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To evaluate continuance rates, bleeding patterns, and patient satisfaction with 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) use in adolescents and young adult women during the first 3 years of use DESIGN: We conducted an observational prospective study.Family Planning Service of a tertiary hospital in Brazil PARTICIPANTS: One hundred adolescents and young women aged 16-24 years.Insertion of 52-mg LNG-IUS for the main purpose of contraception. Follow-up visits were conducted at 12, 24, and 36 months after insertion.Continuance rates, reasons for discontinuation of the method, and women's satisfaction and bleeding patterns RESULTS: Among those who were not lost to follow-up, LNG-IUS continuance rates were 89.1% (82/92), 82.9% (72/87), and 75.3% (64/85) in the first, second, and third years of use, respectively. The main reason for discontinuation was acne, followed by expulsion of/malpositioned LNG-IUS. Other reasons for discontinuation were irregular uterine bleeding, dysmenorrhea, and abdominal pain. The amenorrhea rates were 50%, 54.1%, and 39% at 12, 24, and 36 months, respectively. Spotting rates increased during the first 3 years of use (20.8%, 16.7%, and 26.6%, respectively). Adolescents and young women using the LNG-IUS showed high rates of satisfaction, with 93.9%, 100%, and 96.8% of women being very satisfied/satisfied in the first 3 years of use. Only 2 participants who continued using the LNG-IUS reported being very dissatisfied/dissatisfied in the third year of follow-up.The LNG-IUS showed high rates of continuation and satisfaction in the first 3 years of use in Brazilian adolescents and young adults. Most women reported a favorable bleeding pattern.

The gold standard for diagnosing hirsutism is based on the modified Ferriman-Gallway (mFG) score, requiring trained and in-person evaluation. Our study aimed to evaluate whether using mobile phone images of the nine mFG areas could offer an alternative way to support the diagnostic of hirsutism. All patients from an endocrine outpatient clinic underwent an initial mFG evaluation by two blinded, trained examiners. Then, images of the nine mFG areas were acquired using a mobile device (48 MP) under standard conditions and artificial illumination. A cutoff mFG score of ≥ 4 (suggested by European Society of Human Reproduction and Embryology) or ≥ 6 (proposed by The Endocrine Society) has been established as the criteria for diagnosing hirsutism. After storage, the individual patients' images were submitted for mFG analysis by three independent, blinded examiners. Overall, 70 females were evaluated; 27.5% of the patients had an mFG score ≥ 4. The mean age ± SEM was 33.2 + 1.13 years. The first consideration was the evaluation of the examiners who analyzed the images. In this group, the inter-rater reliability based on the Fleiss' Kappa identified an agreement of 81.4%, with a Kappa index of 0.75 considered strong for clinical evaluations. For mFG score ≥ 6, the agreement was 77%, and the performance of Kappa Index was 0.62 (moderate). Independently of the cutoffs, the Bland-Altman analysis established a concordance of 0.89 (95% CI [0.83, 0.92]) between the in-person and image-based methods to score mFG. The lower limit of agreement of the estimated mFG scores was - 2.08 (95% CI [- 2.73, - 1.43]), and the upper limit of agreement was 4.14 (95% CI [3.491, 4.79]). We observed acceptable concordance between the image-based and in-person evaluation of mFG scores. Our results support the use of image acquisition of mFG areas as a valid approach for diagnosing hirsutism.

PURPOSE This study aimed to assess the pain scores at the insertion of the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS) among nulligravidas, parous women with previous vaginal delivery and parous women with elective caesarean-delivery without any previous labour or cervix dilation. MATERIALS AND METHODS The present research is a prospective, single-cohort study that included 413 women aged 15-49 years who opted for LNG-IUS placement for contraception or treatment of heavy menstrual bleeding. Women who participated in the present study were not submitted to any pharmacological pain-relieving intervention to perform the procedure. Pain at insertion was evaluated by using a Visual Analogue Scale (VAS). Pain was classified as absent (0), mild (1-3), moderate (4-6), or severe (7-10). The women were divided as: (1) nulligravidas, (2) parous women with a previous vaginal delivery, or (3) parous women with elective caesarean-delivery without any previous labour or cervix dilation. RESULTS Nulligravidas women presented a higher mean pain score, when compared to women with elective caesarean-delivery and women with previous vaginal delivery (6.6 ± 2.0 vs 5.5 ± 2.1 and 3.9 ± 2.4, respectively; p

Objective Polycystic ovary syndrome (PCOS) is a recognized risk factor for nonalcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence and factors associated with NAFLD in women with PCOS and evaluate noninvasive indices of hepatic fibrosis in patients with PCOS and NAFLD. Subjects and methods Patients with PCOS (n = 87) and women without PCOS (n = 40; controls) were included. NAFLD was diagnosed by abdominal ultrasonography after exclusion of alcohol consumption and viral or autoimmune liver disease. Anthropometric, clinical and metabolic variables, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid accumulation product (LAP), FIB-4 index, NAFLD score, and transient elastography (TE; FibroScan) were obtained in subsets of patients with PCOS and NAFLD. Results A total of 87 patients with PCOS were included (mean age: 34.4 ± 5.7 years, mean body mass index [BMI]: 34.7 ± 4.7 kg/m 2 ). NAFLD was present in 67 (77.0%) patients with PCOS versus 21 of 40 (52.5%) controls (p = 0.005). Women with PCOS and liver steatosis, compared with their NAFLD-free counterparts, had higher values of BMI, waist circumference, triglycerides, total cholesterol, alanine and aspartate aminotransferases, and γ-glutamyltransferase, along with higher frequencies of obesity, metabolic syndrome, and insulin resistance. NAFLD was independently associated with waist circumference, serum triglycerides, and alanine aminotransferase levels. The FIB-4 index was not compatible with advanced fibrosis in any of the evaluated patients, while NAFLD score and TE were compatible with advanced liver fibrosis in 1 of 26 (3.8%) and 3 of 25 (12%) patients, respectively. Conclusion Women with PCOS had a high risk of NAFLD, and a combination of both was associated with central obesity, dyslipidemia, insulin resistance, and metabolic syndrome. Noninvasive methods suggested low rates of severe hepatic fibrosis in Brazilian women with PCOS. Arch Endocrinol Metab. 2020;64(3):235-42

Polycystic ovary syndrome (PCOS) is a chronic dysfunction associated with obesity and metabolic disorders that can be ameliorated by treatment with metformin. Brown adipose tissue (BAT) has been recently identified in adult humans, and irisin is a myokine that induces BAT formation. The aim of this randomized controlled trial was to evaluate whether a short term treatment with metformin alters BAT activity and plasma irisin levels in women with PCOS. The participants were randomly assigned to receive metformin (1500 mg/day, n=21) or placebo (n=24) during 60 days. BAT activity was assessed by 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by enzyme immunoassay. The groups were similar in age, body measures, metabolic profile and PCOS phenotypes. BAT activity did not change significantly in the women treated with metformin (median Δ SUVmax=–0.06 g/ml, interquartile interval –2.81 to 0.24 g/ml, p=0.484, Wilcoxon’s test) or placebo (median Δ SUVmax=0.98 g/ml, interquartile interval –2.94 to 4.60 g/ml, p=0.386). In addition, plasma irisin levels remained unchanged in the groups treated with metformin (median Δ=–98 ng/ml, interquartile interval –366 to 60 ng/ml, p=0.310) and placebo (median Δ=28 ng/ml, interquartile interval –1260 to 215 ng/ml, p=0.650). These results suggest that in PCOS women BAT activity and plasma irisin levels may not change after a brief treatment with metformin.

