Analysis of hsa-miR-19a-3p and hsa-miR-19b-3p modulation and phosphodiesterase type 5 expression in the vaginal epithelium of premenopausal women with genital arousal disorder.

BACKGROUND: Few studies have investigated the role of the phosphodiesterase type 5A (PDE5A) isoenzyme in female genital tissue disorders, exclusively taken from cadavers, as well as the epigenetic mechanisms responsible for the regulation of PDE5A levels. AIM: The aim was to study the in vivo association between microRNA (miRNA) expression and the expression levels of PDE5A in women with female genital arousal disorder (FGAD) compared with healthy women. METHODS: Premenopausal women affected by FGAD (cases) and sexually healthy women (control group) underwent microbiopsy of the periclitoral anterior vaginal wall for the collection of tissue samples. Computational analyses were preliminarily performed in order to identify miRNAs involved in the modulation of PDE5A by using miRNA-messenger RNA interaction prediction tools. Differences in the expression levels of miRNAs and PDE5A were finally investigated in cases and control subjects by using the droplet digital polymerase chain reaction amplification system and stratifying women considering their age, number of pregnancies, and body mass index. OUTCOMES: Expression levels of miRNAs were able to target PDE5A and the tissue expression in women with FGAD compared with healthy women. RESULTS: The experimental analyses were performed on 22 (43.1%) cases and 29 (56.9%) control subjects. Two miRNAs with the highest interaction levels with PDE5A, hsa-miR-19a-3p (miR-19a) and hsa-miR-19b-3p (miR-19b), were identified and selected for validation analyses. A reduction of the expression levels of both miRNAs was observed in women with FGAD compared with the control subjects (P < .05). Moreover, PDE5A expression levels were higher in women with FGAD and lower in women without sexual dysfunctions (P < .05). Finally, a correlation between body mass index and the expression levels of miR-19a was found (P < .01). CLINICAL IMPLICATIONS: Women with FGAD had higher levels of PDE5 compared with control subjects; therefore, the administration of PDE5 inhibitors (PDE5 inhibitors) could be useful in women with FGAD. STRENGTHS AND LIMITATIONS: The strength of the current study was to analyze genital tissue obtained in vivo from premenopausal women. A limitation was to not investigate other factors, including endothelial nitric oxide synthetases, nitric oxide, and cyclic guanosine monophosphate. CONCLUSION: The results of the present study indicate that the modulation of selected miRNAs could influence PDE5A expression in genital tissues in healthy women or in those with FGAD. Such findings further suggest that treatment with PDE5 inhibitors, as a modulator of PDE5A expression, could be indicated for women with FGAD.

Spontaneous regression of cervical intraepithelial neoplasia 3 in women with a biopsy-cone interval of greater than 11 weeks.

BACKGROUND: Although there is broad consensus that only a subset of CIN3 will progress to cancer, there is currently no surefire way to predict which CIN3 will regress. Understanding the natural history of CIN3 is important, and finding markers for progression or regression could improve treatment strategies. According to the guidelines of the American Society for Colposcopy and Cervical Pathology of 2006, positive CIN3 p16 in women should be managed with excisional treatment (LEEP). For ethical reasons we cannot fail to treat women with CIN3 in order to study their regression capacity so we conducted a retrospective study to evaluate the regression rate of CIN3 diagnosed with a biopsy by studying the histological result of the cone removed by LEEP. We also investigated age, HPV genotypes and biopsy-cone interval distance as possible regression factors. METHODS: We selected 171 women with a histological diagnosis of positive CIN3 p16 as an entry criterion. All patients underwent LEEP / biopsy. A histological diagnosis of the cone of CIN3 or higher was considered as persistence or progression, the diagnosis of CIN1 or lower was considered as regression of the lesion. We used out a logistic model to study the probability of spontaneous regression of CIN3 as a function of the patient's age, the time elapsed between the biopsy and the cone (in weeks) and the HPV genotype. RESULTS: We found that the spontaneous regression rate of CIN3 was 15,8%, which was strongly associated with the biopsy-cone interval > 11 weeks. Genotype 16, the most represented, was present both in cases of regression (77.8%) and in persistence (83.3%). Regarding age, the estimated odds ratio of the probability of observing a regression in women over 25 years of age was 0.0045 times that of women under 25 years of age (CI: 0.00020, 0.036). Neither age nor viral genotype are significant as predictors of regression. CONCLUSION: To wait at least 11 weeks from the biopsy before subjecting the woman to LEEP could prevent unnecessary LEEP procedures, considering also that from CIN3 to carcinoma it takes years before the neoplastic transformation takes place.

