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Lorena Lorefice,1 Maurizio Nicola D’Alterio,2 Davide Firinu,3 Giuseppe Fenu,4 Eleonora Cocco1 1Multiple Sclerosis Center, Binaghi Hospital, ASL Cagliari, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 2Division of Gynecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy; 3Clinical Immunology, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 4Department of Neurosciences, ARNAS Brotzu, Cagliari, ItalyCorrespondence: Lorena Lorefice, Multiple Sclerosis Center, Binaghi Hospital, ASL Cagliari, Department of Medical Sciences and Public Health, University of Cagliari, via Is Guadazzonis 2, Cagliari, 09126, Italy, Email lorena.lorefice@hotmail.itAbstract: Given the aging population, with a peak age-specific prevalence that is shifting beyond the age of 50, several women currently living with MS are very close to menopause. Menopause is usually characterized by several specific symptoms with adverse impacts on different aspects of a woman’s quality of life, such as fatigue, and cognitive, mood and bladder disorders, which overlap with symptoms of MS. Generally, after this biological transition, women with MS appear to be subject to less inflammatory activity. However, several studies have reported an increase of disability accumulation after menopause, suggesting that it is a turning point to a more progressive phase of the disease. This may be attributable to the hormonal and immunological changes associated with menopause, with several effects on neuroinflammation and neurodegeneration increasing due to the immunosenescence of aging. This review summarizes the hormonal and immunological changes associated with menopause, detailing the effects on MS symptoms, outcomes, and the aging process. Furthermore, possible interventions to improve patients’ quality of life are evaluated. In fact, it is increasingly necessary to improve the global management of MS women, as well as their lives, at this multifaceted turning point.Keywords: multiple sclerosis, menopause, hormone therapy, aging, best practice

Study Objective: To evaluate the effectiveness of the Dual Wavelength Laser System (DWLS) diode laser on the treatment of ovarian endometrioma (OMA), with ablation and vaporization of the cystic capsule without performing the stripping technique, in terms of ovarian reserve and recurrence rate., Design: Prospective, single-arm, multicenter, clinical trial., Setting: Multicenter University Hospital., Patients: Seventy patients with symptomatic OMA., Interventions: Patients underwent surgery for primary unilateral or bilateral symptomatic OMA treated with DWLS diode laser vaporization. Following surgical intervention, patients were enrolled in a 12 months surveillance protocol featuring regular clinical assessments aimed at detecting ovarian reserve, pregnancy rate and any recurrence of the cyst and/or symptomatic relapse., Measurements and Main Results: Antimullerian hormone (AMH) levels at the 3-month follow-up exhibited a significant difference from the baseline (p = .034), demonstrating a return to nearly presurgical values in the subsequent months. Antral follicle count (AFC) of the operated ovary showed a significant increase after treatment at the 6-month and 12-month follow-up (p = 0.005 and p = 0.002, respectively). Pregnancies were documented in 48.3% (14/29) of infertile patients who underwent treatment. OMA recurrence was observed in 4 patients (5.7%) at 12 months. No patient exhibited a significant relapse of the analyzed symptoms compared to baseline values., Conclusion: The findings of this study propose that DWLS diode laser presents a good option for treating OMA, demonstrating minimal impact on the surrounding healthy ovarian tissue, favorable pregnancy rate, coupled with low recurrence rates., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate characteristics of endometrial surveillance in women treated for breast cancer to build a clinical prediction model., Design: A multicentric retrospective cohort study was conducted at two tertiary-care university hospitals from January 2020 to June 2023. Perimenopausal and postmenopausal women treated for breast cancer were categorized into two groups: patients with and without diagnosis of endometrial malignancy (endometrial carcinoma) or premalignancy (atypical endometrial hyperplasia). Characteristics of breast cancer and ultrasonographic and hysteroscopic examinations were compared. A prediction model for endometrial malignancy was built using logistic regression. Predictive accuracy was assessed using the receiver operating characteristic (ROC) curve and goodness of fit using the Hosmer-Lemeshow test., Results: One hundred and thirty-two (28 with premalignancy or malignancy and 104 without malignancy) women were analyzed. A nomogram was produced for prediction model development utilizing the presence and duration in months of abnormal uterine (BL)eeding, ultrasound (US) vascular pattern and echogenicity and (H)ysteroscopic appearance of endometrium (BLUSH) as determined by logistic regression. Sensitivity and specificity were 79.17% and 95.19%, respectively, with an area under ROC curve of 0.965, indicating good accuracy. Good goodness of fit and prediction stability were indicated by the calibration curve and Hosmer-Lemeshow test ( χ 2  = 26.36; p  = 0.999)., Conclusions: Breast cancer survivors undergoing endometrial surveillance might benefit from a potentially useful prediction model based on hysteroscopic appearance, ultrasonographic uniformity of endometrium, Doppler flow and presence of abnormal uterine bleeding.

