The association between violence against women and chronic pain: a systematic review and meta-analysis.

Violence against women is a phenomenon that involves at least 35% of women worldwide. Violence can be sexual, physical, and/or psychological, perpetrated by the partner, another family member, or a stranger. Violence is a public health problem because its consequences include higher morbidity, higher mortality, and short and long-term physical and psychological health diseases. Most studies prove an association between any type of violence and some chronic pain diagnoses but no one has done a complete collection of this evidence. This systematic review and meta-analysis aimed to evaluate whether this association is statistically significant, including the largest number of studies. Through the inclusion of 37 articles, the association has been demonstrated. Compared with no history of violence, women who did experience violence showed 2 times greater odds of developing chronic pain. The impact of violence was significant also on fibromyalgia separately, but not on pelvic pain.PROSPERO registrationPROSPERO CRD42023425477.

Pain and other complications of pelvic mesh: a systematic review of qualitative studies and thematic synthesis of women's accounts.

OBJECTIVES: Synthesis of the experience of women with pain from pelvic or vaginal mesh or its removal, to identify pain-related problems and to formulate psychological aspects of pain. DESIGN: Systematic review and thematic analysis of qualitative studies of pain from pelvic or vaginal mesh, or mesh removal, in women over 18 years, using individual interviews, focus groups, free text, or written or oral contributions to formal enquiries. DATA SOURCES: Medline, Embase and PsycINFO, from inception to 26 April 2023. ELIGIBILITY CRITERIA: Qualitative studies of pain and other symptoms from pelvic or vaginal mesh or its removal; adults; no language restriction. DATA EXTRACTION AND SYNTHESIS: Line-by-line coding of participant quotations and study author statements by one author to provide codes that were applied to half the studies by another author and differences resolved by discussion. Codes were grouped into subthemes and themes by both authors, then scrutinised and discussed by a focus group of mesh-injured women for omissions, emphasis and coherence. Studies were appraised using an amalgamation of the CASP and COREQ tools. RESULTS: 2292 search results produced 9 eligible studies, with 7-752 participants, a total of around 2000. Four recruited patients, four totally or partially from mesh advocacy groups, and two were national enquiries (UK and Australia). Four major themes were as follows: broken body, broken mind; distrust of doctors and the medical industry; broken life and keeping going-a changed future. Psychological content mainly concerned the loss of trust in medical care, leaving women unsupported in facing an uncertain future. Mesh-injured women strongly endorsed the findings. CONCLUSIONS: Pain and other problems associated with pelvic mesh are profound and far-reaching for women affected. Worse, they feel subject to continued gaslighting, including denial of their mesh-related problems and dismissal of their concerns about continued mesh insertion. PROSPERO REGISTRATION NUMBER: CRD42022330527.

Acupoint Catgut Embedding for Treatment of Chronic Pelvic Pain due to the Sequelae of Pelvic Inflammatory Disease.

Chronic pelvic pain caused by the sequelae of inflammatory pelvic disease is a common clinical condition of pelvic pain in women. At present, the main challenges in its treatment are the limited effectiveness of pain relief and the frequent recurrence of symptoms, which significantly impact patients' quality of life and impose a considerable psychological burden on them. It is a clinically challenging disease. After summarizing years of treatment experience, the author's team discovered that acupoint catgut embedding demonstrated notable clinical efficacy in managing chronic pelvic pain stemming from pelvic inflammatory disease sequelae. Compared to existing Western medicine treatment methods, acupoint catgut embedding offers advantages such as a good analgesic effect, lower recurrence rate, economic benefits, and a relatively straightforward procedure. This article provides a comprehensive guide on embedding absorbable catgut into patients' acupoints for the treatment of chronic pelvic pain in females resulting from the sequelae of pelvic inflammatory disease.

Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain: the PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial.

OBJECTIVES: To evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain. DESIGN: The PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial. SETTING: 34 UK hospitals. PARTICIPANTS: 405 women of reproductive age undergoing conservative surgery for endometriosis. INTERVENTIONS: Participants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill. MAIN OUTCOME MEASURES: The primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment). RESULTS: 405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference -0.8, 95% confidence interval -5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). CONCLUSIONS: Postoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some. TRIAL REGISTRATION: ISRCTN registry ISRCTN97865475.

Is it time to agree upon a standardised approach to the assessment of contributing factors and impacts of adolescent pelvic pain?

