Epigenetics of violence against women: a systematic review of the literature.

Violence against women is a pervasive global issue with profound impacts on victims' well-being, extending across cultural boundaries. Besides immediate physical harm, it triggers mental health consequences such as post-traumatic stress disorder (PTSD). Indeed, it is the trauma experienced during a violent event that can lead to epigenetic modifications, ultimately contributing to the onset of PTSD. While research on the epigenetic effects of trauma initially focused on war veterans and disaster survivors, there is a dearth of studies on violence against women. In this article, we performed a systematic review aimed to fill this gap, examining existing studies on the epigenetic impact of violence on women. The review assessed sample sizes, study validity, and gene-specific investigations. Currently, there is insufficient data for a comprehensive meta-analysis, highlighting a nascent stage in understanding this complex issue. Future research is crucial for deeper insights into the epigenetic mechanisms related to violence against women, contributing to improved interventions and support healthcare systems for affected individuals.

Reiterated male-to-female violence disrupts hippocampal estrogen receptor ß expression, prompting anxiety-like behavior.

Intimate partner violence (IPV) is a significant public health concern whose neurological/behavioral sequelae remain to be mechanistically explained. Using a mouse model recapitulating an IPV scenario, we evaluated the female brain neuroendocrine alterations produced by a reiterated male-to-female violent interaction (RMFVI). RMFVI prompted anxiety-like behavior in female mice whose hippocampus displayed a marked neuronal loss and hampered neurogenesis, namely reduced BrdU-DCX-positive nuclei and diminished dendritic arborization in the dentate gyrus (DG): effects paralleled by a substantial downregulation of the estrogen receptor ß (ERß). After RMFVI, the DG harbored reduced brain-derived neurotrophic factor (BDNF) pools and tyrosine kinase receptor B (TrkB) phosphorylation. Accordingly, ERß knockout (KO) mice had heightened anxiety and curtailed BDNF levels at baseline while dying prematurely during the RMFVI procedure. Strikingly, injecting an ERß antagonist or agonist into the wild-type (WT) female hippocampus enhanced or reduced anxiety, respectively. Thus, reiterated male-to-female violence jeopardizes hippocampal homeostasis, perturbing the ERß/BDNF axis and ultimately instigating anxiety and chronic stress.

Clinical significance of atypical glandular cells on cytology: 10 years' experience of a colposcopic referral center.

INTRODUCTION: 'Atypical glandular cells' (AGC) is an uncommon cytological result of cervical Pap smears which includes a wide of histopathological diagnoses, from benign to premalignant and malignant cervical disorders, endometrial cancer and, occasionally, other genital malignancies. This study aims to provide a comprehensive overview of AGC, assessing risk factors and clinical and histological features in affected patients. MATERIALS AND METHODS: A retrospective analysis was conducted on a cohort of 239 women diagnosed with AGC between 2012 and 2022 at the 'Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders', Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Following AGC detection, patients underwent colposcopy with endocervical sampling and endometrial assessment via pelvic ultrasound. Selective cases also received endometrial biopsies. RESULTS: Among a total of 190 women who underwent both colposcopy and endometrial assessment, 116 (61%) had negative clinical and histopathological findings. The remainder displayed various abnormalities: 36 women (18.9%) were found to have endometrial or cervical polyps, 23 (12.1%) were diagnosed with preinvasive cervical neoplasia, and 21 (10.9%) with invasive cervical or endometrial disease. Menopause, multiparity, and older age were all significantly associated with endometrial cancer, but none of the abovementioned variables were significantly associated with cervical neoplasia. CONCLUSION: Our data confirm that AGC may reveal the presence of a wide range of histopathological conditions. Patients diagnosed with AGC should undergo a careful evaluation including both colposcopy with endocervical sampling and an endometrial assessment.

Going Beyond Childhood and Gender-Based Violence: Epigenetic Modifications and Inheritance.

