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.

Towards comprehensive management of symptomatic endometriosis: beyond the dichotomy of medical versus surgical treatment.

Except when surgery is the only option because of organ damage, the presence of suspicious lesions, or the desire to conceive, women with endometriosis-associated pain often face a choice between medical and surgical treatment. In theory, the description of the potential benefits and potential harms of the two alternatives should be standardized, unbiased, and based on strong evidence, enabling the patient to make an informed decision. However, doctor's opinion, intellectual competing interests, local availability of specific services and (mis)information obtained from social media, and online support groups can influence the type of advice given and affect patients' choices. This is compounded by the paucity of robust data from randomized controlled trials, and the anxiety of distressed women who are eager to do anything to alleviate their disabling symptoms. Vulnerable patients are more likely to accept the suggestions of their healthcare provider, which can lead to unbalanced and physician-centred decisions, whether in favour of either medical or surgical treatment. In general, treatments should be symptom-orientated rather than lesion-orientated. Medical and surgical modalities appear to be similarly effective in reducing pain symptoms, with medications generally more successful for severe dysmenorrhoea and surgery more successful for severe deep dyspareunia caused by fibrotic lesions infiltrating the posterior compartment. Oestrogen-progestogen combinations and progestogen monotherapies are generally safe and well tolerated, provided there are no major contraindications. About three-quarters of patients with superficial peritoneal and ovarian endometriosis and two-thirds of those with infiltrating fibrotic lesions are ultimately satisfied with their medical treatment although the remainder may experience side effects, which may result in non-compliance. Surgery for superficial and ovarian endometriosis is usually safe. When fibrotic infiltrating lesions are present, morbidity varies greatly depending on the skill of the individual surgeon, the need for advanced procedures, such as bowel resection and ureteral reimplantation, and the availability of expert colorectal surgeons and urologists working together in a multidisciplinary approach. The generalizability of published results is adequate for medical treatment but very limited for surgery. Moreover, on the one hand, hormonal drugs induce disease remission but do not cure endometriosis, and symptom relapse is expected when the drugs are discontinued; on the other hand, the same drugs should be used after lesion excision, which also does not cure endometriosis, to prevent an overall cumulative symptom and lesion recurrence rate of 10% per postoperative year. Therefore, the real choice may not be between medical treatment and surgery, but between medical treatment alone and surgery plus postoperative medical treatment. The experience of pain in women with endometriosis is a complex phenomenon that is not exclusively based on nociception, although the role of peripheral and central sensitization is not fully understood. In addition, trauma, and especially sexual trauma, and pelvic floor disorders can cause or contribute to symptoms in many individuals with chronic pelvic pain, and healthcare providers should never take for granted that diagnosed or suspected endometriosis is always the real, or the sole, origin of the referred complaints. Alternative treatment modalities are available that can help address most of the additional causes contributing to symptoms. Pain management in women with endometriosis may be more than a choice between medical and surgical treatment and may require comprehensive care by a multidisciplinary team including psychologists, sexologists, physiotherapists, dieticians, and pain therapists. An often missing factor in successful treatment is empathy on the part of healthcare providers. Being heard and understood, receiving simple and clear explanations and honest communication about uncertainties, being invited to share medical decisions after receiving detailed and impartial information, and being reassured that a team member will be available should a major problem arise, can greatly increase trust in doctors and transform a lonely and frustrating experience into a guided and supported journey, during which coping with this chronic disease is gradually learned and eventually accepted. Within this broader scenario, patient-centred medicine is the priority, and whether or when to resort to surgery or choose the medical option remains the prerogative of each individual woman.

An evaluation of sexual function and health-related quality of life following laparoscopic surgery in individuals living with endometriosis.

