How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach.

The evaluation of endometriosis in an adolescent girl is a challenging topic. The initial stage of the disease and the limited diagnostic instrument appropriate for the youth age and for its typical features can reduce the ability of the gynecologist. At the same time, missing a prompt diagnosis can delay the beginning of specific and punctual management of endometriosis, which could avoid a postponed diagnosis from 6 to 12 years, typical of adolescent girls complaining of dysmenorrhea. This article aimed to answer all the potential questions around the diagnosis and management of endometriosis in adolescents starting from a clinical case looking at the possible solution that is easily reproducible in the clinical practice.

Efficacy of N-Acetylcysteine on Endometriosis-Related Pain, Size Reduction of Ovarian Endometriomas, and Fertility Outcomes.

BACKGROUND: Endometriosis is a chronic, estrogen-dependent, inflammatory disease, whose pivotal symptoms are dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Besides the usual medical treatments, recent evidence suggests there are potential benefits of oral N-acetylcysteine (NAC) on endometriotic lesions and pain. The primary objective of this prospective single-cohort study was to confirm the effectiveness of NAC in reducing endometriosis-related pain and the size of ovarian endometriomas. The secondary objective was to assess if NAC may play a role in improving fertility and reducing the Ca125 serum levels. METHODS: Patients aged between 18-45 years old with a clinical/histological diagnosis of endometriosis and no current hormonal treatment or pregnancy were included in the study. All patients received quarterly oral NAC 600 mg, 3 tablets/day for 3 consecutive days of the week for 3 months. At baseline and after 3 months, dysmenorrhea, dyspareunia and CPP were assessed using the Visual Analog Scale score (VAS), while the size of the endometriomas was estimated through a transvaginal ultrasound. Analgesics (NSAIDs) intake, the serum levels of Ca125 and the desire for pregnancy were also investigated. Finally, the pregnancy rate of patients with reproductive desire was evaluated. RESULTS: One hundred and twenty patients were recruited. The intensity of dysmenorrhea, dyspareunia and CPP significantly improved (p < 0.0001). The use of NSAIDs (p = 0.001), the size of the endometriomas (p < 0.0001) and the serum levels of Ca125 (p < 0.0001) significantly decreased. Among the 52 patients with reproductive desire, 39 successfully achieved pregnancy within 6 months of starting therapy (p = 0.001). CONCLUSIONS: Oral NAC improves endometriosis-related pain and the size of endometriomas. Furthermore, it decreases Ca125 serum levels and may improve fertility in patients with endometriosis.

Single-cell transcriptomics uncovers an instructive T-cell receptor role in adult γδ T-cell lineage commitment.

After entering the adult thymus, bipotent T-cell progenitors give rise to αß or γδ T cells. To determine whether the γδ T-cell receptor (TCR) has an instructive role in γδ T-cell lineage commitment or only "confirms" a pre-established γδ Τ-cell lineage state, we exploited mice lacking expression of LAT, an adaptor required for γδ TCR signaling. Although these mice showed a T-cell development block at the CD4- CD8- double-negative third (DN3) stage, 0.3% of their DN3 cells expressed intermediate levels of γδ TCR (further referred to as γδint ) at their surface. Single-cell transcriptomics of LAT-deficient DN3 γδint cells demonstrated no sign of commitment to the γδ T-cell lineage, apart from γδ TCR expression. Although the lack of LAT is thought to tightly block DN3 cell development, we unexpectedly found that 25% of LAT-deficient DN3 γδint cells were actively proliferating and progressed up to the DN4 stage. However, even those cells failed to turn on the transcriptional program associated with the γδ T-cell lineage. Therefore, the γδ TCR-LAT signaling axis builds upon a γδ T-cell uncommitted lineage state to fully instruct adult γδ T-cell lineage specification.

Effects of Breastfeeding on Endometriosis-Related Pain: A Prospective Observational Study.

Endometriosis is a gynecological estrogen-dependent disease whose commonest pain symptoms are dysmenorrhea, dyspareunia, and acyclic chronic pelvic pain (CPP). Hormonal changes occurring during breastfeeding seem to reduce pain and disease recurrence. The aim of this observational prospective study was to assess the effect of breastfeeding on pain and endometriotic lesions in patients with endometriosis and to evaluate a possible correlation between the duration of breastfeeding, postpartum amenorrhea, and pain. Out of 156 pregnant women with endometriosis enrolled, 123 who breastfed were included in the study and were monitored for 2 years after delivery; 96/123 exclusively breastfed for at least 1 month. Mode of delivery, type and duration of breastfeeding, intensity of pain symptoms, and lesion size before pregnancy and during the 24-month follow-up were analyzed. All patients experienced a significant reduction in dysmenorrhea proportional to the duration of breastfeeding. CPP was significantly reduced only in women who exclusively breastfed. No significant improvement in dyspareunia was observed. Ovarian endometriomas were significantly reduced. Therefore, breastfeeding, particularly if exclusive, may cause improvement in dysmenorrhea and CPP proportional to the duration of breastfeeding, as well as a reduction in the size of ovarian endometriomas.

A deep insight into pelvic pain and endometriosis: a review of the literature from pathophysiology to clinical expressions.

