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Human Reproduction (Oxford, England) Aug 2023What are the similarities and differences in the systemic proteomic profiles by endometriosis-associated pain subtypes among adolescents and young adults with...
STUDY QUESTION
What are the similarities and differences in the systemic proteomic profiles by endometriosis-associated pain subtypes among adolescents and young adults with endometriosis?
SUMMARY ANSWER
Endometriosis-associated pain subtypes exhibited distinct plasma proteomic profiles.
WHAT IS KNOWN ALREADY
Endometriosis patients, especially those diagnosed in adolescents and young adults, are often plagued by various pain symptoms. However, it is not clear what biological processes underlie this heterogeneity.
STUDY DESIGN, SIZE, DURATION
We conducted a cross-sectional analysis using data and plasma samples from 142 adolescent or young adult participants of the Women's Health Study: From Adolescence to Adulthood cohort with laparoscopically confirmed endometriosis.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We measured 1305 plasma protein levels by SomaScan. We classified self-reported endometriosis-associated pain into subtypes of dysmenorrhea, acyclic pelvic pain, life impacting pelvic pain, bladder pain, bowel pain, and widespread pain phenotype. We used logistic regression to calculate the odds ratios and 95% confidence intervals for differentially expressed proteins, adjusting for age, BMI, fasting status, and hormone use at blood draw. Ingenuity Pathway Analysis identified enriched biological pathways.
MAIN RESULTS AND THE ROLE OF CHANCE
Our study population consisted mainly of adolescents and young adults (mean age at blood draw = 18 years), with nearly all (97%) scored as rASRM stage I/II at laparoscopic diagnosis of endometriosis, which is a common clinical presentation of endometriosis diagnosed at a younger age. Pain subtypes exhibited distinct plasma proteomic profiles. Multiple cell movement pathways were downregulated in cases with severe dysmenorrhea and life impacting pelvic pain compared to those without (P < 7.5×10-15). Endometriosis cases with acyclic pelvic pain had upregulation of immune cell adhesion pathways (P < 9.0×10-9), while those with bladder pain had upregulation of immune cell migration (P < 3.7×10-8) and those with bowel pain had downregulation (P < 6.5×10-7) of the immune cell migration pathways compared to those without. Having a wide-spread pain phenotype involved downregulation of multiple immune pathways (P < 8.0×10-10).
LIMITATIONS, REASONS FOR CAUTION
Our study was limited by the lack of an independent validation cohort. We were also only able to explore any presence of a pain subtype and could not evaluate multiple combinations by pain subtypes. Further mechanistic studies are warranted to elucidate the differences in pathophysiology by endometriosis-pain subtype.
WIDER IMPLICATIONS OF THE FINDINGS
The observed variation in plasma protein profiles by pain subtypes suggests different underlying molecular mechanisms, highlighting the need for potential consideration of pain subtypes for effectively treating endometriosis patients presenting with various pain symptoms.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by the Department of Defense W81XWH1910318 and the 2017 Boston Center for Endometriosis Trainee Award. Financial support for establishment of and data collection within the A2A cohort were provided by the J. Willard and Alice S. Marriott Foundation. N.S., A.F.V., S.A.M., and K.L.T. have received funding from the Marriott Family Foundation. C.B.S. is funded by an R35 MIRA Award from NIGMS (5R35GM142676). S.A.M. and K.L.T. are supported by NICHD R01HD094842. S.A.M. reports serving as an advisory board member for AbbVie and Roche, Field Chief Editor for Frontiers in Reproductive Health, personal fees from Abbott for roundtable participation; none of these are related to this study. Other authors report no conflict of interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Female; Humans; Endometriosis; Dysmenorrhea; Cross-Sectional Studies; Proteomics; Pelvic Pain; Abdominal Pain
PubMed: 37196326
DOI: 10.1093/humrep/dead099 -
Archives of Gynecology and Obstetrics Dec 2023Chronic pelvic pain (CPP) is one of the main problems of endometriosis, leading to a significant impairment of quality of life. Understanding the pain mechanisms and the...
