Ceramides during Pregnancy and Obstetrical Adverse Outcomes.

Ceramides are a group of sphingolipids located in the external plasma membrane layer and act as messengers in cellular pathways such as inflammatory processes and apoptosis. Plasma ceramides are biomarkers of cardiovascular disease, type 2 diabetes mellitus, Alzheimer's disease, various autoimmune conditions and cancer. During pregnancy, ceramides play an important role as stress mediators, especially during implantation, delivery and lactation. Based on the current literature, plasma ceramides could be potential biomarkers of obstetrical adverse outcomes, although their role in metabolic pathways under such conditions remains unclear. This review aims to present current studies that examine the role of ceramides during pregnancy and obstetrical adverse outcomes, such as pre-eclampsia, gestational diabetes mellitus and other complications.

Humanin and diabetes mellitus: A review of in vitro and in vivo studies.

Humanin (HN) is a 24-amino acid mitochondrial-derived polypeptide with cyto-protective and anti-apoptotic effects that regulates the mitochondrial functions under stress conditions. Accumulating evidence suggests the role of HN against age-related diseases, such as Alzheimer's disease. The decline in insulin action is a metabolic feature of aging and thus, type 2 diabetes mellitus is considered an age-related disease, as well. It has been suggested that HN increases insulin sensitivity, improves the survival of pancreatic beta cells, and delays the onset of diabetes, actions that could be deployed in the treatment of diabetes. The aim of this review is to present the in vitro and in vivo studies that examined the role of HN in insulin resistance and diabetes and to discuss its newly emerging role as a therapeutic option against those conditions.

Effect of oral phytoestrogens on endometrial thickness and breast density of perimenopausal and postmenopausal women: A systematic review and meta-analysis.

BACKGROUND: Phytoestrogens constitute an alternative, non-pharmacologic approach for the management of menopausal symptoms. However, few studies have focused on their safety, specifically in relation to endometrial thickness and breast density. AIM: To systematically search for and quantitatively synthesize the evidence regarding the effect of phytoestrogens on endometrial thickness and breast density in perimenopausal and postmenopausal women. METHODS: Randomized controlled trials (RCTs) examining the effect of phytoestrogens compared with placebo or menopausal hormone therapy (MHT) on endometrial thickness and/or breast density in perimenopausal or postmenopausal women were searched for in the MEDLINE, CENTRAL and Scopus databases as well as "gray literature" sources until October 31, 2018. Main outcomes were the change from baseline in endometrial thickness and breast density. Statistical analysis was performed with RevMan 5.3, using R language and Open Meta-Analyst software. RESULTS: The meta-analysis for endometrial thickness included 30 RCTs (with a total of 3497 women), and that for breast density four RCTs (with a total of 674 women). Phytoestrogens did not affect endometrial thickness compared with placebo [weighted mean difference (WMD) -0.04 mm, 95% confidence interval (CI) -0.18 to 0.11, I2 66%] or MHT (WMD -1.40 mm, 95% CI -2.98 to 0.18, I2 84%). In addition, phytoestrogens did not affect breast density compared with placebo [standardized mean difference (SMD) -0.76, 95% CI -1.54 to 0.2, I2 95%). CONCLUSION: Phytoestrogens have no effect on endometrial thickness or breast density, when administered at various doses and for various durations, in perimenopausal and postmenopausal women. However, the high heterogeneity of the studies makes it necessary to conduct RCTs with less risk of systematic error.

Biomarkers of Endothelial Dysfunction in Women With Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. The criteria required for the diagnosis identify various phenotypes, with different reproductive, metabolic, and cardiovascular (CV) risk characteristics. Emerging evidence links adipocyte-secreted hormones as candidates in the pathogenesis of endothelial dysfunction in PCOS, independently of additional risk factors. The aim of this review was to collect, analyze, and qualitatively resynthesize evidence on biomarkers of endothelial dysfunction (visfatin, vascular endothelial growth factor [VEGF], matrix metalloproteinase 9 [MMP-9]) in women with PCOS. Women with PCOS exhibit (a) increased plasma visfatin concentrations compared with controls with a similar body mass index; (b) increased VEGF production along with chronic, mild inflammation; and (c) increased MMP-9 concentrations, which might be related to either excessive CV risk or abnormalities of ovarian extracellular matrix remodeling, multiple cyst formation, follicular atresia, and chronic anovulation. As PCOS has been associated with CV risk, early identification of endothelial dysfunction is clinically relevant.

Personal and parental acceptance of human papillomavirus vaccination prior to and during the economic crisis among women in Greece.