Objective: This study aimed to evaluate the performance of our Facebook fan page and compare it to similar pages. Methods: The authors reviewed page-specific metrics provided by Facebook, including number of fans, their age and sex, and country of origin; number of views, likes, and shares tied to our posts. A search for similar fan pages using keyword "endometriosis" found pages in Portuguese, English, and Spanish. They were analyzed for country of origin, authors, number of fans and posts, and were compared to our page. Results: Our fan page went online on April 2016 and 127 posts have been published up to December 2017. Most of its 1746 fans (89% women; 11% men) were Brazilians (n=1677). Our audience comprised primarily women aged 25-34 (39%) and 35-44 (30%) years. The most viewed posts discussed thrombosis and oral contraceptives (n =11078); continuous use of oral contraceptives (n=6448); deep endometriosis (n=4425); intrauterine levonorgestrel system (n=4045); IVF and endometriosis (n=2885); and endometriosis and cancer (n=2431). Our search found 399 Facebook pages from 44 different countries. The United States (n=81), Brazil (n=49), and the United Kingdom (n=46) topped the list of countries hosting pages, while most of the fan pages were written in English. The majority of the pages were active and 20% claimed they were based on science. Physicians administered four of the 10 most popular pages. Page heterogeneity prevented comparisons between them. Conclusion: Men and women have visited our Facebook fan page to obtain information on endometriosis. The pages found in our search were exceedingly heterogeneous and were not compared. Developing pages with sound information is an important step toward educating individuals about endometriosis and helping them make informed choices on available treatments.

Objective To evaluate whether brown adipose tissue (BAT) activity is altered in women with polycystic ovary syndrome (PCOS), and whether BAT activity correlates with plasma levels of irisin, a myokine that can induce BAT formation. Design We performed a cross-sectional study including women with PCOS (n = 45) and a healthy control group (n = 25) matched by age and body mass index (BMI). Methods BAT activity was measured using 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by a validated enzyme immunoassay. Results Total BAT activity was significantly reduced in women with PCOS (maximal standardized uptake value (SUVmax): median 7.4 g/mL, interquartile range 0.9–15.4) compared to controls (median 13.0 g/mL, interquartile range 4.7–18.4, P = 0.047). However, this difference was no longer significant after adjustment for waist circumference, a surrogate marker of central adiposity. In the PCOS group, BAT activity correlated negatively with BMI (Spearman’s r = −0.630, P = 0.000) and waist circumference (r = −0.592, P = 0.000) but not with plasma irisin levels. Conclusions BAT activity was reduced in women with PCOS possibly due to increased central adiposity. In PCOS women, BAT activity did not correlate with plasma irisin levels.

Background To compare the effectiveness of 550 mg naproxen sodium versus 6 mL 2%-lidocaine intracervical block in pain lowering at the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) placement in young women. Methods In this randomized controlled trial, 100 women aged 15–24 years were block-randomized to receive either 6 mL 2%-lidocaine intracervical block 5 min before the LNG-IUS insertion or 550 mg naproxen 30 min before the procedure. Forty-nine women received 550 mg naproxen and 51 received intracervical block. The primary outcome was pain at LNG-IUS insertion. Secondary outcomes were ease of insertion, insertion failures, and correct IUS positioning. Neither participants nor doctors were blinded. Pain at insertion was assessed by using a Visual Analog Scale (VAS). Results Women randomized to lidocaine intracervical block presented lower mean pain score at insertion, when compared to women who received naproxen (5.4 vs. 7.3, respectively; p p = 0.004). There was a 49.8% reduction in the chance of severe pain for every 1-cm increase in the hysterometry (p = 0.002). The only complication observed during insertion was vasovagal-like reactions (7%). The insertion was performed without difficulty in 82% of the women. Participants in the intracervical block group presented higher proportion of malpositioned IUS on transvaginal ultrasound examination compared to women in naproxen group. Nevertheless, all the malpositioned IUS were inserted by resident physicians. Conclusion Lidocaine intracervical block was found to be more effective than naproxen in reducing LNG-IUS insertion pain. Trial registration number: RBR-68mmbp, Brazilian Registry of Clinical Trials, Retrospectively registered (August 4, 2020), URL of trial registry record: https://ensaiosclinicos.gov.br/rg/RBR-68mmbp/.

IntroductionTumor necrosis factor (TNF) is a proinflammatory and angiogenic factor produced by activated macrophages. TNF acts through the cell membrane receptors TNFR1 and TNFR2, whose soluble forms play an important role in regulating TNF activity through competition with its receptors. The aim of this study was to evaluate whether TNF and/or its soluble receptors are useful to detect endometriosis in women undergoing laparoscopy for gynecological complains.MethodsThis was a prospective, controlled, cross-sectional study including 75 consecutive women scheduled for gynecological laparoscopy due to chronic pelvic pain, infertility, or a pelvic image suggestive of endometrioma. Plasma TNF and soluble TNF receptors (sTNFR1 and sTNFR2) were measured by flow cytometry with the Cytometric Bead Array Human TH1/TH2 Kit (BD Biosciences).ResultsWomen ultimately proven to have endometriosis had lower preoperative plasma levels of sTNFR1 (median 81 pg/mL vs. 121 pg/mL, pConclusionsPlasma sTNFR1 levels are lower in symptomatic women with confirmed endometriosis compared to symptomatic women without endometriosis. The lower plasma sTNFR1 levels may increase the bioavailability of TNF, thereby contributing to the systemic low grade inflammation associated with endometriosis.

Non-alcoholic fatty liver disease (NAFLD) is an insidious pathologic condition that can manifest from simple steatosis to steatohepatitis (NASH) with potential progression to cirrhosis. Like the polycystic ovary syndrome (PCOS), NAFLD is associated with obesity, diabetes mellitus, insulin resistance and metabolic syndrome. PCOS women have an increased risk of NAFLD, but it is debatable which features of PCOS, either specific (androgen excess) or unspecific (metabolic derangements) affect the NAFLD risk. We performed a systematic review and meta-analysis of studies that addressed the association of PCOS and NAFLD. We selected 17 studies published between 2007 and 2017 that included 2734 PCOS patients and 2561 controls of similar age and body mass index (BMI). PCOS patients have increased prevalence of NAFLD (odds ratio 2.54, 95% confidence interval 2.19–2.95). PCOS women with hyperandrogenism (classic phenotype) have a higher prevalence of NAFLD compared to women with PCOS without hyperandrogenism, even after correction for confounding variables. Among women with PCOS, those with NAFLD have higher serum total testosterone (mean difference 0.40 nmol/L, 95% CI 0.29–0.50 nmol/L) and free androgen index (mean difference 4.46, 95% CI 3.53–5.39) than those without NAFLD. The studies that used multivariate analysis controlling for age, BMI, triglycerides, and insulin resistance index confirmed that serum androgens are independent predictors of NAFLD in women with PCOS. The prevalence of NAFLD is increased in women with PCOS and the presence of NAFLD is associated with high serum androgen levels, in addition to obesity and insulin resistance.