STUDY QUESTION: What is the relationship between sexual function, health-related quality of life (HRQoL), and laparoscopic surgery in individuals living with endometriosis? SUMMARY ANSWER: A higher number of laparoscopic surgeries is significantly associated with poorer HRQoL and greater levels of sexual dysfunction in individuals with endometriosis. WHAT IS KNOWN ALREADY: Prior research indicates that endometriosis is associated with lowered HRQoL and sexual function and that these outcomes are influenced by endometriosis-related symptom profiles, medical, and surgical management. A limited number of studies have examined changes in sexual function in individuals with endometriosis following laparoscopic surgery or following repeated surgeries. STUDY DESIGN, SIZE, DURATION: A cross-sectional community-based online survey was used to examine the relationships between sexual function, HRQoL, and laparoscopic surgery (n = 210). PARTICIPANTS/MATERIALS, SETTING, METHODS: Individuals with a self-reported diagnosis of endometriosis were recruited via online advertising through social media and gynaecology clinics. Endometriosis-specific data (e.g. diagnostic delay, symptom experience) was collected in addition to engagement with laparoscopic surgery, level of HRQoL (EuroQol-5 Dimension: EQ-5D-5L), and sexual function (Female Sexual Function Index: FSFI). Bivariate correlational analyses and hierarchical multiple regression were used to determine the associations between the variables of interest. MAIN RESULTS AND THE ROLE OF CHANCE: Individuals with endometriosis have substantially poorer HRQoL in comparison to Australian normative samples, with greater levels of endometriosis-related symptom burden, distress, and pain significantly associated with lower levels of HRQoL. The mean FSFI score was suggestive of clinically significant female sexual dysfunction, with the lowest level of function noted in the domain of sexual pain and the highest level of function noted in the sexual satisfaction domain. A greater number of laparoscopic surgeries was significantly associated with poorer overall HRQoL and greater levels of sexual dysfunction. LIMITATIONS, REASONS FOR CAUTION: The cross-sectional nature of the data precludes direct findings of causality and further longitudinal research is recommended. The information pertaining to engagement in laparoscopic surgery was self-report in nature and was not medically verified. WIDER IMPLICATIONS OF THE FINDINGS: The study's findings highlight the pervasive impact of endometriosis on all domains of living, emphasizing the need to extend treatment planning beyond that of physical pain management alone. Early referral for assessment and management of sexual wellbeing is recommended prior to, and post-surgical intervention, with a focus on maintaining post-surgical changes, potentially reducing the need for multiple surgeries. STUDY FUNDING, COMPETING INTEREST(S): The study was not associated with research funding. Author CN reports grant funding from the Australian Government and Medical Research Future Fund (MRFF) and was a previous employee of CSL Vifor (formerly Vifor Pharma Pty Ltd). TRIAL REGISTRATION NUMBER: N/A.

Screening women in young adulthood for disabling dysmenorrhoea: a nationwide cross-sectional study from the CONSTANCES cohort.

RESEARCH QUESTION: How do different warning indicators help to identify disabling dysmenorrhoea among women in young adulthood? DESIGN: A nationwide cross-sectional study of women aged 18-25 years from the CONSTANCES cohort was constructed. Disability was assessed with the Global Activity Limitation Indicator question 'For the past 6 months, have you been limited in routine activities?Yes, severely limited/Yes, limited/ No, not limited'. Dysmenorrhoea pain intensity and other chronic pelvic pain symptoms (dyspareunia and non-menstrual pain) were evaluated according to questions from a specific questionnaire. Probability of disability was estimated using a logistic prediction model according to dysmenorrhoea intensity, other indicators of pelvic pain symptoms and other obvious covariates. The results of the predictive model of disabling dysmenorrhoea were presented on a nomogram. RESULTS: Among 6377 women, the rate of disability was estimated at 7.5%. Increased intensity of dysmenorrhoea (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.04-1.13), increased frequency of dyspareunia (from OR 1.69, 95% CI 1.33-2.14 up to OR 3.41, 95% CI 2.16-5.38) non-menstrual chronic pelvic pain (OR 1.75, 95% CI 1.40-2.19), body mass index over 25 kg/m2 (OR 1.45, 95% CI 1.17-1.80) and non-use of the hormonal contraceptive pill (OR 1.29, 95% CI 1.05-1.59) were significantly associated with disability. According to the nomogram, a predicted probability of 15% or more could be chosen as a threshold. This represents almost 4.6% of young women in this sample being classified at risk of disabling dysmenorrhoea. CONCLUSIONS: Dysmenorrhoea pain intensity and associated pelvic pain symptoms are warning indicators that can be measured to help screen young women who may suffer from disabling dysmenorrhoea.

Efficacy, tolerability, and bone density outcomes of elagolix with add-back therapy for endometriosis-associated pain: 12 months of an ongoing randomized phase 3 trial.

