Sphingosine 1-phosphate elicits a ROS-mediated proinflammatory response in human endometrial stromal cells via ERK5 activation.

Endometriosis is a chronic gynecological disease affecting ~10% women in the reproductive age characterized by the growth of endometrial glands and stroma outside the uterine cavity. The inflammatory process has a key role in the initiation and progression of the disorder. Currently, there are no available early diagnostic tests and therapy relies exclusively on symptomatic drugs, so that elucidation of the complex molecular mechanisms involved in the pathogenesis of endometriosis is an unmet need. The signaling of the bioactive sphingolipid sphingosine 1-phosphate (S1P) is deeply dysregulated in endometriosis. S1P modulates a variety of fundamental cellular processes, including inflammation, neo-angiogenesis, and immune responses acting mainly as ligand of a family of G-protein-coupled receptors named S1P receptors (S1PR), S1P1-5 . Here, we demonstrated that the mitogen-activated protein kinase ERK5, that is expressed in endometriotic lesions as determined by quantitative PCR, is activated by S1P in human endometrial stromal cells. S1P-induced ERK5 activation was shown to be triggered by S1P1/3 receptors via a SFK/MEK5-dependent axis. S1P-induced ERK5 activation was, in turn, responsible for the increase of reactive oxygen species and proinflammatory cytokine expression in human endometrial stromal cells. The present findings indicate that the S1P signaling, via ERK5 activation, supports a proinflammatory response in the endometrium and establish the rationale for the exploitation of innovative therapeutic targets for endometriosis.

Adenomyosis diagnosis among adolescents and young women with dysmenorrhoea and heavy menstrual bleeding.

RESEARCH QUESTION: What is the prevalence of adenomyosis at ultrasonography among adolescents and young women reporting dysmenorrhoea and/or heavy menstrual bleeding (HMB)? DESIGN: This observational cohort study involved adolescents and young women referred for dysmenorrhoea and/or HMB to the Adolescent Medicine Unit at Careggi University Hospital, Italy. Patients with endometriosis and bleeding disorders were excluded. Transvaginal ultrasonography or transrectal sonography using a transvaginal probe was performed. The myometrium was described according to the Morphological Uterus Sonographic Assessment criteria. Details of baseline characteristics, clinical data and symptoms were collected. The presence of sonographic features of adenomyosis and the association between imaging findings and clinical symptoms were evaluated. RESULTS: The cohort included 95 patients aged between 13 and 25 years, referred for dysmenorrhoea (88.4%), HMB (23.2%) or both (13.7%). According to the MUSA criteria the sonographic diagnosis of adenomyosis was made in 27.4% of patients, with the diffuse type the most prevalent. Uterine wall asymmetry, hyperechoic intramyometrial islands, translesional vascularity and an interrupted junctional zone were the most common features. Patients with imaging findings of adenomyosis had significantly higher rates of HMB than those with a normal myometrial appearance (38.5% versus 17.4%, P = 0.030). In addition, the coexistence of dysmenorrhoea and HMB was significantly associated with adenomyosis (odds ratio 5.68, 95% confidence interval 1.65-19.5). CONCLUSIONS: Adenomyosis may be diagnosed among teenagers and young women referred with dysmenorrhoea and/or HMB. The clinical presentation is relevant for the diagnosis, with HMB alone and HMB plus dysmenorrhoea significantly associated with the sonographic identification of adenomyosis.

Long-term treatment for endometriosis with dienogest: efficacy, side effects and tolerability.