Being exposed to childhood or gender-based violence is associated with subsequent adverse events in individual lives. Not only can it cause psychological distress but violence survivors suffer from a range of long-term adverse health outcomes, including higher morbidity, higher mortality, and higher risk of chronic diseases. Epigenetics may be involved in the determinisms of these long-term detrimental effects. A large body of evidence supports this biological mechanism to explain violence-related health impairment in the long term. However, studies specifically focusing on violence are scant and nonunivocal. Epigenetic modifications of genes involved in stress response and in the hypothalamus-pituitary-adrenal axis regulation are the most commonly and consistently reported. Promising evidence also emerged for the use of epigenetic clocks. Finally, although very limited, there is evidence supporting the notion that long-term health impairment may be transmitted from one generation to the other. Overall, despite promising, available evidence is yet incomplete. The overlap with pure psychological mechanisms of health impairment exposes the findings to confounders and hampers strong conclusions. Based on a literature search on PubMed/Embase, our narrative review aims to illustrate the evidence concerning the potential bond between epigenetics and violence, including also possible impacts on later generations. The goal is to encourage further research to help the development of a more holistic approach for such a vulnerable and often neglected population. Further research is warranted to precisely disentangle the role of epigenetics in mediating the long-term health impairment associated with childhood or gender-based violence. Advances in this area may open new avenues of treatment. Epigenetic modifications may indeed be reversible and could be an attractive therapeutic target to minimize the long-term consequences of childhood or gender-based violence.

Should I stay for local hormone therapy or should I go for radiofrequency to treat vulvovaginal atrophy? A patient preference trial.

OBJECTIVE: To compare patient satisfaction rate in postmenopausal women who chose dynamic quadripolar radiofrequency or topical estrogens as their preferred treatment for genitourinary syndrome of menopause. METHODS: Patients were divided into two groups according to their preference: one was treated with estrogen therapy (ET) and the other with dynamic quadripolar radiofrequency treatment (RF). All patients included fulfilled a series of validated questionnaires, at baseline and at the 6-mo follow-up, in order to evaluate the discomfort degree associated with the presence of vulvovaginal atrophy and the impact of the reported symptoms on QoL and sexuality. RESULTS: After propensity score matching, the proportion of women considering themselves satisfied with their genital health conditions was extremely small at study entry (5.2% of the RF group and 6.9% of the ET group), while at a 6-mo follow-up, it increased to 46.7% and 46.6%, respectively. No statistically significant between-group differences were found regarding mean numerical rating scale scores for dryness and dyspareunia at follow-up (5.6 ± 2.6 vs 5.3 ± 2.3, P = 0.5; and 2.9 ± 2.5 vs 3.0 ± 2.7, P = 0.46). At 6-mo follow-up, we observed no statistically significant differences between the two groups regarding the other items evaluated. RF treatment was overall well tolerated. CONCLUSION: The use of quadripolar radiofrequency devices seems effective, but it is not associated with better clinical outcomes compared with topical hormone treatment, which is a substantially cheaper and more convenient treatment for genitourinary syndrome of menopause. Therefore, we suggest limiting the use of dynamic quadripolar radiofrequency selectively when topical estrogens are not effective, not tolerated, or contraindicated.

Beyond vulvodynia: from a correct diagnosis to a multidisciplinary care program. A referral center experience.

BACKGROUND: Vulvodynia is a chronic pain condition without an identifiable cause. As such, it is a diagnosis of exclusion, and all other causes of vulvar pain should be excluded. Although a standard treatment for vulvodynia has not been established yet, multidisciplinary care programs appear to be effective. PUROPOSE: The aim of this retrospective monocentric study was to analyze the prevalence of vulvodynia among women referred to our institution for a suspected diagnosis and to evaluate the efficacy of a multidimensional treatment plan. The primary outcome was the prevalence of vulvodynia following differential diagnosis. Secondary outcomes included: prevalence of the differential diagnoses, symptom resolution rate following treatment, and the relation between persistence of symptoms and (a) patients' age; (b) coexisting chronic overlapping pain conditions (COPCs). RESULTS: After having ruled out all other causes of vulvar pain, only 40.1% of women were considered as affected by vulvodynia. The most frequent differential diagnoses included lower genital tract infections (25.3%), vulvar lichen sclerosus (17.6%) and vulvovaginal atrophy (8.2%). Following a multidisciplinary care program, resolution of symptoms was observed in 13.6% cases, improvement in 64.3% and persistence in 21.9%. We did not find a statistically significant association between persistence of symptoms and age > 38 years (OR 2.10; p = 0.30). Women with one or more COPCs other than vulvodynia had a 75% increased risk of not obtaining a resolution of symptoms (OR 1.75; p = 0.44). CONCLUSION: A thorough differential diagnosis and a multidisciplinary care program may represent a first way out of the muddle in the management of these patients.