BACKGROUND: Elagolix, an approved oral treatment for endometriosis-associated pain, has been associated with hypoestrogenic effects when used as monotherapy. Hormonal add-back therapy has the potential to mitigate these effects. OBJECTIVE: To evaluate efficacy, tolerability, and bone density outcomes of elagolix 200 mg twice daily with 1 mg estradiol /0.5 mg norethindrone acetate (add-back) therapy once daily compared with placebo in premenopausal women with moderate-to-severe endometriosis-associated pain. STUDY DESIGN: This ongoing, 48-month, phase 3 study consists of a 12-month, double-blind period, with randomization 4:1:2 to elagolix 200 mg twice daily with add-back therapy, elagolix 200 mg twice daily monotherapy for 6 months followed by elagolix with add-back therapy, or placebo. The co-primary endpoints were proportion of patients with clinical improvement (termed "responders") in dysmenorrhea and nonmenstrual pelvic pain at month 6. We report 12-month results on efficacy of elagolix with add-back therapy versus placebo in reducing dysmenorrhea, nonmenstrual pelvic pain, dyspareunia, and fatigue. Tolerability assessments include adverse events and change from baseline in bone mineral density. RESULTS: A total of 679 patients were randomized to elagolix with add-back therapy (n=389), elagolix monotherapy (n=97), or placebo (n=193). Compared with patients randomized to placebo, a significantly greater proportion of patients randomized to elagolix with add-back therapy responded with clinical improvement in dysmenorrhea (62.8% versus 23.7%; P≤.001) and nonmenstrual pelvic pain (51.3% versus 36.8%; P≤.001) at 6 months. Compared with placebo, elagolix with add-back therapy produced significantly greater improvement from baseline in 7 hierarchically ranked secondary endpoints including dysmenorrhea (months 12, 6, 3), nonmenstrual pelvic pain (months 12, 6, 3), and fatigue (months 6) (all P<.01). Overall, the incidence of adverse events was 73.8% with elagolix plus add-back therapy and 66.8% with placebo. The rate of severe and serious adverse events did not meaningfully differ between treatment groups. Study drug discontinuations associated with adverse events were low in patients receiving elagolix with add-back therapy (12.6%) and those receiving placebo (9.8%). Patients randomized to elagolix monotherapy exhibited decreases from baseline in bone mineral density of -2.43% (lumbar spine), -1.54% (total hip), and -1.78% (femoral neck) at month 6. When add-back therapy was added to elagolix at month 6, the change from baseline in bone mineral density remained in a similar range of -1.58% to -1.83% at month 12. However, patients who received elagolix plus add-back therapy from baseline exhibited little change from baseline in bone mineral density (<1% change) at months 6 and 12. CONCLUSION: Compared with placebo, elagolix with add-back therapy resulted in significant, clinically meaningful improvement in dysmenorrhea, nonmenstrual pelvic pain, and fatigue at 6 months that continued until month 12 for both dysmenorrhea and nonmenstrual pelvic pain. Elagolix with add-back therapy was generally well tolerated. Loss of bone mineral density at 12 months was greater in patients who received elagolix with add-back therapy than those who received placebo. However, the change in bone mineral density with elagolix plus add-back therapy was < 1% and was attenuated compared with bone loss observed with elagolix monotherapy.

Sexual function, quality of life, anxiety, and depression in women of reproductive age using hormonal, nonhormonal, and no contraceptive methods.

BACKGROUND: Hormonal contraceptive use has been related to adverse effects, including impacts on sexual function and sexual satisfaction, although the difference in the effects on sexual function with the use of hormonal vs nonhormonal contraceptive methods remains controversial. AIM: In this study we sought to compare the prevalence of dyspareunia, sexual function, sexual satisfaction, quality of life, anxiety, and depression between women using hormonal, nonhormonal, or no contraceptive methods and to compare these outcomes between the most frequently used contraceptive methods. METHODS: This cross-sectional study included sexually active women of reproductive age who were stratified into 3 groups: women using hormonal, nonhormonal, or no contraceptive methods. Based on the use of questionnaires administered to the study participants, we compared sexual function in the 3 groups and more specifically among users of oral contraceptives, copper and hormonal intrauterine devices, and barrier methods. OUTCOMES: Participants completed 4 questionnaires to assess sexual function (Female Sexual Function Index), sexual satisfaction (Sexual Quotient-Feminine Version), quality of life (12-item Medical Outcomes Short Form Health Survey), and anxiety and depression (Hospital Anxiety and Depression Scale). RESULTS: This study included 315 women classified into 3 groups on the basis of contraceptive use: 161 in the hormonal contraceptives group (median [interquartile range] age, 24 [23-28] years), 97 in the nonhormonal contraceptives group (age 26 [23-30] years), and 57 in the no contraceptive methods group (age 28 [24-35] years). Dyspareunia prevalence showed no difference between the groups. In the quality of life domain, compared with women in the nonhormonal contraceptive group, women in the hormonal contraceptive group were younger and had lower sexual function satisfaction, reduced arousal, and heightened pain (P < .05), as well as higher anxiety and depression levels (P = .03, for both), increased pain (P = .01), and poorer overall health (P = .01). No difference was found between these groups in other quality of life domains. Regarding contraceptive methods, women using copper intrauterine devices had better sexual function, including higher rates of arousal and lower anxiety, than women using oral contraceptives (P < .05). CLINICAL IMPLICATIONS: The results of this study highlight worse sexual function and sexual satisfaction and higher levels of anxiety and depression in women using hormonal contraceptive methods than in women using nonhormonal methods. STRENGTHS AND LIMITATIONS: The findings of this study strengthen the evidence of differences in sexual function between women using oral contraceptives and those using copper intrauterine devices. Sexual function was also compared among users of oral contraceptives, copper and hormonal intrauterine devices, and barrier methods. However, less frequently used contraceptive methods, such as hormonal injections and vaginal rings, could not be compared in this sample. CONCLUSION: Women using hormonal contraceptive methods were younger, had lower sexual function and satisfaction, and experienced higher anxiety and depression levels than women using nonhormonal contraceptive methods.