BACKGROUND: Dienogest (DNG) improves endometriosis-associated pain (EAP) and patients' quality of life; however, the modern cornerstone of the management of endometriosis is the long-term adherence of the patient to medical treatment. OBJECTIVE: To evaluate DNG as a long-term treatment of endometriosis, focusing on patients' compliance and side effects, also correlating with different phenotypes of endometriosis. METHODS: This was a cohort study on a group of patients with endometriosis (n = 114) undergoing long-term treatment with DNG. During the follow up visits (12, 24, and 36 months) patients were interviewed: an assessment of EAP was performed by using a visual analogue scale (VAS) and side effects were evaluated by using a specific questionnaire of 15 items. RESULTS: At 12 months, 81% were continuing the DNG treatment, with a significant reduction of dysmenorrhea, dyspareunia, dyschezia, dysuria and chronic pelvic pain. Of the 19% that discontinued the treatment: 62% was due to spotting, reduced sexual drive, vaginal dryness, and mood disorders. The improvement of EAP was significant for all endometriosis phenotypes, especially in patients with the deep infiltrating type. At 36 months, 73% of patients were continuing the treatment, showing a significant reduction of EAP through the follow up, along with an increase of amenorrhea (from 77% at 12 months to 93% at 36 months). In a subgroup of 18 patients with gastrointestinal disorders, DNG was administered vaginally at the same dosage, showing similar results in terms of efficacy and tolerability. CONCLUSIONS: DNG was an effective long-term treatment for all endometriosis phenotypes, with few side effects that caused the discontinuation of the treatment mainly during the first year. Thus, the course of 1-year treatment is a predictive indicator for long-term treatment adherence.

Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhoea.

RESEARCH QUESTION: Women with endometriosis are frequently affected by headache. How many of these have a clear diagnosis of migraine? Are the different forms of migraine related to the phenotypes and/or characteristics of endometriosis? DESIGN: This was a prospective nested case-control study. A consecutive series of 131 women with endometriosis who attended the endometriosis clinic were enrolled and examined for the presence of headache. A headache questionnaire was used to determine the characteristics of the headaches, and the diagnosis of migraine was confirmed by a specialist. The case group included women with endometriosis and a diagnosis of migraine, while the control group included women with only endometriosis. History, symptoms and other comorbidities were collected. A pelvic pain score and associated symptoms were assessed using a visual analogue scale. RESULTS: A diagnosis of migraine was made in 53.4% (70/131) of participants. Pure menstrual migraine was reported by 18.6% (13/70), menstrually related migraine by 45.7% (32/70) and non-menstrual migraine by 35.7% (25/70). Dysmenorrhoea and dysuria were significantly more frequent in patients with endometriosis and migraine than in those without migraine (P = 0.03 and P = 0.01). No difference was found for other variables, including age at diagnosis and duration of endometriosis, endometriosis phenotype, the presence of other autoimmune comorbidities or heavy menstrual bleeding. In most patients with migraine (85.7%) the headache symptoms had started years before the diagnosis of endometriosis. CONCLUSION: The occurrence of headache in many patients with endometriosis is associated with the presence of different forms of migraine, is related to pain symptoms and often precedes the diagnosis of endometriosis.

Standardising outcome reporting for clinical trials of interventions for heavy menstrual bleeding: Development of a core outcome set.

OBJECTIVE: To develop a core outcome set for heavy menstrual bleeding (HMB). DESIGN: Core outcome set (COS) development methodology described by the COMET initiative. SETTING: University hospital gynaecology department, online international survey and web-based international consensus meetings. POPULATION OR SAMPLE: An international collaboration of stakeholders (clinicians, patients, academics, guideline developers) from 20 countries and 6 continents. METHODS: Phase 1: Systematic review of previously reported outcomes to identify potential core outcomes. Phase 2: Qualitative studies with patients to identify outcomes most important to them. Phase 3: Online two-round Delphi survey to achieve consensus about which outcomes are most important. Phase 4: A consensus meeting to finalise the COS. MAIN OUTCOME MEASURES: Outcome importance was assessed in the Delphi survey on a 9-point scale. RESULTS: From the 'long list' of 114, 10 outcomes were included in the final COS: subjective blood loss; flooding; menstrual cycle metrics; severity of dysmenorrhoea; number of days with dysmenorrhoea; quality of life; adverse events; patient satisfaction; number of patients going on to have further treatment for HMB and haemoglobin level. CONCLUSIONS: The final COS includes variables that are feasible for use in clinical trials in all resource settings and apply to all known underlying causes of the symptom of HMB. These outcomes should be reported in all future trials of interventions, their systematic reviews, and clinical guidelines to underpin policy.