PURPOSE
Chronic pelvic pain (CPP) is one of the main problems of endometriosis, leading to a significant impairment of quality of life. Understanding the pain mechanisms and the pelvic floor muscles (PFM) changes in these patients is essential to integrate additional therapeutic strategies. We hypothesize that endometriosis patients have changes in PFM and that targeted vaginal electrostimulation can be a treatment option for CPP in this disease.
METHODS
Fifteen patients with endometriosis and chronic acyclical pelvic pain were included. PFM electromyography with the Multiple Array Probe Leiden (MAPLe) was performed. Mapping of PFM was utilized and targeted electrostimulation of the hypertensive muscles was conducted. Control electromyography was performed afterward to evaluate the electrostimulation therapeutic effect.
RESULTS
In 12/15 (80%) patients, the myofascial trigger point could be localized by digital examination. The most frequently affected muscle was the puborectalis (10/15-66.7%). Most of the patients showed serious changes in the average resting tone (aRT) of PFM. aRT was significantly increased in all patients and decreased after stimulation, whereby the difference prior to and after stimulation was not significant (p = 0.064). The detailed separated analysis of the hypertensive muscles showed a significant (p = 0.026) reduction in their resting tone (hRT), after targeted stimulation.
CONCLUSION
Vaginal electrostimulation is a promising and feasible complementary treatment option for CPP in endometriosis patients. Targeted treatment of pelvic floor dysfunction should be included in clinical trials.
Topics: Female; Humans; Pelvic Floor; Pilot Projects; Endometriosis; Quality of Life; Muscle Contraction; Electromyography; Pelvic Floor Disorders; Pelvic Pain
PubMed: 37672087
DOI: 10.1007/s00404-023-07192-5 -
Physical Therapy Oct 2011Chronic pelvic pain in women is a debilitating, costly condition often treated by physical therapists. The etiology of this condition is multifactorial and poorly... (Review)
Review
Chronic pelvic pain in women is a debilitating, costly condition often treated by physical therapists. The etiology of this condition is multifactorial and poorly understood, given the complex interplay of muscles, bones, and soft tissue that comprise the pelvis. There are few guidelines directing treatment interventions for this condition. In the last decade, several investigators have highlighted the role of psychological variables in conditions such as vulvodynia and painful bladder syndrome. Pain-related fear is the focus of the fear-avoidance model (FAM) of pain, which theorizes that some people are more likely to develop and maintain pain after an injury because of their emotional and behavioral responses to pain. The FAM groups people into 2 classes on the basis of how they respond to pain: people who have low fear, confront pain, and recover from injury and people who catastrophize pain-a response that leads to avoidance/escape behaviors, disuse, and disability. Given the presence of pain-related cognitions in women with chronic pelvic pain, including hypervigilance, catastrophizing, and anxiety, research directed toward the application of the FAM to guide therapeutic interventions is warranted. Isolated segments of the FAM have been studied to theorize why traditional approaches (ie, medications and surgery) may not lead to successful outcomes. However, the explicit application of the FAM to guide physical therapy interventions for women with chronic pelvic pain is not routine. Integrating the FAM might direct physical therapists' clinical decision making on the basis of the pain-related cognitions and behaviors of patients. The aims of this article are to provide information about the FAM of musculoskeletal pain and to provide evidence for the relevance of the FAM to chronic pelvic pain in women.
Topics: Anxiety; Avoidance Learning; Catastrophization; Chronic Disease; Fear; Female; Humans; Models, Psychological; Pain Measurement; Pelvic Pain; Women
PubMed: 21835893
DOI: 10.2522/ptj.20100368 -
Gynecologic and Obstetric Investigation 2013To investigate the independent importance of different types of pelvic pain on quality of life and depressive symptoms.
BACKGROUND/AIMS
To investigate the independent importance of different types of pelvic pain on quality of life and depressive symptoms.
METHODS
A cross-sectional study was performed on patients with pelvic pain. A 10-cm visual-analogue scale (VAS) was used to investigate intensity of intermenstrual pelvic pain, dysmenorrhea or deep dyspareunia. The SF-36 form and the Zung Self-Rating Scale for Depression (SDS) were used to investigate quality of life and depressive symptoms, respectively.
