Association between body mass index and dysmenorrhea in women with endometriosis: a systematic review and meta-analysis

Paracetamol use during pregnancy - a call for precautionary action

Bauer AZ et al., 2021 · Nature reviews. Endocrinology · Free full text on PubMed Central

Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe.

Accurate diagnosis of endometriosis using serum microRNAs

Moustafa S et al., 2020 · American journal of obstetrics and gynecology · Free to read

Endometriosis, a chronic disease that afflicts millions of women worldwide, has traditionally been diagnosed by laparoscopic surgery. This diagnostic barrier delays identification and treatment by years, resulting in prolonged pain and disease progression. Development of a noninvasive diagnostic test could significantly improve timely disease detection. We tested the feasibility of serum microRNAs as diagnostic biomarkers of endometriosis in women with gynecologic disease symptoms. The objective of the study was to validate the use of a microRNA panel as a noninvasive diagnostic method for detecting endometriosis. This was a prospective study evaluating subjects with a clinical indication for gynecological surgery in an academic medical center. Serum samples were collected prior to surgery from 100 subjects. Women were selected based on the presence of symptoms, and laparoscopy was performed to determine the presence or absence of endometriosis. The control group was categorized based on absence of visual disease at the time of surgery. Circulating miRNAs, miR-125b-5p, miR-150-5p, miR-342-3p, miR-451a, miR-3613-5p, and let-7b, were measured in serum by quantitative real-time polymerase chain reaction in a blinded fashion without knowledge of disease status. Receiver-operating characteristic analysis was performed on individual microRNAs as well as combinations of microRNAs. An algorithm combining the expression values of these microRNAs, built using machine learning with a random forest classifier, was generated to predict the presence or absence of endometriosis on operative findings. This algorithm was then tested in an independent data set of 48 previously identified subjects not included in the training set (24 endometriosis and 24 controls) to validate its diagnostic performance. The mean age of women in the study population was 34.1 and 36.9 years for the endometriosis and control groups, respectively. Control group subjects displayed varying pathologies, with leiomyoma occurring the most often (n = 39). Subjects with endometriosis had significantly higher expression levels of 4 serum microRNAs: miR-125b-5p, miR-150-5p, miR-342-3p, and miR-451a. Two serum microRNAs showed significantly lower levels in the endometriosis group: miR-3613-5p and let-7b. Individual microRNAs had receiver-operating characteristic areas under the curve ranging from 0.68 to 0.92. A classifier combining these microRNAs yielded an area under the curve of 0.94 when validated in the independent set of subjects not included in the training set. Analysis of the expression levels of each microRNA based on revised American Society of Reproductive Medicine staging revealed that all microRNAs could distinguish stage I/II from control and stage III/IV from control but that the difference between stage I/II and stage III/IV was not significant. Subgroup analysis revealed that neither phase of the menstrual cycle or use of hormonal medication had a significant impact on the expression levels in the microRNAs used in our algorithm. This is the first report showing that microRNA biomarkers can reliably differentiate between endometriosis and other gynecological pathologies with an area under the curve >0.9 across 2 independent studies. We validated the performance of an algorithm based on previously identified microRNA biomarkers, demonstrating their potential to detect endometriosis in a clinical setting, allowing earlier identification and treatment. The ability to diagnose endometriosis noninvasively could reduce the time to diagnosis, surgical risk, years of discomfort, disease progression, associated comorbidities, and health care costs.

Clinical diagnosis of endometriosis: a call to action

Agarwal SK et al., 2019 · American Journal of Obstetrics and Gynecology · Free to read

Endometriosis can have a profound impact on women's lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating these adverse sequelae is to diagnose the underlying condition. For many women, the journey to endometriosis diagnosis is long and fraught with barriers and misdiagnoses. Inherent challenges include a gold standard based on an invasive surgical procedure (laparoscopy) and diverse symptomatology, contributing to the well-established delay of 4-11 years from first symptom onset to surgical diagnosis. We believe that remedying the diagnostic delay requires increased patient education and timely referral to a women's healthcare provider and a shift in physician approach to the disorder. Endometriosis should be approached as a chronic, systemic, inflammatory, and heterogeneous disease that presents with symptoms of pelvic pain and/or infertility, rather than focusing primarily on surgical findings and pelvic lesions. Using this approach, symptoms, signs, and clinical findings of endometriosis are anticipated to become the main drivers of clinical diagnosis and earlier intervention. Combining these factors into a practical algorithm is expected to simplify endometriosis diagnosis and make the process accessible to more clinicians and patients, culminating in earlier effective management. The time has come to bridge disparities and to minimize delays in endometriosis diagnosis and treatment for the benefit of women worldwide.

Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility

Macer ML et al., 2012 · Obstetrics and Gynecology Clinics of North America · Free full text on PubMed Central

Correlation between endometriosis and pelvic pain

Porpora MG et al., 1999 · J Am Assoc Gynecol Laparosc

To evaluate the relationship between prevalence and severity of chronic pelvic pain (CPP) and stage, site, and type of endometriosis. Prospective, observational study (Canadian Task Force classification II-2). University Hospital. Of 90 consecutive women with biopsy-proved endometriosis, laparoscopy was performed in 69 for pelvic pain and in 21 for infertility or clinical and ultrasonographic suspicion of ovarian endometriosis. Preoperatively, using a 10-point visual analog scale, the severity of dysmenorrhea, CPP, and deep dyspareunia was assessed. During laparoscopy all visible endometriotic lesions were recorded and treated. MAIN Ten women (11.1%) had no pain; 72 had dysmenorrhea (mild in 13, moderate in 37, severe in 22); 55 had CPP (mild in 11, moderate in 25, severe in 19); and 39 deep dyspareunia (mild in 5, moderate in 31, severe in 3). The severity of dysmenorrhea significantly correlated with the presence and extent of pelvic adhesions (p = 0.004); the severity of CPP correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001) and extent of pelvic adhesions (p = 0.02); and deep dyspareunia correlated with deep endometriosis on the uterosacral ligaments (p = 0.04). Total pain score significantly correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001), peritoneal adhesions (p = 0.01), and extent of adnexal adhesions (p = 0.01). No significant correlation was found among revised American Fertility Society stage of endometriosis; presence and size of ovarian endometriomas; extent, type, and site of peritoneal lesions; and pain scores. By logistic regression analysis, the presence and intensity of total pain could be predicted simultaneously by the presence of deep endometriosis (p = 0.0001) and presence and extent of adnexal adhesions without cystic endometriosis (p = 0.01), and by the presence of ovarian endometrioma with periovarian adhesions (p = 0.03). Chronic pelvic pain was predicted by both deep endometriosis (p = 0.0001) and ovarian endometriomas with adnexal adhesions (p = 0.03). Deep dyspareunia was predicted simultaneously by deep endometriosis (p = 0.01) and an ovarian endometrioma with periovarian adhesions (p = 0. 008). Conclusion. Deep endometriosis, pelvic adhesions, and ovarian cystic endometriosis were independent predictors of pelvic pain. These data strongly suggest that it is not the size of ovarian cystic endometriosis but the association with adhesions that causes pelvic pain.

