Investigational drugs for the treatment of dysmenorrhea.

INTRODUCTION: Dysmenorrhea is the most common cause of gynecological pain among women that has considerable impact on quality of life and psychosocial wellbeing. Non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal therapies are most commonly used to treat dysmenorrhea. However, given these drugs are often associated with bothersome side effects and are less effective when there is an underlying cause contributing to dysmenorrhea (e.g. endometriosis), a patient-centered approach to managing dysmenorrhea is important. Various new drugs are currently being investigated for the treatment of primary and secondary dysmenorrhea. AREAS COVERED: This review provides an updated overview on new therapeutic targets and investigational drugs for the treatment of primary and secondary dysmenorrhea. The authors describe the clinical development and implications of these drugs. EXPERT OPINION: Among the investigative drugs discussed in this review, anti-inflammatories show the most promising results for the treatment of dysmenorrhea. However, given some trials have considerable methodological limitations, many drugs cannot be currently recommended. Research focused on understanding the mechanisms involved in menstruation and its associated symptoms will be important to identify new therapeutic targets for dysmenorrhea. Further robust clinical trials are required to better understand the efficacy and safety of investigational drugs for treating primary and secondary dysmenorrhea.

"I wish I knew then what I know now" - pain science education concepts important for female persistent pelvic pain: a reflexive thematic analysis.

ABSTRACT: Pain science education (PSE) provides people with an understanding of "how pain works" grounded in the biopsychosocial model of pain; it has been demonstrated to improve outcomes in musculoskeletal pain conditions. Preliminary evidence suggests PSE may be effective for female individuals with persistent pelvic pain, but how the content of PSE needs to be modified for this group remains to be determined. A reflexive thematic analysis of qualitative data was performed to identify PSE concepts that female individuals with persistent pelvic pain consider important and why. Twenty individual, semistructured interviews were conducted with adult females who had engaged with PSE and had self-identified as having "improved" pelvic pain. Most participants had been diagnosed with endometriosis (n = 16). Four themes were generated capturing PSE concepts considered important by female individuals with "improved" pelvic pain: (1) "A sensitised nervous system leads to overprotective pain" validated their pelvic pain as being real; (2) "Pain does not have to mean the body is damaged (although sometimes it does)" provided reassurance that pelvic pain does not mean their condition is worsening; (3) "How I think, feel, and 'see' my pain can make it worse" enabled participants to find optimal ways to manage their pain; and (4) "I can change my pain… slowly" provided hope that pelvic pain can improve and empowered them to pursue pain improvement as a viable goal. This study generated 4 PSE learning concepts that were important to female individuals with improved pelvic pain and may be incorporated into PSE curricula for female individuals with pelvic pain.

Recommendations for patient education in the management of persistent pelvic pain: a systematic review of clinical practice guidelines.

ABSTRACT: Patient education has a critical role in the management of pain. There is considerable heterogeneity in patient education for females with persistent pelvic pain (PPP), and it remains unclear what is considered best clinical practice. Therefore, this systematic review identified and summarised recommendations for patient education in the management of benign gynaecological and urological conditions associated with PPP, as endorsed by international guidelines. Academic and relevant guideline databases were searched from inception to May 2022. Included guidelines were those for the management of benign gynaecological and urological conditions associated with PPP in adult females published in English, of any publication date, and endorsed by a professional organisation or society. Two independent reviewers screened 3097 records; 17 guidelines were included in the review. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. Recommendations were pooled using descriptive synthesis. Persistent pelvic pain guideline quality was generally poor. Three guidelines were classified as "excellent" (The NICE, RANZCOG, and ESHRE endometriosis guidelines) and therefore recommended for use. Eleven guidelines (64.7%) recommended patient education for females with PPP. Recommendations for education content were variable, however most frequently covered treatment strategies and pelvic pain diagnoses. For education delivery, the most frequent recommendations were for support groups and written/printed materials. Further research into tailored education interventions is needed for females with PPP.

The Efficacy of Self-Management Strategies for Females with Endometriosis: a Systematic Review.