Questionnaires for the Assessment of Central Sensitization in Endometriosis: What Is the Available Evidence? A Systematic Review with a Narrative Synthesis.

It has been suggested that central sensitization (CS) may be involved in the failure of standard medical and surgical treatment to relieve endometriosis-related pain. However, there is no gold standard for the diagnosis of CS, and self-reported questionnaires are used as diagnostic surrogates. The main objective of this review was to identify all CS questionnaires used in clinical endometriosis studies. The secondary objective was to qualitatively analyze strengths and weaknesses of each questionnaire. A PubMed and EMBASE systematic literature search conducted in April 2023 using the terms "endometriosis; central pain; central sensitization; questionnaire; patient-reported outcome measure; screening tool" identified 122 publications: six articles were included in the review. The Central Sensitization Inventory (CSI) is the most frequently used questionnaire for the detection of CS in patients with endometriosis. It has been validated in patients with endometriosis, in whom it appears to have good psychometric proprieties. The Fibromyalgia Survey Questionnaire (FSQ) has also been used, although it has not been specifically validated in endometriosis patients. The debate regarding these questionnaires' construct validity is still open and will be so until a gold standard diagnostic tool for CS is found. In fact, some authors argue these questionnaires are measuring psychological vulnerability and a hypervigilant state that is associated with pain, rather than CS itself. However, their use should not be discouraged as they are able to identify chronic pain patients which warrant further attention and who may benefit from broader treatment strategies.

Central Sensitization in Vulvodynia and Endometriosis: What Have We Been Overlooking So Far?

Importance: Women experience more frequent and greater pain than men, although they receive less adequate treatment and are perceived as more anxious than males. Recent clinical research has lead to hypothesize a common etiology for overlapping chronic pain conditions and mood disorders, namely, central sensitization, which originates from an alteration of pain processing pathways in the central nervous system. Objective: The aim of this review was to collect all available evidence regarding the potential role of central sensitization in vulvodynia and endometriosis. Evidence Acquisition: A systematic literature search was performed between July and August 2022 using the electronic database PubMed. The extracted data were summarized using a narrative approach. Results: Ten articles were chosen for the review. Participants' mean age was 39.2 years (SD = 5.1). Among serum markers of central sensitization, nitric oxide levels were greater in women with endometriosis than in controls, whereas brain-derived neurotrophic factor and S100B levels differed among pain conditions with structural anomalies and those without. Functional magnetic resonance imaging showed different resting state networks between patients with endometriosis and controls. In neurophysiology studies, cases had reduced pain thresholds, compared with healthy controls. Lastly, self-reported questionnaires suggested a central component of pain in women with endometriosis-related dyspareunia and associated bladder/pelvic floor tenderness. Conclusions and Relevance: The management of vulvodynia and endometriosis may benefit from a new perspective, which considers their possible central etiology. It is compelling that treatment of pain starts to be considered a therapeutic goal in its own right.

Prevalence of high-grade anal intraepithelial neoplasia in immunocompetent women treated for high-grade cervical intraepithelial neoplasia.

BACKGROUND: The aim of the study was to evaluate the prevalence of high-grade anal intraepithelial neoplasia (AIN2-3) among immunocompetent women treated for high-grade cervical intraepithelial neoplasia (CIN2-3). Such knowledge is strongly needed to establish whether a screening program should be recommended in this group of patients. METHODS: This prospective study included a cohort of consecutive women with no known causes of immunosuppression treated with LEEP (loop electrosurgical excision procedure) for a histopathological diagnosis of CIN2-3 in our center between 2019 and 2021. Following the procedure, all patients were invited to undergo anal cytology and anal high-risk HPV-DNA testing (aHPV-DNA). In cases in which one or both tests resulted positive, a high-resolution anoscopy with a biopsy of suspicious lesions was performed. All women also completed a questionnaire on sexual habits. RESULTS: At total of 100 women were enrolled in the study. Among these, eight patients had a concomitant or past diagnosis of anogenital warts, while one patient had received a previous diagnosis of high-grade vaginal intraepithelial neoplasia. Anal Pap smears were positive for low-grade lesions in three patients, while 73 women tested positive for aHPV-DNA. Histological examinations revealed the presence of AIN2-3 lesions in four patients (6.5%; 95% C.I., 1.8 to 15.7%), who subsequently underwent excisional treatment. CONCLUSIONS: Women with a history of high-grade cervical intraepithelial neoplasia have an intermediate risk of developing high-grade anal intraepithelial neoplasia. Future studies are needed in order to assess an ideal screening approach for this condition.