PURPOSE: To assess personal and parental human papillomavirus (HPV) vaccination acceptance and how it is influenced by demographic factors prior to (2005-2010) and during (2011-2016) the economic crisis in Greece. METHODS: During 2005-2016, 6,401 women aged 18-65 years, living in different areas of Greece filled in a questionnaire covering demographic characteristics, knowledge of HPV infection's natural history and its consequences and assessing their intention to receive the HPV vaccine for themselves and their children. RESULTS: Women's intention to get vaccinated before the economic crisis was higher (86.2%) than during it (82.8%). In addition, the intention of women to vaccinate their children was higher for girls during 2005-2010 (78.3%), while there was no statistically significant difference concerning boys. HPV vaccination acceptance per year showed a statistically significant variation. The initially high acceptance decreased following vaccine's release, mainly due to fear of side effects, increased following objective public education, and declined again. Demographic characteristics affected HPV vaccination acceptance at the time period before the economic crisis in Greece, but not during it. CONCLUSION: Demographic factors affecting a woman's attitude towards vaccination prior to the economic crisis in Greece, stopped playing a significant role during the crisis, reflecting its devastating effect on most parts of the population.

Serum visfatin, vascular endothelial growth factor and matrix metalloproteinase-9 in women with polycystic ovary syndrome.

AIM: To evaluate serum concentrations of visfatin, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in women with polycystic ovary syndrome (PCOS) and to investigate their possible role as early endothelial markers in PCOS. METHODS: Forty-two women with PCOS and 42 controls, matched for age and weight, were included in the study. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, total testosterone (tT), Δ4-androstenedione (Δ4A), dehydroepinadrosterone sulphate (DHEA-S), 17-OH-progesterone, sex hormone-binding protein (SHBG), thyroid-stimulating hormone (TSH), free thyroxine (fT4), visfatin, VEGF and MMP-9 were measured in all women; free androgen index (FAI) was calculated as well. Receiver-operating characteristic (ROC) analysis was performed to examine if visfatin, tT or FAI can predict the clinical status (PCOS or control). RESULTS: LH, Δ4A, tT and FAI concentrations were higher in PCOS than in controls (p = 0.002, 0.029, 0.0005 and 0.014, respectively). Visfatin, VEGF and MMP-9 concentrations were higher in women with PCOS than controls (p = 0.019, 0.001 and 0.002, respectively). In ROC analysis, area under the curve (AUC) in the prediction of clinical status was 0.641 for visfatin (p = 0.026), 0.731 for tT (p = 0.001) and 0.666 for FAI (p = 0.010), with no difference among them (p = 0.117). CONCLUSIONS: Visfatin may induce the expression of pro-angiogenic factors, such as VEGF and MMP-9, in women with PCOS, inplying gradually development of endothelial dysfunction. Further studies are required to clarify these findings.

The impact on ovarian reserve after laparoscopic ovarian cystectomy versus three-stage management in patients with endometriomas: a prospective randomized study.

OBJECTIVE: To investigate the effect of two different laparoscopic methods on ovarian reserve in patients with ovarian endometriomas. DESIGN: Prospective, randomized clinical trial. SETTING: Endoscopy unit of a university hospital. PATIENT(S): Twenty women with endometriomas. INTERVENTION(S): Patients were randomly selected to undergo either laparoscopic cystectomy for endometrioma (group 1) or the "three-step procedure" (group 2). Before and 6 months after laparoscopy all patients were evaluated, and 12 months postoperatively they underwent ultrasound scan examination. MAIN OUTCOME MEASURE(S): The primary end point was ovarian reserve damage based on the alterations of anti-Müllerian hormone (AMH). Secondary end points were the changes of antral follicle count and serum concentration of FSH, LH, E(2), and inhibin B. RESULT(S): Mean serum AMH was reduced significantly from 3.9-2.9 ng/mL in group 1 compared with the reduction from 4.5-3.99 ng/mL in group 2. CONCLUSION(S): Ovarian reserve determined by AMH is less diminished after the three-step procedure compared with cystectomy of endometriomas.

Tibolone therapy in breast cancer survivors: a retrospective study.

AIM: To investigate a possible relationship between tibolone therapy and recurrence or mortality in breast cancer survivors. METHODS: In a retrospective study, data from files of 247 patients who had been treated for breast cancer were analyzed. Twenty women were treated with tibolone because of menopausal symptoms (Group 1: mean duration of tibolone use 37.1 months). One hundred and one women who did not take tibolone were selected as the control group (Group 2). All women were followed up in our Department on our standard protocol (mean follow up: 73.4 months in Group 1, 67.4 months in Group 2). Comparison of the survival curves was applied with the Wilcoxon (Gehan) statistic. Cox regression analysis was also applied in order to identify significant coefficients in the survival curve. RESULTS: Recurrence of breast cancer was observed in two (10%) Group 1 women versus 21 (21%) Group 2 women (P = NS). Two Group 1 women died (one from breast cancer recurrence) versus 15 Group 2 women (14 from breast cancer recurrence). CONCLUSIONS: Despite of the inherent limitations of this small retrospective study, it seems that tibolone does not reveal an apparent negative impact on breast cancer outcome when given to breast cancer survivors.