To evaluate the efficacy of a levonorgestrel 52-mg intrauterine system (LNG 52-mg IUS) in controlling abnormal uterine bleeding and improving quality of life in women with inherited bleeding disorders.We assessed 20 participants laboratory diagnosed with inherited bleeding disorders, who presented with abnormal uterine bleeding and were registered in a Central Blood Center. The primary outcomes were menstrual bleeding volume and quality of life before and after LNG 52-mg IUS placement. We used the Pictorial Blood Loss Assessment Chart (PBAC) score for measuring menstrual bleeding and the Short Form-36 Health Survey to assess quality of life before and after LNG 52-mg IUS placement. We also conducted blood tests to evaluate the hematimetric level. Follow-up visits were conducted at 1, 3, 6, and 12 months after LNG 52-mg IUS placement. Statistical analyses were performed using the Friedman non-parametric test.The use of LNG 52-mg IUS reduced uterine bleeding in women with inherited bleeding disorders. The median PBAC score was higher before LNG 52-mg IUS placement than at 3, 6, and 12 months after placement (p 0.001). The amenorrhea rate was 70% after 12 months. There was an improvement in all eight parameters of quality of life (p 0.001). The mean hemoglobin, ferritin, and serum iron levels were also higher at 12 months than before LNG 52-mg IUS placement.LNG 52-mg IUS placement can effectively control abnormal uterine bleeding in women with inherited bleeding disorders and consequently improve their quality of life.The results from our study suggest that women with inherited bleeding disorders who present with heavy menstrual bleeding can benefit from the use of a levonorgestrel-releasing intrauterine system similar to women without bleeding disorders.

Endometriosis is a benign gynecological disorder which presents significant challenges in terms of diagnosis and management. Despite decades of research, there are no sufficiently sensitive and specific signs and symptoms nor blood tests for the clinical confirmation of endometriosis, which hampers prompt diagnosis and treatment. The huge majority of potential biomarkers has been discarded in research stage and very few have been translated to clinical practice. Serum CA-125 is the most studied and used one, but studies have shown its poor diagnostic performance. Several factors involved in the chronic inflammatory process of endometriosis, such as hormones, cytokines, chemokines, angiogenic factors, oxidative stress markers and others, have been implicated in the disease's pathogenesis and have been extensively studied, but not a single one has successfully been able to accurately identify the disease. MicroRNAs have emerged more recently but their utility to detect endometriosis remains uncertain. The search for a biomarker or a set of biomarkers is still open and may benefit from novel molecular biology and bioinformatics approaches to mine and uncover molecular signatures specifically associated with the disease.

Chronic lymphocytic leukemia (CLL) may be associated with immune thrombocytopenia (ITP). The standard treatment for CLL-associated ITP is steroids. For refractory cases, various treatment strategies such as rituximab, splenectomy, and thrombopoietic mimetics are available. We report a patient with CLL who developed recurrent ITP and life-threatening pulmonary hemorrhage. Platelet counts remained extremely low despite massive platelet transfusion and treatment including steroids, immunoglobulin, and single-dose rituximab infusion. The bleeding stopped and platelet counts were increased to normal range 13 days after treatment with eltrombopag 25 mg per day. Our experience suggests that eltrombopag is an effective treatment option in CLL-associated, refractory ITP, especially during major bleeding, which requires relatively rapid improvement of thrombocytopenia.

PURPOSE: To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. METHODS: BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. RESULTS: Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. CONCLUSION: There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.

Tubular carcinoma of the breast is a rare variant of invasive ductal carcinoma. We report a case of 42-year-old asymptomatic female with a histopathological proven multifocal tubular carcinoma, studied by mammography, Tomosynthesis, Ultrasound, and Magnetic Resonance. Herein, we discuss the advantages and limitations of Tomosynthesis, an emerging imaging technique, in this particular case.

ResumoObjetivosComparar os custos diretos e indiretos do sistema intra‐uterino de liberação de levonorgestrel (SIU‐LNG), ablação endometrial com balão térmico (AEBT) e histerectomia no tratamento de mulheres com sangramento uterino anormal (SUA).MétodosForam avaliadas retrospectivamente 88 pacientes tratadas para SUA pelo SIU‐LNG (n = 30), AEBT (n = 28) e histerectomia (n = 30). Foram considerados todos os procedimentos, consultas e exames envolvidos no tratamento das pacientes por um período de 5 anos, assim como os custos resultantes das falhas dos tratamentos utilizados. Foram estimados os custos pelo Sistema Único de Saúde (SUS) e sistema de saúde suplementar. As diferenças entre os grupos foram avaliadas pelo teste do t de Student ou ANOVA.ResultadosO custo do tratamento do SUA com AEBT foi significante mais elevado em comparação ao SIU‐LNG e histerectomia após um e cinco anos de seguimento, tanto no SUS quanto na medicina suplementar (p < 0,001). No SUS, o tratamento com o SIU‐LNG foi de 38,2% dos custos da histerectomia no primeiro ano (R$769,61 vs. R$2.012,21, p < 0,001) e de 45,2% após cinco anos (R$927,83 vs. R$2.052,21, p < 0,001). Na saúde suplementar essa diferença foi ainda mais expressiva. Nesse contexto, o custo do SIU‐LNG foi de 29,1% dos custos da histerectomia no primeiro ano (R$1.551,92 vs. R$5.324,74, p < 0,001) e de 37,4% após cinco anos (R$2.069,35 vs. R$5.538,74, p < 0,001).ConclusõesO uso do SIU‐LNG resulta em custos diretos e indiretos menores do que a AEBT e histerectomia no tratamento do SUA. A custo‐efetividade do SIU‐LNG aliado à reversibilidade e por ser um procedimento ambulatorial reforçam o seu papel no tratamento de mulheres com SUA tanto na perspectiva do SUS quanto na saúde suplementar.AbstractObjectivesTo compare direct and indirect costs of the levonorgestrel‐releasing intrauterine system (LNG‐IUS), thermal balloon endometrial ablation (TBEA) and hysterectomy in the treatment of women with abnormal uterine bleeding (AUB).Methods88 patients treated for AUB by LNG‐IUS (n = 30), TBEA (n = 28) and hysterectomy (n = 30) were retrospectively evaluated. All procedures, medical appointments and tests involved in the treatment of patients were considered for a period of five years, as well as all costs arising from failures of the treatments used. The costs for the Unified Health System (SUS) and the private health care system were estimated. Differences between groups were evaluated by the test t of Student or ANOVA.ResultsThe cost of the treatment of AUB with TBEA was significantly higher versus LNG‐IUS and hysterectomy after a five‐year follow‐up in both SUS and private health care system (p