Introduction: This study evaluates the efficacy and safety of non-ablative diode laser therapy for genitourinary syndrome of menopause (GSM) in post-menopausal women unable to use hormonal therapies., Methods: A pilot prospective study was conducted from September 2023 to April 2024, involving 22 post-menopausal women aged 45-73 years. Participants underwent three sessions of diode laser treatment with the Leonardo ® dual-wavelength Diode laser. Assessments were made at baseline, 3 months, and 6 months post-treatment. Main outcome measures included Visual Analog Scale (VAS) scores for GSM symptoms, Vaginal Health Index Score (VHIS), and sexual function evaluated using the Female Sexual Function Index (FSFI-6), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), and Sexual Quality of Life-Female (SQOL-F) questionnaire., Results: Significant improvements were observed in VHIS, increasing from 12 to 19.27 at 6 months (p < 0.001). GSM symptoms improved significantly: vaginal dryness scores decreased from 7.72 ± 2.37 to 3.72 ± 2.53, burning sensation scores dropped from 6.00 ± 3.22 to 1.90 ± 1.81, and dyspareunia scores reduced from 8.09 ± 2.11 to 3.90 ± 2.58 (all p < 0.016). Sexual function improved, indicated by FSFI-6 scores increasing from 12.27 ± 7.29 to 19.30 ± 6.24 (p < 0.016) and SQOL-F scores rising from 63.18 ± 22.93 to 71.45 ± 23.31. No adverse events were reported., Conclusion: Non-ablative diode laser therapy is effective and safe for managing GSM symptoms in post-menopausal women, offering significant symptom relief and enhancing sexual health without serious side effects. Further research with a larger cohort and extended follow-up is needed to confirm these findings., Trial Registration: Clinical Trials ID NCT06503003., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Objective: To assess the quality, reliability, and level of misinformation in TikTok videos about hysteroscopy., Methods: A cross-sectional analysis of TikTok videos retrieved using "hysteroscopy" as search term was performed. Patient education materials assessment tool for audio-visual content (PEMAT A/V), the modified DISCERN (mDISCERN), global quality scale (GQS), video information and quality index (VIQI) and misinformation assessment were used., Results: Of three hundred videos captured, 156 were excluded and 144 were included. Most videos were partially accurate or uninformative (43.8% and 34.7%, respectively). Non-healthcare providers produced more inaccurate or uninformative videos than healthcare workers (51.1% vs 4.0%; P < 0.001). Compared to content by professionals, content by patients showed increased distrust towards gynecologists (11.7% vs 0%; P = 0.012) and increased incidence of anxiety and concern towards hysteroscopy (25.5% vs 2%; P < 0.001). PEMAT A/V scores for understandability and actionability were low at 42.9% (interquartile range [IQR]: 11.1-70) and 0% (IQR: 0-0), respectively. Understandability (P < 0.001) and actionability (P = 0.001) were higher for professionals' created content relative to patients' videos. Similarly, median mDISCERN score was low (1 [IQR 0-2]), with significantly higher score for healthcare professionals compared to patients (P < 0.001). Overall video quality was also low, with median VIQI and GQS score of 7 (IQR 4-11) and 1 (IQR 1-3), respectively, and significantly higher scores for healthcare workers' captions compared to patients' for both (P < 0.001 and P = 0.001, respectively)., Conclusion: TikTok videos' quality on hysteroscopy seems unsatisfactory and misinformative, with low understandability and actionability scores. Videos recorded by healthcare workers show higher quality and less misinformation than those by patients. Raising the awareness regarding the low quality of medical information on social media is crucial to increase future reliability and trustworthiness., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objectives: This study aims to evaluate the safety, efficacy, and cost-effectiveness of the Laparoscopic Organ Suspension (OS) sec. Angioni, an innovative approach to transient OS in laparoscopic gynecological procedures. Recognizing the need to enhance surgical site access and overcome limitations of existing organ retraction methods, the study investigates a novel, in-theater constructed OS device., Design: This retrospective observational study was conducted from March 2019 to May 2021 and included 330 patients who underwent multiport or single-site-port laparoscopic surgery employing Angioni's technique for transient pelvic OS., Participants/materials, Setting, Methods: Participants included individuals undergoing surgery for conditions such as endometriosis, ovarian cancer, endometrial cancer, pelvic prolapse, and benign ovarian cysts. The Laparoscopic OS sec. Angioni utilizes a segment of a Foley catheter connected to a Polyglactin suture to provide adjustable tension, minimizing the need for reconfiguration during surgery., Results: The application of this OS technique resulted in an average suspension time of 1.9 min, with no significant difference between senior and junior surgeons. The method proved more time-efficient for posterior peritoneum suspension than other published methods and showed no additional risks of organ damage, bleeding, conversion to laparotomy, or OS-related complications. The secondary outcomes revealed reduced hospital stays and minimal blood loss, highlighting the procedure's overall efficiency., Limitations: Given its retrospective and single-center nature, the study's results may not be widely generalizable. Prospective multicentric comparative studies are recommended to further validate Angioni's technique., Conclusions: Laparoscopic OS sec. Angioni is introduced as a straightforward, safe, and cost-effective method that significantly streamlines the surgical process. Its adaptability and ease of use suggest that it could be a valuable addition to current gynecological surgical practices, with potential implications for increasing efficiency and reducing procedural costs. Future studies are required to confirm these results across diverse clinical environments., (© 2024 S. Karger AG, Basel.)