RESULTS
The final study group consisted of 248 patients, 175/248 (70.6%) with intermenstrual pelvic pain, 46/248 (18.5%) with dysmenorrhea and 27/248 (10.9%) with deep dyspareunia associated or not with dysmenorrhea. Mean VAS score for dysmenorrhea was higher than that for deep dyspareunia (p < 0.003) and intermenstrual pelvic pain (p < 0.0001). Women with intermenstrual pelvic pain had the worst SF-36 (p < 0.0001) and SDS (p < 0.002) scores. SF-36 was independently and inversely related to intermenstrual pelvic pain (CR -1.522; 95% CI -2.188 to -0.856; p < 0.0001), and less strongly to dysmenorrhea (CR -0.729; 95% CI -1.487 to 0.030; p = 0.06). Indeed, only the physical component summary of SF-36 was independently related to dysmenorrhea (CR -0.956; 95% CI -1.783 to -0.129; p = 0.024). The SDS score was independently related only to intermenstrual pelvic pain (CR 0.573; 95% CI 0.241-0.904; p = 0.0008).
CONCLUSIONS
Patients with intermenstrual pelvic pain have the worst SF-36 and SDS scores. Intermenstrual pelvic pain seems to be more strongly associated with a reduced quality of life and depressive mood.
Topics: Adolescent; Adult; Cross-Sectional Studies; Depression; Dysmenorrhea; Dyspareunia; Female; Humans; Menstruation Disturbances; Middle Aged; Pain Measurement; Pelvic Pain; Quality of Life; Surveys and Questionnaires; Young Adult
PubMed: 23182853
DOI: 10.1159/000343997 -
Women's Health (London, England) Nov 2015Chronic pelvic pain (CPP) is common in women of reproductive age and has a significant impact on quality of life, work efficiency and healthcare utilization. CPP can be... (Review)
Review
Chronic pelvic pain (CPP) is common in women of reproductive age and has a significant impact on quality of life, work efficiency and healthcare utilization. CPP can be a manifestation of many different, often multifactorial conditions, and in the absence of an identified cause, the management can be particularly challenging. High quality epidemiological studies would improve the understanding of CPP and identify risk factors which may be targeted for the development of appropriate management strategies. This review focuses on what is known about the prevalence, risk factors, individual and societal burden of CPP and outlines important management strategies.
Topics: Chronic Pain; Female; Humans; Pelvic Pain; Prevalence; Quality of Life; Risk Factors
PubMed: 26450216
DOI: 10.2217/whe.15.30 -
Medicine Apr 2021Chronic pelvic pain syndrome is difficult for the diagnosis and therapy and that means the patient attending the physician or physiotherapist may present various...
INTRODUCTION
Chronic pelvic pain syndrome is difficult for the diagnosis and therapy and that means the patient attending the physician or physiotherapist may present various symptoms. There are no guidelines concern physiotherapy diagnosis and treatment of chronic pelvic pain syndrome. This study presents the physiotherapeutic assessment and management in men with pelvic pain symptoms.
PATIENT CONCERNS
Forty-six-year-old man attended the physiotherapy consulting room due to symptoms of pain in the perineum, lower abdomen, urethra, and scrotum for a year. Earlier, the patient had consulted a urologist who made a diagnosis of cystitis and prescribed medications that did not get results.
DIAGNOSIS
Ultrasound imaging and manual inspection (per rectum) of the pelvic floor was conducted by physiotherapist. Also, the abdominal and lower extremities muscles were assessed. Patient reported pain symptoms during examination of the musculus ischiocavernosus, puboanalis, pubococcygeus, iliococcygeus, coccygeus, and canalis pudentalis seu Alcocki.
INTERVENTIONS
The patient was given physiotherapeutic interventions consisting in the manual therapy of the lumbopelvic hip complex and the manual therapy per rectum.
OUTCOMES
During 10th session of the physiotherapeutic treatment, patient reported improvement in pain symptoms. A month later, patient reported total alleviation of the pain symptoms during control visit.
CONCLUSION
Therapy of chronic pelvic pain syndrome is a process that involves application of different therapies and different approaches. Functional and structural assessment and also therapy conducted by physiotherapist is becoming an integral part of urology and represents 1 possible conservative treatment form.