BACKGROUND: A biopsychosocial approach to the understanding of pelvic pain is increasingly acknowledged. However, there is a lack of standardised instruments - or their use - to assess risk factors and their impact on pelvic pain in both clinical and research settings. This review aims to identify validated tools used to assess known contributory factors to pelvic pain, as well as the validated tools to measure the impact of pelvic pain in adolescents and young adults, in order to provide a framework for future standardised, adolescent specific assessment and outcome tools. METHODS: Literature searches were performed in MEDLINE, PsycInfo and PubMed. Search terms included pelvic pain, dysmenorrhoea, endometriosis, adolescent, pain measurement, quality of life, sleep, mental health, coping strategies and traumatic experience. RESULTS: We found validated instruments to assess adverse childhood experiences and coping strategies, both known contributing factors to pelvic pain. The impact of pain was measured through validated tools for health-related quality of life, mental health and sleep. CONCLUSIONS: Pelvic pain evaluation in adolescents should include a multi-factorial assessment of contributing factors, such as childhood adversity and coping strategies, and impacts of pelvic pain on quality of life, mental health and sleep, using validated instruments in this age group. Future research should focus on the development of consensus amongst researchers as well as input from young women to establish a standardised international approach to clinical trials involving the investigation and reporting of pelvic pain in adolescents. This would facilitate comparison between studies and contribute to improved quality of care delivered to patients.

Pelvic pain is pain located in the lower abdomen, and includes period pain, which is the most common gynaecologic condition in adolescents and young adults. An approach that includes biological, psychological and social factors is important to understand and manage pelvic pain. Nonetheless, these factors are often poorly assessed in the clinic and research setting. We performed a literature review to identify tools that measure risk factors for pelvic pain, and those that evaluate the impact of pelvic pain. We found instruments that measure exposure to childhood trauma and coping strategies, which are risk factors for developing pelvic pain. We found tools to assess quality of life, mental health and sleep as an impact of pelvic pain. A standardised approach to pelvic pain, including instruments to measure risk factors and impact of pelvic pain, would facilitate comparison between studies and improve quality of care for patients.

Wandering spleen presenting in the form of right sided pelvic mass and pain in a patient with AD-PCKD: a case report and review of the literature.

BACKGROUND: Wandering spleen is a rare clinical entity in which the spleen is hypermobile and migrate from its normal left hypochondriac position to any other abdominal or pelvic position as a result of absent or abnormal laxity of the suspensory ligaments (Puranik in Gastroenterol Rep 5:241, 2015, Evangelos in Am J Case Rep. 21, 2020) which in turn is due to either congenital laxity or precipitated by trauma, pregnancy, or connective tissue disorder (Puranik in Gastroenterol Rep 5:241, 2015, Jawad in Cureus 15, 2023). It may be asymptomatic and accidentally discovered for imaging done for other reasons or cause symptoms as a result of torsion of its pedicle and infarction or compression on adjacent viscera on its new position. It needs to be surgically treated upon discovery either by splenopexy or splectomy based on whether the spleen is mobile or not. CASE PRESENTATION: We present a case of 39 years old female Ethiopian patient who presented to us complaining constant lower abdominal pain especially on the right side associated with swelling of one year which got worse over the preceding few months of her presentation to our facility. She is primiparous with delivery by C/section and a known case of HIV infection on HAART. Physical examination revealed a right lower quadrant well defined, fairly mobile and slightly tender swelling. Hematologic investigations are unremarkable. Imaging with abdominopelvic U/S and CT-scan showed a predominantly cystic, hypo attenuating right sided pelvic mass with narrow elongated attachment to pancreatic tail and absent spleen in its normal position. CT also showed multiple different sized purely cystic lesions all over both kidneys and the pancreas compatible with AD polycystic kidney and pancreatic disease. With a diagnosis of wandering possibly infarcted spleen, she underwent laparotomy, the finding being a fully infarcted spleen located on the right half of the upper pelvis with twisted pedicle and dense adhesions to the adjacent distal ileum and colon. Release of adhesions and splenectomy was done. Her post-operative course was uneventful. CONCLUSION: Wandering spleen is a rare clinical condition that needs to be included in the list of differential diagnosis in patients presenting with lower abdominal and pelvic masses. As we have learnt from our case, a high index of suspicion is required to detect it early and intervene by doing splenopexy and thereby avoiding splenectomy and its related complications.

Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The primary challenge encountered by individuals diagnosed with endometriosis is the experience of pain. Emerging research indicates that oxidative stress is implicated in the initiation of pain associated with endometriosis. Vitamins C and E are known for their antioxidative properties. The primary objective of this study is to assess the efficacy of antioxidant supplementation, consisting of these vitamins, in the management of pain associated with endometriosis. METHODS: A comprehensive search was conducted on the ClinicalTrials.gov, Scopus, Europe PMC, and Medline databases up until August 23rd, 2023, utilizing a combination of relevant keywords. This review incorporates literature that examines the relationship between antioxidant supplementation and pain in endometriosis. We employed fixed-effect models to analyze the risk ratio (RR) and present the outcomes together with their corresponding 95% confidence intervals (CI). RESULTS: A total of five RCTs were incorporated. The results of our meta-analysis indicated that antioxidant supplementation with vitamin C and E combination was associated with higher proportion of endometriosis patients reporting reduced chronic pelvic pain (RR 7.30; 95%CI: 3.27-16.31, p<0.00001, I2 = 0%), alleviations of dysmenorrhea (RR 1.96; 95%CI: 1.25-3.07, p = 0.003, I2 = 39%), and dyspareunia (RR 5.08; 95%CI: 2.10-12.26, p = 0.0003, I2 = 0%) than patients only receiving placebo. CONCLUSIONS: This study suggests the potential ability of vitamin C and E in alleviating pain symptoms experienced by individuals with endometriosis.

Granulosa cell tumor of the ovary: a series of 6 cases.

Granulosa cell tumor (GCT) is a rare ovarian malignancy that represents only 2-3% of all cases. There are two subtypes of GCT: juvenile/JGCT (5% of cases) and adult/AGCT (95% of cases). This study aimed to describe a series of 6 GCT cases. The 6 study patients were managed from June 2011 to November 2022 in a private oncology clinic located in Teresina (PI), Brazil. At diagnosis, the mean patient age was 47 years, and symptoms in 5 patients (83%) were pelvic pain and/or increased abdominal volume. The majority of the patients (N=4/67%) had no comorbidities or findings related to GCT on physical examination. The mean tumor size was 11 cm. Five (83%) tumors were stage Ia and one tumor (17%) was stage III. Regarding tumor subtype, 5 (83%) were AGCT and 1 (17%) was JGCT. Surgical treatment consisted of unilateral salpingo-ophorectomy in 2 patients (33%), total hysterectomy and bilateral salpingo-ophorectomy in 3 patients (50%), and cytoreduction (suboptimal) in 1 patient (17%). After a mean follow-up period of 62.7 months, 5 patients (83%) are still alive and free of disease. One (17%) died from disease progression after 126 months. In the current study, disease-free overall survival was 83%, in a mean follow-up period of 62.7 months.

CGRP neuropeptide levels in patients with endometriosis-related pain treated with dienogest: a comparative study.

BACKGROUND AND OBJECTIVE: Endometriosis (EM) involves the peripheral nervous system and causes chronic pain. Sensory nerves innervating endometriotic lesions contribute to chronic pain and influence the growth phenotype by releasing neurotrophic factors and interacting with nearby immune cells. Calcitonin gene-related peptide (CGRP), a pain-signaling neurotransmitter, has a significant role. This study examines the effect of Dienogest (DNG), a hormone therapy used for managing EM -related pain, on serum CGRP levels in EM patients. MATERIALS AND METHODS: The Visual Analog Scale (VAS) assessed pain in diagnosed EM. INDIVIDUALS: Serum samples were obtained to measure CGRP concentration. Participants received a 2 mg/day oral dose of DNG for six months as prescribed treatment. Additional serum samples were collected after this period to measure CGRP levels. RESULTS: In the EM group, 6.7%, 33.3%, and 20% had ovarian EM, ovarian plus uterosacral, and ovarian plus bladder, respectively. The EM group showed higher CGRP serum levels than the control group (80.53 ± 16.13 vs. 58.55 ± 6.93, P < 0.0001). Still, after drug administration, CGRP serum levels significantly decreased compared to pre-treatment levels (69.66 ± 11.53 vs. 80.53 ± 16.13, P < 0.05). The EM group showed higher pain compared to the control group (7.93 ± 1.58 vs. 0.13 ± 0.35, P < 0.0001), but after drug administration, pain significantly decreased compared to pre-treatment levels (1.00 ± 2.00 vs. 7.93 ± 1.58, P < 0.05). CONCLUSION: DNG administration reduces pain and serum CGRP levels in EM patients, offering the potential for innovative treatments and tailored options. Understanding neurotransmitter roles and drug effects can aid in discovering more effective modulators for these pathways.

