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L’infiammazione è un processo essenziale per la vita, modulato da meccanismi immunoneuroendocrini. In questa Rassegna si analizza il ruolo degli estrogeni naturali umani (estradiolo, estrone, estriolo ed estetrolo) nella regolazione dell’infiammazione, facendo riferimento alla loro interazione con gli altri steroidi sessuali (progesterone e androgeni) nella modulazione di tale processo. L’infiammazione può essere fisiologica, quando è finalizzata (resolving), di breve durata, di intensità limitata e termina con restitutio ad integrum. È patologica quando perde tali caratteristiche diventando non finalizzata, non risolutiva (non resolving), di variabile intensità, con andamento cronico e progressiva distruzione tissutale. Durante la vita fertile della donna si manifestano tre eventi infiammatori fisiologici pertinenti alla sfera riproduttiva: l’ovulazione, la mestruazione e il parto. Tutti e tre sono strettamente correlati con le oscillazioni dei livelli di estrogeni, nonché del progesterone e degli androgeni. L’azione degli estrogeni nei confronti dell’infiammazione è molto articolata, in rapporto al tipo di estrogeno considerato, all’andamento dei suoi livelli plasmatici (fluttuante versusstabile) e al tipo di interazione con i recettori estrogenici, in particolare di tipo αe β. Le fluttuazioni estrogeniche, in particolare dell’estradiolo, influiscono sulla presenza e l’attivazione delle varie classi di cellule immunitarie nell’endometrio e a livello sistemico. Accanto agli estrogeni, progesteronee androgenirivestono un ruolo immunomodulatorio, con prevalenza anti-infiammatoria. La concisa descrizione delle complesse interazioni tra i diversi tipi di estrogeni e il sistema immunitario è stata fatta privilegiando gli aspetti più attinenti alla pratica clinica quotidiana dell’endocrinologo/a.

Le patologie mestruali sono un problema di salute che affligge dal 5 all’80% delle donne, a seconda della specifica patologia considerata e dei diversi studi. Sono rappresentate da alterazioni del ciclo mestruale (alterazioni del ritmo, della quantità e della durata e dismenorrea) e disturbi extra-uterini correlati alla mestruazione, fra i quali rientrano anche le patologie infiammatorie e autoimmunitarie con esacerbazione catameniale. La contraccezione ormonale offre alle donne non solo un importante strumento per evitare gravidanze indesiderate, ma anche un’efficace opzione terapeutica nel trattamento delle patologie mestruali. I contraccettivi ormonali si dividono in metodi a breve durata d’azione (SARCs), quali contraccettivo orale estroprogestinico (COC), contraccettivo orale progestinico (POP), anello vaginale estroprogestinico e cerotto transdermico estroprogestinico, e metodi a lunga durata d’azione (LARCs), quali dispositivi intrauterini medicati al progesterone e impianto sottocutaneo. La combinazione dell’estrogeno e del progestinico in essi contenuto, nonché i differenti dosaggi e le vie di somministrazione, devono essere tenuti in considerazione nella personalizzazione del trattamento, sia al fine di fornire a ogni donna la terapia più adeguata alle sue necessità e ai suoi disturbi, sia in funzione delle specifiche controindicazioni. In questa rassegna analizziamo brevemente le diverse patologie mestruali, proponiamo una panoramica dei diversi contraccettivi ormonali a oggi disponibili sul mercato e riassumiamo le controindicazioni al loro utilizzo.

This study assessed the effectiveness of alpha lipoic acid (ALA) plus omega-3 polyunsaturated fatty acids (n-3 PUFAs) in combination with amitriptyline therapy in patients with vestibulodynia/painful bladder syndrome (VBD/PBS).

