Sex Hormones as Key Modulators of the Immune Response in Multiple Sclerosis: A Review.

BACKGROUND: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and progression, and to play a role in treatment. METHODS: Scientific papers (published between 1998 and 2021) were selected through PubMed, Google Scholar, and Web of Science literature repositories. The search was limited to publications analyzing the hormonal profile of male and female MS patients during different life phases, in particular focusing on sex hormone treatment. RESULTS: Both men and women with MS have lower testosterone levels compared to healthy controls. The levels of estrogens and progesterone increase during pregnancy and then rapidly decrease after delivery, possibly mediating an immune-stabilizing process. The literature examined herein evidences the neuroprotective effect of testosterone and estrogens in MS, supporting further examinations of their potential therapeutic uses. CONCLUSIONS: A correlation has been identified between sex hormones and MS clinical activity. The combination of disease-modifying therapies with estrogen or estrogen plus a progestin receptor modulator promoting myelin repair might represent an important strategy for MS treatment in the future.

Transvaginal Ultrasound in the Diagnosis and Assessment of Endometriosis-An Overview: How, Why, and When.

Endometriosis is a common gynaecological disease, causing symptoms such as pelvic pain and infertility. Accurate diagnosis and assessment are often challenging. Transvaginal ultrasound (TVS), along with magnetic resonance imaging (MRI), are the most common imaging modalities. In this narrative review, we present the evidence behind the role of TVS in the diagnosis and assessment of endometriosis. We recognize three forms of endometriosis: Ovarian endometriomas (OMAs) can be adequately assessed by transvaginal ultrasound. Superficial peritoneal endometriosis (SUP) is challenging to diagnose by either imaging modality. TVS, in the hands of appropriately trained clinicians, appears to be non-inferior to MRI in the diagnosis and assessment of deep infiltrating endometriosis (DIE). The IDEA consensus standardized the terminology and offered a structured approach in the assessment of endometriosis by ultrasound. TVS can be used in the non-invasive staging of endometriosis using the available classification systems (rASRM, #ENZIAN). Given its satisfactory overall diagnostic accuracy, wide availability, and low cost, it should be considered as the first-line imaging modality in the diagnosis and assessment of endometriosis. Modifications to the original ultrasound technique can be employed on a case-by-case basis. Improved training and future advances in ultrasound technology are likely to further increase its diagnostic performance.

Pregnancy outcomes in women with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is the most common endocrinological disease of reproductive-aged women, with an estimated incidence ranging from 5% to 15%. The clinical manifestations of PCOS are heterogeneous and vary according to the age of the patient. Insulin resistance (IR), hyperandrogenism, and obesity are widely assumed to play a pivotal role in the pathophysiological mechanism of PCOS. As previously stated by many conducted meta-analyses, PCOS can cause a rising risk of pregnancy complications, including maternal, fetal, and neonatal complications. Pregnancy-induced hypertension (PIH), preeclampsia (PE), gestational diabetes mellitus (GDM), spontaneous preterm birth (PTB), and an increased necessity for a cesarean section (CS) are the most documented maternal implications. Regarding fetal outcomes, PCOS has also been correlated with elevated neonatal morbidity, prematurity, fetal growth restriction (FGR), birth weight variations (large for gestational age [LGA] and small for gestational age [SGA]), and transfer to the Neonatal Intensive Care Unit (NICU). Owing to the variability of the studies performed, the association of PCOS with an elevated risk of adverse pregnancy outcomes is still controversial. This variability is found in the diagnosis and clinical presentations of PCOS, and can be influenced by prepregnancy circumstances and therapies as well as particular population and environmental features. The Amsterdam Consensus Guidelines confirm that obesity and IR can worsen maternal and fetal complications; thus, a closer follow-up should be offered to PCOS women during pregnancy.

Role of surgical treatment in endometriosis.

