal genitourinary and sexuality symptoms. Clinical trial identification numberNCT04717245.

Comparative study of postpartum sexual function: Second-degree tears versus episiotomy outcomes.

PURPOSE: The effects of episiotomy and second-degree tears on postpartum sexual function are key areas of enquiry in women's health research. Episiotomy and second-degree tears are common procedures and injuries that occur during childbirth. Understanding their impact on post-childbirth sexuality is crucial to women's overall well-being. This study aimed to examine the relationship between episiotomy, second-degree tears, and post childbirth sexuality. METHODS: A cross-sectional design was employed, including 83 women who gave birth to Cáceres in 2017. Participants were evaluated based on sociodemographic and sexual health factors. RESULTS: No significant differences were found in dyspareunia or sexual function between women who underwent episiotomies and those with second-degree tears. However, women who underwent episiotomies waited longer before resuming sexual activity after childbirth. Factors such as age, number of previous births, employment status, educational level, and breastfeeding status affected the timing and frequency of postpartum sexual activity. CONCLUSION: Dyspareunia negatively affects various aspects of sexual function. When comparing episiotomy and second-degree tears, their impacts on postpartum sexual function were similar. However, episiotomy delays the resumption of sexual activity. Sociodemographic factors significantly influence postpartum sexual health. These findings highlight the importance of individualised interventions and support for new mothers during the postpartum period to address potential sexual health concerns.

An effective non-hormonal option with high tolerability for mild to moderate symptoms of vaginal dryness associated with menopause.

OBJECTIVES: The efficacy and tolerability of a non-hormonal pessary (that forms an oil-in-water emollient with the vaginal fluid) were assessed for the treatment of symptoms of vaginal dryness associated with menopause. STUDY DESIGN: Seventy-nine postmenopausal women (mean age 60.8 ± 6.5 years) with mild to moderate symptoms of vaginal dryness (including dyspareunia) were enrolled in this open-label, prospective, post-market clinical follow-up trial, conducted in 2022 by one research center in Germany. The investigational pessary was applied for the first 7 days once daily and the subsequent 31 days twice a week, at bedtime. A treatment-free period of 6 days completed the trial. MAIN OUTCOME MEASURES: During the trial, participants filled out questionnaires that enabled the calculation of a total severity score for subjective symptoms of atrophy-related vaginal dryness and impairment of daily as well as sexual life. Furthermore, vaginal health index and safety were studied. RESULTS: A rapid and significant reduction in the severity scores for symptoms was observed over the 38-day course of treatment and beyond. Quality of life assessed by DIVA (day-to-day impact of vaginal aging) questionnaire, dyspareunia and vaginal health index also clearly improved. The tolerability was mainly rated as "good to very good" by the investigator and 94.9 % of participants. The vast majority were very satisfied with the simple and pleasant handling. No serious adverse events occurred. CONCLUSION: Overall, the presented data suggest that the investigated non-hormonal pessary is an effective and well tolerated treatment option for vaginal symptoms associated with dryness, thus improving quality of life for women, even those who are sexually active. CLINICALTRIALS: gov identifier NCT05211505.

Is there a role for platelet rich plasma injection in vulvar lichen sclerosus? A self-controlled pilot study.

BACKGROUND: Owing to the evidence that as many as 30-40% of patients with vulvar lichen sclerosus (VLS) fail to report a remission of symptoms with first-line corticosteroid treatment (TCS), especially as what regards dyspareunia, we aimed to analyze patients' satisfaction following vulvar injection of autologous platelet-rich plasma (PRP). This is intended as an adjunctive treatment, to be used following TCS, and appears to promote tissue repair. It may also possibly have immunomodulatory proprieties. MATERIALS AND METHODS: Patients with VLS were considered eligible for this pilot study if, despite having been treated with a 3-month TCS regimen, they reported a persistence of symptoms. PRP was produced in a referral center using a manual method and a standardized protocol. Each patient received three treatments 4 to 6 weeks apart. RESULTS: A total of 50 patients with a median age of 53 years [IQR 38-59 years] were included in the study. 6 months after the last injection of PRP all patients were either satisfied or very satisfied with the treatment (100%; 95% CI 93-100%). Median NRS scores for itching, burning, dyspareunia and dysuria were significantly reduced (p < 0.05) and FSFI, HADS and SF-12 questionnaires revealed a significant improvement in sexual function, psychological wellbeing and quality of life (p < 0.05). The number of patients reporting the need for maintenance TCS treatment was reduced by 42% (p < 0.001) and an improvement in vulvar elasticity and color was reported in all patients. CONCLUSION: Following standard medical therapy, PRP may be effective not only in improving symptoms, but also in restoring function.

Efficacy of in-office lysis of clitoral adhesions with excision of keratin pearls on clitoral pain and sexual function: a pre-post interventional study.