Topics: Chronic Pain; Humans; Male; Middle Aged; Musculoskeletal Manipulations; Pelvic Floor; Pelvic Pain; Physical Therapy Modalities; Rectum; Syndrome
PubMed: 33847674
DOI: 10.1097/MD.0000000000025525 -
BioMed Research International 2014The main sequelae of endometriosis are represented by infertility and chronic pelvic pain. Chronic pelvic pain causes disability and distress with a very high economic... (Review)
Review
The main sequelae of endometriosis are represented by infertility and chronic pelvic pain. Chronic pelvic pain causes disability and distress with a very high economic impact. In the last decades, an impressive amount of pharmacological agents have been tested for the treatment of endometriosis-associated pelvic pain. However, only a few of these have been introduced into clinical practice. Following the results of the controlled studies available, to date, the first-line treatment for endometriosis associated pain is still represented by oral contraceptives used continuously. Progestins represent an acceptable alternative. In women with rectovaginal lesions or colorectal endometriosis, norethisterone acetate at low dosage should be preferred. GnRH analogues may be used as second-line treatment, but significant side effects should be taken into account. Nonsteroidal anti-inflammatory drugs are widely used, but there is inconclusive evidence for their efficacy in relieving endometriosis-associated pelvic pain. Other agents such as GnRH antagonist, aromatase inhibitors, immunomodulators, selective progesterone receptor modulators, and histone deacetylase inhibitors seem to be very promising, but there is not enough evidence to support their introduction into routine clinical practice. Some other agents, such as peroxisome proliferator activated receptors-γ ligands, antiangiogenic agents, and melatonin have been proven to be efficacious in animal studies, but they have not yet been tested in clinical studies.
Topics: Endometriosis; Female; Gonadotropin-Releasing Hormone; Histone Deacetylase Inhibitors; Hormone Antagonists; Humans; Pain Management; Pelvic Pain; Progestins
PubMed: 25165691
DOI: 10.1155/2014/191967 -
Acta Obstetricia Et Gynecologica... Nov 2003A systematic review of prospective controlled clinical trials was performed to assess the effectiveness of physical therapy interventions for the prevention and... (Review)
Review
BACKGROUND
A systematic review of prospective controlled clinical trials was performed to assess the effectiveness of physical therapy interventions for the prevention and treatment of pregnancy-related back and pelvic pain. Pregnancy-related low back and pelvic pain has an impact on daily life for many women. Prevention and treatment of back and pelvic pain is therefore an important issue for all those concerned with women's health.
METHODS
All prospective controlled clinical trials retrieved by systematic searching of electronic databases, checking of reference lists and contacting of authors were examined. Two reviewers independently selected trials for inclusion and independently assessed the internal validity of the included trials. Authors were contacted to obtain missing information.
RESULTS
Nine trials with a total of 1350 patients were reviewed. Except for three high-quality studies, the validity of the trials was moderate to low. Two high-quality studies showed no difference in pain intensity and functional status between the exercise groups and the control groups. In the third high-quality study significant reduction in sick leave was found in favor of water gymnastics compared with no intervention. Because the included trials were considered heterogeneous with regard to study design, population intervention and outcome, no meta-analysis was performed.
CONCLUSIONS
Because of heterogeneity and the varying quality of the studies no strong evidence exists concerning the effect of physical therapy interventions on the prevention and treatment of back and pelvic pain related to pregnancy. Future studies should meet current methodological standards, and interventions to be evaluated should be based on established theoretical framework.
Topics: Female; Humans; Low Back Pain; Pelvic Pain; Physical Therapy Modalities; Pregnancy; Pregnancy Complications
PubMed: 14616270
DOI: 10.1034/j.1600-0412.2003.00125.x -
The Cochrane Database of Systematic... Sep 2011Endometriosis is a prevalent gynaecological condition, significantly affecting women's lives. Clinical presentations may vary from absence of symptoms to complaints of... (Review)
Review
BACKGROUND
Endometriosis is a prevalent gynaecological condition, significantly affecting women's lives. Clinical presentations may vary from absence of symptoms to complaints of chronic pelvic pain, most notably dysmenorrhoea. The management of pain in endometriosis is currently inadequate. Acupuncture has been studied in gynaecological disorders but its effectiveness for pain in endometriosis is uncertain.
