Savi Scout Localization for Extrapelvic Endometriosis Resection.

BACKGROUND Endometriosis is a common cause of chronic pelvic pain among women globally. Pharmacological therapy for endometriosis includes non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal contraceptives, while surgical therapy often involves either laparoscopic excision and ablation of endometriosis implants or open surgery. Surgical therapy is one of the mainstays of treatment especially for extrapelvic endometriomas. However, little guidance exists for the treatment of non-palpable or intermittently palpable lesions of this nature. CASE REPORT A 33-year-old woman with a previous cesarean section presented with complaints of intermittent discomfort in the area between her umbilicus and the surgical incision, for the previous 7 years, that worsened during her menstrual cycle. A 3×3-cm area of fullness was only intermittently palpable during various clinic visits, but was visualizable on computed tomography and magnetic resonance imaging. Given the lesion's varying palpability, a Savi Scout radar localization device was placed into the lesion pre-operatively to aid with surgical resection. The mass was excised, pathologic examination revealed endometrial tissue, and the patient had an uncomplicated postoperative course with resolution of her symptoms. CONCLUSIONS Surgical removal of extrapelvic endometrioma lesions can be made difficult by varying levels of palpability or localizability due to a patient's menstrual cycle. The Savi Scout, most commonly used in breast mass localization, is a useful tool in guiding surgical excision of non-palpable or intermittently palpable extrapelvic endometrioma lesions.

Acute diverticulitis of the appendix.

Acute diverticulitis of the appendix (ADA), though uncommon, often presents similarly to acute appendicitis but carries a higher risk of complications such as perforation and malignancy. We report the case of a male patient in his 50s with acute right iliac fossa abdominal pain, diagnosed via CT scan with ADA. Urgent laparoscopic appendicectomy was performed, and the patient was discharged without further issues. This case highlights the importance of promptly identifying and managing such conditions to minimise complications and improve outcomes. Despite the overlap in symptoms between appendiceal diverticulitis and acute appendicitis, accurate diagnosis is crucial for appropriate treatment. Healthcare providers should maintain a high index of suspicion, particularly in older patients presenting with an acute appendicitis, like clinical picture to ensure timely intervention and optimal patient care.

Emergency department attendances for persistent pelvic pain are not reduced following laparoscopic surgery for women with or without endometriosis.

AIM: To explore the change in emergency department (ED) attendances for persistent pelvic pain (PPP) following laparoscopic treatment of endometriosis. METHODS: A retrospective service evaluation was conducted on a convenience sample of 1 calendar year of elective gynaecological laparoscopies for PPP. Data were collected on ED visits for surgical complications, and for PPP in the 12 months prior to and following surgery. RESULTS: Of the 195 women undergoing laparoscopy, 30 had attended the ED owing to their PPP in the preceding year. Endometriosis was found and treated in 51% of the cohort and no cause for pain was found in the other 96 women. Eighteen women suffered postoperative complications. In the subsequent 12 months, 31 of the cohort attended the ED for PPP. Likelihood of unscheduled hospital visits for post-operative complications and for exacerbations of pain in the year prior to and following surgery was independent of the presence of endometriosis lesions. CONCLUSIONS: In a cohort of women living with PPP, laparoscopic surgery failed to reduce the need to attend the ED owing to their pain. Further investigation into interventions that can reduce the burden of pain on these women and the healthcare system is required.

An artificial intelligence approach for investigating multifactorial pain-related features of endometriosis.