Bladder cancer (BCa) is the most frequent urinary tract neoplasm. BCa results in significant mortality when the disease presents as muscle invasive. Around 75% to 80% of patients present with nonmuscle invasive bladder cancer (NMIBC), but recurrence and progression are significant issues, compelling current guidelines to recommend long-term surveillance. There is therefore an urgent and unmet need to identify and validate accurate biomarkers for the detection of disease recurrence to improve quality of life for the patients and reduce costs for health care providers, while maintaining or improving current outcomes. In this review, 38 publications on immunohistochemistry prognostic biomarkers, that were studied may be related in nonmuscle invasive bladder cancer, have been analyzed. The studies were organized according to the evaluated marker and their findings. It was demonstrated that the combination of independent complementary biomarkers could allow a more accurate prognosis than an isolated marker. Biomarkers, including p53, Ki-67, and CK20, with classic and prognostic factors with recurrence and novel markers such as EN2 may provide a more accurate prediction of outcome compared with any single marker, improving risk stratification and clinical management of patients with BCa.

The prevalence of asthma is about 9,7 % in women and 5,5 % in men. Asthma can deteriorate during the perimenstrual period, a phenomenon known as perimenstrual asthma (PMA), which represents a unique, highly symptomatic asthma phenotype. It is distinguished from traditional allergic asthma by aspirin sensitivity, less atopy, and lower lung capacity. PMA incidence is reported to vary between 19 and 40 % of asthmatic women. The presence of PMA has been related to increases in asthma-related emergency department visits, hospitalizations and emergency treatment including intubations. It is hypothesized that hormonal status may influence asthma in women, focusing on the role of sex hormones, and specifically on the impact of estrogens’ fluctuations at ovulation and before periods. This paper will focus on the pathophysiology of hormone triggered cycle related inflammatory/allergic events and their relation with asthma. We reviewed the scientific literature on Pubmed database for studies on PMA. Key word were PMA, mastcells, estrogens, inflammation, oral contraception, hormonal replacement therapy (HRT), and hormone free interval (HFI). Special attention will be devoted to the possibility of reducing the perimenstrual worsening of asthma and associated symptoms by reducing estrogens fluctuations, with appropriate hormonal contraception and reduced HFI. This novel therapeutical approach will be finally discussed.

State of the art in the development of a novel Multi Physical-Chemical profiler (MPCP system) for simultaneous, autonomous, in situ measurements of three environmentally relevant specific fractions of trace metals as well as master variables in natural waters is presented. It has been designed using advanced voltammetric microsensors, microprocessor and telemetry technology. A detailed description of the system is given and examples of environmental applications for in situ measurements in sea water are reported. The results indicate that the system is reliable and that in situ measurements of the three specific fractions of trace metals can be achieved down to concentrations at the ppt level using Square Wave Anodic Stripping Voltammetry (SWASV).

To assess the effectiveness of the association of 2 specific strains, Lactobacillus fermentumLF10 (DSM 19187) and Lactobacillus acidophilusLA02 (DSM 21717), specifically formulated in slow-release effervescent tablets, in patients with recurrent vulvovaginal candidiasis.

Background and Objective: Botulinum neurotoxin (BoNT), now commonly used for reducing muscular spasms in other neuromuscular disorders, is now increasingly proposed also for treating pelvic floor disorders, including chronic pelvic pain syndromes, vaginismus, vulvodynia and vulvar vestibulitis syndrome. To provide up-to-date information on these advances we reviewed the literature about BoNT injections for pain and spasms related to pelvic floor disorders. Methods: We conducted a Medline search using the terms botulinum neurotoxin, pelvic floor disorders, levator ani myalgia, vaginismus, vulvar vestibulitis, vulvodynia, dyspareunia, interstitial cystitis, recurrent cystitis, and postcoital cystitis. We sought information on the indications and techniques used for BoNT treatment for pelvic floor dysfunctions, and related pain syndromes in women. Results: Our search identified 12 studies for review (including a randomized controlled trial) showing that BoNT effectively reduces pain in chronic genital pain syndromes associated with pelvic floor spasm. Before BoNT trials, patients with idiopathic lifelong vaginismus and dyspareunia, associated with hyperactive pelvic floor muscles, had no effective treatment options. BoNT injected under electromyographic (EMG) guidance in pelvic floor muscles improves vaginismus, helping to restore a normal sexual life. BoNT injections also seem to improve vulvodynia and vulvar vestibulitis. Though some patients need periodic injections, in about 65 of affected women BoNT achieves permanent benefit. Conclusions: These encouraging evidence-based results suggest that BoNT injected intramuscularly should extend treatment options for women with lifelong or acquired pelvic floor disorders and genital pain.