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.

Dyspareunia and pelvic pain: comparison of mid-urethral sling methods 10 years after insertion.

INTRODUCTION AND HYPOTHESIS: The mid-urethral sling (MUS) has been used for more than 30 years to cure stress urinary incontinence. The objective of this study was to assess whether surgical technique affects the outcome after more than ten years, regarding dyspareunia and pelvic pain. METHODS: In this longitudinal cohort study we used the Swedish National Quality Register of Gynecological Surgery to identify women who underwent MUS surgery in the period 2006-2010. Out of 4348 eligible women, 2555 (59%) responded to the questionnaire sent out in 2020-2021. The two main surgical techniques, the retropubic and the obturatoric approach, were represented by 1562 and 859 women respectively. The Urogenital Distress Inventory-6 (UDI-6) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), as well as general questions concerning the MUS surgery, were sent out to the study population. Dyspareunia and pelvic pain were defined as primary outcomes. Secondary outcomes included PISQ-12, general satisfaction, and self-reported problems due to sling insertion. RESULTS: A total of 2421 women were included in the analysis. Among these, 71% responded to questions regarding dyspareunia and 77% responded to questions regarding pelvic pain. In a multivariate logistic regression analysis of the primary outcomes, we found no difference in reported dyspareunia (15% vs 17%, odds ratio (OR) 1.1, 95% CI 0.8-1.5) or in reported pelvic pain (17% vs 18%, OR 1.0, 95% CI 0.8-1.3) between the retropubic and obturatoric techniques among study responders. CONCLUSION: Dyspareunia and pelvic pain 10-14 years after insertion of a MUS do not differ with respect to surgical technique.

Prevalence of chronic pelvic pain and associated factors among indigenous women of reproductive age in Ecuador.

BACKGROUND: Chronic pelvic pain is a common disease that affects approximately 4% of women of reproductive age in developed countries. This number is estimated to be higher in developing countries, with a significant negative personal and socioeconomic impact on women. The lack of data on this condition in several countries, particularly those in development and in socially and biologically vulnerable populations such as the indigenous, makes it difficult to guide public policies. OBJECTIVES: To evaluate the prevalence of chronic pelvic pain (dysmenorrhea, dyspareunia, non-cyclical pain) and identify which variables are independently associated with the presence of the condition in indigenous women from Otavalo-Ecuador. DESIGN: A cross-sectional study was carried out including a sample of 2429 women of reproductive age between 14 and 49 years old, obtained from April 2022 to March 2023. A directed questionnaire was used, collected by bilingual interviewers (Kichwa and Spanish) belonging to the community itself; the number of patients was selected by random sampling proportional to the number of women estimated by sample calculation. Data are presented as case prevalence, odds ratio, and 95% confidence interval, with p < 0.05. RESULTS: The prevalence of primary dysmenorrhea, non-cyclic pelvic pain, and dyspareunia was, respectively, 26.6%, 8.9%, and 3.9%.all forms of chronic pain were independently associated with each other. Additionally, dysmenorrhoea was independently associated with hypertension, intestinal symptoms, miscegenation, long cycles, previous pregnancy, use of contraceptives and pear body shape. Pain in other sites, late menarche, exercise, and pear body shape were associated with non-cyclic pelvic pain. And, urinary symptoms, previous pregnancy loss, miscegenation, and pear body shape were associated with dyspareunia. CONCLUSION: The prevalence of primary dysmenorrhea and non-cyclical chronic pelvic pain was notably high, in contrast with the frequency of reported dyspareunia. Briefly, our results suggest an association between dysmenorrhoea and conditions related to inflammatory and/or systemic metabolic disorders, including a potential causal relationship with other manifestations of pelvic pain, and between non-cyclical pelvic pain and signs/symptoms suggesting central sensitization. The report of dyspareunia may be influenced by local cultural values and beliefs.

Prospective, multicenter, uncontrolled study on the effectiveness and safety of a hyaluronic acid water-based vaginal lubricant in alleviating vaginal dryness and dyspareunia.