A 10-Year Observational Study on Twin Pregnancy: Role of Fetal Sex Pairing on Obstetric Outcome.

Fetal sex contributes to the determination of obstetric outcome, as pregnancies carrying male babies seem to have an increased risk of maternal-fetal complications. Most studies have been conducted on singleton pregnancies, whereas less evidence is available for twins. A 10-year retrospective observational study was conducted on a cohort of 1180 women with twin pregnancy delivered at a single tertiary hospital. Clinical data on maternal characteristics, and obstetric and neonatal outcomes were collected, and the analysis was performed on monochorionic (MC) and dichorionic (DC) diamniotic twins separately. The group of DC twins included 837 cases, and those conceived by assisted reproductive technologies (ART) were more likely to have one or both female fetuses rather than males. The incidence of hypertensive disorders of pregnancy (HDP) was higher in same-sex pairs than in opposite-sex pairs. No differences were found regarding other obstetric and neonatal outcomes among the three sex-pairing groups. The MC twins group included 228 cases, and in female-carrying pregnancies a higher incidence of gestational diabetes (GDM) was observed compared to the male group. Furthermore, male pairs had significantly lower Apgar scores than females. Fetal sex seems to have a mild effect in twins compared to singleton pregnancies, suggesting a more complex set of factors contributing to pregnancy outcome in multiple pregnancies. However, we observed a higher incidence of HDP among same-sex DC pairs, a higher rate of GDM among MC female-female pairs, and a worse adaptation to extrauterine life among male-male pairs in MC twins.

The menstrual distress questionnaire (MEDI-Q): reliability and validity of the English version.

BACKGROUND: Menstrual cycle has a significant impact on women's health from different perspectives, both physically and psychologically. The assessment of menstrual-related distress is of pivotal clinical interest, especially in women with chronic exposure to abnormal bleeding or pain. The Menstrual Distress Questionnaire (MEDI-Q) is a new tool originally developed in Italian that comprehensively evaluates menstrual-related distress. OBJECTIVE: To validate the English version of the MEDI-Q in an English-speaking population. METHODS: The study consisted of two phases: an initial translation phase of the original Italian version of the MEDI-Q, and a data collection phase to validate the new English version among 288 native English-speaking women. RESULTS: The English version of MEDI-Q showed excellent psychometric properties, with high internal consistency (Cronbach's alpha = 0.84) and test-retest reliability (intraclass correlation coefficient = 0.95). Construct validity was supported by significant correlations between MEDI-Q scores and scores on measures of psychological distress and premenstrual symptoms. CONCLUSIONS: The English version of the MEDI-Q is a valid and reliable instrument for the assessment of menstrual distress and its impact on psychological well-being. This tool can be utilized in research and clinical settings to comprehensively investigate the impact of menstruation on various populations, identify and monitor menstruation-related disorders promptly and effectively, and to evaluate the effectiveness of targeted treatments for menstrual distress.

The HOPE study: evaluating the impact of an online educational resource for heavy menstrual bleeding on the patient-physician dynamic.