Toxicological analysis in victims of sexual and domestic violence: A retrospective study of a 3-year period (2018-2020).

This manuscript presents an epidemiological investigation carried out on abuse victims who accessed the Sexual and Domestic Violence Service (SVS&D) of IRCCS Ca' Granda in Milan, Italy. The focal point of this research was the detection of alcohol, prescription medications, and illicit substances in victims who solicited help from the SVS&D center between 2018 and 2020. Over this three-year span, biological samples of blood and urine were procured from 207 victims, out of a patient pool of 2470. All collected samples were analyzed via High Performance Liquid Chromatography - Tandem Mass Spectrometry (HPLC-MS/MS) and Gas Chromatography - Mass Spectrometry (GC-MS). Toxicological examination results demonstrated that 43% of the cases tested positive for substances in 2018, 39% in 2019 and 60% of the cases in 2020. Overall, 45% of the victims tested resulted positive to some substance over a 3-year period, equivalent to 3.6% of the overall cases (2470 victims). Substances of toxicological interest were detected in 104 samples (out of 377, corresponding to 27.6%) belonging to 94 patients. The most detected classes of drugs were stimulants, antidepressants, benzodiazepines and antipsychotics. Moreover, BAC (Blood Alcohol Concentration) indicated positivity in 25 cases (out of 184 cases analyzed - 14% of positive cases). Based on this study's findings, we recommend broadening the range of substances evaluated in drug-facilitated sexual assaults and establishing standardized protocols for both national and international implementation. Implementing procedures would significantly enhance forensic support provided to victims of abuse seeking healthcare services post-incident.

Correlation Between Colposcopic Patterns and Histological Grade of Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

BACKGROUND/AIM: Vaginal intraepithelial neoplasia (VaIN) is a rare human papillomavirus (HPV)- related premalignant condition. VaIN lesions are diagnosed histologically through colposcopy-guided biopsies of suspicious areas, conduced by gynecologists with expertise in lower genital tract diseases. The present study aimed to evaluate the accuracy of colposcopy in the diagnosis of VaIN of any grade. PATIENTS AND METHODS: We conducted a retrospective analysis on a cohort of 149 women diagnosed with low grade (LG)-VaIN (VaIN1) and high grade (HG)-VaIN (VaIN2-3) between 2010 and 2022 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Ospedale Maggiore Policlinico, Milan, Italy. All women had been referred to our center for an abnormal Pap smear or as part of routine follow-up of other HPV-related diseases and had undergone a vaginal biopsy under colposcopic guidance. RESULTS: The distribution of the histological grades of VaIN lesions was the following: 62 women (41.6%) were diagnosed with VaIN1, 51 (34.2%) with VaIN2, and 36 (24.2%) with VaIN3. Grade II (major) abnormal colposcopic patterns were recorded in 71 cases (47.7%) and were more commonly observed in women with VaIN3 (80.6%). However, we found a poor and not statistically significant association between colposcopic and histological grade of VaIN. The sensitivity, specificity, positive predictive value, and negative predictive value of colposcopy for histologically confirmed VaIN were 56.3%, 64.5%, 69% and 51.2%, respectively. The overall diagnostic accuracy of colposcopy was 59.7%. CONCLUSION: Colposcopy-guided biopsy plays an important role in the diagnosis of VaIN and in the distinction between low and high-grade lesions. Our data show that major colposcopic abnormalities moderately correlate with HG-VaIN and that grade I colposcopic findings do not exclude HG-VaIN, especially VaIN2. Targeted biopsies of suspicious vaginal areas must be performed in all women with an abnormal Pap smear.

Mitigating the economic burden of GnRH agonist therapy for progestogen-resistant endometriosis: why not?