BACKGROUND: Vaginal dryness (VD) represents a significant concern affecting women across diverse life stages, encompassing both pre- and postmenopausal women at any age. Dyspareunia, defined by genital pain that can be experienced before, during, or after intercourse, is often associated with vaginal dryness. AIM: This study aimed to evaluate the effectiveness and safety of a water-based vaginal lubricant with hyaluronic acid to reduce sexual discomfort associated with vaginal dryness. METHODS: A prospective, multicenter, uncontrolled clinical investigation was conducted over a three-month period in women aged 18 years or older experiencing pain or difficulty during sexual intercourse for whom the use of a vaginal lubricant was recommended. RESULTS: Significant improvements were observed in the FSFI scores, indicating enhanced sexual function (p < .001). Vaginal dryness symptoms, including irritation, dryness, itching, and dyspareunia, significantly decreased after product use (p < .001). CLINICAL IMPLICATIONS: This study contributes to the limited scientific knowledge on the application of lubricants in the context of symptoms associated with VD. STRENGTHS & LIMITATIONS: In addition to the short study period, inherent limitations of the study design, and lack of placebo control, it is pertinent to acknowledge that some of the pros used in this study were not based on validated questionnaires. However, as far as we know, this study is the only one that analyzes well-being and sexual pleasure as results using a lubricant formulated with hyaluronic acid. CONCLUSION: This tested vaginal lubricant with hyaluronic acid has demonstrated efficacy in improving vaginal dryness and female sexual function, particularly in reducing pain and improving lubrication during sexual intercourse, and showed a favorable safety profile, with minimal and transient adverse events.

"The sound of silence" Giving voice to endometriosis-related positional dyspareunia.

Deep dyspareunia is one of the main symptoms of endometriosis. It appears to be submerged by a two-way disconnection between patients and their physicians. The aim of our review is to provide clear, ready-to-use advice on how to manage deep dyspareunia overcoming the gap in communication. Sexual history should always be taken as part of routine health care in these regards, using a patient-centered approach. An educational pelvic examination, which actively includes patients in the identification of painful areas, may prove useful to improve patients' understanding of their condition. Correlating painful pelvic areas with sexual positions and inviting patients to adopt alternative positions may represent a simple but extremely effective coping strategy to mitigate pain. Revealing and explaining to partners the nature of the pain is essential to allow them to take part in shared research of coping mechanisms, empowering the couple to make choices and changes. Couples who do not feel comfortable talking about intimacy by themselves may find that including a psychotherapist or a sexual therapist, may be a good way to start communication. Investigating and managing dyspareunia during medical encounters is a medical and ethical duty all healthcare practitioners should pursue.

Evaluation of long-term efficacy and safety of dienogest in patients with chronic cyclic pelvic pain associated with endometriosis.

PURPOSE: To evaluate the efficacy and long-term safety (up to 108 months) of treatment with Dienogest in patients with endometriosis. METHODS: Patients with chronic pelvic pain endometriosis-related were enrolled in this observational study from June 2012 to July 2021. The patients enrolled took Dienogest 2 mg as a single daily administration. Group B of long-term therapy patients (over 15 months) were compared with group A of short-term therapy patients (0-15 months). The effects of the drug on pain variation were assessed using the VAS scale and endometriomas dimensions through ultrasonographic evaluation. Furthermore, has been valuated the appearance of side effects and the effect of the drug on bone metabolism by performing MOC every 24 months in group B. RESULTS: 157 patients were enrolled. The mean size of the major endometrioma progressively decreased from 33.2 mm (29.4-36.9) at T0 to 7 mm (0-15.8) after 108 months of treatment. We found a significant improvement in dysmenorrhea, dyspareunia, dyschezia and non-cyclic pelvic pain. As for the side effects, both groups complained menstrual alterations present in 22.9%. In 27.6% of group B, osteopenia was found. Group B had a higher percentage statistically significant of side effects such as headaches, weight gain and libido reduction compared to group A. 2 CONCLUSION: Long-term therapy with Dienogest has proven effective in controlling the symptoms of the disease and reducing the size of endometriomas, with an increase in the positive effects related to the duration of the intake and in the absence of serious adverse events. Study approved by the "Palermo 2" Ethics Committee on July 2, 2012 No. 16.

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.

Vaginal atrophy and genital pain in women on depot medroxyprogesterone acetate contraceptive injection.

Depot medroxyprogesterone acetate causes a hypo-estrogenic state in over half of users although clinical vaginal atrophy causing superficial dyspareunia is thought rarely to occur. This is a case series of ten women using depot medroxyprogesterone acetate who presented with superficial dyspareunia and clinical vaginal atrophy. The women were treated with vaginal estriol cream and their contraception was discontinued or changed. All patients had either a complete resolution of symptoms or a substantial improvement at follow-up, and the clinical and laboratory findings of vaginal atrophy had resolved. This case series demonstrates that vaginal atrophy may occur more frequently than previously thought.