Multifactorial contributors to the severity of chronic pelvic pain in women

Yosef A et al., 2016 · American journal of obstetrics and gynecology

Chronic pelvic pain affects ∼15% of women, and is associated with significant societal cost and impact on women's health. Identifying factors involved in chronic pelvic pain is challenging due to its multifactorial nature and confounding between potential factors. For example, while some women with endometriosis have chronic pelvic pain, there may be comorbid conditions that are implicated in the chronic pelvic pain rather than the endometriosis itself. We sought to explore multifactorial variables independently associated with the severity of chronic pelvic pain in women. We used baseline cross-sectional data from an ongoing prospective cohort, collected from patient online questionnaires, physical examination, and physician review of medical records. Participants were recruited from a tertiary referral center for endometriosis and chronic pelvic pain in Vancouver, British Columbia, Canada, from December 2013 through April 2015. Exclusion criteria included menopausal status or age >50 years. Primary outcome was self-reported severity of chronic pelvic pain in the last 3 months (0-10 numeric rating scale). Potential associated factors ranged from known pain conditions assessed by standard diagnostic criteria, validated psychological questionnaires, musculoskeletal physical exam findings, as well as pain-related, reproductive, medical/surgical, familial, demographic, and behavioral characteristics. Mann-Whitney, Kruskal-Wallis, or Spearman test were used to identify variables with an association with the primary outcome (P < .05), followed by multivariable linear regression to control for confounding and to identify independent associations with the primary outcome (P < .05). Overall, 656 women were included (87% consent rate), of whom 55% were diagnosed with endometriosis. The following factors were independently associated with higher severity of chronic pelvic pain: abdominal wall pain (P = .005), pelvic floor tenderness (P = .004), painful bladder syndrome (P = .019), higher score on Pain Catastrophizing Scale (P < .001), adult sexual assault (P = .043), higher body mass index (P = .023), current smoking (P = .049), and family history of chronic pain (P = .038). Severity of chronic pelvic pain was similar between women with and without endometriosis. Multifactorial variables independently associated with severity of chronic pelvic pain were identified, ranging from myofascial/musculoskeletal, urological, family history, and psycho-social factors. Continued research is required to validate these factors and to determine whether any are potentially modifiable for the management of chronic pelvic pain.

Endometriosis, dysmenorrhoea and diet

Hansen SO et al., 2013 · Eur J Obstet Gynecol Reprod Biol

To review the literature on the effects of diet on endometriosis and dysmenorrhoea. A systematic search for trials investigating a relationship between diet and endometriosis/dysmenorrhoea was undertaken, and 23 studies were included in this review. Data on the relationship between diet and endometriosis were limited to 12 trials, three of which were animal studies, resulting in a total of 74,708 women. One large study (n=70,709) found a relatively strong association between endometriosis and trans-fatty acid consumption, and a lower risk of endometriosis with increased consumption of long-chain omega-3 fatty acids. The latter finding was also supported by smaller studies. No further dietary recommendations for reducing the risk of endometriosis were possible, and results for intake of vegetable, fibre and fruit were equivocal. The relationship between diet and dysmenorrhoea was investigated in 11 trials with different designs, including a total of 1433 women. Intake of fish oil seemed to reduce dysmenorrhoea. The literature on endometriosis and dysmenorrhoea in relation to diet is sparse, yielding equivocal results on specific elements. Overall, however, the literature suggests that specific types of dietary fats are associated with endometriosis and/or dysmenorrhoea, thereby indicating that there may be modifiable risk factors. Further research is recommended on both subjects.

Adiposity and Endometriosis Severity and Typology

Byun J et al., 2020 · J Minim Invasive Gynecol · Free full text on PubMed Central

Prior research has collectively shown that endometriosis is inversely related to women's adiposity. The aim of this study was to assess whether this inverse relationship holds true by disease severity and typology. Cross-sectional study among women with no prior diagnosis of endometriosis. Fourteen clinical centers in Salt Lake City, UT, and San Francisco, CA. A total of 495 women (of which 473 were analyzed), aged 18-44 years, were enrolled in the operative cohort of the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study. Gynecologic laparoscopy/laparotomy regardless of clinical indication. MAIN Participants underwent anthropometric assessments, body composition measurements, and evaluations of body fat distribution ratios before surgery. Surgeons completed a standardized operative report immediately after surgery to capture revised American Society for Reproductive Medicine staging (I-IV) and typology of disease (superficial endometriosis [SE], ovarian endometrioma [OE], and deep infiltrating endometriosis [DIE]). Linear mixed models, taking into account within-clinical-center correlation, were used to generate least square means (95% confidence intervals) to assess differences in adiposity measures by endometriosis stage (no endometriosis, I-IV) and typology (no endometriosis, SE, DIE, OE, OE + DIE) adjusting for age, race/ethnicity, and parity. Although most confidence intervals were wide and overlapping, 3 general impressions emerged: (1) women with incident endometriosis had the lowest anthropometric/body composition indicators compared with those without incident endometriosis, (2) women with stage I or IV endometriosis had lower indicators compared with women with stage II or III, and (3) women with OE and/or DIE tended to have the lowest indicators, whereas women with SE had the highest indicators. Our research highlights that the relationship between women's adiposity and endometriosis severity and typology may be more complicated than prior research indicates.