BACKGROUND: Keratin pearls are foci of central keratinization within concentric layers of squamous cells that can form under the clitoral prepuce and cause pain (clitorodynia); in-office removal of keratin pearls may reduce clitoral pain and improve sexual function. AIM: This study aims to investigate clitoral pain and sexual function in women with partial clitoral phimosis and keratin pearls before and after in-office lysis of clitoral adhesions with keratin pearl excision (LCA-KPE). METHODS: A pre-post interventional study evaluated patients who underwent LCA-KPE between January 2017 and February 2023 in 2 metropolitan gynecology clinics specializing in vulvar pain. Patients presenting with keratin pearls and partial clitoral phimosis identified through retrospective chart review were asked to complete postprocedure questionnaires and provide subjective responses on clitoral discomfort, sexual function, sexual distress, and their experience with in-office LCA-KPE. Bivariate analyses with paired t tests were conducted to determine the effect of LCA-KPE. Qualitative data were analyzed with thematic coding. OUTCOMES: An 11-point pain visual analog scale was utilized to determine pre- and postprocedure clitoral discomfort and difficulty with orgasm. Female sexual dysfunction was measured with the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised. RESULTS: A total of 32 of 74 patients who met inclusion criteria completed postprocedure surveys (43% response rate). Mean clitoral pain for respondents was 6.91 at baseline and 2.50 after LCA-KPE (P < .001). Mean difficulty with orgasm was significantly decreased from 5.45 at baseline to 3.13 after LCA-KPE (P < .001). Participants had a mean FSFI total score of 17.68 after treatment compared with a mean total baseline FSFI of 12.12 (P = .017). The mean FSFI score for pain was 2.43 at follow-up compared with 1.37 at baseline (P = .049). There was no significant difference in the mean Female Sexual Distress Scale-Revised score before vs after the procedure (P = .27). Qualitative themes described the procedure as painful but worthwhile, with 77% of participants reporting the overall experience as positive. Recurrence rate overall was 28%, with a median of 2 repeat procedures. CLINICAL IMPLICATIONS: Recognizing keratin pearls as a structural cause of clitoral pain and offering in-office treatment is an important tool in addressing clitorodynia and improving sexual function. STRENGTHS AND LIMITATIONS: This is the largest study to date documenting the occurrence, identifying associated pain conditions, and evaluating procedural outcomes for clitoral keratin pearls. This study was limited by a relatively small sample size. CONCLUSION: In-office LCA-KPE significantly reduced clitoral discomfort and difficulty with orgasm.

Postmenopausal endometriosis: a challenging condition beyond menopause.

IMPORTANCE AND OBJECTIVE: Postmenopausal endometriosis is a complex condition that challenges the conventional belief that endometriosis resolves with menopause. Despite the cessation of menstruation, a subset of women continues to experience or develop endometriosis-related symptoms during the postmenopausal period. Thus, this review aimed to shed light on postmenopausal endometriosis, exploring its clinical features, diagnostic considerations, management approaches, and the potential impact on women's health. METHODS: PubMed/Medline, Scopus, and Web of Science databases were used for the research, with only articles in English language, using the following terms: "postmenopausal endometriosis," "menopause," "management," "treatment," and "quality of life," from inception to 2023. DISCUSSION AND CONCLUSION: The clinical features of postmenopausal endometriosis include persistent or recurrent pelvic pain, dyspareunia, bowel, or urinary symptoms and, occasionally, abnormal vaginal bleeding. The absence of menstrual cycles presents a diagnostic challenge, as the traditional diagnostic criteria for endometriosis rely on menstrual patterns. Visual cues may be less evident, and the symptoms often overlap with other gynecological conditions, necessitating a thorough evaluation to differentiate postmenopausal endometriosis from other potential causes. Management approaches for postmenopausal endometriosis encompass surgical intervention, hormonal therapies, pain management, and individualized care. Postmenopausal endometriosis significantly impacts the quality of life, sexual health, and long-term well-being of women. Understanding the clinical features, diagnostic challenges, and management approaches of postmenopausal endometriosis is crucial for healthcare professionals to provide effective care and to improve the quality of life of women affected by this condition.

A Comprehensive Evaluation of Sexual Life in Women After Laparoscopic Sacrocolpopexy using PISQ-IR.