The Heavy menstrual bleeding: Evidence-based Learning for best Practice (HELP) Group developed an educational website about heavy menstrual bleeding (HMB). The "HMB improving Outcomes with Patient counseling and Education" (HOPE) project examined the website's impact on women's knowledge, confidence, and consultations with healthcare providers (HCPs). HOPE was a quantitative online survey of gynecologists and women with HMB in Brazil. After an initial consultation, patients had unlimited access to the website and completed a survey. HCPs also completed a survey about the sconsultation. After a second consultation, HCPs and patients completed another survey. HCP surveys assessed their perception of patients' awareness, understanding, and willingness to discuss HMB. Patient surveys assessed their knowledge, experience, and confidence in discussing HMB. Forty HCPs recruited 400 women with HMB. Based on HCP perceptions at the first consultation, 18 percent of patients had "good knowledge" or "very good knowledge" of HMB, increasing to 69 percent after patients had visited the website. Before and after visiting the website, 34 percent and 69 percent of patients, respectively, regarded their HMB knowledge as "goo.d" Additionally, 17 percent of women reported their anxiety as "highest" during the first consultation; this decreased to 7 percent during the second consultation. After visiting the HELP website, patients' knowledge of HMB improved and they were less anxious.

Hormonal treatments for endometriosis: The endocrine background.

Endometriosis is a benign uterine disorder characterized by menstrual pain and infertility, deeply affecting women's health. It is a chronic disease and requires a long term management. Hormonal drugs are currently the most used for the medical treatment and are based on the endocrine pathogenetic aspects. Estrogen-dependency and progesterone-resistance are the key events which cause the ectopic implantation of endometrial cells, decreasing apoptosis and increasing oxidative stress, inflammation and neuroangiogenesis. Endometriotic cells express AMH, TGF-related growth factors (inhibin, activin, follistatin) CRH and stress related peptides. Endocrine and inflammatory changes explain pain and infertility, and the systemic comorbidities described in these patients, such as autoimmune (thyroiditis, arthritis, allergies), inflammatory (gastrointestinal/urinary diseases) and mental health disorders.The hormonal treatment of endometriosis aims to block of menstruation through an inhibition of hypothalamus-pituitary-ovary axis or by causing a pseudodecidualization with consequent amenorrhea, impairing the progression of endometriotic implants. GnRH agonists and antagonists are effective on endometriosis by acting on pituitary-ovarian function. Progestins are mostly used for long term treatments (dienogest, NETA, MPA) and act on multiple sites of action. Combined oral contraceptives are also used for reducing endometriosis symptoms by inhibiting ovarian function. Clinical trials are currently going on selective progesterone receptor modulators, selective estrogen receptor modulators and aromatase inhibitors. Nowadays, all these hormonal drugs are considered the first-line treatment for women with endometriosis to improve their symptoms, to postpone surgery or to prevent post-surgical disease recurrence. This review aims to provide a comprehensive state-of-the-art on the current and future hormonal treatments for endometriosis, exploring the endocrine background of the disease.

Sphingosine 1-phosphate pathway is dysregulated in adenomyosis.

RESEARCH QUESTION: Is sphingosine 1-phosphate (S1P) pathway involved in the process of fibrosis in adenomyosis? DESIGN: RNA was extracted from paraffin-embedded slices collected from the ectopic endometrium of patients with nodular adenomyosis (n = 27) and eutopic endometrium of healthy controls women (n = 29). Expression of genes involved in the metabolism and signalling of S1P, and actin-alpha-2 smooth muscle, encoded by ACTA2 gene, a gene involved in fibrogenesis, was evaluated by real-time polymerase chain reaction analysis. RESULTS: In adenomyotic samples, the expression of sphingosine kinase 1 (SPHK1), the enzyme responsible for the synthesis of S1P, and of S1P phosphatase 2 (SGPP2), the enzyme responsible for the conversion of S1P back to sphingosine, was lower (P = 0.0006; P = 0.0015), whereas that of calcium and integrin-binding protein 1, responsible for membrane translocation of SPHK1, was higher (P = 0.0001) compared with healthy controls. In S1P signalling, a higher expression of S1P receptor S1P3 (P = 0.001), and a lower expression of S1P2 (P = 0.0019) mRNA levels, were found compared with healthy endometrium. In adenomyotic nodules, a higher expression of ACTA2 mRNA levels were observed (P = 0.0001), which correlated with S1P3 levels (P = 0.0138). CONCLUSION: Present data show a profound dysregulation of the S1P signalling axis in adenomyosis. This study also highlights that the bioactive sphingolipid might be involved in the fibrotic tract of the disease, correlated with the expression of ACTA2, suggesting its role as novel potential biomarker of adenomyosis.