Psychological and sexological assessment of patients with chronic prostatitis.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by a multiform clinical presentation requiring a differentiated treatment based on different phenotypes including the psychosocial and sexual domains. The aim of this study was assessing the complex correlations between somatic, psychological, and sexual symptoms of CP/CPPS patients. MATERIALS AND METHODS: We performed a cross-sectional study on patients attending a Prostatitis Clinic. Patients were administered the following questionnaires: National Institutes of Health- Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF), Premature Ejaculation Diagnostic Tool (PEDT), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Oxford Happiness Questionnaire (OHQ), and Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A). RESULTS: Linear regression analyses show highly significant correlations between scores of the NIH-CPSI and the scores of the GAD-7, PHQ-9 and OHQ psychometric questionnaires. IPSS scores correlate significantly with the psychometric scores only when a non-parametric analysis is performed. IIEF and PEDT sexual function scores did not correlate with any of the psychometric tests. NIH-CPSI scores correlate positively with most of the TEMPS-A profiles but the hyperthymic profile correlated negatively with the total and QoL NIH-CPSI and with PEDT scores. CONCLUSIONS: Scores measuring anxiety, depression, and psychological well-being in patients with CP/CPPS are strictly correlated with prostatitis-like symptoms although they are poorly correlated with symptoms of prostatism, as measured by IPSS, and not correlated with scores of sexual dysfunctions, as measured by IIEF and PEDT. A hyperthymic temperament may increase resilience against the disease.

[Metabolic features of the inflammatory syndrome of chronic pelvic pain (category IIIA of chronic non-bacterial prostatitis) in young men, depending on the somatotype].

PURPOSE: dentification of bioimpedance and clinical features in young men with chronic pelvic pain inflammatory syndrome (CP/CPPS NIH IIIa) depending on the somatotype. METHOD: s. 150 men of the first period of adulthood from 22 to 35 years old with CP/CPPS NIH IIIa were examined from 2018 to 2022 years. The average age was 31 [28; 34] year. Somatotypes were computed according to Carter and Heath. Body composition was assessed anthropometry and bioimpedance analysis. RESULTS: Ectomorphs had the least clinical, laboratory and instrumental manifestations of CP/CPPS NIH IIIa, the levels of total and free testosterone were the highest. The active cell mass predominated in the component composition of the body. Manifestations in mesomorphs had a moderate degree of severity. Endomorphs had the most severe manifestations of CP/CPPS NIH IIIa, the largest amount of fat mass was noted in the body composition than in men of other somatotypes, the hormonal status was characterized by the lowest levels of free and total testosterone, and the highest level of estradiol. DISCUSSION: Based on the literature data and our own results, it can be assumed that the identified changes in the body component composition and hormonal status of men contribute to the maintenance of chronic inflammation in the prostate, organ ischemia, impaired intracranial metabolism, recurrent course of CP/CPPS NIH IIIa, which significantly reduces the patients quality of life and increases the risk of prostate inflammation with age. CONCLUSION: Determining the somatotype and conducting a component analysis of body composition allows patients to be divided into groups according to the severity of manifestations of CP/CPPS NIH IIIa. The revealed patterns allow us to classify male endomorphs into the group with the most severe manifestations of CP/CPPS NIH IIIa.

Assessment of quality of life, psychological aspects, and sexual function of women with endometriosis according to pain and infertility: a cross sectional study.