Endometriosis is a debilitating, chronic disease that is estimated to affect 11% of reproductive-age women. Diagnosis of endometriosis is difficult with diagnostic delays of up to 12 years reported. These delays can negatively impact health and quality of life. Vague, nonspecific symptoms, like pain, with multiple differential diagnoses contribute to the difficulty of diagnosis. By investigating previously imprecise symptoms of pain, we sought to clarify distinct pain symptoms indicative of endometriosis, using an artificial intelligence-based approach. We used data from 473 women undergoing laparoscopy or laparotomy for a variety of surgical indications. Multiple anatomical pain locations were clustered based on the associations across samples to increase the power in the probability calculations. A Bayesian network was developed using pain-related features, subfertility, and diagnoses. Univariable and multivariable analyses were performed by querying the network for the relative risk of a postoperative diagnosis, given the presence of different symptoms. Performance and sensitivity analyses demonstrated the advantages of Bayesian network analysis over traditional statistical techniques. Clustering grouped the 155 anatomical sites of pain into 15 pain locations. After pruning, the final Bayesian network included 18 nodes. The presence of any pain-related feature increased the relative risk of endometriosis (p-value < 0.001). The constellation of chronic pelvic pain, subfertility, and dyspareunia resulted in the greatest increase in the relative risk of endometriosis. The performance and sensitivity analyses demonstrated that the Bayesian network could identify and analyze more significant associations with endometriosis than traditional statistical techniques. Pelvic pain, frequently associated with endometriosis, is a common and vague symptom. Our Bayesian network for the study of pain-related features of endometriosis revealed specific pain locations and pain types that potentially forecast the diagnosis of endometriosis.

The association of endosalpingiosis with chronic pelvic pain.

BACKGROUND: Endosalpingiosis is a pathologic diagnosis of ectopic epithelium resembling the fallopian tubes. It has been described with clinical characteristics that are similar to endometriosis. The primary objective is to determine if endosalpingiosis (ES) has a similar association with chronic pelvic pain when compared to endometriosis (EM). METHODS: This is a retrospective case-control analysis of patients with a histologic diagnosis of endosalpingiosis or endometriosis at three affiliated academic hospitals between 2000 and 2020. All ES patients were included, and 1:1 matching was attempted to obtain a comparable EM cohort. Demographic and clinical data were obtained, and statistical analysis was performed. RESULTS: A total of 967 patients (515 ES and 452 EM) were included. ES patients were significantly older than EM patients (median age 52 vs. 48 years, P<0.001), but other demographic variables were similar. Fewer ES patients had baseline chronic pelvic pain than EM patients (25.3% vs. 47%, P<0.001), and patients with ES were less likely to undergo surgery for the primary indication of pelvic pain (16.1% vs. 35.4%, P<0.001). Pelvic pain as the surgical indication remained lower in the ES group in multivariable analysis (OR=0.49, P<0.001). There were similar rates of persistent postoperative pain between ES and EM groups (10.1% vs. 13.5%, P=0.109). CONCLUSIONS: Although endosalpingiosis can be associated with chronic pelvic pain, the incidence of pain is significantly lower than in patients who have endometriosis. These findings suggest that ES is a unique condition that differs from EM. Further research including long-term follow-up and patient-reported outcomes is imperative.

Treatment of rectosigmoid endometriosis by laparoscopic reverse submucosal dissection (LRSD): The Sydney partial thickness discoid excision technique.

BACKGROUND: Laparoscopic reverse submucosal dissection (LRSD) is a standardised surgical technique for removal of rectosigmoid endometriosis which optimises the anatomical dissection plane for excision of endometriotic nodules. AIM: This cohort study assesses the outcomes of the first cohort of women treated by LRSD, for deeply infiltrating rectosigmoid endometriosis. MATERIALS AND METHODS: Primary outcomes assessed were complication rate as defined by the Clavien-Dindo system, and completion of the planned LRSD. Secondary outcomes include mucosal breach, specimen margin involvement, length of hospital admission, and a comparison of pre-operative and post-operative pain, bowel function and quality of life surveys. These included the Endometriosis Health Profile Questionnaire (EHP-30), the Knowles-Eccersley-Scott Symptom Questionnaire (KESS) and the Wexner scale. RESULTS: Of 19 patients treated, one required a segmental resection. The median length of hospital admission was two days (range 1-5) and no post-operative complications occurred. Median pain visual analogue scales (scale 0-10) were higher prior to surgery (dysmenorrhoea 9.0, dyspareunia 7.5, dyschezia 9.0, pelvic pain 6.0) compared to post-surgical median scores (dysmenorrhoea 5.0, dyspareunia 4.0, dyschezia 2.0, pelvic pain 4.0) at a median of six months (range 4-32). Quality of life studies suggested improvement following surgery with pre-operative median EHP-30 and KESS scores (EHP-30: 85 (5-106), KESS score 9 (0-20)) higher than post-operative scores (EHP-30: 48.5 (0-80), KESS score: 3 (0-19)). CONCLUSION: This series highlights the feasibility of LRSD with low associated morbidity as a progression of partial thickness discoid excision (rectal shaving) for the treatment of rectosigmoid deep infiltrating endometriosis.

