Thyroid autoimmunity in different phenotypes of polycystic ovary syndrome: a single-center experience.

PURPOSE: Polycystic ovary syndrome (PCOS) has been associated with Hashimoto's thyroiditis (HT) and 4 phenotypes have been described in this syndrome. The aim of this work was to investigate the frequency of anti-thyroid antibodies (TAb) and thyroid function in the 4 phenotypes of PCOS. PATIENTS: This study included 448 patients with PCOS: 260 (58.0%) with phenotype A, 119 (26.6%) with phenotype B, 38 (8.5%) with phenotype C and 31 (6.9%) with phenotype D. RESULTS: TAb positivity was detected in 90/448 patients (20.1%) and was statistically significant higher (p = 0.03) in the grouped phenotypes A-B (83/379, 21.9%) than in phenotypes C-D (7/69, 10.1%). Positive anti-thyroglobulin antibodies (TgAb) were detected in 74/448 (16.5%) patients and positive anti-thyroperoxidase antibodies (TPOAb) in 66/448 (14.7%) patients. Both TgAb and TPOAb positivity was higher but not statistically significant in phenotype A-B than phenotype C-D. High titer TgAb (> 100 UI/ml) frequency was significantly higher (p = 0.005) in grouped phenotypes A-B (39/379, 10.3%) than in phenotypes C-D (0/69, 0.0%), while no significant difference was observed for low titer TgAb (≤ 100 UI/ml). According to a binary logistic regression analysis hypothyroidism was significantly associated with TAb positivity (OR 4.19; CI 2.25-7.79; p < 0.01) but not with PCOS phenotype. Androgen profile was not associated with TAb positivity. CONCLUSION: A higher frequency of positive TAb and of high titer TgAb and TPOAb have been detected in PCOS women with phenotypes A and B, probably in relation to the greater imbalances between estrogen and progesterone levels present in these phenotypes.

Experts' view on the role of oestrogens in combined oral contraceptives: emphasis on oestetrol (E4).

Introduction: The evolution of contraception has been crucial for public health and reproductive well-being. Over the past 60 years, combined oral contraceptives (COCs) have remained an important part of the contraceptive landscape worldwide; continued development has worked toward maintaining efficacy and improving safety. Methods: Seven global experts convened to discuss the clinical relevance of the oestrogen in COCs, focusing on the impact of the new oestrogen, oestetrol (E4). Participants then commented through an online forum on the summary content and other participants' feedback. We prepared this report to describe the experts' views, their follow-up from the open forum and the evidence supporting their views. Results: Ethinylestradiol (EE) and oestradiol (E2) affect receptors similarly whereas E4 has differential effects, especially in the liver and breast. Adequate oestrogen doses in COCs ensure regular bleeding and user acceptability. EE and E4 have longer half-lives than E2; accordingly, COCs with EE and E4 offer more predictable bleeding than those with E2. Oestrogen type and progestin influence VTE risk; E2 poses a lower risk than EE; although promising, E4/DRSP VTE risk is lacking population-based data. COCs alleviate menstrual symptoms, impact mental health, cognition, libido, skin, and bone health. Conclusion: Oestrogens play an important role in the contraceptive efficacy, bleeding patterns, and overall tolerability/safety of COCs. Recent studies exploring E4 combined with DRSP show promising results compared to traditional formulations, but more definitive conclusions await further research.

Expert opinion on the treatment of vulvovaginal atrophy with ospemifene based on new evidence.

Vulvovaginal atrophy (VVA) is an underdiagnosed and undertreated chronic condition resulting in physiological and histological changes in the genitourinary tract of postmenopausal women. Treatment of moderate to severe VVA includes local estrogens, dehydroepiandrosterone (DHEA) and oral ospemifene, a third-generation selective estrogen receptor modulator (SERM). Due to venous thromboembolism (VTE) safety concerns classically associated with the SERM class, and as part of its original marketing authorization approval (MAA), the European Medicines Agency (EMA) requested the performance of a 5-year post-authorization safety study (PASS) to study the incidence rate of VTE among women receiving ospemifene. The results have led to important regulatory changes to ospemifene's labeling, extending its indication and eliminating concerted risk management measures. A panel of experts discussed and reached consensus on the impact of these regulatory changes on clinical practice, reflecting on the reassurance of ospemifene's benefit-risk balance and recommending its positioning as a first-line pharmacological treatment option for moderate to severe VVA together with local therapies. In a scenario where different treatments present similar efficacy and safety profiles, a shared decision between clinician and patient, according to her needs and preferences over time, is fundamental to improve adherence and persistence with sequential treatment, contributing to the achievement of health outcomes.