Purpose: This case series examined the safety and effectiveness of hysteroscopic myolysis using laser-induced interstitial thermo-therapy (LITT) for treating heavy menstrual bleeding (HMB) in premenopausal women with FIGO type 1 or 2 uterine fibroids, not planning for future fertility. Additionally, a comprehensive review of innovative, minimally invasive, incisionless myolysis techniques was conducted., Methods: Women with HMB, sonographically diagnosed with a single FIGO type 1 or 2 fibroid, underwent hysteroscopic myolysis using the Leonardo ® diode laser. Effectiveness was assessed via transvaginal ultrasound measurement of myoma size, volume and vascularization pre and post-procedure. Moreover, we also evaluated any improvements in symptoms using the Pictorial Blood Loss Assessment Chart (PBAC score) scores., Results: The procedure resulted in significant HMB reductions and noticeable fibroid size, volume, and vascularization decrease in all three patients, with no reported complications. The literature review revealed both advantages and limitations of the minimally invasive, incisionless myolysis techniques., Conclusions: Hysteroscopic laser myolysis is a safe and effective therapeutic intervention for patients experiencing HMB, diagnosed with FIGO type 1 or 2 fibroids, and not planning for future fertility. The procedure resulted in significant reductions in menstrual blood loss and fibroid size. Despite the promising results, it is essential to note the limitations of this report, including its case series design, a small number of patients, and a short follow-up period. Further research is necessary to confirm these results., (© 2023. The Author(s).)

Background: Hysteroscopy currently represents the gold standard for the diagnosis and treatment of intrauterine pathologies. Recent technological progress has enabled the integration of diagnostic and operative time, leading to the "see and treat" approach. Diode laser technology is emerging as one of the most innovative and intriguing techniques in this context. Methods: A comprehensive search of the literature was carried out on the main databases. Only original studies reporting the treatment of intrauterine pathologies using diode laser were deemed eligible for inclusion in this systematic review (PROSPERO ID: CRD42023485452). Results: Eight studies were included in the qualitative analysis for a total of 474 patients undergoing laser hysteroscopic surgery. Eighty-three patients had female genital tract abnormalities, 63 had submucosal leiomyomas, 327 had endometrial polyps, and one patient had a scar pregnancy. Except for leiomyomas, whose technique already included two surgical times at the beginning, only seven patients required a second surgical step. Cumulative rates of intraoperative and postoperative complications of 2.7% and 0.6%, respectively, were reported. Conclusions: Diode laser through "see and treat" hysteroscopy appears to be a safe and effective method. However, additional studies with larger sample sizes and improved designs are needed to consolidate the evidence currently available in the literature.

Recent advances in surgical technology and innovative techniques have revolutionized surgical gynecology, including transcervical hysteroscopic procedures. Surgical lasers (Nd-Yag, Argon, diode, and CO2 lasers) have been promoted to remove a variety of gynecological pathologies. For hysteroscopic surgery, the diode laser represents the most versatile and feasible innovation, with simultaneous cut and coagulate action, providing improved hemostasis compared with CO2 laser. The newest diode laser devices exhibit increased power and a dual wavelength, to work precisely with reduced thermal dispersion and minimal damage to surrounding tissues. Their efficacy and safety have been validated both in the hospitals as well as in the office setting. Updated evidence reports that several hysteroscopic procedures, including endometrial polypectomies, myomectomies and metroplasties can be successfully performed with a diode laser. Therefore, this review aimed to give a deeper understanding of the role of laser energy in gynecology and subsequently in hysteroscopy in order to safely incorporate this technology into clinical practice.

Purpose: The aim of this narrative review is to offer an overview about the role of progesterone levels on pregnancy outcome in patients undergoing assisted reproductive technologies (ARTs)., Methods: A detailed computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science) to determine the importance of elevated progesterone levels at different stages of the cycle for pregnancy rates in the in vitro fertilization (IVF) cycle. Our review also provides information on the differences between elevated progesterone levels and their interpretation in normal and in poorly responding women., Results: After careful evaluation, our search strategy yielded a total of 15 included articles, showing the possible factors that may have had an impact on the increased progesterone level before human chorionic gonadotropin (HCG) injection and the different thresholds above which the pregnancy rate was lower. Furthermore, increased progesterone on cycle day 2 or 3 could serve as a marker for increased progesterone in the late follicular phase, which is associated with a lower pregnancy rate., Conclusion: Despite the literature data that support the negative effect of elevated progesterone on fresh cycles, due to lack of randomized controlled trials, the value of measuring progesterone in daily practice is questionable. Available evidence supports the detrimental effect of elevated progesterone in different subgroups of women, although there is still the need for defining different thresholds and durations of high progesterone exposure. The need for various thresholds for different cohorts of women, the inter-assay variability is making this decision harder.