STUDY QUESTION: Is it possible to reduce the cost of GnRH agonist treatment for endometriosis by using non-standard dosing regimens? SUMMARY ANSWER: An extended-interval dosing regimen of a 3.75 mg depot formulation of triptorelin injected every 6 weeks instead of every 4 weeks reduces the cost by one-third without compromising the effect on pain relief. WHAT IS KNOWN ALREADY: Cost constitutes a limit to prolonged GnRH agonists use. Alternative modalities to reduce the economic burden of GnRH agonist treatment have been anecdotally attempted. STUDY DESIGN SIZE DURATION: A systematic review was conducted to evaluate and compare the effect of three alternative modalities for GnRH use in women with endometriosis, i.e. intermittent oestrogen deprivation therapy, reduced drug dosage, and extended-interval dosing regimens of depot formulations. A PubMed and Embase search was initially conducted in October 2022 and updated in January 2023 using the following search strings: (endometriosis OR adenomyosis) AND (GnRH-agonists OR gonadotropin-releasing hormone agonists OR triptorelin OR leuprorelin OR goserelin OR buserelin OR nafarelin). Full-length articles published in English in peer-reviewed journals since 1 January 1980, and reporting original data on GnRH agonist treatment of pain symptoms associated with endometriosis were selected. PARTICIPANTS/MATERIALS SETTING METHODS: Information was extracted on study design, GnRH-agonist used, dosage, total duration of therapy, side effects, treatment adherence, and pelvic pain relief. Reviews, commentaries, conference proceedings, case reports, and letters to the editor were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 1664 records screened, 14 studies regarding clinical outcomes associated with the 3 considered alternative modalities for GnRH agonist use were eventually included (intermittent oestrogen deprivation therapy, n = 2; low-dose or 'draw-back' therapy, n = 8; extended-interval dosing regimen, n = 4). Six studies were randomized controlled trials (RCTs) (double blind, n = 2) and eight adopted a prospective cohort design (non-comparative, n = 6; comparative, n = 2). A total of 776 women with endometriosis were recruited in the above studies (intermittent oestrogen deprivation therapy, n = 77; low-dose or 'draw-back' therapy, n = 528; extended-interval dosing regimen, n = 171). Robust data demonstrating cost saving without detrimental clinical consequences were available for the extended-interval dosing regimen only. In particular, the 3.75 mg triptorelin depot preparation inhibits ovarian function for a longer period compared with the 3.75 mg leuprorelin depot preparation, allowing injections every 6 instead of 4 weeks. Based on the cost indicated by the Italian Medicine Agency for the 3.75 mg triptorelin depot preparation, this would translate in a yearly saving of €744.60 (€2230.15-€1485.55; -33.4%). LIMITATIONS REASONS FOR CAUTION: The quality of the evidence reported in the selected articles was not formally evaluated and a quantitative synthesis could not be performed. Some studies were old and the tested therapeutic approaches were apparently obsolete. Only cost containment associated with GnRH analogue use, and not cost-effectiveness, has been addressed. WIDER IMPLICATIONS OF THE FINDINGS: Consuming less resources without negatively impacting on health outcomes carries ethical and practical implications for individuals and the community, as this approach may result in overall increased healthcare access. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Italian Ministry of Health (Ricerca Corrente 2023, IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano). E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest. REGISTRATION NUMBER: N/A.

Pediatric vulvar lichen sclerosus: Does it resolve or does it persist after menarche?

BACKGROUND AND OBJECTIVES: Although data regarding the rates of remission and progression of the disease are still scarce, it is generally now acknowledged that pediatric vulvar lichen sclerosus (pVLS) can persist beyond puberty. Recent studies reveal that this condition may persist in as many as 75% of cases. The present study aims to answer the following query: how does pVLS evolve after menarche? METHODS: This observational retrospective study conducted on premenarchal girls diagnosed with pVLS in our institution between 1990 and 2011 describes 31 patients who returned for multidisciplinary clinical evaluation following menarche. RESULTS: The mean follow-up time was 14 years. At the post-menarche clinical examination, patients were classified as follows: 58% were still affected by VLS, 16% presented with a complete remission of disease, and 26% were completely asymptomatic although with persistent clinical signs of VLS. CONCLUSIONS: In our series, pVLS persists following menarche in the majority of patients. These findings suggest the importance of a long-term follow-up even among patients who report resolution of symptoms following menarche.

Violence against Women and Stress-Related Disorders: Seeking for Associated Epigenetic Signatures, a Pilot Study.