Improvement in chronic pelvic pain, orthostatic intolerance and interstitial cystitis symptoms after treatment of pelvic vein insufficiency.

OBJECTIVES: Comorbidities associated with venous origin chronic pelvic pain (VO-CPP) were evaluated pre and post venous treatment to assess change. MATERIALS AND METHODS: 45 women with VO-CPP were treated with venous stenting and/or embolization. Four surveys assessed symptoms pre- and post-treatment: IPPS (chronic pelvic pain), PUF (interstitial cystitis), OHQ (dysautonomia), and modified ROME III (IBS). Prevalence of joint hypermobility was investigated. RESULTS: Ages were 18-65. Pretreatment, 64% and 49% of women were in the severe range for PUF and OHQ, respectively. 40% and 56% met criteria for IBS and Ehlers-Danlos syndrome/Hypermobility Spectrum Disorder (EDS/HSD), respectively. 17eceived an iliac stent, 5 pelvic embolization, and 23 both. Post-treatment, average scores improved: IPPS (by 55%), PUF (34%), and OHQ (49%). Rome III improved only slightly. CONCLUSION: Pelvic pain, interstitial cystitis, and dysautonomia were frequently found with VO-CPP and improved after venous treatment. EDS/HSD and IBS were common in these women.

Evaluation and Management of Endometriosis in the Adolescent.

Endometriosis is a chronic condition, with debilitating symptoms affecting all ages. Dysmenorrhea and pelvic pain often begin in adolescence, affecting school, daily activities, and relationships. Despite the profound burden of endometriosis, many adolescents experience suboptimal management and significant delay in diagnosis. The symptomatology and laparoscopic findings of endometriosis in adolescents are often different than in adults, and the medical and surgical treatments for adolescents may differ from those for adults as well. This Narrative Review summarizes the diagnosis, evaluation, and management of endometriosis in adolescents. Given the unique challenges and complexities associated with diagnosing endometriosis in this age group, it is crucial to maintain a heightened level of suspicion and to remain vigilant for signs and symptoms. By maintaining this lower threshold for consideration, we can ensure timely and accurate diagnosis, enabling early intervention and improved management in our adolescent patients.

Endometriosis-related infertility: severe pain symptoms do not impact assisted reproductive technology outcomes.