Objectives: Several studies indicated leukocyte telomere length (LTL) as a biomarker of multiple sclerosis (MS) evolution. This study aimed to investigate LTL in women with multiple sclerosis (MS) compared to that in healthy women (HW) across different reproductive phases, and to evaluate its relationship with MS activity., Methods: Blood samples were collected from women with MS and HW during the fertile phase, pregnancy, and puerperium. LTL was determined using quantitative fluorescence in situ hybridization (Q-FISH)., Results: Blood samples from 68 women with MS (22 during fertile life, 23 during pregnancy, and 23 post-partum) and 52 HW (23 during fertile life, 20 during pregnancy, and 9 post-partum) were analyzed. During pregnancy, LTL in MS women and HW was 84.7 ± 10.5 and 77.6 ± 11.5, respectively (p < 0.005). Regression analysis showed that shorter LTL was associated with pregnancy in HW (p = 0.021); this relationship was not observed in MS women, for whom shorter LTL was related to a higher EDSS (p = 0.036). A longitudinal analysis was performed in eight MS women, showing LTL shortening from pregnancy to puerperium (p = 0.003), which was related to MS reactivation (p = 0.042)., Conclusion: Our results highlight the possible associations between LTL, reproductive biological phases, and MS activity after delivery., Competing Interests: Declaration of Competing Interest Lorefice L., Fenu G., Frau J, and Cocco E. received honoraria for consultancy or speaking from Biogen, Novartis, Sanofi, Genzyme, Serono and Teva and Almirall. Caria P., Pilotto S., D'Alterio MN, Fronza M., Murgia F., Dettori T., Frau DV, Atzori L., and Angioni S., have nothing to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Endometriosis affects women of reproductive age, and its pathogenesis is still unclear. Typically, it overlaps other similar medical and surgical conditions, determining a delay in early diagnosis. Metabolomics allows studying metabolic changes in different physiological or pathological states to discover new potential biomarkers. We used the gas chromatography-mass spectrometer (GC-MS) to explore metabolic alterations in endometriosis to better understand its pathophysiology and find new biomarkers., Methods: Twenty-two serum samples of patients with symptomatic endometriosis and ten without it were collected and subjected to GC-MS analysis. Multivariate and univariate statistical analyses were performed, followed by pathway analysis., Results: Partial least squares discriminant analysis was performed to determine the differences between the two groups ( p = 0.003). Threonic acid, 3-hydroxybutyric acid, and proline increased significantly in endometriosis patients, while alanine and valine decreased. ROC curves were built to test the diagnostic power of metabolites. The pathway analysis identified the synthesis and degradation of ketone bodies and the biosynthesis of phenylalanine, tyrosine, and tryptophan as the most altered pathways., Conclusions: The metabolomic approach identifies metabolic alterations in women with endometriosis. These findings may improve our understanding of the pathophysiological mechanisms of disease and the discovery of new biomarkers., Competing Interests: The authors declare no conflict of interest.

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.

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.

In women with deep endometriosis, the spontaneous fertility rate might range from 2 to 10%. The optimal management of these women is still an area of debate. Therefore, this review aims to explore the literature on the impact of deep endometriosis surgery on reproductive outcomes and pregnancy rates in women with and without prior infertility. A total of 392 articles were identified through database searching. Twenty-three studies were eligible to be included in the review. A total of 1548 women were identified, 814 of whom became pregnant, with a mean pregnancy rate of 52.6% (95% CI 49.7-63%). Our review suggests that surgery may improve fertility outcomes. Due to the variability in the studies, it is impossible to stratify fertility outcomes of surgery by the localization of deep endometriosis. More investigations are needed to determine whether surgical management should be first-intention or limited to the failure of medically assisted reproduction treatment.

Objective: The aim of this systematic review is to recap the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on non-hormonal therapeutic options alleviating endometriosis-associated pelvic pain. Methods: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 179 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, seven primary articles met the inclusion criteria. A systematic review of the data was conducted. Results: This review included several, non-hormonal emerging drug therapies for endometriosis-associated pelvic pain. Based on our results, we divided well-founded studies into three subgroups: antiangiogenic agents, immunomodulators, and natural components. Randomized control trials showed promising results with dopamine agonists (cabergoline, quinagolide, and bromocriptine), and the immunomodulatory JNK inhibitor bentamapimod. Agents that have not been represented in randomized control trials or have failed to demonstrate efficacy include statins and TNF-α inhibitors. Conclusion: Although there are substantial improvements in non-hormonal therapy options, majority of the currently available treatment options are supressive rather than curative and do not present a final solution for patients. Future research priorities should be to identify novel target therapies and to evalute the effects of available drugs through different routes of administration.

Objective: The aim of this systematic review is to summarize the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on hormonal therapeutic options for endometriosis-associated pelvic pain (EAPP), excluding studies focusing on fertility., Methods: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 219 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, 11 primary articles met the inclusion criteria. A systematic review of the data was conducted., Results: This review included several emerging drug therapies for EAPP. Randomized control trials showed promising results with several oral gonadotropin-releasing hormone antagonists (elagolix, relugolix, ASP1707, linzagolix). However, studies of other hormonal agents such as aromatase inhibitors and selective progesterone receptor modulators have not yielded significant or new advantages. Selective estrogen receptor modulators have not been represented in randomized control trials and have failed to demonstrate clinical efficacy., Conclusion: Although numerous novel agents are being investigated for the treatment of endometriosis, there is still no significant progress in the development of curative rather than suppressive drugs. Therefore, further efforts are needed to develop an effective and hopefully curative treatment for this chronic, costly, and overwhelming disease.

MicroRNAs (miRNAs) are small, non-coding RNAs that are essential for the regulation of post-transcriptional gene expression during tissue development and differentiation. They are involved in the regulation of manifold metabolic and hormonal processes and, within the female reproductive tract, in oocyte maturation and folliculogenesis. Altered miRNA levels have been observed in oncological and inflammatory diseases, diabetes or polycystic ovary syndrome (PCOS). Therefore, miRNAs are proving to be promising potential biomarkers. In women with PCOS, circulating miRNAs can be obtained from whole blood, serum, plasma, urine, and follicular fluid. Our systematic review summarizes data from 2010-2021 on miRNA expression in granulosa and theca cells; the relationship between miRNAs, hormonal changes, glucose and lipid metabolism in women with PCOS; and the potential role of altered miRNAs in fertility (oocyte quality) in PCOS. Furthermore, we discuss miRNAs as a potential therapeutic target in PCOS and as a diagnostic marker for PCOS.