Self-management is critical for the care of endometriosis. Females with endometriosis frequently use self-management strategies to manage associated symptoms; however, the efficacy of such strategies is unknown. The aim of this review was to systematically appraise the evidence concerning efficacy of self-management strategies for endometriosis symptoms. Electronic databases, including Medline, Embase, Emcare, Web of Science Core Collection, Scopus, and the Cochrane Central Register of Controlled Trials, were searched from inception to March 2021. We included peer-reviewed experimental studies published in English evaluating the efficacy of self-management strategies in human females laparoscopically diagnosed with endometriosis. Studies underwent screening, data extraction, and risk of bias appraisal (randomised studies: Risk of Bias 2 tool; non-randomised studies: Risk Of Bias In Non-randomized Studies - of Interventions tool). Of the fifteen studies included, 10 evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter medication, and one evaluated exercise. Most studies had a high-critical risk of bias. Many self-management strategies were not more effective at reducing endometriosis symptoms compared to placebo or hormonal therapies. Where studies suggest efficacy for self-management strategies, no recommendations can be made due to the poor quality and heterogeneity of evidence. High-quality empirical evidence is required to investigate the efficacy of self-management strategies for females with endometriosis.

The accessibility of pelvic health physiotherapy for adolescents with persistent pelvic pain: a qualitative framework analysis.

BACKGROUND: Physiotherapy, with a specific focus on pelvic health, is one service used in the multidisciplinary management of adolescent persistent pelvic pain (PPP). However, there has been little investigations into the accessibility of physiotherapy for adolescents with PPP. OBJECTIVE: This qualitative study aimed to detail the experiences of adolescents with PPP accessing a tertiary hospital physiotherapy service. METHODS: Two focus groups included six adolescent females diagnosed with PPP that had either a) been referred and attended the physiotherapy clinic (n = 5), or b) been referred to physiotherapy but yet to attend their appointment (n = 1 plus one support person). Focus group transcripts were deductively thematically analyzed according to four domains from the patient-centered healthcare accessibility framework. RESULTS: The domain of 'Approachability and ability to perceive' was impacted by limited information and poor patient health literacy. 'Acceptability and ability to seek' was hindered by adolescent mental health struggles and failures of previous PPP management. 'Availability and accommodation, and ability to reach' was influenced by lengthy referral processes, and reliance on familial support for transport. 'Acceptability and ability to engage' was facilitated by engaging clinicians and group environments, however, adolescents became dependent on physiotherapy for pain management. CONCLUSION: Physical, social, and environmental factors influence the accessibility of physiotherapy for adolescents with PPP. Healthcare services should consider the specific needs of adolescents with PPP for optimizing accessibility.

Treatment recommendations for the management of persistent pelvic pain: a systematic review of international clinical practice guidelines.

BACKGROUND: Females with persistent pelvic pain (PPP) report great variability in the treatments recommended to them despite the availability of clinical practice guidelines (CPGs) that aim to standardise care. A clear consensus for the best practice care for PPP is required. OBJECTIVE: To identify and summarise treatment recommendations across CPGs for the management of PPP, and appraise their quality. SEARCH STRATEGY: MEDLINE, CENTRAL, EMBASE, EmCare, SCOPUS, the Cochrane Database of Systematic Reviews, Web of Science Core Collection and relevant guideline databases were searched from their inception to June 2021. SELECTION CRITERIA: Included CPGs were those for the management of urogynaecological conditions in adult females published in English, of any publication date, and endorsed by a professional organisation or society. DATA COLLECTION AND ANALYSIS: We screened 1379 records and included 20 CPGs. CPG quality was assessed using The Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. Descriptive synthesis compiled treatment recommendations across CPGs. MAIN RESULTS: The CPGs for seven conditions provided 270 individual recommendations. On quality appraisal, guidelines on average scored 'excellent' for the domains 'scope and purpose' (80.6%, SD = 13.3) and 'clarity and presentation' (74.4%, SD = 12.0); for other domains, average scores were satisfactory or poor. Four guidelines (for Endometriosis: NICE, RANZCOG and ESHRE; for polycystic ovary syndrome: Teede et al. 2018, International Evidence Based Guideline for the Assessment and Management of Polycystic Ovary Syndrome, Monash University, Melbourne, Australia) were deemed recommended for use. Recommendations were most frequent for pharmaceutical and surgical interventions. Recommendations were variable for psychological, physiotherapy and other conservative interventions. CONCLUSIONS: The quality of CPGs for PPP is generally poor. Several CPGs endorse the consideration of biopsychosocial elements of PPP. Yet most recommend pharmaceutical, surgical and other biomedical interventions.

Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain.

ABSTRACT: We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.