INTRODUCTION: Endometriosis is a chronic inflammatory disease that affects approximately 10% of women of reproductive age. Its clinical manifestations are highly heterogeneous, but pelvic pain is the most frequent, causing functional disability. Cyclic or acyclic chronic pelvic pain (CPP), dysmenorrhea and dyspareunia are frequent symptoms which often compromise all aspects of the women's quality of life (QoL). The pathophysiology of endometriosis-related pain is extremely complex and not always clear. The aim of this systematic review was to focus on recent updates on the clinical presentation, the pathophysiology and the most important mechanisms involved in the pathogenesis of pelvic pain in endometriosis. EVIDENCE ACQUISITION: A literature search in the Cochrane library, PubMed, Scopus and web of Science databases has been performed, identifying articles from January 1995 to November 2020. EVIDENCE SYNTHESIS: Several processes seem to be involved in the pathogenesis of pain, but many aspects are still unclear. Scientific evidence has shown that a correlation between pain severity and stage of endometriosis rarely occurs, whereas there is a significant correlation between pain and the presence of deep endometriosis. Onset and intensity of pain may be due to a complex process involving central sensitization and peripheral activation of nociceptive pathways as well as dysfunction of the immune system and of the hypothalamic-pituitary-adrenal (HPA) axis. CONCLUSIONS: A deeper understanding of these different pathogenetic mechanisms may improve future treatments in women with painful endometriosis.

Dienogest versus continuous oral levonorgestrel/EE in patients with endometriosis: what's the best choice?

OBJECTIVE: Combined oral contraceptives (COC) and progestogens are widely used for the treatment of endometriosis. The objective of the study is to compare the efficacy of dienogest 2 mg vs continuous oral levonorgestrel/EE (levonorgestrel 0.1 mg/ethinyl estradiol 0.02 mg) on ovarian endometriomas, deep infiltrating endometriosis (DIE), chronic pelvic pain (CPP), dyspareunia, analgesic use, quality of life (QoL), compliance and side effects. METHODS: Prospective cohort study. Two cohorts of patients with endometriosis, 50 taking dienogest (group A) and 50 taking continuous levonorgestrel/EE (group B), were evaluated at the beginning of therapy (t0), after 3 (t3) and 6 months (t6). Size of endometriomas, DIE, QoL, pain symptoms, and side effects were assessed. RESULTS: Dienogest was significantly effective on CPP (p = .002), dyspareunia (p = .021) ovarian endometriomas (p = .015) and DIE lesions reduction (p = .014). Levonorgestrel/EE was significantly effective on dyspareunia (p = .023). Analgesics consumption significantly decreased in both groups (p < .001). Both treatments significantly improved the QoL. Over 6 months a significant improvement was found, more frequently in patients taking dienogest. The only side effect that both groups complained about was vaginal bleeding, present in the first 3 months of treatment (p < .001). CONCLUSIONS: Both treatments are effective and safe for patients with endometriosis. Patients compliance and side effects are similar in both groups, however, there was a significantly higher reduction in endometriotic lesions, pain symptoms, and improvement of the QoL in women taking dienogest than in women taking continuous COC.

Cabergoline as an adjuvant to standard heart failure treatment in peripartum cardiomyopathy: A case report and review of the literature.

INTRODUCTION: Peripartum cardiomyopathy (PPCM) is a rare and idiopathic form of dilated cardiomyopathy presenting late in pregnancy or early postpartum. Since the 16-kDa fragment of prolactin has been identified as a key factor in the pathophysiology of PPCM, prolactin inhibitors have been used as an adjuvant to standard heart failure treatment. Although bromocriptine is the current first choice, promising results have been reported with cabergoline, albeit scant. CASE PRESENTATION: We presented the case of a 41-year-old woman who received a diagnosis of PPCM one week after delivery and was successfully treated with cabergoline, finally experiencing a complete recovery. CONCLUSION: The case adds to the scant evidence supporting the use of cabergoline in PPCM patients. We argue that the favorable pharmacokinetic and metabolic profiles of this drug should prompt its consideration as a valid alternative prolactin inhibitor in these critical patients.

Endometriosis and Pregnancy: A Single Institution Experience.

Endometriosis may compromise the physiological course of pregnancy. The aim of this prospective observational study was to evaluate whether endometriosis causes a higher prevalence of obstetric and neonatal complications as well as a higher risk of caesarean section and to detect a possible correlation between the presence, type, and location of endometriosis and obstetric complications, previous surgery, and pregnancy outcome, as well as the influence of pregnancy on the course of the disease. We compared two cohorts of women with spontaneous pregnancy, with and without endometriosis. Obstetric and neonatal outcomes, mode of delivery, presence, type, and location of endometriotic lesions and the effect of pregnancy on the disease were analyzed. A total of 425 pregnancies were evaluated: 145 cases and 280 controls. Patients with endometriosis showed a higher incidence of miscarriage, threatened miscarriage, threatened preterm labor, preterm delivery, placental abruption, and a higher incidence of caesarean section. A significant correlation with pregnancy-induced hypertension and preeclampsia was found in the presence of adenomyosis. No difference in fetal outcome was found. One case of hemoperitoneum during pregnancy was observed. Pregnancy in women with endometriosis carries a higher risk of obstetric complications, such as miscarriage, threatened miscarriage, preterm labor, preterm birth, and a higher caesarean section rate. Endometriosis does not seem to influence fetal well-being.

Environmental Contaminants Exposure and Preterm Birth: A Systematic Review.

Preterm birth is an obstetric condition associated with a high risk of infant mortality and morbidities in both the neonatal period and later in life, which has also a significant public health impact because it carries an important societal economic burden. As in many cases the etiology is unknown, it is important to identify environmental factors that may be involved in the occurrence of this condition. In this review, we report all the studies published in PubMed and Scopus databases from January 1992 to January 2019, accessible as full-text articles, written in English, including clinical studies, original studies, and reviews. We excluded articles not written in English, duplicates, considering inappropriate populations and/or exposures or irrelevant outcomes and patients with known risk factors for preterm birth (PTB). The aim of this article is to identify and summarize the studies that examine environmental toxicants exposure associated with preterm birth. This knowledge will strengthen the possibility to develop strategies to reduce the exposure to these toxicants and apply clinical measures for preterm birth prevention.