PURPOSE: To evaluate the quality of life, sexual function, anxiety, and depression of women with endometriosis according to pain symptoms and infertility. METHODS: This cross-sectional multicenter study included 229 women with endometriosis followed up at a tertiary hospital in Campinas, a tertiary hospital in São Paulo, and a reproductive medicine clinic in Campinas from 2018 to 2021. The women were divided into four groups according to the presence of pain symptoms and infertility. The Endometriosis Health Profile Questionnaire, Female Sexual Function Index, Beck Depression Inventory, and Beck Anxiety Index were applied to assess quality of life, sexual function, depression, and anxiety of women with endometriosis. RESULTS: The women were grouped as follows: group 1 (45 women without infertility and without pain), group 2 (73 women without infertility and with pain), group 3 (49 women with infertility and without pain), and group 4 (62 women with infertility and pain). Of the women with infertility, the majority had primary infertility. Most women had deep endometriosis (p = 0.608). Women with pain had higher anxiety and depression scores and worse quality of life than women without pain (p < 0.001). Regarding sexual function, all the groups were at risk for sexual dysfunction (p = 0.671). The group of women with pain and infertility have worse anxiety scores (25.31 ± 15.96) and depression (18.81 ± 11.16) than the other groups. CONCLUSION: Pain symptoms worsen anxiety, depression, and quality of life of women with endometriosis and when associated with infertility, greater impairment of psychological aspects may occur.

Do we want to know the enormity of women's severe menstrual disorders and chronic pelvic pain?

OBJECTIVE: The purpose of this paper is to call for a nationwide study to assess the prevalence and incidence of women health problems related to menstrual disorders and severe pelvic pain. RATIONALE: The exact prevalence and incidence of endometriosis, adenomyosis, severe painful menstrual disorders, and of severe chronic pelvic pain are unknown. These issues severely impact women's quality of life and represent huge costs for our societies. Using adapted questionnaires, recent progresses in diagnosis and increased fundings announced by politicians, we can and should change this situation by performing a nationwide study to assess prevalence and incidence of these women problems in the French general population. The huge, anticipated costs of this study do appear quite reasonable when accounting for the enormous costs and societal consequences of endometriosis, menstrual disorders and severe pelvic pain. CONCLUSION: These long-awaited data will improve our understanding of the causes, consequences, and natural history of endometriosis. These data will allow women to better understand that pain is not always related to endometriosis, thus preventing unjustified fears. Physicians will be able to adapt and improve medical managements, particularly the diagnosis. Politicians will have the tools to improve women's health and gender equality.

Long-term treatment for endometriosis with dienogest: efficacy, side effects and tolerability.

BACKGROUND: Dienogest (DNG) improves endometriosis-associated pain (EAP) and patients' quality of life; however, the modern cornerstone of the management of endometriosis is the long-term adherence of the patient to medical treatment. OBJECTIVE: To evaluate DNG as a long-term treatment of endometriosis, focusing on patients' compliance and side effects, also correlating with different phenotypes of endometriosis. METHODS: This was a cohort study on a group of patients with endometriosis (n = 114) undergoing long-term treatment with DNG. During the follow up visits (12, 24, and 36 months) patients were interviewed: an assessment of EAP was performed by using a visual analogue scale (VAS) and side effects were evaluated by using a specific questionnaire of 15 items. RESULTS: At 12 months, 81% were continuing the DNG treatment, with a significant reduction of dysmenorrhea, dyspareunia, dyschezia, dysuria and chronic pelvic pain. Of the 19% that discontinued the treatment: 62% was due to spotting, reduced sexual drive, vaginal dryness, and mood disorders. The improvement of EAP was significant for all endometriosis phenotypes, especially in patients with the deep infiltrating type. At 36 months, 73% of patients were continuing the treatment, showing a significant reduction of EAP through the follow up, along with an increase of amenorrhea (from 77% at 12 months to 93% at 36 months). In a subgroup of 18 patients with gastrointestinal disorders, DNG was administered vaginally at the same dosage, showing similar results in terms of efficacy and tolerability. CONCLUSIONS: DNG was an effective long-term treatment for all endometriosis phenotypes, with few side effects that caused the discontinuation of the treatment mainly during the first year. Thus, the course of 1-year treatment is a predictive indicator for long-term treatment adherence.

Relugolix/Estradiol/Norethisterone Acetate: A Review in Endometriosis-Associated Pain.