Abnormal uterine bleeding (AUB) is a frequent symptom in perimenopausal women. It is defined as uterine bleeding in which the duration, frequency, or amount of bleeding is considered excessive and negatively affects the woman's quality of life (QoL) and psychological well-being. In cases of structural uterine pathology, hysterectomy (usually performed via a minimally invasive approach) offers definitive symptom relief and is associated with long-lasting improvement of QoL and sexuality. However, over the past 30 years, uterus-preserving treatments have been introduced as alternatives to hysterectomy. Hysteroscopic polypectomy, myomectomy, or endometrial resection/endometrial ablation are minimally invasive techniques that can be used as an alternative to hysterectomy to treat AUB due to benign conditions. Although associated with high patient satisfaction and short-term improvement in their QoL, hysteroscopic treatments do not eliminate the risk of AUB recurrence or the need for further intervention. Therefore, considering the impact of different treatment options on QoL and sexuality during preoperative shared decision making could help identify the most appropriate and personalized treatment options for perimenopausal women suffering from AUB.

Introduction: Pregnancy represents an important event for women with multiple sclerosis (MS) and is often accompanied by post-partum disease reactivation. To date, the influence of this reproductive phase on long-term MS outcomes is still largely unexplored. The objective of the study was characterise a large real-world cohort of women with MS to evaluate the effects of pregnancy and breastfeeding on short- and long-term clinical and magnetic resonance imaging (MRI) outcomes while exploring the relationships with MRI measurements of brain atrophy., Methods: MS patients with and without pregnancy were recruited. Clinical relapses and MRI activity of the year before conception versus the year after delivery were evaluated. Regression models were performed to investigate the relationships between long-term MS outcomes (EDSS score and MRI brain measurements obtained by SIENAX software) and pregnancy and breastfeeding duration., Results: Two hundred ten women with MS were enrolled; of them, 129 (61.4%) had at least one pregnancy. Of all pregnancies (n = 212), those that occurred after MS onset (90 [42.4%]) were examined to evaluate the short-term outcomes. A higher annualised relapse rate in the post-partum year versus the pre-conception year (0.54 ± 0.84 vs. 0.45 ± 0.71; p = 0.04) was observed. A regression analysis showed that clinical activity after delivery was associated with clinical activity of the year before conception (p = 0.001) as well as duration of breastfeeding (p = 0.022). Similarly, post-partum MRI activity was associated with pre-conception MRI activity (p = 0.026) and shorter breastfeeding duration (p = 0.013). Regarding long-term outcomes, having had at least one pregnancy during MS was associated with a lower EDSS score (p = 0.021), while no relationships were reported with MRI measurements. Conversely, a breastfeeding duration > 6 months was associated with lower white matter volume (p = 0.008)., Conclusions: Our study underlines the importance of considering the effects of pregnancy and breastfeeding on short- and long-term MS outcomes. In the current therapeutic landscape, pregnancy planning and treatment optimisation in the post-partum period, in particular for women who choose to breastfeed, are fundamental for the management of these biological phases so central in a woman's life., (© 2021. The Author(s).)

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.

Purpose: To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy., Methods: Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis., Results: Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22-4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23-3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23-3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49-79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69-38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38-22.09)., Conclusion: Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery., Trial Registration: Clinical trial registration number: NCT03354793., (© 2021. The Author(s).)

Purpose: To evaluate whether laparoscopic treatment with a diode laser is feasible, safe, and effective in symptomatic patients affected by deep endometriosis (DE)., Methods: This retrospective study was performed using medical record data. The surgical reports, chronic pain scores, and quality of life (QoL) data were evaluated for 50 patients who had undergone laparoscopic surgery between November 2017 and March 2019 at two university hospitals (Monserrato (CA) and Foggia, Italy). Indications for surgery were chronic pelvic pain and/or infertility in patients who wished to conceive spontaneously. Endometriosis lesions/nodules were excised using a diode laser (Leonardo®, Biolitec® DUAL 45) that can combine 980 and 1470 nm wavelengths transmitted through a 1000 µm conical optical fibre., Results: The median patient age was 32 years (range 21-44), with a body mass index (BMI) mean of 21.7  ±  2.9 kg/m 2 . The mean operation time was 147 min (range 106-190). No intraoperative or early complications (< 30 days) were reported. All patients left the hospital, on average, within 3 days (range 2-9 days) after surgery. A significant improvement in pain was observed at the 3-, 6-, and 12-month follow-up (p < 0.01) in all patients. Moreover, patients reported a significant QoL improvement at the 12-month follow-up., Conclusion: The diode laser confirmed its feasibility and safety for treating endometriosis. During the shaving surgical procedure, the diode laser system ensures a safe and effective laparoscopic dissection of deep endometriotic lesions. Further comprehensive randomized trials are necessary to confirm these preliminary data in terms of efficacy, recurrence rates, and pregnancy outcomes., (© 2021. The Author(s).)