Nodal is a growth factor of the transforming growth factor β superfamily that is expressed in high turnover tissues, such as the human endometrium, and in several malignancies. The effects of Nodal are modulated by the coreceptor Cripto and mediated by SMAD proteins. This study evaluated the gene and protein expression of Nodal, Cripto, total and phosphorylated (p) SMAD3, and SMAD4 in the proliferative endometrium of women with and without endometriosis. Total RNA was isolated and complementary DNA synthesized from eutopic endometrium of women with (n = 15) and without (n = 12) endometriosis, followed by quantitative real-time polymerase chain reaction (PCR) to evaluate the gene expression of Nodal, Cripto, SMAD3, and SMAD4. Western blot was used to evaluate the protein levels of Nodal and Cripto, and immunohistochemistry was performed to localize SMAD3, pSMAD3, and SMAD4. Although Nodal expression was unchanged in women with endometriosis, real-time PCR indicated lower gene expression of Cripto (fold change 0.27, P < .05) in the endometriosis group. This difference, however, was not maintained at protein expression level as assessed by Western blot. The immunostaining of total SMAD3 was reduced in the endometriosis group (P < .01), but the localization of pSMAD3 and the nuclear staining of SMAD4 were unchanged. These findings suggest that the Nodal signaling pathway has subtle changes in the endometrium of women with endometriosis, but this imbalance may not cause functional damage as it seems not to affect the nuclear expression of SMAD4.

Accurate noninvasive diagnostic tests for endometriosis are still missing. This study evaluated the predictive value of the neuropeptide urocortin 1 (Ucn1) to detect pelvic endometriosis in symptomatic women. We enrolled prospectively 97 consecutive women submitted to gynecologic laparoscopy for chronic or acute pelvic pain, infertility or adnexal mass. Preoperative blood samples were assayed for Ucn1 using enzyme immunoassay. Patients with endometriosis had higher plasma Ucn1 levels compared to patients with no lesions (median 59 vs. 34 pg/ml, p .01, Dunn's test). Elevated plasma Ucn1 levels were found among all endometriosis phenotypes (superficial peritoneal lesions, ovarian endometrioma, and deep infiltrating endometriosis, p .05 vs. no lesions). Receiver operating characteristics curve analysis identified plasma Ucn1 46 pg/mL as the best cutoff point to detect endometriosis vs. no lesions, with 76% sensitivity and 88% specificity (area under the curve [AUC] 0.827, 95% confidence interval [CI] 0.695 - 0.959), but no cutoff could accurately distinguish endometriosis from other pathological conditions (AUC 0.593 [95% CI 0.474 - 0.711]). In women with chronic pelvic pain, infertility, or both symptoms, the probability of endometriosis (positive predictive value) increased consistently with the increase of plasma Ucn1 levels. The present findings suggest that high plasma Ucn1 levels increase the likelihood of endometriosis in symptomatic women.

Aim: To test whether plasma BDNF levels are useful to predict the presence of endometriosis in women with pelvic pain. Patients & methods: Prospective cross-sectional study including 67 consecutive women aged 24–49 years, scheduled for laparoscopy due to chronic pelvic pain. Preoperative plasma samples were assayed for BDNF using a commercial enzyme immunoassay. Results: Women with ovarian endometrioma had higher preoperative plasma BDNF (1063 ± 157 pg/ml) compared with women with other benign ovarian tumors (537 ± 131 pg/ml, F = 2.53; p = 0.02). However, plasma BDNF levels were not helpful to indicate the presence of peritoneal or deep infiltrating endometriosis. Plasma BDNF levels were positively correlated with the severity of pelvic pain (r = 0.489; p < 0.0001). Conclusion: Plasma BDNF might be a biomarker of ovarian endometrioma but not a useful diagnostic marker to detect other forms of endometriosis in women with painful symptoms.

Obese women have special safety requirements for contraceptive choice, but the evidence supporting such decision is dispersed and sometimes conflicting. Despite being effective, well tolerated and safe for most women, hormonal contraceptives are underused by obese women due to fear of contraceptive failure, weight gain and venous thrombosis. Areas covered: We performed a comprehensive literature search to identify studies about hormonal contraception in overweight and obese women, including safety concerns. We considered the safety of hormonal contraceptives for otherwise healthy obese women and for those with comorbidities such as hypertension, diabetes, vascular disease, or a history of deep venous thrombosis. Expert opinion: Over time there is no convincing evidence that obesity increases the risk of contraceptive failure. Hormonal contraceptive users may have a modest weight gain that is comparable to that of non-users. Current evidence supports the safe use of combined hormonal contraceptives by obese women after detailed clinical screening to exclude comorbidities that may contraindicate the use of estrogens. Progestin-only methods are generally safe, and long-acting reversible contraceptives hold the best combination of efficacy, safety and convenience for this group, although individualization is advisable.

Summary The rate of motile sperm recovery after cryopreservation is very variable and difficult to predict. Anti-Mullerian hormone (AMH) and inhibin B are produced by Sertoli cells and released into the seminal plasma, where they could be functional markers of spermatogenesis and sperm resistance to thermal stress. The aim of this study was to evaluate whether seminal plasma levels of AMH and inhibin B predict sperm recovery after cryopreservation. The study included 153 men enrolled prospectively during a semen analysis. The cohort was stratified by the fresh semen characteristics into: normal (n = 52), high sperm count (n = 55), asthenozoospermia (n = 23), and oligozoospermia (n = 23). The main outcome measure was motile sperm recovery rate, defined as post-thaw total motile sperm count × 100/pre-freezing total motile sperm count. In men with asthenozoospermia there was a significant correlation between motile sperm recovery rate and the pre-freezing concentrations of AMH (r = 0.522, p

The present study investigated expression and protein localization of FOXL2 messenger RNA (mRNA) in endometrium of healthy women and in patients with endometriosis during endometrial cycle. In endometriotic lesions, FOXL2 mRNA and protein were evaluated and a possible correlation with activin A mRNA expression changes was also studied. Endometrium was collected from healthy women (n = 52) and from women with endometriosis (n = 31) by hysteroscopy; endometriotic tissues were collected by laparoscopy (n = 38). FOXL2 gene expression analysis in endometrium of healthy women showed a significant expression and no significant changes in mRNA levels between proliferative and secretory phases; a similar pattern was observed in endometrium of patients with endometriosis. Immunohistochemical evaluation showed that FOXL2 protein localized in stromal and glandular cells and colocalized with SUMO-1. FOXL2 mRNA expression was 3-fold higher in endometriosis than in healthy endometrium (P < .01) and a positive correlation between FOXL2 and activin A mRNA was found (P < .05) in endometriosis. In conclusion, FOXL2 mRNA expression and its protein localization do not change during endometrial cycle in eutopic endometrium from healthy individuals or patients with endometriosis; the hyperexpression of FOXL2 in endometriotic lesions suggests an involvement of this transcriptional regulator, probably associated with activin A expression and related to the pathogenesis of endometriosis.