Pain is a complex subjective experience, associated with neurovegetative, affective and cognitive rapid changes. Biological, psychosocial and contextual factors may contribute. Chronic inflammation, of whatever cause, is the leading contributor to chronic pain. The mast cell directs both the inflammatory process and the shift to chronic pain, mediating through the production of Nerve Growth Factor (NGF) and other neurotrophic molecules. Women, in the fertile age, are biologically more vulnerable to chronic inflammation, as fluctuations of estrogens are agonist factors of mast cells degranulation, mostly in the premenstrual phase. Pain is defined as “nociceptive” when it indicates an ongoing damage; “neuropathic” when it becomes a disease per se.Chronic Pelvic Pain (CPP) indicates an invalidating, persistent or recurrent pelvic pain, persisting for more than 6 months. CPP is the main complaint of 10–15% of gynaecologic consultations, leading to 40% of diagnostic laparoscopies and 15% of hysterectomies. Comorbidity, i.e. the coexistence of pathologies and painful syndromes in different pelvic organs, is another common feature. Cystitis, vulvar vestibulitis, endometriosis, irritable bowel syndrome all play an important role and contribute to identifying the hyperactive mast cell and related chronic inflammation as the common pathophysiologic factor. The paper reviews nociception characteristics, the emerging role of mast cells, the pathophysiology of comorbidity, biological, psychosexual and contextual predictors, and stresses the need to move from a “hyperspecialistic” perspective to a multisystemic reading of CPP, with special attention to the urologic perspective.

This article gives a review of the analytical and environmental criteria which must be considered and the relevant specific developments needed for direct, reliable voltammetric measurements of trace metal speciation in environmental systems. In particular, this article will focus on the tools which enable remote, long‐term in situ measurements. The development of such tools is a challenging task. The strategies that can be used to achieve this goal are described for the development of innovative and versatile gel‐integrated voltammetric microsensors, micro‐/mini‐integrated analytical systems, and submersible probes. The advantages of these new tools with respect to selectivity, sensitivity, reliability, spatial and temporal resolution of data, and thus efficient environmental monitoring of the biogeochemical cycle of trace metals are demonstrated by providing examples of measurements made in various aquatic samples in laboratory (water, soils, solid–liquid interface) and in situ in fresh and seawaters.

To determine patterns of symptoms across age groups, identify symptom groups associated with ovarian hormonal depletion or other variables, and develop a prediction model for each symptom.

The assessment and then treatment of a change in libido, or a change in the desire to partake in sexual activity, during the menopausal transition and beyond has been a challenging and elusive area of clinical research. This is partly due to the multidimensional nature of female sexuality, the difficulties of measuring testosterone in women in a reliable and accurate manner, and the complexity of the neurobiology and neurobehavior of female sexual desire. In addition, there is a lack of evidence for diagnostic specificity of low free testosterone levels for the symptom of low libido in women for whom there are no confounding interpersonal or psychological factors; although, in the symptomatic population of surgically or naturally menopausal women, a low level of free testosterone often accompanies a complaint of reduced desire/libido. The randomized clinical trial research on testosterone replacement for naturally and/or surgically menopausal women with sexual dysfunction has been criticized for a high placebo response rate, supraphysiological replacement levels of testosterone, the perception of modest clinical outcome when measuring objective data such as the frequency of sexual intercourse relative to placebo, and the unknown safety of long-term testosterone replacement in the estrogen-replete surgically or naturally menopausal woman. A careful review of current evidence from randomized, controlled trials lends support to the value of the replacement of testosterone in the estrogen-replete menopausal woman for whom libido and desire has declined. The issue of long-term safety remains to be answered.