Long-term treatment of endometriosis-related pain among women seeking hormonal contraception.

OBJECTIVE: To evaluate the different effects of a progestin-only contraceptive with desogestrel (DSG) vs combined oral contraceptives (COCs) for a first line long-term treatment of endometriosis-related pain among patients seeking hormonal contraception. METHODS: An observational retrospective cohort study was conducted in collaboration with a local outpatient clinic for endometriosis among a group of nulliparous young women (n = 216) with endometriosis-related pain and seeking contraception. The cohort was subdivided into a group (n = 73) treated as first line by DSG and another group (n = 75) treated by a COC. During the study, clinical symptoms, side effects and possible changes in OC type use were recorded. RESULTS: No significant difference was found between the two groups in terms of clinical characteristics and pain scores before treatment. After 6 months both treatments were effective in reducing endometriosis-related pain, and those treated with DSG showed lower levels of dysmenorrhea, dyspareunia and nonmenstrual pelvic pain than COCs group (p < .01). After 12 months, in DSG Group some patients (15%) switched from DSG to a COC for breakthrough bleeding, whereas in COC Group 48% of patients switched to another type of COC for reduced efficacy on pain and/or for side effects. After 3 years of OC treatment, in DSG Group 79% of patients maintained the same therapy, whereas in COC Group only 14% continued the same COC type, 37% switched to another COC and 47% to DSG. CONCLUSIONS: A progestin-only contraceptive with DSG is a valid option for long term management of endometriosis-related pain in patients seeking hormonal contraception.

Urinary Tract Endometriosis: How to Predict and Prevent Recurrence after Primary Surgical Excision.

STUDY OBJECTIVE: To investigate the clinical and surgical predictors of urinary tract endometriosis (UTE) relapse. DESIGN: Retrospective single institutional study. SETTING: Italian multidisciplinary referral center for endometriosis. PATIENTS: Consecutive patients affected by UTE and surgically treated between January 2016 and March 2020. INTERVENTION: Surgical excision for UTE. Uni- and multivariate logistic regression analyses were fitted to evaluate clinical and surgical predictors of recurrence. MEASUREMENTS AND MAIN RESULTS: A total of 105 female age-reproductive patients were enrolled. Median age was 32 years (interquartile range, 24-37). Ureteral involvement was recorded in 53 patients (50.5%), being unilateral and bilateral in 46 patients (43.8%) and 7 patients (6.7%), respectively. Bladder involvement occurred in 52 patients (49.5%). Open surgical approach was performed in 24 cases (22.9%), whereas 30 patients (28.5%) and 51 patients (48.6%) were treated with laparoscopic and robot-assisted approach, respectively. Overall, 53 patients (50.5%) received adjuvant hormonal therapy. At a median follow-up of 39 months (interquartile range, 22-51), 30 patients (28.6%) experienced disease relapse, with 14 recurrences (13.3%) recorded at the level of the urinary tract. At multivariable analysis, age at first surgery <25 years (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.10-1.84; p = .02) and the presence of a concomitant autoimmune disease (OR, 1.45; 95% CI, 1.24-2.17; p = .02) were found as predictors of deep infiltrating endometriosis recurrence, whereas adjuvant postsurgical therapy showed a protective role (OR, 0.83; 95% CI, 0.53-0.98; p = .01). CONCLUSIONS: Young age (<25 years) and the presence of autoimmune diseases were significant predictors for the development of disease recurrence, whereas adjuvant hormonal therapy showed a protective role.

Maternal hemodynamic changes in gestational diabetes: a prospective case-control study.