This study investigated the usefulness of serum antimüllerian hormone (AMH) measurements at two distinct menstrual cycle phases to predict in vitro fertilization (IVF) outcomes.This was a prospective observational study enrolling 135 consecutive patients referred for conventional IVF or ICSI in a university hospital. Blood samples were obtained for serum AMH measurements on days 3 and 18-20, while transvaginal ultrasound was performed for antral follicle count (AFC) at day 3 of the menstrual cycle immediately before treatment. AMH was measured with the new Beckman Coulter Generation II (GenII) assay. The main outcome measures were cycle cancellation due to poor ovarian response, clinical pregnancy, and live birth.There was a strong correlation between AMH levels measured at day 3 and day 18-20 of the menstrual cycle (r = 0.837; P 0.0001). Day 18-20 serum AMH was comparable to day 3 serum AMH and AFC for the prediction of cycle cancellation (areas under the ROC curve were 0.84 for day 3 AMH, 0.89 for day 18-20 AMH, and 0.80 for AFC). Day 18-20 AMH had a modest predictive value for pregnancy or live birth (area under ROC curve 0.71 for both), which was comparable to that of day 3 AMH; however, AFC had no predictive value for these outcomes.Day 18-20 AMH was comparable to day 3 AMH for the prediction of cycle cancellation, clinical pregnancy, and live birth after IVF. Both AMH measurements were accurate for the prediction of cancellation but were significantly less useful for the prediction of pregnancy or live birth.

The aim of this study was to evaluate ovarian reserve markers in women with systemic lupus erythematosus (SLE) and regular menstrual cycles, and explore the relationship of such markers with clinical and treatment features. This was a case-control study including 27 women with SLE and 27 controls. All participants were aged 18-40 years, were eumenorrheic and had not used hormone therapy or hormone contraceptives in the past six months. Clinical manifestations of SLE, past and current use of immunosuppressive therapy and organ damage index were assessed at a regular follow-up visit, while antral follicle count (AFC), serum anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH) were assessed at early follicular phase of menstrual cycle. AFC was significantly reduced in SLE women [median (interquartile interval) 7 (5-11) versus 11 (7-12), p = 0.029]. AMH levels were more heterogeneous in SLE patients compared to the control group [1.23 (0.24-4.63) ng/ml versus 1.52 (1.33-1.88) ng/ml]. The SLE and control groups had similar serum FSH levels [6.44 (4.19-7.69) versus 7.5 (6.03-8.09) IU/L, p = 0.135]. AFC was inversely correlated with organ damage index (p = 0.046) and cumulative dose of cyclophosphamide (p = 0.028), while AMH levels were negatively correlated with the maximal dose of corticosteroid ever used (p = 0.003). These findings suggest that ovarian reserve may be decreased in women with SLE despite regular menstrual cycles.

Objective To evaluate antimullerian hormone (AMH) and AMH receptor II (AMHRII) mRNA and protein expression in endometrium and in ovarian or deep lesions of women with endometriosis. Design Prospective study. Setting University hospitals in Italy and Brazil. Patients Patients with endometriosis (n = 55) and healthy women (n = 45). Interventions Specimens of endometrium obtained by hysteroscopy from patients with endometriosis and from healthy control subjects; specimens of ovarian endometriosis (n = 29) or of deep endometriosis (n = 26) were collected by laparoscopy. Serum samples were collected in some endometriotic patients (n = 23) and healthy control subjects (n = 20). Main Outcome Measure(s) AMH and AMHRII mRNA levels were evaluated by quantitative reverse-transcription polymerase chain reaction and protein localization by immunohistochemistry. AMH levels in tissue homogenates and in serum were assessed by ELISA. Result(s) Endometrium from women with endometriosis showed higher AMH and AMHRII mRNA levels than control women, with no significant differences between proliferative and secretory phases. Specimens collected from ovarian or deep endometriosis showed the highest AMH and AMHRII mRNA expression. Immunolocalization study confirmed the high AMH and AMHRII protein expression in endometriotic lesions. No difference of serum AMH levels between the groups was found. Conclusion(s) The increased AMH and AMHRII mRNA and protein expression in endometrium and in endometriotic lesions suggests a possible involvement of AMH in endometriosis.

Polycystic ovary syndrome (PCOS) is a multifaceted condition characterized by chronic anovulation and excess ovarian activity, in contrast to other causes of anovulation that involve ovarian dormancy or primary insufficiency. Recent studies indicated that PCOS is associated with low-grade chronic inflammation and that women with PCOS are at increased risk of non-alcoholic fatty liver disease. The inflammatory and metabolic derangements associated with PCOS are explained in part by the coexistence of insulin resistance and obesity but are further fueled by the androgen excess. New insights into the regulation of hormones and cytokines in muscle and fat tissue support the concept that PCOS is a systemic syndrome. The therapeutic plan should be tailored to the patient phenotype, complaints, and reproductive desire. Of note, the aromatase inhibitor letrozole seems to be more effective than the reference drug clomiphene citrate to treat infertility due to PCOS. Integral management by a multidisciplinary team may help the patients to adhere to lifestyle interventions and thereby reduce body adiposity and recover their metabolic and reproductive health.

Objective To understand the extent to which barriers and misperceptions about intrauterine contraception (IUC) remain among Brazilian gynaecologists, particularly for nulliparous women. Methods An online survey was developed to assess Brazilian gynaecologists’ knowledge and attitudes towards IUC. Data collected included demographic and professional data, main barriers when considering IUC for women in general and/or nulliparous women, attitudes towards inclusion of IUC in contraceptive counselling, and opinions on what could increase IUC prescription for nulliparous women. A question regarding knowledge about WHO medical eligibility criteria (WHO MEC) was also included in the survey. Results 101 gynaecologists completed the survey. The insertion rate in nulliparous women was 79.2%. Brazilian gynaecologists were more likely to consider IUC in counselling or provide it on request for parous than for nulliparous women (p Conclusions The three most commonly reported barriers to considering IUC as a contraceptive option for nulliparous woman were concerns about PID and difficult or painful insertion. The challenge is to ensure that gynaecologists understand the evidence and do not disregard IUC as a potential option for nulliparous women.

Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder in women between menarche and menopause. Clinical hyperandrogenism is the most important diagnostic criterion of the syndrome, which manifests as hirsutism in 70% of cases. Hirsute carriers of PCOS have high cardiovascular risk. Lipid accumulation product (LAP) is an index for the evaluation of lipid accumulation in adults and the prediction of cardiovascular risk. The aim of this study was to evaluate the association between LAP and hirsutism in women with PCOS.This was a cross-sectional observational study of a secondary database, which included 263 patients who had visited the Hyperandrogenism Outpatient Clinic from November 2009 to July 2014. The exclusion criteria were patients without Ferriman-Gallwey index (FGI) and/or LAP data. We used the Rotterdam criteria for the diagnosis of PCOS. All patients underwent medical assessment followed by measurement and recording of anthropometric data and the laboratory tests for measurement of the following: thyroid-stimulating hormone, follicle-stimulating hormone, prolactin, total testosterone, sex hormone binding globulin, 17-α-hydroxyprogesterone (follicular phase), glycohemoglobin A1c, and basal insulin. In addition, the subjects underwent lipid profiling and oral glucose tolerance tests. Other laboratory measurements were determined according to clinical criteria. LAP and the homeostatic model assessment index (HOMA-IR) were calculated using the data obtained. We divided patients into two groups: the PCOS group with normal LAP (34.5) and the PCOS group with altered LAP (34.5) to compare the occurrence of hirsutism. For statistical analysis, we used SPSS Statistics for Windows® and Microsoft Excel programs, with descriptive (frequencies, percentages, means, and standard deviations) and comparative analyses (Student's t-test and Chi-square test). We considered relations significant when the p-value was ≤ 0.05.LAP was high in most patients (n = 177; 67.3%) and the FGI indicated that 58.5% of the patients (n = 154) had hirsutism. The analysis by LAP quartiles showed a positive correlation (p = 0.04) among patients with a high FGI and an upper quartile LAP (79.5) when compared with those with LAP 29.0 (lower quartile).This study demonstrated an association between high LAP and hirsutism. The FGI could represent a simple and low-cost tool to infer an increased cardiovascular risk in women with PCOS.

This study sought to understand women's perceived barriers to the use of hormonal and non-hormonal intrauterine contraception in Latin America.We developed an online survey for women in Argentina, Brazil, Colombia and Mexico who were seeking contraception. The questions aimed at evaluating patient awareness of negative stories and statements, as well as perceived barriers to the copper intrauterine device (IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS).The survey was mailed to 2300 women. A total of 1953 responses were received from Argentina (n = 465), Brazil (n = 380), Colombia (n = 613) and Mexico (n = 495). More women reported having heard negative stories about the copper IUD than about the LNG-IUS. More women believed that the copper IUD, rather than the LNG-IUS, was suitable only for those who had already had children. More women believed that weight gain (14.3% vs. 38.2%; p 0.001), mood swings (14.1% vs. 38.7%; p 0.001) and infertility (16.3% vs. 19.9%; p = 0.016) were possible side effects of the LNG-IUS. By contrast, more women believed that abortion (36% vs. 22.7%; p 0.001), pelvic infections (42.1% vs. 15.7%; p 0.001) and ectopic pregnancy (43.5% vs 23.5%; p 0.001) were side effects more associated with the copper IUD. More believed the copper IUD was associated with less pain during placement and removal compared with the LNG-IUS (42.8% vs. 31.2%; p 0.001). The perception of increased risk of contracting a sexual transmitted disease did not differ between the methods (IUD vs. LNG-IUS, 21.7% vs. 20.3%; p = 0.388).Respondents to a web-based survey in four Latin American countries have misperceptions regarding the adverse effects and risks of intrauterine contraception, which may hamper the use of these safe and efficient contraceptive methods. Education about the true risks and benefits involved is fundamental to improving patient acceptance and compliance as well as reducing unplanned pregnancies and unsafe abortions.

Objective Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder in women between menarche and menopause. Clinical hyperandrogenism is the most important diagnostic criterion of the syndrome, which manifests as hirsutism in 70% of cases. Hirsute carriers of PCOS have high cardiovascular risk. Lipid accumulation product (LAP) is an index for the evaluation of lipid accumulation in adults and the prediction of cardiovascular risk. The aim of this study was to evaluate the association between LAP and hirsutism in women with PCOS. Methods This was a cross-sectional observational study of a secondary database, which included 263 patients who had visited the Hyperandrogenism Outpatient Clinic from November 2009 to July 2014. The exclusion criteria were patients without Ferriman-Gallwey index (FGI) and/or LAP data. We used the Rotterdam criteria for the diagnosis of PCOS. All patients underwent medical assessment followed by measurement and recording of anthropometric data and the laboratory tests for measurement of the following: thyroid-stimulating hormone, follicle-stimulating hormone, prolactin, total testosterone, sex hormone binding globulin, 17-α-hydroxyprogesterone (follicular phase), glycohemoglobin A1c, and basal insulin. In addition, the subjects underwent lipid profiling and oral glucose tolerance tests. Other laboratory measurements were determined according to clinical criteria. LAP and the homeostatic model assessment index (HOMA-IR) were calculated using the data obtained. We divided patients into two groups: the PCOS group with normal LAP (< 34.5) and the PCOS group with altered LAP (> 34.5) to compare the occurrence of hirsutism. For statistical analysis, we used SPSS Statistics for Windows(r) and Microsoft Excel programs, with descriptive (frequencies, percentages, means, and standard deviations) and comparative analyses (Student's t-test and Chi-square test). We considered relations significant when the p-value was≤0.05. Results LAP was high in most patients (n = 177; 67.3%) and the FGI indicated that 58.5% of the patients (n = 154) had hirsutism. The analysis by LAP quartiles showed a positive correlation (p = 0.04) among patients with a high FGI and an upper quartile LAP (> 79.5) when compared with those with LAP < 29.0 (lower quartile). Conclusion This study demonstrated an association between high LAP and hirsutism. The FGI could represent a simple and low-cost tool to infer an increased cardiovascular risk in women with PCOS. Objetivo A síndrome dos ovários policísticos (SOP) é o distúrbio endócrino mais comumemmulheres entre amenarca e a menopausa. O hiperandrogenismo clínico é o critério diagnóstico mais importante da síndrome, que se manifesta como hirsutismo em70% dos casos. Portadores de SOP hirsutas têmelevado risco cardiovascular. O Lipid accumulation product (LAP) é um índice para a avaliação da acumulação de lípidos nos adultos e é um preditor de risco cardiovascular. O objetivo deste estudo é avaliar a associação entre LAP e hirsutismo em portadoras da SOP. Métodos Estudo observacional transversal de banco de dados secundário, que incluiu 263 pacientes do Ambulatório de Hiperandrogenismo no período de novembro de 2009 a julho de 2014. Foram excluídas pacientes sem o índice de Ferriman-Gallwey e/ ou LAP. Foram utilizados como critérios diagnósticos da SOP os critérios de Rotterdam. Todas as pacientes foram submetidas à avaliação médica seguida da aferição e registro dos dados antropométricos e a realização dos seguintes exames laboratoriais: hormônio estimulante da tireoide (TSH), hormônio folículo estimulante (FSH), prolactina (PRL), Testosterona total, globulina ligadora dos hormônios sexuais (SHBG), 17-α- hidroxiprogesterona, (fase folicular), perfil lipídico, teste oral de tolerância à glicose, glico-hemoglobina a1C, insulina basal. Outras dosagens laboratoriais foram determinadas à critério clínico. O LAP e o HOMA-IR (homeostatic model assessment) foram calculados com os dados obtidos. As pacientes foram divididas em dois grupos: grupo das portadoras de SOP com LAP normal (LAp < 34,5) e grupo das portadoras de SOP com LAP alterado (LAP >34,5) para as comparações do hirsutismo. Para a análise estatística, foram utilizados os programas SPSS Statistics for Windows(r) e Microsoft Excel(r), sendo feitas análises descritivas (frequências, percentuais, médias, desviospadrão) e comparativas (t-Student e qui-quadrado). Foram consideradas relações significativas quando p-valor foi menor ou igual a 0,05. Resultados O LAP foi elevado na maioria das pacientes (n = 177; 67,3%) e o índice de Ferriman-Gallwey (IF) demonstrou que 58,5% das pacientes (n = 154) eram hirsutas. A análise por quartis de LAP, demonstrou correlação positiva (p = 0,04) entre pacientes comIF elevado e LAP no quartil superior (>79,5) quando comparadas àquelas com LAP menor que 29,0 (quartil inferior). Conclusão O estudo demonstrou associação do LAP elevado e hirsutismo. O escore de Ferriman-Gallwey poderia representar uma ferramenta simples e de baixo custo para inferir risco cardiovascular aumentado em portadoras da síndrome.