An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate [Myfembree® (USA); Ryeqo® (EU)] (hereafter referred to as relugolix combination therapy) has been approved in the USA for the management of moderate to severe pain associated with endometriosis in premenopausal women and in the EU for the symptomatic treatment of endometriosis in adult women of reproductive age with a history of previous medical or surgical treatment for their endometriosis. The gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix decreases estradiol and progesterone levels, while the addition of estradiol/norethisterone acetate mitigates hypoestrogenic effects including bone mineral density (BMD) loss and vasomotor symptoms. In two pivotal phase III trials, relugolix combination therapy significantly improved dysmenorrhoea and non-menstrual pelvic pain in premenopausal women with moderate to severe endometriosis. The combination also reduced overall pelvic pain and dyspareunia, reduced analgesic and opioid use, and improved health-related quality of life. The efficacy of relugolix combination therapy was sustained over the longer term (up to 2 years). Relugolix combination therapy was generally well tolerated and BMD loss over time was minimal. With the convenience of a once daily oral dosing regimen, relugolix combination therapy is a valuable addition to the options currently available for the management of endometriosis-associated pain.

Endometriosis is a disease where tissue similar to the lining of the uterus grows outside the uterus and may reach other organs. This causes chronic pain as a result of increased inflammation and scar tissue. Women with endometriosis may experience painful menstrual periods, pelvic pain between periods, pain during sex, painful bowel movements and painful urination. Recently, a fixed-dose tablet comprising relugolix, estradiol and norethisterone (also known as norethindrone) acetate [Myfembree^® (USA); Ryeqo^® (EU)] (hereafter referred to as relugolix combination therapy) has been approved to treat endometriosis-associated pain. The treatment works by decreasing levels of ovarian hormones (estrogen and progesterone). In clinical trials, relugolix combination therapy improved period pain and pain between periods in women with moderate to severe pain associated with endometriosis. The treatment also improved other symptoms (overall pelvic pain and pain during sex), reduced the need for pain medications and improved health-related quality of life. Relugolix combination therapy was generally well tolerated and caused minimal bone loss, which is known to occur with some hormone therapies. With the convenience of a once daily oral pill, relugolix combination therapy is a valuable addition to the options currently available for women with endometriosis-associated pain.

Linzagolix therapy versus a placebo in patients with endometriosis-associated pain: a prospective, randomized, double-blind, Phase 3 study (EDELWEISS 3).