INTRODUCTION AND HYPOTHESIS: Although laparoscopic sacrocolpopexy is a recommended procedure for sexually active women, its full impact on sexual life remains underexplored. This study is aimed at comprehensively assessing changes in the quality of sexual life and the prevalence of dyspareunia in women 1 year after laparoscopic sacrocolpopexy. METHODS: This prospective observational study enrolled women undergoing laparoscopic sacrocolpopexy for pelvic organ prolapse stage≥ 2. Included were women with a completed Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA Revised (PISQ-IR) questionnaire before and at 1 year after surgery. Individual domains of the PISQ-IR were compared separately. Dyspareunia, single summary PISQ-IR and PISQ-12 scores were additionally compared in sexually active women. Statistical analyses included paired signed rank, Wilcoxon, Median, Chi-squared, and Fisher tests (p < 0.05). RESULTS: Between February 2015 and December 2019, a total of 333 women were included. Mean age was 61.0 ± 11.2 and 141 (42%) reported being sexually active at baseline. At 12 months postoperatively, sexual activity was preserved in 110 (78%) of these women and an additional 26 women (14%) became sexually active. Both single-summary PISQ-IR (3.4 vs 3.6, p < 0.01) and PISQ-12 (36.0 vs 38.1, p < 0.01) scores increased significantly. The only variable that was associated with deteriorated scores postoperatively was a higher BMI. Individual domain analyses revealed significant improvement in condition-specific and condition-impact domains, except for the desire domain, which deteriorated. Prevalence of dyspareunia decreased post-surgery from 21.8% to 16.4%, p < 0.05. Newly sexually active women were older, had shorter vaginal length preoperatively, but lower PISQ-IR scores postoperatively than sexually inactive women pre- and postoperatively. Women ceasing sexual activity were older and had lower preoperative PISQ-IR scores than sexually active women pre- and postoperatively. CONCLUSIONS: Although the overall rate of sexually active women and sexual desire declined 12 months after sacrocolpopexy, overall sexual function scores improved and the prevalence of dyspareunia decreased.

Correlation Between Surgical Phenotype and Pain Improvement After Endometriosis Surgery.

STUDY OBJECTIVE: To examine pain improvement after endometriosis surgery and whether it can be predicted by the observed surgical phenotype. DESIGN: Prospective longitudinal survey study. SETTING: A University hospital. PATIENTS: A total of 125 patients completed a preoperative questionnaire (response rate: n = 227 of 277, 81.9%), had surgically confirmed endometriosis (n = 202 of 227), and returned a second postoperative questionnaire (response rate: n = 125 of 202, 61.9%). INTERVENTIONS: All patients underwent complete laparoscopic removal of the endometriotic lesions. Surgical phenotype was classified according to the rASRM and #Enzian classification. MEASUREMENTS AND MAIN RESULTS: The intensity of 5 specific pain symptoms was questioned by postal paper-pencil questionnaires with a numerical rating scale (0-10) both preoperatively (3.01 ± 2.72 months before surgery) and one year after surgery (12.62 ± 1.59 months). A postoperative pain improvement score was computed (postoperative pain-preoperative pain) for each specific pain symptom (0-10) and for the overall/global pain sum score (0-50). The mean intensity of all pain scores was lower postoperatively as compared with preoperatively (p <.0001). A statistically significant weak correlation was observed between the surgical phenotype "rectovaginal endometriosis" and postoperative improvement of dyspareunia (r = .265; p = .003). The other 11 hypothesized correlations between surgical phenotype and postoperative improvement of pain intensity failed to reach statistical significance. CONCLUSION: Clinicians can inform patients that surgery is effective in reducing endometriosis-related pain symptoms and the overall/global pain scores at 12 months postoperatively. From our data, we can conclude that patients with rectovaginal endometriosis might benefit the most from the reduction of their sexual pain. On the basis of these results, we could suggest that deep dyspareunia (even if present as an isolated symptom) might be a valid indication for surgery. Further research could explore the association between a certain surgical phenotype and more detailed assessments of sexual functioning, as well as explore whether feedback from the surgeon on expected pain improvement affects patient-reported outcomes.

Clinical assessment and management of vaginismus.

BACKGROUND: Vaginismus is one of the leading causes of painful sex (dyspareunia) for women. General practitioners (GPs) play a vital role in diagnosing and treating vaginismus, as well as coordinating a multidisciplinary team to support people with vaginismus. OBJECTIVE: The aim of this article is to summarise what is currently known about vaginismus, including its aetiology and contributing factors, how a diagnosis can be made, the implications of vaginismus on primary care clinical practice and the available treatment options for people with vaginismus. The article focuses on treating vaginismus exclusively, where other possible medical causes or comorbidities have been examined and excluded (eg vulvodynia). DISCUSSION: GPs play a vital role in helping people recover from vaginismus through validating people's experiences, making an accurate diagnosis and making referrals to other relevant health professionals. GPs can also offer a range of treatment options for people with vaginismus. While the management of vaginismus can be time-consuming and take some trial and error, multidisciplinary care with multimodal therapy often results in positive patient outcomes.

The quality, suitability, and readability of web-based resources on endometriosis-associated dyspareunia: A systematic review.

People commonly and increasingly rely on the internet to search for health information, including those related to endometriosis-associated dyspareunia. Yet the content of such websites may be of variable accuracy and quality. This review aims to evaluate the quality, readability, and suitability of web-based resources on endometriosis-associated dyspareunia for patients. We searched 3 databases - Google, Bing, and Yahoo - to identify websites related to endometriosis-associated dyspareunia. Two independent reviewers screened the search results against inclusion and exclusion criteria. Another set of two reviewers evaluated the selected websites using validated measurement instruments. Out of 450 websites, 21 met the inclusion criteria and were evaluated. More than half of the websites had information on content updates, reported on authorship, or disclosed sponsorship information. The mean quality and suitability scores were 47.5 (SD = 13.3) and 65.2 (SD = 13.6) respectively, thus suggesting generally adequate quality and suitability levels. However, the mean readability scores exceeded the recommended level for health-related websites. The poor readability of the websites might limit accessibility for a significant proportion of patients with low educational levels. The findings of this review have implications for designing high-quality, readable and up-to-date web interventions for people who rely on web platforms as an alternative or complementary source of health information on dyspareunia.