OBJECTIVES
To determine the effectiveness and safety of acupuncture for pain in endometriosis.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group (MSDG) Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL, AMED, PsycINFO, CNKI and TCMDS (from inception to 2010) and reference lists of retrieved articles.
SELECTION CRITERIA
Randomised single or double-blind controlled trials enrolling women of reproductive age with a laparoscopically confirmed diagnosis of endometriosis and comparing acupuncture (body, scalp or auricular) to either placebo or sham, no treatment, conventional therapies or Chinese herbal medicine.
DATA COLLECTION AND ANALYSIS
Three authors independently assessed risk of bias and extracted data; we contacted study authors for additional information. Meta-analyses were not performed as only one study was included. The primary outcome measure was decrease in pain from endometriosis. Secondary outcome measures included improvement in quality of life scores, pregnancy rate, adverse effects and rate of endometriosis recurrence.
MAIN RESULTS
Twenty-four studies were identified that involved acupuncture for endometriosis; however only one trial, enrolling 67 participants, met all the inclusion criteria. The single included trial defined pain scores and cure rates according to the Guideline for Clinical Research on New Chinese Medicine. Dysmenorrhoea scores were lower in the acupuncture group (mean difference -4.81 points, 95% confidence interval -6.25 to -3.37, P < 0.00001) using the 15-point Guideline for Clinical Research on New Chinese Medicine for Treatment of Pelvic Endometriosis scale. The total effective rate ('cured', 'significantly effective' or 'effective') for auricular acupuncture and Chinese herbal medicine was 91.9% and 60%, respectively (risk ratio 3.04, 95% confidence interval 1.65 to 5.62, P = 0.0004). The improvement rate did not differ significantly between auricular acupuncture and Chinese herbal medicine for cases of mild to moderate dysmenorrhoea, whereas auricular acupuncture did significantly reduce pain in cases of severe dysmenorrhoea. Data were not available for secondary outcomes measures.
AUTHORS' CONCLUSIONS
The evidence to support the effectiveness of acupuncture for pain in endometriosis is limited, based on the results of only a single study that was included in this review. This review highlights the necessity for developing future studies that are well-designed, double-blinded, randomised controlled trials that assess various types of acupuncture in comparison to conventional therapies.
Topics: Acupuncture, Ear; Drugs, Chinese Herbal; Dysmenorrhea; Endometriosis; Female; Humans; Pelvic Pain; Randomized Controlled Trials as Topic
PubMed: 21901713
DOI: 10.1002/14651858.CD007864.pub2 -
Archives of Gynecology and Obstetrics Oct 2023The aim of this NMA is to comprehensively analyze evidence of oral GnRH antagonist in the treatment of moderate-to-severe endometriosis-associated pain. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The aim of this NMA is to comprehensively analyze evidence of oral GnRH antagonist in the treatment of moderate-to-severe endometriosis-associated pain.
METHODS
Literature searching was performed to select eligible studies published prior to April 2022 in PubMed, Cochrane, Embase and Web of Science. Randomized controlled trials involving patients who suffered from moderate-to-severe endometriosis-associated pain and treated with oral nonpeptide GnRH antagonists or placebo were included.
RESULTS
Elagolix 400 mg and ASP1707 15 mg were most efficient in reducing pelvic pain, dysmenorrhea and dyspareunia. Relugolix 40 mg was best in reducing the analgesics use. The rates of any TEAEs and TEAEs-related discontinuation were highest in relugolix 40 mg and elagolix 250 mg, respectively, while rates of hot flush and headache were highest in relugolix 40 mg and elagolix 150 mg. Significantly decreased spinal BMD was observed in elagolix 250 mg.
CONCLUSION
Oral GnRH antagonists were effective in endometriosis-associated pain in 12w, and most of the efficiency and safety outcomes were expressed in a dose-dependent manner, but linzagolix 75 mg was an exception.
Topics: Female; Humans; Endometriosis; Network Meta-Analysis; Gonadotropin-Releasing Hormone; Hormone Antagonists; Pelvic Pain
PubMed: 36656435
DOI: 10.1007/s00404-022-06862-0