Introduction: Uterine myomas and endometriosis are benign hormone-dependent diseases affecting women of reproductive age. Substantial efforts have been made to develop innovative medical options for treating these gynecologic diseases. Elagolix and relugolix have been approved in some countries for treating endometriosis and myomas, respectively; however, linzagolix (OBE 2109, KLH 2109) is a new oral gonadotropin-releasing hormone (GnRH) antagonist in phase II-III trials. Treatment options for women with contraindications for hormonal therapies or who refuse particular options, are the driving force behind the development of new drugs in this area., Area Covered: This drug evaluation highlights definitive and preliminary results from previous and ongoing studies of linzagolix for the treatment of endometriosis and myomas., Expert Opinion: Linzagolix showed a dose-dependent and rapidly reversible action on the pituitary-gonadal axis. In a recent phase II trial (EDELWEISS), linzagolix significantly reduced pain related to endometriosis and improved quality of life at single daily doses of 75-200 mg. The preliminary results of international, double-blind phase III trials (PRIMROSE 1 and 2) reported its efficacy in treating heavy menstrual bleeding related to myomas with a good safety profile. Further studies will determine the necessity of add-back therapy during long-term use of linzagolix.

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). 1 Among 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.

Deep infiltrating endometriosis (DIE) is the most aggressive of the three phenotypes that constitute endometriosis. It can affect the whole pelvis, subverting the anatomy and functionality of vital organs, with an important negative impact on the patient's quality of life. The diagnosis of DIE is based on clinical and physical examination, instrumental examination, and, if surgery is needed, the identification and biopsy of lesions. The choice of the best therapeutic approach for women with DIE is often challenging. Therapeutic options include medical and surgical treatment, and the decision should be dictated by the patient's medical history, disease stage, symptom severity, and personal choice. Medical therapy can control the symptoms and stop the development of pathology, keeping in mind the side effects derived from a long-term treatment and the risk of recurrence once suspended. Surgical treatment should be proposed only when it is strictly necessary (failed hormone therapy, contraindications to hormone treatment, severity of symptoms, infertility), preferring, whenever possible, a conservative approach performed by a multidisciplinary team. All therapeutic possibilities have to be explained by the physicians in order to help the patients to make the right choice and minimize the impact of the disease on their lives., Competing Interests: The authors declare no conflicts of interest., (Copyright© by Royan Institute. All rights reserved.)

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.

Endometriosis is a common disease affecting women in reproductive age. There are several hypotheses on the pathogenesis of this disease. Often, its lesions and symptoms overlap with those of many other medical and surgical conditions, causing a delay in diagnosis. Metabolomics represents a useful diagnostic tool for the study of metabolic changes during a different physiological or pathological status. We used 1 H-NMR to explore metabolic alteration in a cohort of patients with endometriosis in order to contribute to a better understanding of the pathophysiology of the disease and to suggest new useful biomarkers. Thirty-seven patients were recruited for the metabolomic analysis: 22 patients affected by symptomatic endometriosis and 15 not affected by it. Their serum samples were collected and analyzed with 1 H-NMR. Multivariate statistical analysis was conducted, followed by univariate and pathway analyses. Partial Least Square Discriminant Analysis (PLS-DA) was performed to determine the presence of any differences between the non-endometriosis and endometriosis samples (R 2 X = 0.596, R 2 Y = 0.713, Q 2  = 0.635, and p < 0.0001). β-hydroxybutyric acid and glutamine were significantly increased, whereas tryptophan was significantly decreased in the endometriosis patients. ROC curves were built to test the diagnostic power of the metabolites (β-hydroxybutyric acid: AUC = 0.85 CI = 0.71-0.99; glutamine: AUC = 0.83 CI = 0.68-0.98; tryptophan: AUC = 0.75 CI = 0.54-0.95; β-hydroxybutyric acid + glutamine + tryptophan AUC = 0.92 CI = 0.81-1). The metabolomic approach enabled the identification of several metabolic alterations occurring in women with endometriosis. These findings may provide new bases for a better understanding of the pathophysiological mechanisms of the disease and for the discovery of new biomarkers. Trial registration number NCT02337816.

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Endometriosis is a chronic inflammatory disease of women of reproductive age. Small bowel (SB) permeability and lipopolysaccharides (LPS) could play a role in the perduration of low grade inflammation status and the pathogenesis of endometriosis. To clarify this hypothesis, we measured SB permeability through plasma values of LPS and urinary secretion of lactulose (La), mannitol (Ma) and their ratio (L/M) in patients with endometriosis compared with healthy controls (HC). Eight patients and 14 HC entered the study. SB permeability was evaluated by high-performance liquid chromatography of urine concentrations of La and Ma. Plasma levels of LPS were measured in the blood. Moreover, a nutritional, gastroenterological, quality of life evaluation was performed through validates questionnaires and complete gynaecological evaluations. The statistical analysis of the obtained data did not show differences in anthropometric and nutritional characteristics and gastrointestinal functional disease in the two groups. Patients reported higher levels of pelvic chronic pain (3.87 ± 2.99 vs 0.15 ± 0.55; pe = 0.001) and significantly higher LPS plasma levels (0.529 ± 0.11 vs 0.427 ± 0.08; p value = .027) than HC. Our results indicate that intestinal permeability is abnormal in endometriosis patients, and it might play a role in the pathogenesis of this chronic disease.

