Objective. Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. The objective of this study was to investigate the degree of connectivity between multiple brain networks in patients with FM, as well as how activity in these networks correlates with the level of spontaneous pain.Methods. Resting-state functional magnetic resonance imaging (FMRI) data from 18 patients with FM and 18 age-matched healthy control subjects were analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic, or resting-state, connectivity was evaluated in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also analyzed for covariance with intrinsic connectivity.Results. Patients with FM had greater connectivity within the DMN and right EAN (corrected P [P corr ] < 0.05 versus controls), and greater connectivity between the DMN and the insular cortex, which is a brain region known to process evoked pain. Furthermore, greater intensity of spontaneous pain at the time of the FMRI scan correlated with greater intrinsic connectivity between the insula and both the DMN and right EAN (P corr < 0.05).Conclusion. These findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in patients with FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay among multiple brain networks.

Uterine leiomyomas are one of the most common and yet understudied diseases in women. These tumors, commonly known as fibroids, affect women mainly during their reproductive years and are diagnosed in up to 70% of white women and more than 80% of women of African ancestry during their lifetime. This disease has a profound impact on health care delivery and costs worldwide. Though most women with fibroids are asymptomatic, approximately 30% of them will present with severe symptoms which can include abnormal uterine bleeding, anemia, pelvic pain and pressure, back pain, urinary frequency, constipation, or infertility, and will require intervention. Furthermore, fibroids have been associated with poor obstetrical outcomes. The current options for symptomatic fibroid treatment include expectant, medical, and surgical management, and interventional radiology procedures. This article reviews the recent progress and available management strategies for uterine fibroids and highlights areas where further research is needed to find new therapeutic targets and better personalize treatments.

No abstract

Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15-20% of women in the United States. Endometriosis is often associated with CPP, however other factors, such as pre-existing or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing.Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, as well as 23 healthy controls. All patients with endometriosis and/or CPP were surgically-confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception including the left thalamus, left cingulategyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis that had no CPP. We conclude thatCPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis.

BACKGROUND Endometriosis is an often chronic, inflammatory gynaecologic condition affecting 190 million women worldwide. Studies have reported an elevated cancer risk among patients with endometriosis. However, prior research has included methodologic issues that impede valid and robust interpretation. OBJECTIVE AND RATIONALE We conducted a meta-analysis of studies investigating the association between endometriosis and cancer risk and analysed the results by methodologic characteristics. We discuss the implications of cancer screening in patients and management challenges faced by clinicians. SEARCH METHODS We searched PubMed and Embase databases for eligible studies from inception through 24 October 2019. We included cohort and case-control studies examining the association between endometriosis and cancer risk; cross-sectional studies and case reports were excluded. Publications had to present risk/rate/odds estimates with 95% CI. Random effects meta-analysis was used to estimate summary relative risks (SRR) and CIs. Heterogeneity across studies was assessed by the Q test and I2 statistics, and publication bias using Egger's and Begg's tests. Risk of bias and quality of the included studies were assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. OUTCOMES Forty-nine population-based case-control and cohort studies were included. Twenty-six studies were scored as having a ‘serious’/‘critical’ risk of bias, and the remaining 23 ‘low’/‘moderate’. Cancer-specific analyses showed a positive association between endometriosis and ovarian cancer risk (SRR = 1.93, 95% CI = 1.68–2.22; n = 24 studies) that was strongest for clear cell (SRR = 3.44, 95% CI = 2.82–4.42; n = 5 studies) and endometrioid (SRR = 2.33, 95% CI = 1.82–2.98; n = 5 studies) histotypes (Pheterogeneity &lt; 0.0001), although with significant evidence of both heterogeneity across studies and publication bias (Egger’s and Begg’s P-values &lt; 0.01). A robust association was observed between endometriosis and thyroid cancer (SRR = 1.39, 95% CI =1.24–1.57; n = 5 studies), a very small association with breast cancer (SRR = 1.04, 95% CI =1.00–1.09; n = 20 studies) and no association with colorectal cancer (SRR = 1.00, 95% CI =0.87–1.16; n = 5 studies). The association with endometrial cancer was not statistically significant (SRR = 1.23, 95% CI =0.97–1.57; n = 17 studies) overall and wholly null when restricted to prospective cohort studies (SRR = 0.99, 95% CI =0.72–1.37; n = 5 studies). The association with cutaneous melanoma was also non-significant (SRR = 1.17, 95% CI =0.97–1.41; n = 7 studies) but increased in magnitude and was statistically significant when restricted to studies with low/moderate risk of bias (SRR = 1.71, 95% CI = 1.24–2.36, n = 2 studies). The most robust finding both in terms of statistical significance and magnitude of effect was an inverse association with cervical cancer (SRR = 0.68, 95% CI =0.56–0.82; n = 4 studies); however, this result has a high potential to reflect heightened access to detection of dysplasia for women who reached an endometriosis diagnosis and is thus likely not causal. Several additional cancer types were explored based on &lt;4 studies. WIDER IMPLICATIONS Endometriosis was associated with a higher risk of ovarian and thyroid, and minimally (only 4% greater risk) with breast cancer, and with a lower risk of cervical cancer. However, this meta-analysis confirms that: a majority of studies had severe/critical risk of bias; there is impactful heterogeneity across studies—and for ovarian cancer, publication bias; and causal inference requires temporality, which in many studies was not considered. We discuss the implications of these potential associations from the perspectives of patients with endometriosis, clinicians involved in their care, and scientists investigating their long-term health risks.