STUDY QUESTION: Do severe endometriosis-related painful symptoms impact ART live birth rates? SUMMARY ANSWER: Severe pain symptoms are not associated with reduced ART live birth rates in endometriosis patients. WHAT IS KNOWN ALREADY: ART is currently recognized as one of the main therapeutic options to manage endometriosis-related infertility. Presently, no data exist in the literature regarding the association between the core symptom of the disease, e.g. pain and ART reproductive outcomes. STUDY DESIGN, SIZE, DURATION: Observational cohort study of 354 endometriosis patients, who underwent ART at a tertiary care university hospital, between October 2014 and October 2021. Diagnosis of endometriosis was based on published imaging criteria using transvaginal sonography and magnetic resonance imaging, and histologically confirmed in women who had a previous history of endometriosis surgery (n = 127, 35.9%). PARTICIPANTS/MATERIALS, SETTING, METHODS: The intensity of painful symptoms related to dysmenorrhea (DM), dyspareunia (DP), noncyclic chronic pelvic pain, gastrointestinal (GI) pain, or lower urinary tract pain was evaluated using a 10-point visual analog scale (VAS), before ART. Severe pain was defined as having a VAS of 7 or higher for at least one symptom. The main outcome measure was the cumulative live birth rate (CLBR) per patient. We analyzed the impact of endometriosis-related painful symptoms on ART live births using univariable and multivariate analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Three hundred and fifty-four endometriosis patients underwent 711 ART cycles. The mean age of the population was 33.8 ± 3.7 years, and the mean duration of infertility was 3.6 ± 2.1 years. The distribution of the endometriosis phenotypes was 3.1% superficial endometriosis, 8.2% ovarian endometrioma, and 88.7% deep infiltrating endometriosis. The mean VAS scores for DM, DP, and GI pain symptoms were 6.6 ± 2.7, 3.4 ± 3.1, and 3.1 ± 3.6, respectively. Two hundred and forty-two patients (68.4%) had severe pain symptoms. The CLBR per patient was 63.8% (226/354). Neither the mean VAS scores for the various painful symptoms nor the proportion of patients displaying severe pain differed significantly between patients who had a live birth and those who had not, based on univariate and multivariate analyses (P = 0.229). The only significant factors associated with negative ART live births were age >35 years (P < 0.001) and anti-Müllerian hormone levels <1.2 ng/ml (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The diagnosis of endometriosis was based on imaging rather than surgery. This limitation is, however, inherent to the design of most studies on endometriosis patients reverting to ART first. WIDER IMPLICATIONS OF THE FINDINGS: Rather than considering a single argument such as pain, the decision-making process for choosing between ART and surgery in infertile endometriosis patients should be based on a multitude of aspects, including the patient's choice, the associated infertility factors, the endometriosis phenotypes, and the efficiency of medical therapies in regard to pain symptoms, through an individualized approach guided by a multidisciplinary team of experts. STUDY FUNDING/COMPETING INTEREST(S): No funding; no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Latest insights into the pathophysiology of bladder pain syndrome/interstitial cystitis.

PURPOSE OF REVIEW: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a common medical problem in both sexes affecting people of all ages. Patients might report overactive bladder symptoms with additional bladder pain at maximum bladder filling, during and after micturition. This review aims to highlight pathophysiological mechanisms associated with this disease. RECENT FINDINGS: Latest literature exposes different pathophysiological mechanisms such as impaired urothelial barrier function, alteration of urothelial factors and cytokines, chronic inflammation, vascular lesions, neurogenic inflammation and processes in the central nervous system leading to central sensitization. According to the involved mechanisms, BPS/IC may be arranged in clusters according to the clinical phenotype thus helping in clinical decision-making and treatment. Moreover, patients with BPS/IC suffer from other comorbidities such as fibromyalgia, irritable bowel syndrome, chronic pain and functional syndromes and psychosomatic diseases making the management challenging for medical professionals. SUMMARY: Bladder pain syndrome/interstitial cystitis is a complex heterogeneous medical condition involving different pathomechanisms leading to bladder pain and dysfunction, consequently, impairing quality-of-life in affected individuals. However, these mechanisms are still not fully understood, so that patient treatments often remain unsatisfactory. For this reason, continuing research is important to understand the underlying pathomechanisms to discover biomarkers and treatment targets eventually improving diagnostic and therapeutic measures of BPS/IC.

Infertility in patients with uterine fibroids: a debate about the hypothetical mechanisms.

Fibroids are benign tumours of the myometrium and are the most common gynaecologic abnormality. Although most fibroids are asymptomatic, they can cause symptoms like heavy menstrual bleeding, pelvic pain, sexual dysfunction, pressure complaints, and infertility. The association between fibroids and infertility has been debated for decades. It is generally acknowledged that the closer the fibroid is to the uterine cavity and the endometrium lining, the more unfavourable effect it might have on fertility, reducing the odds for successful implantation and gestation. Based on the limited available literature, we propose and discuss seven hypotheses on the underlying mechanism by which fibroids may reduce fertility. (i) Fibroids can cause sexual dysfunction, as fibroids can cause dyspareunia, pelvic pain, and prolonged and heavy menstrual bleeding, which could interfere with sexual arousal and as a consequence the frequency of intercourse, resulting in a reduced probability of conception. (ii) Mechanical compression by fibroids on theinterstitial part of the fallopian tubes or deformation of uterine cavity could disturb oocyte and sperm transport. (iii) Fibroids can disturb peristalsis of the junctional zone in the myometrium, which could negatively influence oocyte and sperm transport as well as implantation. In addition, fibroids could induce a detrimental environment for implantation in other ways, by: (iv) changing the vagino-uterine microbiome; (v) disturbing the levels of inflammation and autophagy; (vi) inducing molecular changes in the endometrium; and (vii) inducing aberrant angiogenesis and altering the endometrial blood supply. After the discussion of these hypotheses, the implication of the influence of fibroids on early pregnancy loss is discussed. Surgical fibroid treatment is not tailored nor focussed on the pathophysiology of the fibroid; consequently it may be accompanied by recurrence of fibroids and risks of complications. Unravelling the pathogenic mechanisms about how fibroids influence fertility is essential to evolve classic surgical fibroid treatment. Instead of treatment of fibroid-related symptoms, the research should supports development of fibroid-targeted (pharmaceutical) treatment that is compatible with an active wish to become pregnant.