The pathogenesis of endometriosis is unknown, but some evidence supports a genetic predisposition. The purpose of this study was to evaluate the recent literature on the genetic characterization of women affected by endometriosis and to evaluate the influence of polymorphisms of the wingless-type mammalian mouse tumour virus integration site family member 4 (WNT4), vezatin (VEZT), and follicle stimulating hormone beta polypeptide (FSHB) genes, already known to be involved in molecular mechanisms associated with the proliferation and development of endometriotic lesions in the Sardinian population. Materials and Methods: In order to provide a comprehensive and systematic tool for those approaching the genetics of endometriosis, the most cited review, observational, cohort and case-control studies that have evaluated the genetics of endometriosis in the last 20 years were collected. Moreover, 72 women were recruited for a molecular biology analysis of whole-blood samples-41 patients affected by symptomatic endometriosis and 31 controls. The molecular typing of three single nucleotide polymorphisms (SNPs) was evaluated in patients and controls: rs7521902, rs10859871 and rs11031006, mapped respectively in the WNT4, VEZT and FSHB genes. In this work, the frequency of alleles, genotypes and haplotypes of these SNPs in Sardinian women is described. Results: From the initial search, a total of 73 articles were chosen. An analysis of the literature showed that in endometriosis pathogenesis, the contribution of genetics has been well supported by many studies. The frequency of genotypes observed in the groups of the study population of 72 women was globally coherent with the law of the Hardy-Weinberg equilibrium. For the SNP rs11031006 (FSHB), the endometriosis group did not show an increase in genotypic or allelic frequency due to this polymorphism compared to the control group (p = 0.9999, odds ratio (OR) = 0.000, 95% confidence interval (CI), 0.000-15.000 and p = 0.731, OR = 1639, 95% CI, 0.39-683, respectively, for the heterozygous genotype and the polymorphic minor allele). For the SNP rs10859871 (VEZT), we found a significant difference in the frequency of the homozygous genotype in the control group compared to the affected women (p = 0.0111, OR = 0.0602, 95% CI, 0.005-0.501). For the SNP rs7521902 (WNT4), no increase in genotypic or allelic frequency between the two groups was shown (p = 0.3088, OR = 0.4133, 95% CI, 0.10-1.8 and p = 0.3297, OR = 2257, 95% CI, 0.55-914, respectively, for the heterozygous genotype and the polymorphic minor allele). Conclusion: An analysis of recent publications on the genetics of endometriosis showed a discrepancy in the results obtained in different populations. In the Sardinian population, the results obtained do not show a significant association between the investigated variants of the genes and a greater risk of developing endometriosis, although several other studies in the literature have shown the opposite. Anyway, the data underline the importance of evaluating genetic variants in different populations. In fact, in different ethnic groups, it is possible that specific risk alleles could act differently in the pathogenesis of the disease.

Objective: The present study analyzed long-term outcomes and complications of laparoscopic lateral suspension (LLS) with mesh to treat apical and anterior pelvic organ prolapse (POP)., Study Design: A prospective cohort study on 125 patients with vaginal bulge and apical +/- anterior prolapse scheduled for LLS who consecutively underwent LLS between April 2013 and January 2017 in Gynecologic Department of Santa Chiara Hospital in Trento and University of Pisa. The main outcome measure was anatomic and symptomatic POP outcome; the secondary outcomes measures were recurrence, reoperation rate, de novo posterior POP and complications. Percentage distribution of the pre- and postoperative POP-Q stages was compared at mean follow-up. Wilcoxon signed rank sum test was used to compare preoperative POP-Q stage and postoperative POP-Q stage ate mean follow up, for each patient (paired data) and for each type of prolapse., Results: 120 patients were included in the study. At 2 years 89 % of patients were asymptomatic and anatomic success rate was 94.2 % for the anterior compartment, 94.9 % for the apical compartment. Concerning posterior compartment prolapse 2 (1.7 %) patients referred stage 3 de novo prolapse during follow-up. The complication rate of Clavien-Dindo >3 was 0,8 %. Repeat surgery for POP occurred in 6.4 % of cases. The appearance of POP-Q recurrences was concentrated at 6 months follow-up. BMI > 25 was correlated with de novo posterior compartment appearance during follow-up., Conclusions: LLS for the treatment of apical and anterior POP is a technique with optimal results in term of safety and effectiveness after 2 years follow-up., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.

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.

Introduction: Septate uterus is one of the most common congenital uterine anomalies and it may effect female reproductive health causing different obstetric complications, in particular miscarriages and reduction of fertility., Materials and Methods: We conducted a retrospective case-control (1:4) comparative study (Canadian Task Force Classification II-2) with the purpose to evaluate pregnancy complications (abnormal fetal presentations, preterm deliveries, and caesarean sections) and reproductive outcome after hysteroscopic metroplasty. We studied retrospectively two groups: 62 women that delivered after metroplasty (group A); and a control group of 248 women with no history of hysteroscopic metroplasty that delivered in the same period in our hospital (group B)., Results: The rate of abnormal fetal presentations was significantly higher in study group A versus control group B (22.58% [14/62] vs. 4.03% [10/248], p<0.0001). Caesarean section rate was significantly higher in group A versus group B (66.12% [41/62] vs. 35.08% [87/248], p<0.0001), and preterm deliveries rate was significantly higher in group A versus group B (14.51% [9/62] vs. 6.45% [16/248], p= 0.037). Furthermore, in group A, we observed a significant reduction of the abortion rate and an increase in the total number of live births after metroplasty., Conclusions: In our series of cases, we have observed a high rate of some pregnancy complications after metroplasty compared to the general population, such as preterm deliveries and fetal malpresentations with a higher rate of caesarean sections. Hysteroscopic metroplasty has been proven to improve the overall reproductive outcome by reducing miscarriage rate and increasing live birth rate. In our opinion, benefits obtained after metroplasty must be considered greater than the adverse pregnancy outcomes observed with our series.