[Sex therapy and support for women and couples]. / Sexothérapie et accompagnement de la femme et du couple.

Sexuality is shaped by experience and by what has been passed down. Body image and sex influence desire and pleasure. In the case of endometriosis, suffering and pain can lead to shame and guilt. Encouraging people to talk to each other helps to create a free eroticism that resembles the couple.

Testosterone use and sexual function among transgender men and gender diverse people assigned female at birth.

BACKGROUND: Testosterone use among transgender people likely impacts their experience of sexual function and vulvovaginal pain via several complex pathways. Testosterone use is associated with decreased estrogen in the vagina and atrophic vaginal tissue, which may be associated with decreased vaginal lubrication and/or discomfort during sexual activity. At the same time, increased gender affirmation through testosterone use may be associated with improved sexual function. However, data on pelvic and vulvovaginal pain among transgender men and nonbinary people assigned female at birth are scarce. OBJECTIVE: This study aimed to assess the association between testosterone and sexual function with a focus on symptoms that are commonly associated with vaginal atrophy. STUDY DESIGN: We conducted a cross-sectional analysis of 1219 participants aged 18 to 72 years using data collected from 2019 to 2021 from an online, prospective, longitudinal cohort study of sexual and/or gender minority people in the United States (The Population Research in Identity and Disparities for Equality Study). Our analysis included adult transgender men and gender diverse participants assigned female at birth who were categorized as never, current, and former testosterone users. Sexual function was measured across 8 Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction domains. RESULTS: Overall, 516 (42.3%) participants had never used testosterone, and 602 (49.4%) currently used testosterone. The median duration of use was 37.7 months (range, 7 days to >27 years). Most participants (64.6%) reported genital pain or discomfort during sexual activity in the past 30 days, most commonly in the vagina or frontal genital opening (52.2%), followed by around the clitoris (29.1%) and labia (24.5%). Current testosterone use was associated with a greater interest in sexual activity (ß=6.32; 95% confidence interval, 4.91-7.74), higher ability to orgasm (ß=1.50; 95% confidence interval, 0.19-2.81), and more vaginal pain or discomfort during sexual activity (ß=1.80; 95% confidence interval, 0.61-3.00). No associations were observed between current testosterone use and satisfaction with sex life, lubrication, labial pain or discomfort, or orgasm pleasure. CONCLUSION: Testosterone use among transgender men and gender diverse people was associated with an increased interest in sexual activity and the ability to orgasm, as well as with vaginal pain or discomfort during sexual activity. Notably, the available evidence demonstrates that >60% of transgender men experience vulvovaginal pain during sexual activity. The causes of pelvic and vulvovaginal pain are poorly understood but are likely multifactorial and include physiological (eg, testosterone-associated vaginal atrophy) and psychological factors (eg, gender affirmation). Given this high burden, there is an urgent need to identify effective and acceptable interventions for this population.

Effects of preoperative intravaginal estrogen on pelvic floor disorder symptoms in postmenopausal women with pelvic organ prolapse.