Isthmoceles: A Growing Concern.

An isthmocele is described as a pouch-like defect in the uterus with a thin roof formed by inadequate healing of the smooth muscle of the anterior uterine wall at the site of a hysterotomy. With increased rates of deliveries by cesarean section, isthmoceles are becoming a more common cause of gynecologic and obstetric complications. Gynecologic issues include pelvic pain, postmenstrual bleeding, and reduced fertility or infertility. Therefore, it is important that providers consider these defects in their differential diagnosis as their presentation can mimic other gynecologic conditions, such as endometriosis. Fortunately, many effective treatment options are available, such as conservative hormonal treatment or surgical repair by laparoscopic, hysteroscopic, or transvaginal methods.

The role of CD8+ T cells in endometriosis: a systematic review.

Background: Endometriosis is a chronic disease affecting 6-10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood aetiology. CD8+ T (CD8 T) cells were shown to be linked to infertility and chronic pain and play a significant role in lesion clearance in other pathologies, yet their function in endometriosis is unknown. We systematically evaluated the literature on the CD8 T in peripheral blood and endometriosis-associated tissues to determine the current understanding of their pathophysiological and clinical relevance in the disease and associated conditions (e.g. infertility and pelvic pain). Methods: Four databases were searched (MEDLINE, EMBASE, Web of Science, CINAHL), from database inception until September 2022, for papers written in the English language with database-specific relevant terms/free-text terms from two categories: CD8 T cells and endometriosis. We included peer-reviewed papers investigating CD8 T cells in peripheral blood and endometriosis-associated tissues of patients with surgically confirmed endometriosis between menarche and menopause, and animal models with oestrous cycles. Studies enrolling participants with other gynaecological pathologies (except uterine fibroids and tubal factor infertility used as controls), cancer, immune diseases, or taking immune or hormonal therapy were excluded. Results: 28 published case-control studies and gene set analyses investigating CD8 T cells in endometriosis were included. Data consistently indicate that CD8 T cells are enriched in endometriotic lesions in comparison to eutopic endometrium, with no differences in peripheral blood CD8 T populations between patients and healthy controls. Evidence on CD8 T cells in peritoneal fluid and eutopic endometrium is conflicting. CD8 T cell cytotoxicity was increased in the menstrual effluent of patients, and genomic analyses have shown a clear trend of enriched CD8 T effector memory cells in the eutopic endometrium of patients. Conclusion: Literature on CD8 T cells in endometriosis-associated tissues is inconsistent. Increased CD8 T levels are found in endometriotic lesions, however, their activation potential is understudied in all relevant tissues. Future research should focus on identifying clinically relevant phenotypes to support the development of non-invasive diagnostic and treatment strategies. Systematic Review Registration: PROSPERO identifier CRD42021233304.

Severe pelvic pain is associated with sexual abuse experienced during childhood and/or adolescence irrespective of the presence of endometriosis.