Activin A is an endometrial secretory product involved in inflammation and angiogenesis. The present study aimed to evaluate the effect of activin A and its antagonist follistatin on interleukin (IL)-6, IL-8, and vascular endothelial growth factor (VEGF) expression and release from cultured human endometrial stromal cells (HESCs) from women with and without endometriosis. The HESCs were collected from women with endometriosis (n = 6) and controls (n = 6). Primary cultures were treated with activin A at different doses or activin A plus follistatin. The IL-6, IL-8, and VEGF messenger RNA expression was evaluated by real-time polymerase chain reaction and protein release was evaluated by enzyme-linked immunosorbent assay. Unstimulated HESC from women with endometriosis secreted more IL-6 and IL-8 than controls. The addition of activin A increased IL-8 and VEGF secretion in HESC from controls and decreased IL-6 and IL-8 secretion in HESC from women with endometriosis. These effects were counteracted by follistatin. Activin A regulates the expression and secretion of IL-8 and VEGF in cultured HESC, and this mechanism appears to be disrupted in eutopic endometrial cells from women affected by endometriosis.

Endometriosis is a benign sex hormone-dependent gynecological disease, characterized by the presence and growth of endometrial tissue outside the uterus; it affects 10% of women of reproductive age and is associated with infertility and pain. Treatment of endometriosis involves conservative or radical surgery, or medical therapies. The goals for endometriosis treatment may be the relief of pain and/or a successful pregnancy achievement in infertile patients. Treatment must be individualized with a multidisciplinary approach. The classical treatments carry adverse side effects and in some cases a negative impact on quality of life. New agents promise a distinct perspective in endometriosis treatment.The aim of this paper is to systematically review the literature evidence of new medical treatments for endometriosis, defined as pharmacological treatments not yet commonly available and currently under investigation.These new medical therapies would be used associated with surgical treatment and, in the future, will render possible the association of hormone therapy with non-hormonal treatment for endometriosis.

background: Activin A is a growth factor, produced by the endometrium, whose actions are modulated by the binding protein follistatin. Both proteins are detectable in the peripheral serum and their concentrations may be increased in women with endometriosis. The present study was designed to evaluate whether serum levels of activin A and follistatin are altered, and therefore have a potential diagnostic value, in women with peritoneal, ovarian and deep infiltrating endometriosis. methods: We performed a multicenter controlled study evaluating simultaneously serum activin A and follistatin concentrations in women with and without endometriosis. Women with endometriosis (n ¼ 139) were subdivided into three groups: peritoneal endometriosis (n ¼ 28); ovarian endometrioma (n ¼ 61) and deep infiltrating endometriosis (n ¼ 50). The control group (n ¼ 75) consisted of healthy women with regular menstrual cycles. Blood samples were collected from a peripheral vein and assayed for activin A and follistatin using commercially available enzyme immunoassay kits. results: The ovarian endometrioma group had serum activin A levels significantly higher than healthy controls (0.22+ 0.01 ng/ml versus 0.17+ 0.01 ng/ml, P , 0.01). None of the endometriosis groups had serum follistatin levels which were significantly altered compared with healthy controls; however, levels found in the endometrioma group (2.34+ 0.32 ng/ml) were higher than that in the deep endometriosis group (1.50+ 0.17 ng/ml, P , 0.05). The area under the receiver operating characteristic curve of activin A was 0.700 (95% confidence interval: 0.605 –0.794), while that of follistatin was 0.620 (95% confidence interval: 0.510–0.730) for the diagnosis of ovarian endometrioma. The combination of both markers into a duo marker index did not improve significantly their diagnostic accuracy. conclusions: The present study demonstrated that serum activin A and follistatin are not significantly altered in peritoneal or deep infiltrating endometriosis and have limited diagnostic accuracy in the diagnosis of ovarian endometrioma.

Objective To evaluate the expression pattern of activin A, activin receptors, and activin modulators messenger RNA (mRNA) in the eutopic endometrium of patients with endometriosis at different phases of the menstrual cycle and to evaluate the mRNA expression of the same proteins in endometriomas during the menstrual cycle. Design Prospective study. Setting University hospital. Patient(s) Women with and without endometriosis. Intervention(s) Samples of endometrial and endometriotic tissue from women with endometrioma (n = 48), and endometrial samples from women without endometriosis (controls) (n = 48). Main Outcome Measure(s) Quantification of activin A, activin B, activin receptor II, nodal, cripto, inhibin α, and follistatin expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Result(s) The eutopic endometrium of patients with endometriosis showed [1] higher activin A mRNA expression in the proliferative phase and a lack of late secretory phase peak, [2] a lack of endometrial cycle-related variations of cripto and inhibin α mRNA expression, and [3] an inverse expression pattern of follistatin mRNA. Endometriomas showed similar variations in the expression of activin-related protein mRNA during the menstrual cycle as eutopic endometrium. Conclusion(s) The disturbed expression of endometrial activin A, cripto (activin receptor antagonist), and follistatin (activin-binding protein) suggests a dysfunction of the activin pathway in endometriosis. Endometriomas showed similar changes of activin-related proteins during the menstrual cycle, which supports a common biology for eutopic and ectopic endometrium in endometriosis.