In contrast to women with relatively asymptomatic endometriosis, women with endometriosis-associated chronic pelvic pain (CPP) exhibit non-pelvic hyperalgesia and decreased gray matter volume in key neural pain processing regions. While these findings suggest central pain amplification in endometriosis-associated CPP, the underlying changes in brain chemistry and function associated with central pain amplification remain unknown. We performed proton spectroscopy and seed-based resting functional connectivity MRI to determine whether women with endometriosis display differences in insula excitatory neurotransmitter concentrations or intrinsic brain connectivity to other pain-related brain regions. Relative to age-matched pain-free controls, women with endometriosis-associated CPP displayed elevated levels of combined glutamine-glutamate (Glx) within the anterior insula, and greater anterior insula connectivity to the medial prefrontal cortex (mPFC). Increased connectivity between these regions was positively correlated with anterior insula Glx concentrations (r=0.87), as well as clinical anxiety (r=0.61,p=0.02), depression (r=0.60,p=0.03), and pain intensity (r=0.55,p=0.05). There were no significant differences in insula metabolite levels or resting-state connectivity in endometriosis without CPP subjects versus controls. We conclude that enhanced anterior insula glutamatergic neurotransmission and connectivity with the mPFC, key regions of the salience and default mode networks, may play a role in the pathophysiology of CPP independent of the presence of endometriosis.

OBJECTIVE To determine if women with chronic pelvic pain and variable degrees of endometriosis demonstrate altered pain sensitivity relative to pain-free healthy controls, and whether such differences are related to the presence or severity of endometriosis or comorbid pain syndromes. METHODS Four patient subgroups (endometriosis with chronic pelvic pain (n=42), endometriosis with dysmenorrhea (n=15), pain-free endometriosis (n=35), and chronic pelvic pain without endometriosis (n=22)) were each compared to 30 healthy controls in this cross-sectional study. All patients completed validated questionnaires regarding pain symptoms and underwent screening for comorbid pain disorders. Pain sensitivity was assessed by applying discrete pressure stimuli to the thumbnail using a previously validated protocol. RESULTS While adjusting for age and education, pain thresholds were lower in all subgroups of women with pelvic pain, relative to healthy controls (all p-values <0.01). There was no difference in pain thresholds when comparing endometriosis patients without pelvic pain to healthy controls (mean difference 0.02 kg/m2, 95% confidence interval -0.43, 0.47). The presence and severity of endometriosis and number of comorbid pain syndromes were not associated with a difference in pain thresholds. CONCLUSION Women with chronic pelvic pain demonstrate increased pain sensitivity at a nonpelvic site compared to healthy controls, which is independent of the presence or severity of endometriosis or comorbid pain syndromes. These findings support the notion that central pain amplification may play a role in the development of pelvic pain, and may explain why some women with pelvic pain do not respond to therapies aimed at eliminating endometriosis lesions.

Objective To quantify physician prescribing patterns and patient opioid use in the two weeks after hysterectomy at an academic institution, and determine whether patient factors predict postsurgical opioid use and pain recovery. Methods We conducted a prospective quality initiative study by recruiting all English-speaking patients undergoing hysterectomy for benign, non-obstetric indications at a university hospital between August and December 2015, excluding those with major medical morbidities or substance abuse. Before hysterectomy, patients completed the Fibromyalgia Survey, a validated measure of centralized pain. Following hysterectomy, opioid use (converted to oral morphine equivalents) and pain scores (0–10 numeric rating scale) were collected by a daily diary and a structured telephone interview 14 days after surgery. Primary outcomes were total opioid prescribed and consumed in the 2 weeks after hysterectomy. Secondary outcomes included daily opioid use and daily pain severity for 14 days after hysterectomy. Results Of 103 eligible patients, 102 (99%) agreed to participate, including 44 (43.1%) laparoscopic, 42 (41.2%) vaginal, and 16 (15.7%) abdominal hysterectomies. Telephone surveys were completed on 89 (87%) participants, diaries were returned from 60 (59%) participants. Diary non-responders had different baseline characteristics than non-responders. Median amount of opioid prescribed was 200 oral morphine equivalents (interquartile range (IQR) 150–250). Patients reported using approximately half of the opioids prescribed, with a median excess of 110 morphine equivalents (IQR 40–150). The best fit model of total opioid consumption identified preoperative Fibromyalgia Score, overall body pain, preoperative opioid use, prior endometriosis, abdominal hysterectomy (compared to laparoscopic), and uterine weight as significant predictors. Highest tertile of Fibromyalgia Score was associated with greater daily opioid consumption (13.9 [95% CI 3.0 – 24.8] greater OME at baseline, p=0.02). Conclusion Gynecologists at a large academic medical center prescribe twice the amount of opioids than the average patient uses after hysterectomy. A personalized approach to prescribing opioids for postoperative pain should be considered.