Endometriosis can take one of three forms depending on its clinical presentation and management: endometriotic ovarian cyst (ovarian endometrioma), superficial or peritoneal endometriosis and deep infiltrating endometriosis (DIE).1Among them, DIE is considered the most aggressive, and the patient is often affected by more than one type together. The therapeutic methodology should not be influenced by a combination of different types of endometriotic lesion. According to the clinical context and the patient's needs, the treatment of this pathology can be medical or surgical. Although medical therapy could improve endometriosis-associated symptoms, it never offers a definite treatment for symptomatic patients, who often require surgical treatment. The rationale behind endometriosis surgical treatment is to achieve the complete removal of all lesions through a one-step surgical procedure; to obtain promising long-term results for pelvic pain, recurrence rate, and fertility; and to protect the functionality of the involved organs. Achieving these results depends on the total removal of the pathology from the pelvis, in an attempt to preserve, as much as possible, the healthy tissues surrounding the site of the disease. The choice of a surgical approach rather than medical therapy is subject to the patient's expectations, such as pregnancy desire, the effectiveness of treatment compared to possible complications, the type of pain and its intensity, and the location and severity of the disease. In this context, surgical management using a multidisciplinary endometriosis team is an important factor for achieving good outcomes.

Possible role of microbiome in the pathogenesis of endometriosis.

INTRODUCTION: There is an urgent necessity to explore the complex pathophysiological nature of endometriosis, which may enable the rationale for new diagnostic and therapeutic strategies to be discovered. This systematic review aimed to clarify the bidirectional relationship between endometriosis and the microbiome and evaluate if the microbiome may be involved in endometriosis's pathogenesis, establishing a potential connection between the different studies. EVIDENCE ACQUISITION: Studies were identified through a systematic literature search of papers that evaluated the microbiomes of human or other animal species with endometriosis and of those without in the electronic database PubMed/Medline, and Embase without a date restriction. We included all cohort studies focusing on the interaction between endometriosis and the microbiomes of humans or other mammals, evaluating if the microbiome may be involved in endometriosis's pathogenesis. EVIDENCE SYNTHESIS: Endometriosis appears to be associated with elevated levels of different microorganisms across various microbiome sites. An ineffective immune response seems to play a key role in endometriosis pathogenesis, and there is some scientific proof to state that the immune response may be modulated by the microbiome. Interestingly, nine studies of our review detected species belonging to the phyla Proteobacteria, Bacteroidetes, and Negativicutes characterized by Gram-negative staining, that were significantly increased in endometriosis cohorts. CONCLUSIONS: Laboratory and clinical investigations indicate that hosts' microbiome profiles with and without endometriosis can be significantly different. To further our understanding of the relationships between endometriosis and the host microbiome, more studies are necessary.

Highlights on Medical Treatment of Uterine Fibroids.

Uterine fibroids (leiomyomas or myomas) are the most frequent benign tumors in women. Heavy menstrual bleeding with resultant anemia, dysmenorrhea, chronic pelvic pain, infertility, urinary symptoms and constipation are generally associated with uterine fibroids (UFs). Although strategies mainly resort to surgical intervention, medical treatments are considered the first-line treatment to preserve fertility and avoid surgery. The aim of this review is to offer available and the newest medical treatment options for symptomatic UFs. Various medical therapies are now available for women with uterine fibroids, although each therapy has its own advantages and disadvantages. Our topic specifically explores gonadotropin-releasing hormone (GnRH) analogs and selective progesterone receptor modulators (SPRMs), but also provides the reader with useful advice on the therapies for fibroids available after the recent European Medicines Agency (EMA) warning (EMA/160220/2020). The treatment options depend on the personal treatment objectives of the patients, in addition to treatment effectiveness and necessity for recurrent interventions.

Genetics of endometriosis: a comprehensive review.

This review aimed to critically evaluate the review, observational, cohort, and case-control studies performed so far in order to assess the association between endometriosis and genetics. The search strategies used included an online search of the MEDLINE database and a manual search of relevant publications and reviews. Additional reports were collected by systematically reviewing all references from the retrieved papers. Family studies have long suggested that genetic factors play a role in the etiology of endometriosis. Nevertheless, until now, studies on candidate genes have revealed inconsistent and contradictory evidence, leading to more questions rather than clear answers. It is possible that recent technological improvements in genetic evaluation could allow for a better understanding of the pathogenic mechanisms of endometriosis in the near future.