Genital chronic graft-versus-host disease: an unmet need that requires trained gynecologists.

OBJECTIVE: Menopause and chronic graft-versus-host disease (cGvHD) are the leading causes of morbidity after allogeneic hematopoietic stem cell transplantation (alloHSCT). Genitalia are one of the target organs of cGvHD causing sexual dysfunction and local symptoms, which may impair women's quality of life. The aim of this study is to describe the prevalence and clinical characteristics of genital cGvHD. METHODS: A retrospective cross-sectional observational study was performed including 85 women with alloHSCT. All women were diagnosed and counseled by a trained gynecologist. Health-related quality of life was assessed by the Cervantes Short-Form Scale and sexual function was evaluated by the Female Sexual Function Index. RESULTS: Seventeen women (20%) included in the study were diagnosed with genital cGvHD. The main complaints were vulvovaginal dryness (42.2%) and dyspareunia (29.4%), the presence of erythema/erythematous plaques (52.9%) being the most frequent sign. Median time from transplant to diagnosis of genital cGvHD was 17 months among those with mild involvement, 25 months for moderate and 42 months for severe forms. Mortality was 29.4% in patients who developed cGvHD with genital involvement versus 8.8% among those without (p = 0.012). CONCLUSION: Early gynecological evaluation might allow to identify patients with mild forms of genital cGvHD, potentially enabling better management and improved outcomes.

Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study.

STUDY QUESTION: What is the efficacy and safety of long-term treatment (up to 2 years) with relugolix combination therapy (CT) in women with moderate to severe endometriosis-associated pain? SUMMARY ANSWER: For up to 2 years, treatment with relugolix CT improved menstrual and non-menstrual pain, dyspareunia, and function in women with endometriosis; after an initial decline of <1%, the mean bone mineral density (BMD) remained stable with continued treatment. WHAT IS KNOWN ALREADY: Endometriosis is a chronic condition characterized by symptoms of dysmenorrhea, non-menstrual pelvic pain (NMPP), and dyspareunia, which have a substantial impact on the lives of affected women, their partners, and families. SPIRIT 1 and 2 were phase 3, randomized, double-blind, placebo-controlled studies of once-daily relugolix CT (relugolix 40 mg, oestradiol 1 mg, norethisterone acetate 0.5 mg) in premenopausal women (age 18-50 years) with endometriosis and moderate-to-severe dysmenorrhea and NMPP. These trials demonstrated a significant improvement of dysmenorrhea, NMPP, and dyspareunia in women treated with relugolix CT, with minimal decline (<1%) in BMD versus placebo at 24 weeks. STUDY DESIGN, SIZE, DURATION: Patients participating in this open-label, single-arm, long-term extension (LTE) study of the 24-week SPIRIT pivotal studies (SPIRIT 1 and 2) received up to an additional 80 weeks of once-daily oral relugolix CT treatment between May 2018 and January 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Premenopausal women with confirmed endometriosis and moderate to severe dysmenorrhea and NMPP who completed the 24-week pivotal studies (SPIRIT 1 and 2 trials; Giudice et al., 2022) and who met all entry criteria were eligible to enrol. Two-year results were analysed by treatment group based on original randomization in pivotal studies: relugolix CT, delayed relugolix CT (relugolix 40 mg monotherapy for 12 weeks, followed by relugolix CT), or placebo→relugolix CT (placebo for 24 weeks followed by relugolix CT). The primary endpoints of the LTE study were the proportion of dysmenorrhea and NMPP responders at Week 52 and Week 104/end-of-treatment (EOT). A responder was a participant who achieved a predefined, clinically meaningful reduction from baseline in Numerical Rating Scale (NRS) scores (0 = no pain, 10 = worst pain imaginable) for the specific pain type with no increase in analgesic use. The predefined clinically meaningful threshold for dysmenorrhea was 2.8 points and for NMPP was 2.1 points. Secondary efficacy endpoints included change from baseline in Endometriosis Health Profile-30 (EHP-30) pain domain scores, a measure of the effects of endometriosis-associated pain on daily activities (function), NRS scores for dysmenorrhea, NMPP, dyspareunia, and overall pelvic pain, and analgesic/opioid use. Safety endpoints included adverse events and changes in BMD. MAIN RESULTS AND THE ROLE OF CHANCE: Of 1261 randomized patients, 1044 completed the pivotal studies, 802 enrolled in the LTE, 681 completed 52 weeks of treatment, and 501 completed 104 weeks of treatment. Demographics and baseline characteristics of the extension population were consistent with those of the original randomized population. Among patients randomized to relugolix CT at pivotal study baseline who continued in the LTE (N = 277), sustained improvements in endometriosis-associated pain were demonstrated through 104 weeks. The proportion of responders at Week 104/EOT for dysmenorrhea and NMPP was 84.8% and 75.8%, respectively. Decreases in dyspareunia and improvement in function assessed by EHP-30 pain domain were also sustained over 2 years. At Week 104/EOT, 91% of patients were opioid-free and 75% of patients were analgesic-free. Relugolix CT over 104 weeks was well tolerated with a safety profile consistent with that observed over the first 24 weeks. After initial least squares mean BMD loss <1% at Week 24, BMD plateaued at Week 36 and was sustained for the duration of 104 weeks of treatment. Efficacy and safety results were generally consistent in women in the placebo→relugolix CT and delayed relugolix CT groups. LIMITATIONS, REASONS FOR CAUTION: The study was conducted as an open-label study without a control group over the 80 weeks of the extension period. Of the 802 patients who were enrolled in this LTE study, 681 patients (84.9%) and 501 patients (62.5%) of patients completed 52 and 104 weeks of treatment, respectively. In addition, there currently are no comparative data to other hormonal medications. Finally, a third (37.4%) of the study population terminated participation early. WIDER IMPLICATIONS OF THE FINDINGS: In conclusion, relugolix CT offers an additional option to help address an important unmet clinical need for effective, safe, and well-tolerated medical treatments for endometriosis that can be used longer-term, reducing the need for opioids and improving quality of life. The findings from this study may help support the care of women with endometriosis seeking longer-term effective medical management of their symptoms. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Myovant Sciences GmbH (now Sumitomo Pharma Switzerland GmbH). C.M.B. reports fees from Myovant, grants from Bayer Healthcare, fees from ObsEva, and Chair of ESHRE Endometriosis Guideline Group (all funds went to the University of Oxford); N.P.J. reports personal fees from Myovant Sciences, during the conduct of the study, personal fees from Guerbet, personal fees from Organon, personal fees from Roche Diagnostics; S.A.-S. reports personal fees from Myovant Sciences, personal fees from Bayer, personal fees from Abbvie, personal fees from UpToDate; J.S.P., and R.B.W. are employees and shareholders of Myovant Sciences; J.C.A.F. and S.J.I. are shareholders of Myovant Sciences (but at time of publicaion are no longer employess of Myovant Sciences); M.S.A. and K.W. have no conflicts to declare; V.M. is a consultant to Myovant; L.C.G. reports personal fees from Myovant Sciences, Inc and Bayer. The authors did not receive compensation for manuscript writing, review, and revision. TRIAL REGISTRATION NUMBER: NCT03654274.