Women with endometriosis have altered endometrial function. CRH and urocortin (Ucn) are neuropeptides produced by human endometrium and modulate endometrial decidualization.To evaluate endometrial mRNA expression of CRH and Ucn, their role in in vitro decidualization of cultured human endometrial stromal cells (HESCs) in patients with endometriosis, and the role of CRH receptors (CHR-Rs).Obstetrics and Gynecology, University of Siena.Endometrial specimens were obtained from patients with and without endometriosis.Endometrial biopsy obtained at both phases of menstrual cycle. In vitro decidualization of HESCs collected from endometriosis or control was done in the presence of CRH, Ucn, or CRH receptor type 1 (CRH-R1, antalarmin) or type 2 (CRH-R2, astressin 2b) antagonists.Endometrial mRNA expression of CRH and Ucn during endometrial cycle; prolactin, CRH-R1, and CRH-R2 mRNA expression during in vitro decidualization.In healthy women CRH and Ucn expression were significantly higher (P0.05) in secretory than in proliferative phase; no differences were observed in endometriotic women. During in vitro decidualization, prolactin mRNA expression and release in endometriosis was lower than in control (P0.001). CRH and Ucn were able to significantly increase (P0.01) prolactin release only in control group; moreover, in this group antalarmin reduced prolactin release (P0.01). CRH-R1 mRNA expression increased during in vitro decidualization of HESCs in control (P0.01) but not in endometriosis.Women with endometriosis show an impaired endometrial expression of CRH and Ucn mRNA, and these neuropeptides are no more active in modulating the in vitro decidualization of HESCs, associated with a reduced expression of CRH-R1 mRNA.

Background: Endometriosis is a chronic inflammatory disease for which no accurate peripheral diagnostic marker is available. Many cytokines and chemokines have been found altered in the plasma and peritoneal fluid of women with endometriosis compared to healthy controls, but little is known about their diagnostic utility to confirm or discard endometriosis among symptomatic women. Objective: The study aims to assess the diagnostic value of a panel of plasma cytokines and chemokines to detect endometriosis in women undergoing laparoscopy for gynecological complains. Methods: We performed a prospective cohort study evaluating simultaneously plasma concentrations of interleukin (IL)-2, IL-4, IL-6, IL-10, MCP-1/CCL2, IP-10/CXCL10 and eotaxin/CCL11 in 75 symptomatic women (chronic pelvic pain, infertility or ovarian cyst) submitted to laparoscopy. Assays were performed by Cytometric Bead Array System. Endometriosis was confirmed by histopathological examination of surgical specimens. Results: Plasma IL-2, IL-4, IL-6, IL-10, MCP-1/CCL2, IP-10/CXCL10 and eotaxin/CCL11 concentrations were not able to distinguish the women who eventually were diagnosed with endometriosis. Conclusion: Although previously shown to be altered in women with endometriosis compared to healthy women, the tested cytokines and chemokines were not useful to predict the presence of endometriosis among symptomatic women. This finding suggests that inflammatory markers modified by endometriosis may also be altered by other conditions associated with similar symptoms, which limits their use in clinical practice.

A comprehensive review was performed to survey the role of angiogenesis in the pathogenesis of endometriosis. This is a multifactorial disease in which the development and maintenance of endometriotic implants depend on their invasive capacity and angiogenic potential. The peritoneal fluid of patients with endometriosis is a complex suspension carrying inflammatory cytokines, growth factors, steroid hormones, proangiogenic factors, macrophages, and endometrial and red blood cells. These cells and their signaling products concur to promote the spreading of new blood vessels at the endometriotic lesions and surroundings, which contributes to the endometriotic implant survival. Experimental studies of several antiangiogenic agents demonstrated the regression of endometriotic lesions by reducing their blood supply. Further studies are necessary before these novel agents can be introduced into clinical practice, in particular the establishment of the safety of anti-angiogenic medications in women who are seeking to become pregnant.

Objetivos: (1) Avaliar a expressão de folistatina, da subunidade beta-A da ativina/inibina (ativina A) e das proteínas relacionadas à ativina A, durante as fases do ciclo menstrual, no endométrio eutópico de pacientes com e sem endometriose e em lesões endometrióticas; (2) Verificar se as concentrações séricas de ativina A e folistatina diferem entre as várias formas de endometriose e se essas proteínas podem ser utilizadas como marcadores de endometriose; (3) Investigar os efeitos da ativina A e da folistatina sobre a expressão de citocinas pró-inflamatórias e mediadores de angiogênese em cultura in vitro de células derivadas de endométrio de mulheres com e sem endometriose. Material e métodos: Estudo prospectivo desenvolvido nos Hospital das Clínicas da UFMG e na Università di Siena. Pacientes: Mulheres com e sem endometriose. Culturas de células estromais de endométrio eutópico de mulheres com e sem endometriose. Métodos: (1) Quantificação da expressão da ativina A, ativina B, receptor da ativina, nodal, cripto, inibina , e folistatina através da reação em cadeia da polimerase (Real Time-PCR) (96 pacientes); (2) Dosagens de ativina A e folistatina no sangue periférico de mulheres com e sem endometriose através de Kits ELISA (214 pacientes); (3) quantificação da expressão de IL-6, IL-8, VEGF por Real Time-PCR nas células das culturas e dosagens de IL-6, IL-8 e VEGF no meio de cultura de pacientes com e sem endometriose (12 culturas). Resultados: O endométrio eutópico de pacientes com endometriose mostrou (1) expressão maior de ativina A RNAm na fase proliferativa e o não aumento de sua expressão na fase secretora , (2) falha na variação da expressão endometrial do cripto e da inibina relacionadas com o ciclo menstrual, (3) padrão de expressão de folistatina RNAm inverso ao do grupo controle, (4) Endometriomas apresentaram variações semelhantes ao endométrio eutópico na expressão de ativina A e proteínas relacionadas à ativina A durante o ciclo menstrual. Com relção às dosagens séricas, o grupo do endometrioma apresentou níveis séricos de ativina A significativamente mais elevados do que os controles (0,22 ± 0,01 ng / ml vs 0,17 ± 0,01 ng / ml, p

Urocortin 2 (Ucn 2) and urocortin 3 (Ucn 3) are neuropeptides expressed by human endometrium. This study evaluated (i) the expression of Ucn 2 and Ucn 3 mRNA in endometriotic lesions and in endometrium of women with endometriosis; (ii) the effect of Ucn 2 and Ucn 3 on cytokines secretion from cultured endometrial stromal cells. Endometriotic tissue was collected from endometrioma (n=39); endometrial specimens were obtained from women with (n=39) and without (n=41) endometriosis throughout menstrual cycle. Tissue specimens were analysed for Ucn 2 and Ucn 3 mRNA expression and peptide localization; the effects of Ucn 2 or Ucn 3 on tumour necrosis factor (TNF-α) and interleukin (IL-4) secretion from cultured endometrial stromal cells was studied. Ucn 2 and Ucn 3 mRNA expression and localization were assessed by RT-PCR and by immuohistochemistry, respectively; cytokines secretion were measured by ELISA. Results showed that endometriotic tissue expressed both Ucn 2 and Ucn 3, with Ucn 3 expression higher in ectopic than in eutopic endometrium. Endometrial Ucn 2 mRNA expression in controls showed peak values at early proliferative phase, while in endometriotic patients low expression and no significant changes throughout menstrual cycle were observed. Endometrial Ucn 3 mRNA expression was highest in late secretory phase in controls, while in endometriotic patients low levels and no menstrual-cycle-related changes were found. When added to cultured endometrial cell cultures, Ucn 2 significantly increased TNF-α (P