Effects of ospemifene on overactive bladder in postmenopausal women with vulvovaginal atrophy.

OBJECTIVE: Overactive bladder (OAB) is a complex and multifactorial syndrome associated with urinary frequency, urgency and incontinence. The menopause-associated hormonal changes play a role in the development of this condition. Vaginal estrogens are effective in improving OAB in postmenopausal women (PMW) with vulvovaginal atrophy (VVA). Ospemifene is a selective estrogen receptor modulator licensed for the treatment of VVA. This study aimed to evaluate the effects of ospemifene on OAB symptoms in PMW with VVA. METHODS: Forty PMW suffering from OAB and VVA received oral ospemifene (60 mg/day) for 12 weeks. All patients were assessed with a urodynamic study, a 3-day bladder diary and validated questionnaires (International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form [ICIQ-UI SF] and International Consultation on Incontinence Questionnaire - Overactive Bladder [ICIQ-OAB]) at enrollment and at the end of the study. RESULTS: Cytometric capacity, bladder compliance and verbal sensory threshold responses during bladder filling were improved after treatment. The voiding diary showed a significant reduction of daily voids, urge urinary incontinence episodes and nocturnal events. The median overall scores of the ICIQ-UI and ICIQ-OAB were also significantly improved. CONCLUSIONS: Our study suggest that treatment with ospemifene in PMW suffering from OAB is associated with a reduction of OAB symptoms due to a decreased bladder sensitivity and with an improvement in quality of life.

Mode of delivery and peripartum outcome in women with heart disease according to the ESC guidelines: an Italian multicenter study.

INTRODUCTION: The European Society of Cardiology (ESC) guidelines (GL) provide indications on the mode of delivery in women with heart disease. However available data suggests that the rate of Cesarean Delivery (CD) is high and widely variable among such patients. In this study, we aimed to investigate the degree of adherence to the ESC recommendations among women delivering in four tertiary maternity services in Italy and how this affects the maternal and neonatal outcomes. MATERIAL AND METHODS: Retrospective multicenter cohort study including pregnant women with heart disease who gave birth between January 2014 and July 2020. Composite adverse maternal outcome (CAM) was defined by the occurrence of one or more of the following: major postpartum hemorrhage, thrombo-embolic or ischemic event, de novo arrhythmia, heart failure, endocarditis, aortic dissection, need for re-surgery, sepsis, maternal death. Composite Adverse Neonatal outcome (CAN) was defined as cord arterial pH <7.00, APGAR <7 at 5 min, admission to the intensive care unit, and neonatal death. We compared the incidence of CAM and CAN between the cases with planned delivery in accordance (group "ESC consistent") or in disagreement (group "ESC not consistent") with the ESC GL. RESULTS: Overall, 175 women and 181 liveborn were included. A higher frequency of CAN was found when delivery was not planned accordingly to the ESC guidelines [("ESC consistent" 9/124 (7.2%) vs "ESC not consistent" 13/57 (22.8%) p = 0.002 OR 3.74 (CI 95% 1.49-9.74) , while the occurrence of CAM was comparable between the two groups. At logistic regression analysis, the gestational age at delivery was the only parameter independently associated with the occurrence of CAN (p = 0.006). CONCLUSION: Among pregnant women with heart disease, deviating from the ESC guidelines scheduling cesarean delivery does not seem to improve maternal outcomes and it is associated with worse perinatal outcomes, mainly due to lower gestational age at birth.

Single feature constrained manual registration method for Augmented Reality applications in gynecological laparoscopic interventions.

Augmented Reality (AR) can avoid some of the drawbacks of Minimally Invasive Surgery and may provide opportunities for developing innovative tools to assist surgeons. In laparoscopic surgery, the achievement of easy and sufficiently accurate registration is an open challenge. This is particularly true in procedures, such as laparoscopic abdominal Sacro-Colpopexy, where there is a lack of a sufficient number of visible anatomical landmarks to be used as a reference for registration. In an attempt to address the above limitations, we developed and preliminarily testes a constrained manual procedure based on the identification of a single anatomical landmark in the laparoscopic images, and the intraoperative measurement of the laparoscope orientation. Tests in a rigid in-vitro environment show good accuracy (median error 2.4 mm obtained in about 4 min) and good preliminary feedback from the technical staff who tested the system. Further experimentation in a more realistic environment is needed to validate these positive results. Clinical Relevance - This paper provides a new registration method for the development of AR educational videos and AR-based navigation systems for laparoscopic interventions.