Efficacy and safety of a novel pain management device, AT-04, for endometriosis-related pain: study protocol for a phase III randomized controlled trial.

BACKGROUND: Endometriosis-related pain encompassing dysmenorrhea, dyspareunia, and chronic pelvic pain, reduces the quality of life in premenopausal women. Although treatment options for endometriosis alleviate this pain, approximately one-third of women still experience pain even after receiving treatment, indicating the need for novel approaches to pain relief in those women. The Angel Touch device (AT-04) is a portable magnetic fields irradiation device that incorporates a combination of mixed alternative magnetic fields at 2 kHz and 83.3 MHz. A phase III trial confirmed the efficacy and safety of AT-02, a prototype of AT-04, for pain relief in patients with fibromyalgia. METHODS: This is a phase III, multicenter, prospective, randomized, sham device-controlled, double-blind, parallel study. The participants will be premenopausal women aged > 18 years who have endometriosis-related pain with at least moderate severity. Considering dropouts, 50 participants have been deemed appropriate. Eligible women will be centrally registered, and the data center will randomly allocate them in a 1:1 ratio to the intervention and control groups. Women in the intervention group will receive electromagnetic wave irradiation generated by AT-04 and those who in the control group will wear a sham device for 16 weeks, and both groups will wear AT-04 for another 4 weeks. The primary outcome measure is the change in the Numeric Rating Scale score at 16 weeks compared with the baseline. Secondary outcome measures are efficacy for pelvic pain including dysmenorrhea and non-menstrual pain, and chronic pelvic pain not related to menstruation, dysmenorrhea, and dyspareunia, and improvement of quality of life during the study period. Safety will be evaluated by device defects and the frequency of adverse events. The study protocol has been approved by the Clinical Study Review Board of Chiba University Hospital, Chiba, Japan, and will be conducted in accordance with the principles of the Declaration of Helsinki and the Japanese Clinical Trials Act and relevant notifications. DISCUSSION: This study aims to develop a novel method of managing endometriosis-related pain. The AT-04 is an ultralow-invasive device that can be used without inhibiting ovulation, suggesting potential benefits to women of reproductive-age. Trial registration number Japan Registry of Clinical Trials (jRCTs032230278).