STUDY QUESTION: Is endometriosis associated with childhood and/or adolescent sexual abuse? SUMMARY ANSWER: Endometriosis is not associated with a history of sexual abuse, unlike the presence of severe pelvic pain. WHAT IS KNOWN ALREADY: Several studies have highlighted a link between pelvic pain and sexual abuse during childhood/adolescence. Moreover, an inflammatory state has been described in patients with a history of childhood maltreatment. Given that inflammation and pelvic pain are two entities often encountered with endometriosis, several teams have investigated whether endometriosis is associated with abuse during childhood/adolescence. However, the results are conflicting, and the link between sexual abuse and the presence of endometriosis and/or pain is hard to disentangle. STUDY DESIGN, SIZE, DURATION: A survey nested in a cohort study of women surgically explored for benign gynecological indications at our institution between January 2013 and January 2017. For each patient, a standardized questionnaire was completed during a face-to-face interview with the surgeon in the month preceding the surgery. Pelvic pain symptoms (dysmenorrhea, deep dyspareunia, non-cyclic chronic pelvic pain, and gastrointestinal or lower urinary tract symptoms) and their intensities were assessed with a 10 cm visual analog scale (VAS). Pain was considered to be severe when the VAS score was ≥7. PARTICIPANTS/MATERIALS, SETTING, METHODS: A 52-question survey was sent in September of 2017 to evaluate abuses, especially sexual abuse during childhood and/or adolescence, and the psychological state during childhood and adolescence. The survey was structured to cover the following sections: (i) abuses and other life events during childhood and adolescence; (ii) puberty and body changes; (iii) onset of sexuality; and (iv) family relationships during childhood and adolescence. The patients were divided into groups according to whether or not they exhibited histologically proven endometriosis. Statistical analyses were conducted using univariate and multivariate logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Two hundred and seventy-one patients answered all the questions of the survey: 168 with (endometriosis group) and 103 without endometriosis (control group). The mean ± SD overall population age was 32.2 ± 5.1 years. There were 136 (80.9%) and 48 (46.6%) women who experienced at least one severe pelvic pain symptom in the endometriosis and the control groups, respectively (P < 0.001). No differences were found between the two study groups regarding the following characteristics: (i) a history of sexual, physical, or emotional abuse; (ii) a history of abandonment or bereavement; (iii) the psychological state regarding puberty; and (iv) the family relationships. After multivariable analysis, we found no significant association between endometriosis and a history of sexual abuse during childhood and/or adolescence (P = 0.550). However, the presence of at least one severe pelvic pain symptom was independently associated with a history of sexual abuse (odds ratio = 3.6, 95% CI (1.2-10.4)). LIMITATIONS, REASONS FOR CAUTION: Evaluation of the psychological state during childhood and/or adolescence can be subject to recall bias. In addition, selection bias is also a possibility given that some of the patients surveyed did not return the questionnaire. WIDER IMPLICATIONS OF THE FINDINGS: Severe gynecological painful symptoms in women with or without histologically proven endometriosis may be linked to sexual abuse experienced during childhood and/or adolescence. Patient questioning about painful symptoms and abuses is important to provide comprehensive care to the patients, from a psychological to a somatic point of view. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests. TRIAL REGISTRATION NUMBER: N/A.

Current status of patient-reported outcome measures and other subjective assessment grading tools in bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is characterised by chronic pain in the bladder area accompanied by urgency and/or frequency without the presence of other confusable diseases. Owing to a lack of gold standard diagnostic tests and definitive cure it is paramount to define treatment goals and validated measurements of outcomes. Patient-reported outcome measures (PROMs) are validated questionnaires completed by patients that can help to reduce ambiguity in the BPS patient treatment pathway, but they are currently underutilised. We present to our knowledge the first summary and analysis of all available PROMs in BPS patients. METHODS: Review and critical evaluation of all relevant BPS guidelines presented in English language and a systematic search for PubMed database articles relating to PROMs and subjective assessment grading tools in BPS, interstitial cystitis and chronic pelvic pain syndrome. RESULTS: The ideal PROMs for BPS should assess urinary symptoms, pain, quality of life and sexual health. There are five PROMs designed specifically for BPS patients. The most universally used and quoted is the O'Leary-Sant questionnaire followed by the Pelvic Pain and Urgency Score and the Wisconsin Interstitial Cystitis scale. However, there is no single PROM for BPS that is ideal, and for comprehensive assessment several questionnaires are often used simultaneously. CONCLUSIONS: Patient-reported outcome measures are a valuable tool for use in the long-term management of patients burdened with BPS. There are now several disease-specific PROMs in use that have their respective advantages and disadvantages. Their use should be encouraged in future research as well as continued efforts to develop new PROMs that can address current shortcomings.