STUDY QUESTION: Does linzagolix administered orally once daily for up to 3 months at a dose of 75 mg alone or 200 mg in combination with add-back therapy (ABT) (1.0 mg estradiol; 0.5 mg norethindrone acetate, also known as norethisterone acetate [NETA]) demonstrate better efficacy than placebo in the management of endometriosis-related dysmenorrhea and non-menstrual pelvic pain? SUMMARY ANSWER: Combining 200 mg linzagolix with ABT was found to significantly reduce dysmenorrhea and non-menstrual pelvic pain at 3 months of therapy, while a daily dose of 75 mg linzagolix yielded a significant decrease only in dysmenorrhea at 3 months. WHAT IS KNOWN ALREADY?: A previously published Phase 2, dose-finding study reported that at a dose of 200 mg daily, linzagolix promotes full suppression of estradiol secretion to serum levels below 20 pg/ml and noted that the addition of ABT may be needed to manage hypoestrogenic side effects. At lower doses (75 mg and 100 mg/day), linzagolix maintains estradiol values within the target range of 20-60 pg/ml, which could be ideal to alleviate symptoms linked to endometriosis. STUDY DESIGN, SIZE, DURATION: EDELWEISS 3 was a multicenter, prospective, randomized, placebo-controlled, double-blind, double-dummy Phase 3 study to evaluate the safety and efficacy of linzagolix for the treatment of moderate-to-severe endometriosis-associated pain. Treatment was administered orally once daily for up to 6 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: In the EDELWEISS 3 trial, 486 subjects with moderate-to-severe endometriosis-associated pain were randomized at a 1:1:1 ratio to one of the three study groups: placebo, 75 mg linzagolix alone or 200 mg linzagolix in association with ABT. Pain was measured daily on a verbal rating scale and recorded in an electronic diary. MAIN RESULTS AND THE ROLE OF CHANCE: At 3 months, the daily 200 mg linzagolix dose with ABT met the primary efficacy objective, showing clinically meaningful and statistically significant reductions in dysmenorrhea and non-menstrual pelvic pain, with stable or decreased use of analgesics. The proportion of responders for dysmenorrhea in the 200 mg linzagolix with ABT group was 72.9% compared with 23.5% in the placebo group (P < 0.001), while the rates of responders for non-menstrual pelvic pain were 47.3% and 30.9% (P = 0.007), respectively. The 75 mg linzagolix daily dose demonstrated a clinically meaningful and statistically significant reduction in dysmenorrhea versus placebo at 3 months. The proportion of responders for dysmenorrhea in the 75 mg linzagolix group was 44.0% compared with 23.5% in the placebo group (P < 0.001). Although the 75 mg dose showed a trend toward reduction in non-menstrual pelvic pain at 3 months relative to the placebo, it was not statistically significant (P = 0.279). Significant improvements in dyschezia and overall pelvic pain were observed in both linzagolix groups when compared to placebo. Small improvements in dyspareunia scores were observed in both linzagolix groups but they were not significant. In both groups, hypoestrogenic effects were mild, with low rates of hot flushes and bone density loss of <1%. A daily dose of 200 mg linzagolix with ABT or 75 mg linzagolix alone was found to significantly reduce dysmenorrhea and non-menstrual pelvic pain also at 6 months of therapy. LIMITATIONS, REASONS FOR CAUTION: Efficacy was compared between linzagolix groups and placebo; however, it would be useful to have results from comparative studies with estro-progestogens or progestogens. It will be important to ascertain whether gonadotropin-releasing hormone antagonists have significant benefits over traditional first-line medications. WIDER IMPLICATIONS OF THE FINDINGS: Linzagolix administered orally once daily at a dose of 200 mg in combination with add-back therapy (ABT) demonstrated better efficacy and safety than placebo in the management of moderate-to-severe endometriosis-associated pain. The quality of life was improved and the risks of bone loss and vasomotor symptoms were minimized due to the ABT. The 75 mg dose alone could be suitable for chronic treatment of endometriosis-associated pain without the need for concomitant hormonal ABT, but further research is needed to confirm this. If confirmed, it would offer a viable option for women who do not want to wish to have ABT or for whom it is contraindicated. STUDY FUNDING/COMPETING INTEREST(S): Funding for the EDELWEISS 3 study was provided by ObsEva (Geneva, Switzerland). Analysis of data and manuscript writing were partially supported by ObsEva (Geneva, Switzerland), Theramex (London, UK) and Kissei (Japan) and grant 5/4/150/5 was awarded to M.-M.D. by FNRS. J.D. was a member of the scientific advisory board of ObsEva until August 2022, a member of the scientific advisory board of PregLem, and received personal fees from Gedeon Richter, ObsEva and Theramex. J.D. received consulting fees, speakers' fees, and travel support from Gedeon Richter, Obseva and Theramex, which was paid to their institution. C.B. has received fees from Theramex, Gedeon Richter, and Myovant, and travel support from Gedeon Richter-all funds went to the University of Oxford. He was a member of the data monitoring board supervising the current study, and served at an advisory board for endometriosis studies of Myovant. H.T. has received grants from Abbvie and was past president of ASRM. F.C.H. has received fees from Gedeon Richter and Theramex. O.D. received fees for lectures from Gedeon Richter and ObsEva and research grants for clinical studies from Preglem and ObsEva independent from the current study. A.H. has received grants from NIHR, UKRI, CSO, Wellbeing of Women, and Roche Diagnostics; he has received fees from Theramex. A.H.'s institution has received honoraria for consultancy from Roche Diagnostics, Gesynta, and Joii. M.P. has nothing to declare. F.P. has received fees from Theramex. S.P.R. has been a member of the scientific advisory board of Gedeon Richter and received fees from Gedeon Richter. A.P. and M.B. are employees of Theramex. E.B. was an employee of ObsEva, sponsor chair of the data monitoring board supervising the current study, and has been working as a consultant for Theramex since December 2022; she owns stock options in ObsEva. M.-M.D. has received fees and travel support from Gedeon Richter and Theramex. TRIAL REGISTRATION NUMBER: NCT03992846. TRIAL REGISTRATION DATE: 20 June 2019. DATE OF FIRST PATIENT'S ENROLLMENT: 13 June 2019.

Outcomes After Surgery at an Interdisciplinary Centre of Expertise for Endometriosis and Pelvic Pain in Canada: A Prospective Cohort Study.