PURPOSE: The aim of the study is to compare maternal hemodynamic adaptations in gestational diabetes (GDM) versus healthy pregnancies. METHODS: A prospective case-control study was conducted, comparing 69 singleton pregnancies with GDM and 128 controls, recruited between September 2018 and April 2019 in Maternal-Fetal Medicine Unit, Careggi University Hospital, Florence, Italy. Hemodynamic assessment by UltraSonic Cardiac Output Monitor (USCOM) was performed in both groups in four gestational age intervals: 17-20 weeks (only in early GDM cases), 26-30 weeks, 32-35 weeks and 36-39 weeks. We evaluated six hemodynamic parameters comparing GDM cases versus controls: cardiac output (CO), cardiac index (CI), stroke volume (SV), total vascular resistance (TVR), inotropy index (INO) and potential to kinetic energy ratio (PKR). RESULTS: GDM group had significantly lower values of CO and SV than controls from the early third trimester (26-30 weeks) until term (p < 0.001). CI is significantly lower in GDM women already at the first evaluation (p = 0.002), whereas TVR and PKR were significantly higher in GDM (p < 0.001). GDM women showed also lower INO values than controls in all assessments. CONCLUSIONS: A hemodynamic maternal maladaptation to pregnancy can be detected in GDM women. The effect of hyperglycemia on vascular system or a poor pre-pregnancy cardiovascular (CV) reserve could explain this hemodynamic maladaptation. The abnormal CV response to pregnancy in GDM women may reveal a predisposition to develop CV disease later in life and might help in identifying patients who need a CV follow-up.

Perinatal outcomes of pregnant women with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO): a case series and literature review.

PURPOSE: Pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have a higher risk of hospitalization, admission to intensive care unit (ICU) and invasive ventilation, and of acute respiratory distress syndrome (ARDS). In case of ARDS and critical severe coronavirus disease 2019 (COVID-19), the use of extracorporeal membrane oxygenation (ECMO) is recommended when other respiratory support strategies (oxygen insufflation, non-invasive ventilation [NIV], invasive ventilation through an endotracheal tube) are insufficient. However, available data on ECMO in pregnant and postpartum women with critical COVID-19 are very limited. METHODS: A case series of three critically ill pregnant women who required ECMO support for COVID-19 in pregnancy and/or in the postpartum period. RESULTS: The first patient tested positive for COVID-19 during the second trimester, she developed ARDS and required ECMO for 38 days. She was discharged in good general conditions and a cesarean-section [CS] at term was performed for obstetric indication. The second patient developed COVID-19-related ARDS at 28 weeks of gestation. During ECMO, she experienced a precipitous vaginal delivery at 31 weeks and 6 days of gestation. She was discharged 1 month later in good general conditions. The third patient, an obese 43-year-old woman, tested positive at 38 weeks and 2 days of gestation. Because of the worsening of clinical condition, a CS was performed, and she underwent ECMO. 143 days after the CS, she died because of sepsis and multiple organ failure (MOF). Thrombosis, hemorrhage and infections were the main complications among our patients. Neonatal outcomes have been positive. CONCLUSION: ECMO should be considered a life-saving therapy for pregnant women with severe COVID-19.

The global pandemic and changes in women's reproductive health: an observational study.

OBJECTIVE: The COVID-19 global pandemic has led to the death of millions around the world and impacted the overall health of many people. In this article we aim to compare reproductive health indicators in the first 6 months of 2020 to the prior year, as well as explore stress and quality of life during this time. METHODS: This retrospective observational study examined the menstrual cycles of 1159 women who were using a fertility tracking device to record their menstrual cycle and BBT data. We utilised a supplemental mobile application to administer a supplemental survey to collect data on stress and quality of life. Descriptive analyses were conducted with t-tests for two-group comparisons. RESULTS: Study participants from 15 countries contributed to a total of 13,194 cycles. 23.1% (268/1159) responded to the survey focussed on assessing psychosocial distress. 44.4% (119/268) of the study participants reported that they had noticed a change in their menstrual cycle, temperature curve, or menstruation in the past 12 months. Cycle analysis found the average cycle length and pre-ovulation phase length was longer in the first 6 months of 2019, while the average days of menstruation was slightly longer in 2020. DISCUSSION: Our findings indicate that menstrual cycle indicators changed only slightly in the first 6 months of 2020 but were still statistically significant. We were also able to understand that these study participants had some level of awareness of changes to their menstrual health.