Endometriosis is a chronic inflammatory disorder that negatively impacts reproductive health via endometriosis-related pain, infertility, and endometriosis-associated ovarian cancer. Although current therapeutic options for endometriosis are effective for the endometriosis-related pain, approximately one-third of women still experience pain even after receiving treatment, indicating the need for novel approaches to pain relief in those women. This is the first randomized controlled trial to investigate the efficacy and safety of a novel portable pain management device, AT-04, that incorporates a combination of mixed alternating magnetic fields, for endometriosis-related pain. This is a multicenter, prospective, sham device-controlled, double-blind, parallel study. Enrolled women will have undergone standard hormonal treatment for endometriosis at baseline, and this allows for assessing whether the device remains effective when used in conjunction with existing treatment methods. The study also will explore the impact of AT-04 on reducing the size of ovarian endometriotic cysts that reflect the activity of endometriosis. The study reflects the strong desire by physicians to liberate women from the unbearable pain associated with endometriosis. The sole efficacy of AT-04 in treating endometriosis-related pain is difficult to evaluate as there is a possibility that menstrual cycles may influence the assessment of pain and quality of life. However, the study findings regarding the effectiveness of AT-04 for the treatment of endometriosis-related pain may benefit women with endometriosis who have pain that is not effectively relieved by other treatments. Consequently, it may contribute to the improvement of reproductive health within society.

Quality of life and symptoms of pain in patients with endometriomas compared to those with other endometriosis lesions: a cross-sectional study.

BACKGROUND: Endometriomas are genetically distinct from other endometriosis lesions and could be associated with a predisposition to excessive inflammation. However, differences in clinical presentation between types of endometriosis lesions have not been fully elucidated. This study aimed to investigate the quality of life and pain scores of patients with endometriomas compared to those with other types of endometriosis lesions. METHODS: A cross-sectional observational study was conducted between January 2020 and August 2023. Patients diagnosed with endometriosis completed the Endometriosis Health Profile 30 pain subscale questionnaire for their quality of life score and rated their endometriosis-associated pain symptoms using an 11-point numerical rating scale. The data were analyzed for comparison through multivariate linear regression models. RESULTS: A total of 248 patients were included and divided into endometrioma (81, 33%) and nonendometrioma (167, 67%) groups. The mean age of the patients was 37.1 ± 7.5 years. Most participants were Canadian or North American (84%). One-third of the patients reported experiencing up to four concurrent pain symptoms. The most reported pain included deep dyspareunia (90%), chronic pelvic pain (84%) and lower back pain (81%). The mean quality of life score was 45.9 ± 25.9. We observed no difference in quality of life scores between patients with and without endometriomas. Patients with endometriomas had lower mean scores for deep dyspareunia (0.8; 95% CI [0 to 1.5]; p = 0.049) and higher mean scores for superficial dyspareunia (1.4; 95% CI [0.2 to 2.6]; p = 0.028). Comorbid infertility (p = 0.049) was a factor that modified superficial dyspareunia intensity in patients with endometriomas. CONCLUSION: In patients with endometriosis, evidence was insufficient to conclude that the presence of endometriomas was not associated with a greater or lesser quality of life, but differences in specific symptoms of dyspareunia were identified.

Sexual Dysfunction and Dyspareunia in the Setting of the Genitourinary Syndrome of Menopause.

Sexual dysfunction is a common consequence of the genitourinary syndrome of menopause (GSM). In this book chapter, we discuss the pathophysiology, prevalence, evaluation, and evidence-based management of sexual dysfunction in patients affected by GSM. Additionally, we present an algorithm to guide clinicians in the management and treatment of sexual dysfunction in this setting based on available evidence and best practices.

Searching for a "Window of Opportunity" in the Treatment of Vulvar Lichen Sclerosus: Evidence for Therapeutic Benefits of an Early Corticosteroid Treatment.

INTRODUCTION: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a "window of opportunity" exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs. METHODS: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016-2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation. RESULTS: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy. CONCLUSION: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a "window of opportunity" in VLS treatment.

Diagnosis and management of complications following pelvic organ prolapse surgery using a synthetic mesh: French national guidelines for clinical practice.