Menopause, aging and the failing pelvic floor: a clinician's view.

The management of pelvic organ disorders is common and challenging work. Nowadays, midlife women are more active than they were in the past, and the development of pelvic organ prolapse (POP) disrupts quality of life and impairs social and personal activities. The aging process and hormonal changes have a role in influencing the structure and function of the lower urinary and genital tract. Correct diagnosis of pelvic organ disorders and the identification of women's symptoms are the hallmarks of tailored management. Treatment is multimodal and multidisciplinary; it requires competence in pelvic medicine and surgery. When conservative treatments fail, women with symptomatic POP are candidates for reconstructive surgery: the optimal management requires clinicians who are familiar with all of the available strategies and who are able to choose the best strategies in a tailored manner. Knowing and understanding the management of POP should be integrated into the practice of health-care professionals dealing in menopause.

Anti-goat antibodies as a rare cause of high gonadotropin levels during menopausal transition.

Objective: To understand the origin of extremely high gonadotropin levels in a perimenopausal woman.Methods: A 52-year-old woman with a 2 months of amenorrhea followed spontaneous menstrual cycles recovery was referred to our outpatient clinic with elevated follicle-stimulating hormone (FSH, 483 mUI/ml), luteinizing hormone (LH, 475 mUI/ml) and prolactin (PRL, 173 ng/ml). She was known to take levosulpiride. The gonadotropin levels did not fit with the clinical features.Results: A gonadotroph tumor was ruled out. Further analysis confirmed constantly high FSH, LH and PRL levels. The measurements were repeated using different analytical platforms with different results. After serial dilutions, nonlinearity was present suggesting an immunoassay interference. After post-polyethylene glycol recovery, hormone levels appeared in the normal range. Anti-goat antibodies were recognized in the serum of the patient.Conclusions: This case report shows a case of falsely abnormal high gonadotropin and PRL levels in a woman during menopause transition. In the clinical practice the evaluation of gonadotropin profile is not recommended at this age, but the abnormal levels stimulated further evaluation. An interference in the assay due to anti-goat antibodies resulted in abnormally high level of FSH and LH. A strict collaboration between clinicians and the laboratory is needed, when laboratory findings do not correspond to clinical findings.

Perimenopause, body fat, metabolism and menopausal symptoms in relation to serum markers of adiposity, inflammation and digestive metabolism.

BACKGROUND: Perimenopausal women gain weight that may alter inflammatory status, endocrine equilibrium, and the intensity of vasomotor symptoms. OBJECTIVE: To measure serum levels of markers related to adiposity, inflammation/angiogenesis and digestive metabolism and correlate them with body mass index (BMI), waist-to-hip ratio (WHR), metabolic parameters and menopausal symptoms (assessed with the 10-item Cervantes Scale [CS-10]). METHODS: Serum of perimenopausal women (n = 24), STRAW stages-2 and -1, was analyzed using the Bio-Plex 200 System technology to assess 30 proposed analytes. The MetS was defined by the American Heart Association criteria and women were divided as: normal BMI (NBMI), excessive BMI (EBMI), and EBMI with MetS (EBMI-MetS). RESULTS: Weight, BMI, abdominal circumference, WHR, systolic blood pressure, glucose and triglyceride levels were significantly higher and high-density lipoprotein cholesterol (HDL-C) was lower in EBMI-MetS women compared to NBMI ones. Insulin, C-peptide, resistin, adipsin, GIP, leptin, IL-6, FGF21 and PAI-1 levels were significantly higher and ghrelin and IGFBP-1 lower in EBMI-MetS women as compared to NBMI ones. Spearman's correlation of pooled data showed a significant positive correlation between abdominal perimeter and WHR and C-peptide, insulin, adipsin, resistin, leptin, PAI-1 and FGF21 and a negative correlation with IGFBP-1 levels. Total CS-10 scores and hot flush intensity did not differ between studied groups, yet positively correlated with anthropometric values but not with studied analytes. CONCLUSION: Perimenopausal women with EBMI and the MetS showed an altered metabolic profile, but no differences in menopausal symptoms which also did not correlate with changes in studied biomarkers.