BACKGROUND: Violence against women is a relevant health and social problem with negative consequences on women's health. The interaction between genome and environmental factors, such as violence, represents one of the major challenges in molecular medicine. The Epigenetics for WomEn (EpiWE) project is a multidisciplinary pilot study that intends to investigate the epigenetic signatures associated with intimate partner and sexual violence-induced stress-related disorders. MATERIALS AND METHODS: In 2020, 62 women exposed to violence (13 women suffering from sexual violence and 49 from Intimate Partner Violence, IPV) and 50 women with no history of violence were recruited at the Service for Sexual and Domestic Violence. All women aged 18-65 were monitored for their physical and psychological conditions. Blood samples were collected, and DNAs were extracted and underwent the epigenetic analysis of 10 stress-related genes. RESULTS: PTSD prevalence in victims was assessed at 8.1%. Quantitative methylation evaluation of the ten selected trauma/stress-related genes revealed the differential iper-methylation of brain-derived neurotrophic factor, dopamine receptor D2 and insulin-like growth factor 2 genes. These genes are among those related to brain plasticity, learning, and memory pathways. CONCLUSIONS: The association of early detection of posttraumatic distress and epigenetic marker identification could represent a new avenue for addressing women survivors toward resilience. This innovative approach in gender-based violence studies could identify new molecular pathways associated with the long-term effects of violence and implement innovative protocols of precision medicine.

High-grade vaginal intraepithelial neoplasia and recurrence risk: analysis of an Italian regional referral center series.

PURPOSE: The main aim of this study was to investigate the long-term risk of disease recurrence in women treated for high-grade vaginal intraepithelial neoplasia (HG-VaIN). METHODS: We conducted a retrospective analysis on a cohort of 82 women diagnosed with HG-VaIN between 2010 and 2021 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. All women underwent either ablative treatment (CO2 laser ablation or electrocoagulation) or cold-knife excision. RESULTS: In our series, the recurrence rate following treatment was 17%. The 5-year cumulative probability of recurrence was 30.4% and the median time to recurrence was 15.5 months. None of the patients progressed to invasive vaginal cancer during follow-up. A concomitant cervical or vulvar intraepithelial lesion was significatively associated with an increased risk of recurrence (p = 0.006). CONCLUSIONS: The results of our study suggest that women with HG-VaIN are at high risk of developing disease recurrence after treatment, especially patients with a concomitant cervical or vulvar intraepithelial lesion. In these women strict monitoring is mandatory to obtain an early identification of recurrence.

Clinical Features and Management of Umbilical Endometriosis: A 30 Years' Monocentric Retrospective Study.

INTRODUCTION: Umbilical endometriosis (UE) is defined as the presence of endometrial-like tissue within the umbilicus and represents around 0.5-1% of all cases of endometriosis. UE is classified into primary or secondary UE. In this retrospective study, we aimed to assess symptoms, signs, recurrence rate of treated lesions, psychological wellbeing and health-related quality of life in women with UE. MATERIAL AND METHODS: We retrospectively reviewed all cases of women diagnosed with UE in the period 1990-2021 in our center. Post-operative recurrence of UE was considered as the reappearance of the umbilical endometriotic lesion, or as the recurrence of local symptoms in the absence of a well-defined anatomical recurrence of the umbilical lesion. Moreover, participants were invited to fill in standardized questionnaires on their health conditions. RESULTS: A total of 55 women with histologically proven UE were assessed in our center during the study period. At time of diagnosis, local catamenial pain and swelling were reported by 51% and 53.2% of women, respectively. A total of 46.8% of women reported catamenial umbilical bleeding. Concomitant non-umbilical endometriosis was identified in 66% of cases. As regards the treatment of UE, 83.6% of women underwent an en-bloc excision with histological confirmation of UE. During the follow-up period, 37 women (67.3%) agreed to undergo a re-evaluation. Recurrence of either umbilical symptoms, or umbilical nodule, was observed in 27% of patients, 11% of which did not receive post-operative hormonal therapy. Specifically, a recurrence of the umbilical endometriotic lesion was observed only in two women. Among the 37 women which we were able to contact for follow-up, 83.8% were satisfied with the treatment they had received. CONCLUSIONS: The high rate of patient satisfaction confirmed that surgical excision should be considered the gold standard treatment for umbilical endometriosis. Future studies should investigate the role of post-operative hormonal therapy, particularly in reducing the risk of symptom recurrence.