Complications associated with pelvic organ prolapse (POP) surgery using a synthetic non-absorbable mesh are uncommon (<5%) but may be severe and may hugely diminish the quality of life of some women. In drawing up these multidisciplinary clinical practice recommendations, the French National Authority for Health (Haute Autorité de santé, HAS) conducted an exhaustive review of the literature concerning the diagnosis, prevention, and management of complications associated with POP surgery using a synthetic mesh. Each recommendation for practice was allocated a grade (A,B or C; or expert opinion (EO)), which depends on the level of evidence (clinical practice guidelines). PREOPERATIVE PATIENTS' INFORMATION: Each patient must be informed concerning the risks associated with POP surgery (EO). HEMORRHAGE, HEMATOMA: Vaginal infiltration using a vasoconstrictive solution is not recommended during POP surgery by the vaginal route (grade C). The placement of vaginal packing is not recommended following POP surgery by the vaginal route (grade C). During laparoscopic sacral colpopexy, when the promontory seems highly dangerous or when severe adhesions prevent access to the anterior vertebral ligament, alternative surgical techniques should be discussed per operatively, including colpopexy by lateral mesh laparoscopic suspension, uterosacral ligament suspension, open abdominal mesh surgery, or surgery by the vaginal route (EO). BLADDER INJURY: When a bladder injury is diagnosed, bladder repair by suturing is recommended, using a slow resorption suture thread, plus monitoring of the permeability of the ureters (before and after bladder repair) when the injury is located at the level of the trigone (EO). When a bladder injury is diagnosed, after bladder repair, a prosthetic mesh (polypropylene or polyester material) can be placed between the repaired bladder and the vagina, if the quality of the suturing is good. The recommended duration of bladder catheterization following bladder repair in this context of POP mesh surgery is from 5 to 10 days (EO). URETER INJURY: After ureteral repair, it is possible to continue sacral colpopexy and place the mesh if it is located away from the ureteral repair (EO). RECTAL INJURY: Regardless of the approach, when a rectal injury occurs, a posterior mesh should not be placed between the rectum and the vagina wall (EO). Concerning the anterior mesh, it is recommended to use a macroporous monofilament polypropylene mesh (EO). A polyester mesh is not recommended in this situation (EO). VAGINAL WALL INJURY: After vaginal wall repair, an anterior or a posterior microporous polypropylene mesh can be placed, if the quality of the repair is found to be satisfactory (EO). A polyester mesh should not be used after vaginal wall repair (EO). MESH INFECTION (ABSCESS, CELLULITIS, SPONDYLODISCITIS): Regardless of the surgical approach, intravenous antibiotic prophylaxis is recommended (aminopenicillin + beta-lactamase inhibitor: 30 min before skin incision +/- repeated after 2 h if surgery lasts longer) (EO). When spondylodiscitis is diagnosed following sacral colpopexy, treatment should be discussed by a multidisciplinary group, including especially spine specialists (rheumatologists, orthopedists, neurosurgeons) and infectious disease specialists (EO). When a pelvic abscess occurs following synthetic mesh sacral colpopexy, it is recommended to carry out complete mesh removal as soon as possible, combined with collection of intraoperative bacteriological samples, drainage of the collection and targeted antibiotic therapy (EO). Non-surgical conservative management with antibiotic therapy may be an option (EO) in certain conditions (absence of signs of sepsis, macroporous monofilament polypropylene type 1 mesh, prior microbiological documentation and multidisciplinary consultation for the choice of type and duration of antibiotic therapy), associated with close monitoring of the patient. BOWEL OCCLUSION RELATED TO NON-CLOSURE OF THE PERITONEUM: Peritoneal closure is recommended after placement of a synthetic mesh by the abdominal approach (EO). URINARY RETENTION: Preoperative urodynamics is recommended in women presenting with urinary symptoms (bladder outlet obstruction symptoms, overactive bladder syndrome or incontinence) (EO). It is recommended to remove the bladder catheter at the end of the procedure or within 48 h after POP surgery (grade B). Bladder emptying and post-void residual should be checked following POP surgery, before discharge (EO). When postoperative urine retention occurs after POP surgery, it is recommended to carry out indwelling catheterization and to prefer intermittent self-catheterization (EO). POSTOPERATIVE PAIN: Before POP surgery, the patient should be asked about risk factors for prolonged and chronic postoperative pain (pain sensitization, allodynia, chronic pelvic or non-pelvic pain) (EO). Concerning the prevention of postoperative pain, it is recommended to carry out a pre-, per- and postoperative multimodal pain treatment (grade B). The use of ketamine intraoperatively is recommended for the prevention of chronic postoperative pelvic pain, especially for patients with risk factors (preoperative painful sensitization, allodynia, chronic pelvic or non-pelvic pain) (EO). Postoperative prescription of opioids should be limited in quantity and duration (grade C). When acute neuropathic pain (sciatalgia or pudendal neuralgia) resistant to level I and II analgesics occurs following sacrospinous fixation, a reintervention is recommended for suspension suture removal (EO). When chronic postoperative pain occurs after POP surgery, it is recommended to systematically seek arguments in favor of neuropathic pain with the DN4 questionnaire (EO). When chronic postoperative pelvic pain occurs after POP surgery, central sensitization should be identified since it requires a consultation in a chronic pain department (EO). Concerning myofascial pain syndrome (clinical pain condition associated with increased muscle tension caused by myofascial trigger points), when chronic postoperative pain occurs after POP surgery, it is recommended to examine the levator ani, piriformis and obturator internus muscles, so as to identify trigger points on the pathway of the synthetic mesh (EO). Pelvic floor muscle training with muscle relaxation is recommended when myofascial pain syndrome is associated with chronic postoperative pain following POP surgery (EO). After failure of pelvic floor muscle training (3 months), it is recommended to discuss surgical removal of the synthetic mesh, during a multidisciplinary discussion group meeting (EO). Partial removal of synthetic mesh is indicated when a trigger point is located on the pathway of the mesh (EO). Total removal of synthetic mesh should be discussed during a multidisciplinary discussion group meeting when diffuse (no trigger point) chronic postoperative pain occurs following POP surgery, with or without central sensitization or neuropathic pain syndromes (EO). POSTOPERATIVE DYSPAREUNIA: When de novo postoperative dyspareunia occurs after POP surgery, surgical removal of the mesh should be discussed (EO). VAGINAL MESH EXPOSURE: To reduce the risk of vaginal mesh exposure, when hysterectomy is required during sacral colpopexy, subtotal hysterectomy is recommended (grade C). When asymptomatic vaginal macroporous monofilament polypropylene mesh exposure occurs, systematic imaging is not recommended. When vaginal polyester mesh exposure occurs, pelvic +/- lumbar MRI (EO) should be used to look for an abscess or spondylodiscitis, given the greater risk of infection associated with this type of material. When asymptomatic vaginal mesh exposure of less than 1 cm2 occurs in a woman with no sexual intercourse, the patient should be offered observation (no treatment) or local estrogen therapy (EO). However, if the patient wishes, partial excision of the mesh can be offered. When asymptomatic vaginal mesh exposure of more than 1 cm2 occurs or if the woman has sexual intercourse, or if it is a polyester prosthesis, partial mesh excision, either immediately or after local estrogen therapy, should be offered (EO). When symptomatic vaginal mesh exposure occurs, but without infectious complications, surgical removal of the exposed part of the mesh by the vaginal route is recommended (EO), and not systematic complete excision of the mesh. Following sacral colpopexy, complete removal of the mesh (by laparoscopy or laparotomy) is only required in the presence of an abscess or spondylodiscitis (EO). When vaginal mesh exposure recurs after a first reoperation, the patient should be treated by an experienced team specialized in this type of complication (EO). SUTURE THREAD VAGINAL EXPOSURE: For women presenting with vaginal exposure to non-absorbable suture thread following POP surgery with mesh reinforcement, the suture thread should be removed by the vaginal route (EO). Removal of the surrounding mesh is only recommended when vaginal mesh exposure or associated abscess is diagnosed. BLADDER AND URETERAL MESH EXPOSURE: When bladder mesh exposure occurs, removal of the exposed part of the mesh is recommended (grade B). Both alternatives (total or partial mesh removal) should be discussed with the patient and should be debated during a multidisciplinary discussion group meeting (EO).