Tailored hormonal approach in women with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is probably one of the most devastating diagnoses for women of reproductive age. The major implications for fertility, climacteric symptoms, and quality of life, the great impact of long-term consequences such as bone loss and cardiovascular health, and the lack of a coherent and shared clinical approach make the choice for the right hormonal therapy challenging. In this review we propose an integrated and patient-based hormonal approach for women with POI, from puberty to late reproductive age.

Cranberry, D-mannose and anti-inflammatory agents prevent lower urinary tract symptoms in women undergoing prolapse surgery.

Objective: We assessed the effect on lower urinary tract symptoms (LUTS) of a supplement containing cranberry, D-mannose and anti-inflammatory molecules in postmenopausal women undergoing surgery for cystocele.Study design: Forty postmenopausal women were randomized 1:1 to an active group receiving the nutritional supplement twice a day for 2 weeks starting from surgery, or to a control group receiving surgery only. Primary outcomes were the effectiveness in the postoperative LUTS and urinary tract infections (UTI). LUTS were investigated by a validated questionnaire (ICIQ-FLUTS) at baseline and at week 4. Secondary outcomes were the safety and tolerability of the supplement and other perioperative outcomes.Results: No significant differences were found in perioperative outcomes and in incidence of UTI. After surgery, women treated with the supplement experienced significantly better scores on the filling domain of the questionnaire. A non-significant decrease in voiding scores was also found. No adverse events were detected.Conclusion: The use of an oral supplement containing cranberry, D-mannose and anti-inflammatory molecules decreases the perception of LUTS in postmenopausal women after anterior colporraphy. Our data suggest that perioperative use of nutritional supplements may be useful in the management of postoperative LUTS.

Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disorders.

Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.

Delayed delivery of the second twin: Case report and literature review of diamniotic dichorionic twin pregnancy with very early preterm premature rupture of membranes.

In multiple pregnancies with threatened premature delivery or preterm premature rupture of membranes (pPROM) of a single sac, prolonging pregnancy after the delivery of the first baby may improve the chances of survival of the second baby. We report the delayed delivery of a second baby in a twin pregnancy with pPROM and very premature delivery of the first baby. This condition is exceptional and there are no validated medical protocols for its management; the scientific evidence is still controversial. In our case, after the birth of the first baby, pregnancy was continued for 29 days, with monitoring of maternal and fetal parameters, which enabled the delivery of the second baby with improved neonatal outcomes. This case supports the prolongation of the pregnancy of the second twin.

The role of adipokines in the pathogenesis of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a complex condition whose physiopathology to date has not been completely clarified. Two major metabolic disorders, insulin resistance and ß-cells dysfunction, play currently major role in pathogenesis of GDM. These elements are influenced by the amount of adipose tissue present before and/or during the pregnancy. Consequently, adipokines (adiponectin (APN), leptin (LPT), adipocyte fatty acid-binding protein, resistin, visfatin, omentin, vaspin, apelin, chemerin) secreted by adipose tissue, may contribute directly and/or indirectly, through the enhancement of chronic inflammation, aggravating insulin resistance and promoting GDM onset. This review aims to outline the potential physiopathological and prognostic role in GDM of adipokines, mainly APN and LPT.

Oral dehydroepiandrosterone restores ß-endorphin response to OGTT in early and late postmenopause.

ß-endorphin is a neuropeptide involved in several brain functions: its plasma levels are higher in obese women and its release increases after oral glucose tolerance test (OGTT) in normal or obese women. The study included 46 healthy women and evaluated the effect of oral dehydroepiandrosterone [DHEA] (50 mg/day) in early postmenopausal women (50-55 years) both of normal weight (group A, n = 12, BMI = 22.1 ± 0.5) and overweight (group B, n = 12, BMI = 28.2 ± 0.5), and late postmenopausal women (60-65 years) both normal weight (group C, n = 11, BMI = 22.5 ± 0.6) and overweight (group D, n = 11, BMI = 27.9 ± 0.4) undergone OGTT, in order to investigate if DHEA could restore/modify the control of insulin and glucose secretion and ß-endorphin release in response to glucose load. The area under the curve (AUC) of OGTT evaluated plasma levels of different molecules. DHEA, DHEAS, and ß-endorphin plasma levels were lower in baseline conditions in older women than younger women. Considering the AUC of ß-endorphin response to OGTT, all groups showed a progressive significant increase after 3 and also after 6 months of treatment in comparison to baseline and 3 months of treatment.

Advances in surgical strategies for prolapse.