Laparoscopic management of unicornuate uterus with non-communicating rudimentary horn (three cases).

This article describes the laparoscopic management of unicornuate uterus with a non-communicating rudimentary horn in three women who presented with lower abdominal pain and dysmenorrhoea. The patients were managed with laparoscopic removal of the rudimentary horn along with the ipsilateral salpinx. No complications were noted intraoperatively and the patients remain asymptomatic.

Unilateral vulvar edema after operative laparoscopy: a case report and literature review.

OBJECTIVE: To report a case of unilateral vulvar edema occurring after operative laparoscopy and to review the relevant literature. DESIGN: Case report. SETTING: University hospital. PATIENT(S): An 18-year-old woman with a single ovarian cyst. INTERVENTION(S): The patient underwent laparoscopic ovarian cystectomy and 1,000 mL of adhesion barrier solution was instilled in the peritoneal cavity at the end of the procedure. MAIN OUTCOME MEASURE(S): Treatment of ovarian cyst and prevention of adhesion formation with adhesion barrier solution. RESULT(S): Development of unilateral vulvar edema 3 hours postoperatively. CONCLUSION(S): Vulvar edema after operative laparoscopy is an uncommon complication, the mechanism of which remains unclear. The condition is self-limited and resolves with conservative management.

Aromatase inhibitor anastrozole for treating endometrial hyperplasia in obese postmenopausal women.

This is a preliminary study investigating the efficacy of aromatase inhibitor anastrozole in treating endometrial hyperplasia in obese postmenopausal women. We administered anastrozole for 12 months to 11 obese postmenopausal women with high operative risk, in order to treat endometrial hyperplasia (four simple, five complex and two atypical). Endometrial thickness in all cases and histology too in the two cases with atypia, revealed atrophical endometrium during treatment and additional mean follow-up of 10.2 months. The safety and tolerance profile was satisfactory. Anastrozole appears to be an interesting new modality for the treatment of endometrial hyperplasia in obese postmenopausal women.

Prolonged use of gonadotropin-releasing hormone agonist and tibolone as add-back therapy for the treatment of endometrial hyperplasia.

OBJECTIVES: To investigate the response of the various hyperplastic disorders of the endometrium to a prolonged treatment with leuprolide acetate, a gonadotropin-releasing hormone agonist (GnRH-a), plus tibolone, as add-back therapy, and further to study if the tibolone addition reduces the hypoestrogenic actions of the GnRH-analogue. METHODS: We treated 26 women with histologically confirmed simple (n = 9), complex (n = 15) or atypical (n = 2) endometrial hyperplasia (EH) for 12 months with monthly injections of 1Ampulle/3.75 mg of leuprolide acetate, followed by tibolone, 2.5mg per day per os. Every woman underwent a hysteroscopic evaluation and biopsy of the endometrium after 3 (in cases with atypical EH), 6 and 12 months of treatment, as well as after 12 and 24 months of follow-up. The clinical, paraclinical and laboratory course of the disease was followed-up by using of a climacteric scoring system and by testing of various parameters. RESULTS: The histopathologic evaluation of the endometria revealed regression of EH in all women after 12 months of treatment, however, during the first 2 years of follow-up EH reappeared in four women (4/21, 19%). Bone mineral density and serum parameters did not show significant changes during treatment, whereas only a mild suffering from hypoestrogenic side-effects was noted. CONCLUSIONS: It seems that the combined GnRH-a/tibolone treatment in women with EH is a potent alternative, so far as the endometrial status and the clinical course of the disease are concerned, whereas tibolone appears to act sufficiently as add-back therapy to prolonged GnRH-a treatment. The probability of relapse of the disease during the follow-up period makes the close monitoring of the endometrium after cessation of the treatment absolutely necessary.

Postparacentesis bilateral massive vulvar edema in a patient with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To report a case of bilateral massive vulvar edema following lower abdominal paracentesis in a patient with ovarian hyperstimulation syndrome. DESIGN: Case report. SETTING: University teaching hospital. PATIENT(S): A 32-year-old woman with primary infertility. INTERVENTION(S): The patient underwent ovarian stimulation with leuprolide acetate, highly purified FSH, and hCG. Because of the development of severe ovarian hyperstimulation syndrome, bilateral paracentesis through the lower abdominal quadrants was performed. MAIN OUTCOME MEASURE(S): Treatment of ovarian hyperstimulation syndrome. RESULT(S): Development of bilateral massive vulvar edema 24 hours after lower abdominal paracentesis. CONCLUSION: This case report suggests that lower abdominal paracentesis could be the cause of vulvar edema development in ovarian hyperstimulation syndrome, probably due to a fistulous tract created between the peritoneal cavity and the subcutaneous tissues.