BACKGROUND: Menopause and the decline in systemic estrogen are associated with the development of pelvic floor disorders, such as prolapse, urinary incontinence, overactive bladder, and vulvovaginal atrophy symptoms. Past evidence suggests that postmenopausal women with symptomatic prolapse gain benefit from the preoperative application of intravaginal estrogen, but it is unknown whether they would experience improvement in other pelvic floor symptoms when treated with intravaginal estrogen. OBJECTIVE: This study aimed to determine the effects of intravaginal estrogen (compared with placebo) on stress and urgency urinary incontinence, urinary frequency, sexual function and dyspareunia, and vaginal atrophy symptoms and signs in postmenopausal women with symptomatic prolapse. STUDY DESIGN: This was a planned ancillary analysis of a randomized, double-blind trial, "Investigation to Minimize Prolapse Recurrence Of the Vagina using Estrogen," which included participants with ≥stage 2 apical and/or anterior prolapse scheduled for transvaginal native tissue apical repair at 3 US sites. The intervention was 1 g conjugated estrogen intravaginal cream (0.625 mg/g) or identical placebo (1:1), inserted nightly for 2 weeks and then twice weekly for ≥5 weeks total before surgery and continued twice weekly for 1 year postoperatively. For this analysis, question responses were compared from participants' baseline and preoperative visits: lower urinary tract symptoms (Urogenital Distress Inventory-6 Questionnaire); sexual health questions, including dyspareunia (Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised); and atrophy-related symptoms (dryness, soreness, dyspareunia, discharge, and itching; each scored 1-4, 4 being quite a bit bothersome). Masked examiners assessed vaginal color, dryness, and petechiae (each scored 1-3, total range 3-9, with 9 being the most estrogenized appearing). Data were analyzed by intent to treat and "per protocol" (ie, those adherent with ≥50% of expected intravaginal cream use, per objective tube before and after weights). RESULTS: Of 199 participants randomized (mean age of 65 years) and contributing baseline data, 191 had preoperative data. The characteristics were similar between groups. Total Urogenital Distress Inventory-6 Questionnaire scores showed minimal change during this median time of 7 weeks between baseline and preoperative visits, but for those with at least moderately bothersome baseline stress urinary incontinence (32 in the estrogen group and 21 in the placebo group), 16 (50%) in the estrogen group and 9 (43%) in the placebo group showed improvement (P=.78). In addition, 43% of participants in the estrogen group and 31% of participants in the placebo group showed improvement in urgency urinary incontinence (P=.41), and 41% of participants in the estrogen group and 26% of participants in the placebo group showed improvement in urinary frequency (P=.18). There was minimal change in the Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised scores among sexually active women; dyspareunia rates did not differ between intravaginal estrogen and placebo at the preoperative assessment: 42% and 48%, respectively (P=.49). The maximum score for most bothersome atrophy symptom (among those with baseline symptoms and adherent to study cream) improved slightly more with intravaginal estrogen (adjusted mean difference, -0.33 points; 95% confidence interval, -0.98 to 0.31), but this was not statistically significant (P=.19). However, on examination, among adherent participants, objective signs of atrophy were more improved with intravaginal estrogen treatment (+1.54 vs +0.69; mean difference, 0.85; 95% confidence interval, 0.05-1.65; P=.01). CONCLUSION: Despite objective changes in the vaginal epithelium consistent with increased estrogenization among drug-adherent participants, the results were inconclusive regarding whether 7 weeks of preoperative intravaginal estrogen cream in postmenopausal women with symptomatic pelvic organ prolapse was associated with improved urinary function, sexual function, dyspareunia symptoms, and other symptoms commonly attributed to atrophy. Additional study is needed.

Postpartum dyspareunia: clinical evaluation, causes, and treatment outcomes.

BACKGROUND: Dyspareunia affects approximately half of postpartum women and is attributed to multiple factors. Despite its high prevalence and resultant negative effects, data are lacking regarding the causes and different pain components, the usefulness of recommended treatments, and the prognosis. AIM: To evaluate causes of postpartum dyspareunia, targeted treatment modalities, and their effectiveness. METHODS: A retrospective observational study was conducted of women diagnosed with postpartum dyspareunia between September 2008 and January 2017 at a single designated vulvovaginal disorder clinic. The inclusion criterion was complaint of painful intercourse commencing postdelivery. The cohort was divided into 4 groups based on the causes of dyspareunia: muscle hypertonicity, scar tenderness, vestibular tenderness, and atrophy. OUTCOMES: The following were assessed for each group: patient background demographics, clinical and obstetric data, physical findings, recommended therapy, adherence to the suggested treatment, level of improvement at follow-up visits, and length of time until maximal improvement. RESULTS: A hundred women met the inclusion criterion; the majority (n = 60) presented with >1 causative factor. The most common finding was vestibular tenderness (n = 78, 78%), which was significantly associated with atrophy (adjusted odds ratio [aOR], 15.08; 95% CI, 2.45-93.35), contraceptive usage (aOR, 4.76; 95% CI, 1.07-21.39), and primiparity (aOR, 4.89; 95% CI, 1.01-23.88). Episiotomy was the only risk factor for scar tenderness (aOR, 5.43; 95% CI, 1.20-24.53), while the existence of a spontaneous perineal tear was not. No specific correlation was found with pelvic floor muscle hypertonicity. Targeted treatment resulted in significant improvement in most patients. CLINICAL IMPLICATIONS: A targeted diagnostic and treatment approach for postpartum dyspareunia is effective and can be beneficial for caregivers treating postpartum women. STRENGTHS AND LIMITATIONS: A uniform and consistent protocol for patient selection and management is a major strength, which magnifies the clinical implication of our findings. The retrospective nature of the study is the primary limitation. CONCLUSION: Postpartum dyspareunia is a common problem; however, many women refrain from discussing it with their providers. Therefore, it is important to assess this condition with all women during the postpartum visit as targeted diagnosis and treatment can significantly improve outcomes.

Acceptability, reliability, and validity of a vaginal insert for the self-assessment of endometriosis-associated deep dyspareunia: a cross-sectional study.