Pelvic floor dysfunctions are a complex condition in elderly women; pelvic organ prolapse, urinary or fecal incontinence, constipation, pelvic pain, and sexual dysfunction are common problems. The goal of surgical treatment is functional reconstruction with symptom management and repair of anatomic defects. The recent advancements in surgical treatment of pelvic floor dysfunction allow several good options for choosing the best surgery for each patient. The vaginal procedure is traditionally the gold standard approach for elderly patients, but abdominal surgery is increasing as a mini-invasive approach and the robotic approach is gaining acceptance for treatment of pelvic floor dysfunctions. In elderly individuals, a multitude of factors affects the final result of any reconstructive surgery such as postmenopausal or aging-associated changes in muscle tone and nerve function or changes in the function of the bladder or of the rectum: an understanding of the underlining functional status of pelvic organs is very important in aging women before proceeding to surgery. In this context, pelvic floor dysfunction, particularly in elderly women, should be addressed in a multidisciplinary manner and, at the forefront, centers for surgical planning could be helpful to perform safer, patient-tailored surgery.

Diagnosis and laparoscopic management of a 5-week ectopic pregnancy in a rudimentary uterine horn: A case report.

Uterine anomalies result from the failure of complete fusion of the Müllerian ducts during embryogenesis. A unicornuate uterus with a rudimentary horn is the rarest anomaly and results from the failure of one of the Müllerian ducts to develop completely and an incomplete fusion with the contralateral side. Diagnosis and surgical management of a 5-week ectopic pregnancy in a non-communicating rudimentary horn in an 18-year-old nulliparous woman in whom this congenital uterine anomaly was previously unknown are described.

Optimizing quality of life through sex steroids by their effects on neurotransmitters.

Menopause-related symptoms such as hot flushes, night sweats, weight gain, and decreased sexual functioning all have negative impacts on quality of life and affect daily activities such as sleep, work, and leisure activities. During the menopause transition, neurotransmitters, neuropeptides, and neurosteroids undergo important changes as a consequence of the failure of gonadal hormone production, at a time when many central nervous system activities deteriorate. Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination, and other important mechanisms of neural plasticity. Knowledge of interactions between sex steroid hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA, and glutamate, will give women and health providers an important tool for improving their health and well-being. From the concept of neurosteroids derives another treatment strategy: the use of pharmaceutical agents that increase the synthesis of endogenous neurosteroids within the nervous system. This approach has so far been hampered by lack of knowledge concerning the regulation of the biosynthetic pathways of neurosteroids and their relationship with sex steroids produced by the peripheral gland or with exogenous steroids. The present review summarizes some of the available clinical and experimental findings supporting the critical role of neurosteroids in postmenopausal women and their impact on quality of life.

Nitric oxide and the biology of pregnancy.

Nitric oxide (NO) is a key regulator of both maternal and fetal homeostasis during pregnancy, facilitating the maternal cardio-vascular changes, fetal development and growth and adaptation to extrauterine life. Dysfunction of the NO system during pregnancy is associated to placental and vascular-related diseases such as hypertensive disorders of pregnancy (HDP) and intrauterine growth restriction (IUGR). Emerging therapeutic strategies involving NO precursors, NO donors, natural derivatives or pharmacological modulators of the NO system seem hold promise for the treatment of such conditions of pregnancy.

Dehydroepiandrosterone and Cardiovascular Disease.

The dehydroepiandrosterone and its metabolite, dehydroepiandrosterone sulfate, have been for a long while at the center of interest for endocrinologists and cardiologists. Consolidated data show that the dehydroepiandrosterone and the dehydroepiandrosterone sulfate present protective actions on the cardiovascular system. These actions are accomplished directly through target tissues such as endothelial cells, smooth muscle cells, and cardiomyocytes. At this level, they are able to activate a complex group of receptor, not completely identified, which modulate important functions such as vasodilation, antiinflammation, and antithrombosis. These data support the hypothesis that dehydroepiandrosterone could be used as drug for primary prevention of cardiovascular disease especially during aging and potentially also in addition of the common therapeutic strategy for the treatment and prevention of cardiovascular disease recurrence. In this publication, the effects of dehydroepiandrosterone and dehydroepiandrosterone sulfate on the cardiovascular system have been elucidated, starting with an analysis of the molecular action at target organ levels. In the second part, we evaluated the clinical effects of this administration, considering ultimately possible implications in introducing this hormone into clinical practice.