Menstrual Distress Questionnaire (MEDI-Q): a new tool to assess menstruation-related distress.

RESEARCH QUESTION: Menstruation is a physiological event often associated with subjective distress. Is there a tool that assesses and objectively evaluates the global distress experienced by women during their period? DESIGN: An observational cross-sectional study conducted between June 2019 and May 2020 at Careggi University Hospital, Florence, Italy. A new questionnaire, The Menstrual Distress Questionnaire (MEDI-Q), was developed and administered to a group of healthy women (n = 418) of fertile age (18-50 years), without known uterine, psychiatric disorders, or both. The MEDI-Q investigated 25 items, covering the following areas: pain, discomfort, psychic or cognitive changes, gastrointestinal symptoms and changes in physiological functions. MEDI-Q Total Score and the three sub-scales, Menstrual Symptoms (MS), Menstrual Symptoms Distress (MSD) and Menstrual Specificity Index (MESI) were evaluated. The validation of MEDI-Q was achieved by testing test-retest reliability and internal consistency, convergent and concurrent validity. RESULTS: The MEDI-Q produced reliable results with good internal consistency, convergent and concurrent validity. MEDI-Q Total Score, MS and MSD all positively correlated with general psychopathology and premenstrual symptoms. A receiver operating characteristic analysis was used to determine the cut-off value of 20 (inclusive) and to identify the women with clinically relevant menstrual distress (area under the curve 0.90, 95% CI 0.86 to 0.93; P < 0.001). CONCLUSION: MEDI-Q is a new tool for evaluating menstruation-related distress, and provides a representative score of stress perception. MEDI-Q may be added to routine women's healthcare to help identify and adequately monitor menstruation-related disorders, and their effect on wellbeing, promptly.

Long-term hormonal treatment reduces repetitive surgery for endometriosis recurrence.

RESEARCH QUESTION: How effective is medical hormonal treatment in preventing endometriosis recurrence and in improving women's clinical symptoms and quality of life? DESIGN: This observational cross-sectional study evaluated the effects of hormonal medical treatment (progestins, gonadotrophin-releasing hormone analogues or continuous oral contraceptives) on endometriosis recurrence, current clinical symptoms and quality of life in three groups of patients: Group A (n = 34), no hormonal treatment either before or after the first endometriosis surgery; Group B (n = 76), on hormonal treatment after the first endometriosis surgery; and Group C (n = 75), on hormonal treatment both before and after the first endometriosis surgery. RESULTS: Group C patients were characterized by a lower rate of endometriosis reoperation (P = 0.011) and a lower rate of dysmenorrhoea (P = 0.006). Women who experienced repetitive endometriosis surgery showed worse physical (P = 0.004) and mental (P = 0.012) status than those who received a single surgery, independent of the treatment. CONCLUSION: Hormonal treatments represent a valid cornerstone of endometriosis management and may be useful as an alternative to surgery, but also before surgery, to plan better, and after surgery in order to reduce the risk of recurrence. Medical counselling is very helpful in choosing the correct and individualized endometriosis treatment. In fact, the gold standard for modern endometriosis management is the individualized approach and surgery should be considered, depending on the clinical situation and a patient's symptoms.

Is primary dysmenorrhea a precursor of future endometriosis development?