BACKGROUND: Approximately half of people with endometriosis experience deep dyspareunia; however, there is no means of objective self-testing of endometriosis-associated deep dyspareunia. AIM: The aim of this study was to assess the acceptability, test-retest reliability, and validity of a vaginal insert for a self-assessment of endometriosis-associated deep dyspareunia. METHODS: Participants were recruited from a tertiary endometriosis center. Inclusion criteria were: 19 to 49 years of age, self-reported deep dyspareunia of ≥4 of 10, and surgically confirmed endometriosis. Participants completed 2 self-assessments using the vaginal insert to self-assess tenderness at the right and left pelvic floor, bladder, cervix-uterus, and posterior cul-de-sac (vaginal fornix). The participants recorded tenderness at each pelvic site and completed a questionnaire regarding the acceptability of the vaginal insert to assess deep dyspareunia. Test-retest reliability was assessed by correlating the tenderness scores between the 2 assessment dates. Over a 4-week period, the participants also recorded deep dyspareunia severity at each penetrative vaginal sex encounter. Validity was assessed by correlating vaginal insert tenderness to deep dyspareunia severity, and also to tenderness reported on a prior gynecologic pelvic examination. OUTCOMES: The main outcome measures were the acceptability index score, tenderness (0-10) at each pelvic site, and prospective deep dyspareunia scores (0-10) over 4 weeks. RESULTS: There were 19 participants (mean age 34 ± 7 years) who completed the study. The majority identified as female (94.7%), heterosexual (89.5%), and white (89.5%). The median acceptability index score was 0.72 (interquartile range, 0.66-0.81). For test-retest reliability, the intraclass correlation coefficients were 0.79 (P = .001) for the left pelvic floor, 0.82 (P < .001) for the right pelvic floor, 0.54 (P = .07) for the bladder, 0.89 (P < .001) for the cervix-uterus, and 0.77 (P = .003) for the cul-de-sac. The correlation between the highest self-assessed mean tenderness in each participant and self-reported deep dyspareunia over 4 weeks was r = 0.32, but correlations for each pelvic site varied significantly. Tenderness at each site on prior gynecologist pelvic exam was associated with higher self-assessed mean tenderness with the vaginal insert in each participant (effect sizes = 0.42-0.88). CLINICAL IMPLICATIONS: The vaginal insert is acceptable and reliable for the objective self-assessment of endometriosis-associated deep dyspareunia, with initial evidence of validity. STRENGTHS AND LIMITATIONS: A strength was the inclusion of participants who were avoiding sexual activity and a limitation was the small sample size. CONCLUSION: Future studies with larger sample sizes are required to further establish the validity of the vaginal insert for the self-assessment of endometriosis-associated deep dyspareunia.

Are pelvic pain and increased pelvic floor muscle tone associated in women with persistent noncancer pelvic pain? A systematic review and meta-analysis.

BACKGROUND: The association between pelvic pain and pelvic floor muscle (PFM) tone in women with persistent noncancer pelvic pain (PNCPP) is unclear. AIM: To synthesize the evidence of the association between pelvic pain and PFM tone in women with PNCPP. METHODS: A systematic review was conducted via MEDLINE, Emcare, Embase, CINAHL, PsycINFO, and Scopus to identify relevant studies. Studies were eligible if pelvic pain and PFM tone outcome measures were reported among women aged >18 years. The National Heart, Lung, and Blood Institute's Quality Assessment Tool for Observational Cohort and Cross-sectional Studies was used to assess study quality. Studies were pooled by assessment of PFM tone via a random effects model. Associations between the presence of pelvic pain and PFM tone were assessed with odds ratio (OR), while linear associations were assessed with Pearson or Spearman correlation. OUTCOMES: Pelvic pain measures (intensity, threshold, and frequency) and resting PFM tone in women with PNCPP, as evaluated by any clinical assessment method or tool. RESULTS: Twenty-four studies were included in this review. The presence of pelvic pain was significantly associated with increased PFM tone as assessed by digital palpation (OR, 2.85; 95% CI, 1.66-4.89). Pelvic pain intensity was inversely but weakly associated with PFM flexibility when evaluated through dynamometry (r = -0.29; 95% CI, -0.42 to -0.17). However, no significant associations were found between pelvic pain and PFM tone when measured with other objective assessment methods. CLINICAL IMPLICATIONS: Pelvic pain and increased PFM tone may not be directly associated; alternatively, a nonlinear association may exist. A range of biopsychosocial factors may mediate or moderate the association, and clinicians may need to consider these factors when assessing women with PNCPP. STRENGTHS AND LIMITATIONS: This review was reported according to the PRISMA guidelines. All possible findings from relevant theses and conference abstracts were considered in our search. However, nonlinear associations between pelvic pain and increased PFM tone were not assessed as part of this review. CONCLUSION: Pelvic pain may be linearly associated with increased PFM tone and decreased PFM flexibility when measured with digital palpation or dynamometry; however, this association was not observed when other aspects of PFM tone were assessed through objective methods. Future studies are required using robust assessment methods to measure PFM tone and analyses that account for other biopsychosocial factors that may influence the association.