Prolactin and pain of endometriosis.

Women experience chronic pain more often than men with some pain conditions being specific to women while others are more prevalent in women. Prolactin, a neuropeptide hormone with higher serum levels in women, has recently been demonstrated in preclinical studies to sensitize nociceptive sensory neurons in a sexually dimorphic manner. Dysregulation of prolactin and prolactin receptors may be responsible for increased pain especially in female predominant conditions such as migraine, fibromyalgia, and pelvic pain. In this review, we focus on the role of prolactin in endometriosis, a condition characterized by pelvic pain and infertility that affects a large proportion of women during their reproductive age. We discuss the symptoms and pathology of endometriosis and discuss how different sources of prolactin secretion may contribute to this disease. We highlight our current understanding of prolactin-mediated mechanisms of nociceptor sensitization in females and how this mechanism may apply to endometriosis. Lastly, we report the results of a systematic review of clinical studies conducted by searching the PubMed and EMBASE databases to identify association between endometriosis and blood levels of prolactin. The results of this search strongly indicate that serum prolactin levels are increased in patients with endometriosis and support the possibility that high levels of prolactin may promote pelvic pain in these patients and increase vulnerability to other comorbid pain conditions likely by dysregulating prolactin receptor expression. Targeting of prolactin and prolactin receptors may improve management of pain associated with endometriosis.

Serum concentrations of IL-16 and its genetic polymorphism rs4778889 affect the susceptibility and severity of endometriosis in Nigerian women.

BACKGROUND: Endometriosis is the presence of active ectopic endometrial glands and stroma at other sites outside the uterine cavity. It is a common cause of chronic pelvic pain which is sometimes debilitating, and inflammation is one of the known triggers of endometriosis. Interleukins 6 and 16 (IL-6 and IL-16) are proinflammatory cytokines which play essential roles in inflammatory diseases. We therefore investigated the relationship between genetic polymorphisms of interleukins 6 and 16, and the development of endometriosis in Nigerian women. METHOD: One hundred and thirty (130) consenting women were consecutively enrolled, sixty-five (65) of whom had endometriosis and 65 age-matched women as reference group, surgically confirmed as not having endometriosis. Spectrophotometric determination of serum concentrations of Interleukins 6 and 16 was carried out and the genotyping of IL-6 (rs1800795) and IL-16 (rs4778889, rs11556218, rs4072111) genes were performed using TaqMan assays. RESULTS: Serum IL-16 concentration was significantly higher in women with severe chronic pelvic pain compared to those with mild pain (p = 0.023). The C allele of rs4778889 was associated with endometriosis (OR: 1.80, 95% CI: 1.08 - 3.02, p = 0.024). CONCLUSION: Serum IL-16 and IL-16 rs4778889 may be important markers for endometriosis in Nigerian, and by extension, African women. Multicentre African studies would clarify this.

Pelvic pain comorbidities associated with quality of life after endometriosis surgery.