OBJECTIVES: To prospectively evaluate pain-related quality-of-life (Endometriosis Health Profile-30 [EHP-30] pain subscale) after surgery at an interdisciplinary centre of expertise for endometriosis and pelvic pain. METHODS: A prospective cohort study was completed of persons undergoing surgical management for pelvic pain between December 2013 and July 2016 at an interdisciplinary tertiary referral centre for pelvic pain and endometriosis. We compared the change in EHP-30 scores for the following scenarios: (1) type of surgery (conservative surgery vs. hysterectomy), (2) stage of endometriosis (stage I/II vs. III/IV), and (3) age (age <40 vs. age ≥40 years). We used mixed-effects models to evaluate changes in pain during follow-up after surgery. RESULTS: Overall, 595 individuals met our inclusion criteria; the follow-up rate was 65.9% (392/595). In total, 436 (73.3%) underwent conservative surgery, while 159 (26.7%) underwent hysterectomy. Improvements in pain-related quality-of-life were seen for both conservative surgery and hysterectomy but greater improvements were seen with hysterectomy (P < 0.001). For conservative surgery, similar improvements in quality-of-life were observed regardless of endometriosis stage (I/II vs. III/IV) (P = 0.84) or age (<40 or ≥40 years old) (P = 0.87). We also observed similar improvements in quality-of-life regardless of stage (P = 0.24) or age (P = 0.71) after hysterectomy. CONCLUSIONS: At an interdisciplinary centre of expertise, there were significant improvements in quality-of-life after endometriosis surgery. These improvements were seen for both conservative surgery and hysterectomy (although greater improvement with the latter), for early and advanced stage disease, and younger and older patients.

Changes in Pelvic Floor Ultrasonographic Features after Flat Magnetic Stimulation in Women with Chronic Pelvic Pain and Levator Ani Muscle Hypertonicity.

Background and Objectives: Chronic pelvic pain (CPP) represents a major public health problem for women with a significant impact on their quality of life. In many cases of CPP, due to gynecological causes-such as endometriosis and vulvodynia-improper pelvic floor muscle relaxation can be identified. Treatment of CPP with pelvic floor hypertonicity (PFH) usually involves a multimodal approach. Traditional magnetic stimulation has been proposed as medical technology to manage muscle hypertonicity and pelvic pain conditions through nerve stimulation, neuromodulation, and muscle relaxation. New Flat Magnetic Stimulation (FMS)-which involves homogeneous rather than curved electromagnetic fields-has the potential to induce sacral S2-S4 roots neuromodulation, muscle decontraction, and blood circulation improvement. However, the benefits of this new technology on chronic pelvic pain symptoms and biometrical muscular parameters are poorly known. In this study, we want to evaluate the modification of the sonographic aspect of the levator ani muscle before and after treatment with Flat Magnetic Stimulation in women with chronic pelvic pain and levator ani hypertonicity, along with symptoms evolution. Materials and Methods: A prospective observational study was carried out in a tertiary-level Urogynaecology department and included women with CPP and PFH. Approval from the local Ethics Committee was obtained before the start of the study (protocol code: MAGCHAIR). At the baseline, the intensity of pelvic pain was measured using a 10 cm visual analog scale (VAS), and patients were asked to evaluate their pelvic floor symptoms severity by answering the question, "How much do your pelvic floor symptoms bother you?" on a 5-answer Likert scale. Transperineal ultrasound (TPU) was performed to assess anorectal angle (ARA) and levator ani muscle minimal plane distance (LAMD). Treatment involved Flat Magnetic Stimulation alone or with concomitant local or systemic pharmacological therapy, depending on the patient's preferences. FMS was delivered with the DR ARNOLD system (DEKA M.E.L.A. Calenzano, Italy). After the treatment, patients were asked again to score the intensity of pelvic pain using the 10 cm visual analog scale (VAS) and to evaluate the severity of their pelvic floor symptoms on the 5-answer Likert scale. Patients underwent TPU to assess anorectal angle (ARA) and levator ani muscle minimal plane distance (LAMD). Results: In total, 11 patients completed baseline evaluation, treatment, and postoperative evaluation in the period of interest. All patients underwent eight sessions of Flat Magnetic Stimulation according to the protocol. Adjuvant pharmacological treatment was used in five (45.5%) patients. Specifically, we observed a significant increase in both ARA and LAMD comparing baseline and post-treatment measurements (p < 0.001). Quality of life scale scores at baseline and after treatment demonstrated a significant improvement in both tools (p < 0.0001). Conclusions: Flat Magnetic Stimulation, with or without adjuvant pharmacological treatment, demonstrated safety and efficacy in reducing pelvic floor hypertonicity, resulting in improvement in symptoms' severity and sonographic parameters of muscular spasm.