Adenomyosis is a heterogeneous gynaecologic condition with a range of clinical presentations, the most common being heavy menstrual bleeding and dysmenorrhoea; however, patients can also be asymptomatic. Several studies support the theory that adenomyosis results from invasion of the endometrium into the myometrium, causing alterations in the junctional zone. These changes are commonly seen on imaging studies, such as transvaginal ultrasound and magnetic resonance imaging. The aim of this review is to discuss the medical approach to the management of adenomyosis symptoms, including pain and abnormal uterine bleeding. The standard treatment of adenomyosis is hysterectomy, but there is no medical therapy to treat the symptoms of adenomyosis while still allowing patients to conceive. Medical therapies using suppressive hormonal treatments, such as continuous use of oral contraceptive pills, high-dose progestins, selective oestrogen receptor modulators, selective progesterone receptor modulators, the levonorgestrel-releasing intrauterine device, aromatase inhibitors, danazol, and gonadotrophin receptor hormone agonists can temporarily induce regression of adenomyosis and improve the symptoms.

Introduction: Suppression of sex-steroid secretion is required in a variety of gynecological conditions. This can be achieved using gonadotropin releasing hormone (GnRH) agonists that bind pituitary gonadotropin receptors and antagonize the link-receptor of endogenous GnRH, inhibiting the mechanism of GnRH pulsatility. On the other hand, GnRH antagonists immediately reduce gonadal steroid levels, avoiding the initial stimulatory phase of the agonists. Potential benefits of GnRH antagonists over GnRH agonists include a rapid onset and reversibility of action. Older GnRH antagonists are synthetic peptides, obtained by modifications of certain amino acids in the native GnRH sequence. They require subcutaneous injections, implantation of long-acting depots. The peptide structure is responsible for histamine-related adverse events and the tendency to elicit hypersensitivity reactions., Areas Covered: Research has worked towards the development of non-peptidic molecules exerting antagonist action on GnRH. They are available for oral administration and may have a more beneficial safety profile in comparison with peptide GnRH antagonists. This article focuses on the data of the literature about elagolix, a novel non-peptidic GnRHantagonist, in the treatment of endometriosis., Expert Opinion: Elagolix demonstrated efficacy in the management of endometriosis-associated pain and had an acceptable safety and tolerability profile. However, further studies are necessary to evaluate its non-inferiority in comparison with other endometriosis's treatments.

In the menopausal transition (MT), combined oral contraceptive (COC) should be chosen accordingly to its neutrality on liver metabolism and to its ability to counter the increase of fat mass (FM) that occurs in this reproductive period of life. This prospective multi-centric observational study was conducted on 36 women in their MT at the Universities of Cagliari, Modena and Naples. The body weight (BW), the Body Mass Index (BMI), the waist to hip ratio (WHR), the measurement of body composition (BC) with the Multi-frequency Bioelectrical Impedance (MF-BIA) were performed before, at the 6th and at the 12th month of the study in which a group of women (control group; N.18) did not assume COC, whereas the other 18 women assumed the four-phasic COC containing estradiol valerate (EV) associated with dienogest (EV/DNG group). In comparison to controls in the EV/DNG group, a significant decrease (p < 0.05) of BW (58.8 ± 7.6 to 57.3 ± 7.0), BMI (24.1 ± 2.7 to 23.5 ± 2.8), WHR (0.82 ± 0.052 to 0.79 ± 0.048) and FM (17.7 ± 5.4 to 16.4 ± 5.6) was observed. In controls, FM significantly increased (17.0 ± 11 to 17.7 ± 2.7; p < 0.05). In conclusion, these results suggest that the anti-androgenic and progestinic activities of DNG associated with a weak estrogenic activity of EV, is a contraceptive method capable of counteracting the negative changes of BC occurring in the MT.

The study was performed to compare the clinical effect of a hormone replacement therapy (HRT) with two different progestins. Postmenopausal women (PMW) with climacteric symptoms (CS) randomly received for 12 months orally, either placebo (n = 20), 1 mg estradiol (E) plus 0.5 mg noretisterone acetate (NETA; n = 40), or 2 mg drospirenone (DRSP; n = 40), a testosterone- and spironolactone-derived molecule, respectively. Weight (W) declined only during E/DRSP (p < 0.04 versus placebo). Fat mass (FM) decreased, similarly, during E/NETA and E/DRSP. Intracellular water (ICW) did not change, while extracellular water (ECW) decreased during E/DRSP (p < 0.0001) (p < 0.002 versus E/NETA). During E/NETA and E/DRSP, similar decreases were observed for insulin resistance (IR) by the homeostatic model assessment for IR (HOMA-IR) (p < 0.0001 versus placebo for both), systolic (p < 0.04 versus placebo for both) and diastolic (p < 0.002) blood pressure (BP). Lipids did not change. In comparison to placebo CS, by the Kupperman Index (KI), significantly declined (p < 0.0001) during E/NETA or E/DRSP. Menopause-specific Quality of Life (MENQoL) significantly declined versus placebo (p < 0.04) during both E/NETA and E/DRSP. In conclusion, differences between the two progestins are mainly limited to body composition (BC), where the addition of DRSP decreases ECW and body W (BW).