Measurement properties of sexual function assessment questionnaires in women with endometriosis: A systematic review following COSMIN guidelines.

INTRODUCTION: Sexual function of patients with endometriosis should be assessed by patient-reported outcome measures (PROMs) that present high reliability and validity. The objective was to study the PROMs used to assess sexual function for patients with endometriosis to improve their selection for research and clinical practice. MATERIAL AND METHODS: We performed a systematic literature review from January 2000 to September 2023. All studies including women with confirmed endometriosis and assessing sexual quality of life or sexual function or sexual distress were retrieved. Different properties of PROMs used for sexual dysfunction were assessed according to the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) recommendations. Properties evaluated were: structural validity, internal consistency, cross-cultural validity, reliability, measurement error, criterion validity, construct validity, and responsiveness. This literature review was registered on Prospero as 2018 CRD42018102278. RESULTS: Seventy-four articles with evaluation of sexual function were included. Of the 25 PROMs assessing sexual function, the Female Sexual Function Index (FSFI) was the most frequently used (34/74 [45.9%] items), followed by the Female Sexual Distress Scale (9/74 [12.2%] items) and the Sexual Activity Questionnaire (SAQ) (8/74 [10.8%] items). The most commonly used measurement properties were "hypothesis testing" and "responsiveness". The PROMs with a high level of evidence for these two measurement properties were the FSFI, the SAQ, the Short Sexual Functioning Scale, the Sexual Satisfaction Scale for Women, Sexual Quality of Life-Female, the Brief Profile of Female Sexual Function, and the Sexual Health Outcomes in Women Questionnaire. The FSFI questionnaire appeared to be more relevant for evaluating medical treatment, and the SAQ for evaluating surgical treatment. Only one instrument was specific to endometriosis (the Subjective Impact of Dyspareunia Inventory [SIDI]). CONCLUSIONS: In this systematic literature review of sexual function assessment questionnaires in endometriosis, the FSFI and the SAQ questionnaires emerged as having the best measurement properties according to the COSMIN criteria. The FSFI questionnaire appears to be suited for evaluating medical treatment, and the SAQ for surgical treatment. The SIDI is the only specific questionnaire, but its responsiveness remains to be defined.