BACKGROUND: After endometriosis surgery, pain can persist or recur in a subset of patients. A possible reason for persistent pain after surgery is central nervous system sensitization and associated pelvic pain comorbidities. Surgery addresses the peripheral component of endometriosis pain pathophysiology (by lesion removal) but may not treat this centralized pain. Therefore, endometriosis patients with pelvic pain comorbidities related to central sensitization may experience worse pain-related outcomes after surgery, such as lower pain-related quality of life. OBJECTIVE: This study aimed to determine whether baseline (preoperative) pelvic pain comorbidities are associated with pain-related quality of life at follow-up after endometriosis surgery. STUDY DESIGN: This study used longitudinal prospective registry data from the Endometriosis Pelvic Pain Interdisciplinary Cohort at the BC Women's Centre for Pelvic Pain and Endometriosis. Participants were aged ≤50 years with confirmed or clinically suspected endometriosis, and underwent surgery (fertility-sparing or hysterectomy) for endometriosis pain. Participants completed the pain subscale of the Endometriosis Health Profile-30 quality of life questionnaire preoperatively and at follow-up (1-2 years). Linear regression was performed to measure the individual relationships between 7 pelvic pain comorbidities at baseline and follow-up Endometriosis Health Profile-30 score, controlling for baseline Endometriosis Health Profile-30 and type of surgery received. These baseline (preoperative) pelvic pain comorbidities included abdominal wall pain, pelvic floor myalgia, painful bladder syndrome, irritable bowel syndrome, Patient Health Questionnaire 9 depression score, Generalized Anxiety Disorder 7 score, and Pain Catastrophizing Scale score. Least absolute shrinkage and selection operator regression was then performed to select the most important variables associated with follow-up Endometriosis Health Profile-30 from 17 covariates (including the 7 pelvic pain comorbidities, baseline Endometriosis Health Profile-30 score, type of surgery, and other endometriosis-related factors such as stage and histologic confirmation of endometriosis). Using 1000 bootstrap samples, we estimated the coefficients and confidence intervals of the selected variables and generated a covariate importance rank. RESULTS: The study included 444 participants. The median follow-up time was 18 months. Pain-related quality of life (Endometriosis Health Profile-30) of the study population significantly improved at follow-up after surgery (P<.001). The following pelvic pain comorbidities were associated with lower quality of life (higher Endometriosis Health Profile-30 score) after surgery, controlling for baseline Endometriosis Health Profile-30 score and type of surgery (fertility-sparing vs hysterectomy): abdominal wall pain (P=.013), pelvic floor myalgia (P=.036), painful bladder syndrome (P=.022), Patient Health Questionnaire 9 score (P<.001), Generalized Anxiety Disorder 7 score (P<.001), and Pain Catastrophizing Scale score (P=.007). Irritable bowel syndrome was not significant (P=.70). Of the 17 covariates included for least absolute shrinkage and selection operator regression, 6 remained in the final model (lambda=3.136). These included 3 pelvic pain comorbidities that were associated with higher follow-up Endometriosis Health Profile-30 scores or worse quality of life: abdominal wall pain (ß=3.19), pelvic floor myalgia (ß=2.44), and Patient Health Questionnaire 9 depression score (ß=0.49). The other 3 variables in the final model were baseline Endometriosis Health Profile-30 score, type of surgery, and histologic confirmation of endometriosis. CONCLUSION: Pelvic pain comorbidities present at baseline before surgery, which may reflect underlying central nervous system sensitization, are associated with lower pain-related quality of life after endometriosis surgery. Particularly important were depression and musculoskeletal/myofascial pain (abdominal wall pain and pelvic floor myalgia). Therefore, these pelvic pain comorbidities should be candidates for a formal prediction model of pain outcomes after endometriosis surgery.

Evaluation and management of endometriosis.

The initial diagnostic investigations for endometriosis are physical examination and pelvic ultrasound. The pelvic examination should include a speculum examination and vaginal palpation. Mobility, fixation and/or tenderness of the uterus and site-specific tenderness in the pelvis should be evaluated. Transvaginal ultrasound and pelvic magnetic resonance imaging are recommended to evaluate the extent of the endometriosis and to determine whether any urinary tract or bowel procedures might also be required during surgical resection. Quality of life should be assessed by using the Endometriosis Health Profile-30, its short version EHP-5 or the generic quality of life questionnaire SF-36. Management of endometriosis is recommended when it has a functional impact (pain, infertility) or causes organ dysfunction. Many gynecological societies have published different guidelines for the evaluation and management of endometriosis. However, the complexity of this disease together with the different available treatments lead to significant discrepancies between the recommendations. Postmenopausal endometriosis should be considered when a patient has a history of symptoms before menopause including dysmenorrhea, dyspareunia, dyschezia, infertility and chronic pelvic pain. Malignant transformation of endometriosis is estimated to occur in about 0.7-1.6% of women affected by endometriosis. Endometriosis is associated with an increased risk of ovarian cancer, specifically clear cell, endometrioid and low-grade serous types.