Primary dysmenorrhea (PD) is the most common gynecologic disorder during adolescence and it is characterized by crampy lower abdominal pain that occurs during menstruation. Secondary dysmenorrhea, in contrast, has the same clinical features but occurs in women with a disease that could account for their symptoms (endometriosis, adenomyosis, uterine fibroids, pelvic inflammatory disease). Endometriosis is the most common cause of secondary dysmenorrhea and it should be considered in patients with persistent and clinically significant dysmenorrhea despite treatment. It is often diagnosed after a long delay, increasing the likelihood of pain chronicity and fertility problems at a later age. Women who suffer from dysmenorrhea in adolescence have higher risk of endometriosis in future. The open question is if endometriosis was already present at the onset of dysmenorrhea but undiagnosed or if PD favors subsequent development of endometriosis-associated pain. Since PD is associated with higher risk for developing chronic pain state and shares some of the same pain pathways of endometriosis (prostaglandins overproduction, inflammation, peripheral sensitization, central sensitization and abnormal stress responses), a correlation between PD and endometriosis is suggested. To know whether it is a risk factor for the development of endometriosis-associated pain may provide an opportunity for early intervention and prevention. The present review aims to investigate the clinical and pathogenetic features of PD and endometriosis in order to identify a possible association between the two conditions.

Emergency surgery for appendectomy and incidental diagnosis of superficial peritoneal endometriosis in fertile age women.

RESEARCH QUESTION: This study aimed to evaluate the presence of superficial peritoneal endometriosis (SUP) in women referred to emergency surgery for right iliac fossa (RIF) pain and undergoing an appendectomy, considering which factors may be useful to suspect and identify endometriosis. DESIGN: An observational case-control study was conducted on a group (n = 149) of fertile age women. After surgery, Group A was selected upon the diagnosis of endometriosis (n = 34); Group B (n = 115) represented the controls. Demographics, comorbidities and clinical findings were registered and analysed. RESULTS: Appendicitis of various grades of severity was diagnosed in all patients, but SUP was also identified in 23%, of which 14.7% also presented with endometriosis of the appendix. Women in Group A reported chronic pelvic pain, dysmenorrhoea, dyspareunia and oral contraceptive use more frequently. At multivariate analysis, factors associated with endometriosis were: age <40 years, autoimmune disorders, multiple allergies, abdominal chronic pain, associated gynaecological pain symptoms, Alvarado score ≤6, and inconclusive ultrasound findings. CONCLUSIONS: The incidental finding of SUP in fertile age women presenting with an acute RIF pain and undergoing emergency surgery is a relevant observation. Clinical history and symptoms should guide surgeons in performing a correct diagnosis and in referring the patient to the gynaecology specialist.

Ultrasound findings in infertile women with endometriosis: evidence of concomitant uterine disorders.

Endometriosis is a gynecological disease characterized by pain and infertility. The diagnosis is very often made during the infertility work-up, together with other reproductive diseases and uterine disorders. A retrospective cohort study was conducted on infertile women with clinical or ultrasound suspect of endometriosis, undergoing an ultrasound (US) evaluation by a team of expert sonographers (n = 419), with the aim to evaluate the prevalence of concomitant uterine disorders. The US coexistence of endometriosis with uterine fibroids and/or adenomyosis was investigated according to three age intervals (<35years; 35 ≥ years <45; ≥45 years) and to endometriosis phenotypes: ovarian endometriosis (OMA), deep infiltrating endometriosis (DIE), or both. The US diagnosis of fibroids was made in 3.1% of cases, adenomyosis was found in 21.2%, and the co-existence of both uterine disorders with endometriosis was reported in 14.6% of patients. When analyzed according to age, patients aged >35 years were more likely to be affected by uterine fibroids (p = .003), adenomyosis (p = .030) and both adenomyosis and fibroids (p < .0001). No statistically significant association was found between endometriosis phenotypes and myometrial pathologies. Uterine disorders coexistence should be considered in the assessment of women with endometriosis, in order to better define a treatment strategy for infertility, especially in women older than 35 years.