Liposomal ferric pyrophosphate and ascorbic acid supplementation in pregnant women with iron deficiency anaemia: haematochemical, obstetric, neonatal and psychological outcomes in a prospective observational study.

This study aimed to determine the effects of liposomal iron pyrophosphate/ascorbic acid on clinical and psychological outcomes in pregnant women. Women at the 11th-13th weeks of gestation with iron deficiency anaemia assuming Sideremil™ from April 2018 to May 2019 were recruited. Haematochemical, obstetric, neonatal and psychological outcomes were investigated at the enrolment, 21-23 weeks of gestation, 30-32 weeks of gestation and after 6 weeks from childbirth. Results showed significant positive effects on haemoglobin, ferritin, sideremia and transferrin levels, compared to baseline data. A significant improvement of anxiety and depression levels was also observed. Regarding the quality of life, all the domains significantly improved, especially the Physical Role domain. Our results indicate that Sideremil™ may be a valid treatment for iron deficiency anaemia in pregnant women, since it significantly improves haematological and mental health outcomes. However, further studies are needed to confirm these results.

Vaginal health and quality of sexual life of postmenopausal women on hyaluronic acid and Biosaccharide Gum-1 vaginal gel.

OBJECTIVE: To evaluate the efficacy of daily vaginal gel containing hyaluronic acid (HA) and Biosaccharide Gum-1 (BG-1) on vulvovaginal atrophy (VVA) and on sexual function and quality of life (QoL). MATERIALS AND METHODS: One hundred-four postmenopausal women with VVA were enrolled in the nonrandomized comparison cohort study. Of them, 50 women on HA/BG-1 participated in the study group and 54 women on lubricants/moisturizers on-demand as a control group. The primary endpoint was the efficacy of the vaginal gel on VVA evaluated by the Vaginal Health Index (VHI) score. Secondary endpoints included sexual behavior by the self-administered female sexual function index (FSFI) questionnaire, and quality of life (QoL), by the Short Form-36 questionnaire (SF-36). RESULTS: All symptoms of AVV improved after 12 weeks of treatment in women on HA/BG-1. The VMI, although improved at the 12-week follow-up compared to baseline, it connoted a low estrogenic stimulation value. Sexual function improved significantly in women on HA/BG-1. Moreover, women reported a significant improvement in the somatic aspects of QoL. No benefits were obtained by the women in the control group. CONCLUSIONS: Treatment with HA/BG-1 could have used in postmenopausal women who complain of vaginal dryness. The amelioration of VVA-related signs could improve sexual function and QoL.

Performance of p16/Ki67 Immunostaining for Triage of Elderly Women with Atypical Squamous Cells of Undetermined Significance.

BACKGROUND: The p16/Ki67 technique has been poorly studied in postmenopausal women with ASC-US cytology. The objective of this study was to compare the accuracy of p16/Ki67 staining, HPV testing and HPV 16 genotyping for the identification of CIN2 + lesions in postmenopausal women with ASC-US cytology. METHOD: A total of 324 postmenopausal women with positive ASC-US were included. The women underwent HPV test, colposcopy, and biopsy. The slides were discolored and then stained with the CINtec Plus Kit for p16/Ki67. The HPV test results were classified as HPV16 +, hrHPV+ (other hrHPV genotypes), or HPV negative. RESULTS: The p16/Ki67 sensitivity for CIN2+ was 94.5%, the specificity 86.6%, PPV of 59% and NPV of 95.9%. The HPV test showed a sensitivity of 96.4% for CIN2+, a specificity of 62.8%, a PPV of 35% and a NPV of 98.8%. In postmenopausal women, the prevalence of genotype 16 decreases in favor of the other high-risk genotypes. CONCLUSION: Given the low sensitivity of cytology and the low percentage of HPV16-positive cancers among elderly women, triage via cytology and genotyping is not the best strategy; double staining cytology shows high profiles of sensibility and specificity for CIN2+ in ASCUS postmenopausal women.