A clinician's dilemma: what should be communicated to women with oncogenic genital HPV and their partners regarding the risk of oral viral transmission?

Head and neck cancer, the sixth most common cancer worldwide, account for about 1 out of 20 malignant tumors. In recent years a reduction in the incidence of cervical cancer, but a concomitant major increase in the incidence of HPV-mediated oropharyngeal cancer caused by orogenital HPV transmission has been observed. Consequently, in wealthy countries oropharyngeal squamous-cell carcinomas (OPSCC) is now the most frequent HPV-related cancer, having overtaken cervical cancer. Without effective medical interventions, this incidence trend could continue for decades. As no specific precursor lesion has been consistently identified in the oral cavity and oropharynx, HPV vaccination is the logical intervention to successfully counteract also the rising incidence of OPSCCs. However, HPV vaccine uptake remains suboptimal, particularly in males, the population at higher risk of OPSCC. Alternative primary prevention measures, such as modifications in sexual behaviors, could be implemented based on knowledge of individual genital HPV status. Until recently, this information was not available at a population level, but the current gradual shift from cytology (Pap test) to primary HPV testing for cervical cancer screening is revealing the presence of oncogenic viral genotypes in millions of women. In the past, health authorities and professional organizations have not consistently recommended modifications in sexual behaviors to be adopted when a persistent high-risk HPV cervicovaginal infection was identified. However, given the above changing epidemiologic scenario and the recent availability of an immense amount of novel information on genital HPV infection, it is unclear whether patient counseling should change. The right of future partners to be informed of the risk could also be considered. However, any modification of the provided counseling should be based also on the actual likelihood of a beneficial effect on the incidence of HPV-associated oropharyngeal cancers. The risk is on one side to induce unjustified anxiety and provide ineffective instructions, on the other side to miss the opportunity to limit the spread of oral HPV infections. Thus, major health authorities and international gynecologic scientific societies should issue or update specific recommendations, also with the aim of preventing inconsistent health care professionals' behaviors.

Novel pharmacological therapies for the treatment of endometriosis.

INTRODUCTION: Endometriosis is a chronic, estrogen-dependent, inflammatory disease associated with pelvic pain, infertility, impaired sexual function, and psychological suffering. Therefore, tailored patient management appears of primary importance to address specific issues and identify the appropriate treatment for each woman. Over the years, abundant research has been carried out with the objective to find new therapeutic approaches for this multifaceted disease. AREAS COVERED: This narrative review aims to present the latest advances in the pharmacological management of endometriosis. In particular, the potential role of GnRH antagonists, selective progesterone receptor modulators (SPRMs), and selective estrogen receptors modulators (SERMs) will be discussed. We performed a literature search in PubMed and Embase, and selected the best quality evidence, giving preference to the most recent and definitive original articles and reviews. EXPERT OPINION: Medical therapy represents the cornerstone of endometriosis management, although few advances have been made in the last decade. Most studies have focused on the evaluation of the efficacy and safety of GnRH antagonists (plus add-back therapy in cases of prolonged treatment), which should be used as second-line treatment options in selected cases (i.e. non-responders to first-line treatments). Further studies are needed to identify the ideal treatment for women with endometriosis.

Older adult abuse in a service for sexual and domestic violence: Medico-legal implications from the experience of an Italian center.

Older adults are subject to vulnerability and abusive behaviors have serious negative health consequences. Since the phenomenon is underestimated, several challenges are faced to prevent, diagnose, and treat abuses on older adults. In this context, clinical forensic medicine practitioners can play a pivotal role. A retrospective monocentric analysis of all the files concerning victims of violence observed in the SVSeD Center in Milan over the age of 65 for a five-year period was performed. For each medical report, data regarding the variables of the victims, the type of violence, and the variables of the perpetrators were analysed. Older adult victims of abuses were 166. Abuses against women were more frequent than against men (less than 6 % of consultations). In one third of cases, subjects also suffered from disabling diseases and reported signs of physical violence. Perpetrators were male known individuals in almost 90 % of cases. Violence was perpetrated by a partner or a family member. The present study may help in identifying risk factors for domestic violence against older adults. Consequently, preventive policies should be designed to interrupt the vicious circle of violence. Older adult abuse deserves additional focus and better education for healthcare professionals and further research should be carried out to better understand the actual epidemiology of the phenomenon and to develop therapeutical and caring strategies.