To obtain data on sleep quality in women attending menopause clinics in Italy.

The aim of the study was to analyse the socio-demographic and epidemiological characteristics of the Italian male population affected by sexual disturbances. Men complaining of erectile dysfunction (ED) who called the Pfizer program “Man and Woman in Health” between April 18th 2001 and May 27th 2002 and asked for information about their medical condition, were interviewed by trained doctors using a computerassisted questionnaire. 16007 out of 25018 calls were considered for statistical analysis. Mean age of callers was 48.8±14.2 yr, reporting ED in 83% of cases. In the majority of men ED was severe (58%) and lasting more than 3 yr (25%). Multivariate analysis revealed that diabetes, depression, prostate surgery, heart disease, neurological disorders, liver and renal diseases were all significant and independent contributors to the degree of erectile impairment adjusted for age (p<0.001). The principal concomitant medications were anti-hypertensive (23%), antidiabetic (9%) and cardiovascular agents (6%). Cigarette smoking was present in 24%. On directed questioning of the caller, anxiety and distress were perceived as the most frequent causes of ED (42%) across all age groups, followed by the presence of concomitant disease/s (26%) especially in aging men. Also, a large number of men (41%) with severe ED waited for more than 3 yr before looking for medical referral. Interestingly, only 19% had ever tried any specific medication for ED. These data indicate that 5 yr after worldwide approval and release of sildenafil, ED is still largely undiagnosed and under-treated, possibly because it is still perceived as a condition mainly due to distress or advancing age and therefore not deserving medical referral. Effective prevention of ED commences with better awareness of the pathological causes by the population and modification of risk factors by the doctors.

In light of various shortcomings of the traditional nosology of women's sexual disorders for both clinical practice and research, an international multi-disciplinary group has reviewed the evidence for traditional assumptions about women's sexual response. It is apparent that fullfillment of sexual desire is an uncommon reason/incentive for sexual activity for many women and, in fact, sexual desire is frequently experienced only after sexual stimuli have elicited subjective sexual arousal. The latter is often poorly correlated with genital vasocongestion. Complaints of lack of subjective arousal despite apparently normal genital vasocongestion are common. Based on the review of existing evidence-based research, many modifications to the definitions of women's sexual dysfunctions are recommended. There is a new definition of sexual interest/desire disorder, sexual arousal disorders are separated into genital and subjective subtypes and the recently recognized condition of persistent sexual arousal is included. The definition of dyspareunia reflects the possibility of the pain precluding intercourse. The anticipation and fear of pain characteristic of vaginismus is noted while the assumed muscular spasm is omitted given the lack of evidence. Finally, a recommendation is made that all diagnoses be accompanied by descriptors relating to associated contextual factors and to the degree of distress.

Neurogenic impotence is a common complication after radical pelvic surgery, irradiation or perineal trauma. Neuronal transplantation is a new frontier for treating neurological disorders. We investigated whether the major pelvic ganglion can survive and become functional after being implanted into the corpus cavernosum in adult rats.

Using an animal model we studied the long-term effects of ovariectomy and simulated birth trauma in the development of apoptosis as well as the urodynamic, histological and ultrastructural findings 9 months after such procedures.

We tested the hypothesis that intracavernous injection of vascular endothelial growth factor (VEGF) can restore erectile function in a rat model of traumatic arteriogenic erectile dysfunction.

Objectives:The aim of this study was to assess the longterm mechanical reliability of AMS (American Medical Systems) three–piece inflatable implants and their impact on patient–partner satisfaction in 200 consecutive patients with erectile dysfunction who underwent surgery in five different institutions.Methods:Patient charts included in the study were collected and extensively assessed to record pre– and intraoperative data and postoperative complications. All patients and 120 partners were then seen often in the office at a mean follow–up of 59 months (range 6–130) and they were extensively questioned about function of the device and its impact on the couple’s sexual life.Results:At the long–term follow–up, 185 patients (92.5%) were still engaging in sexual intercourse with a mean frequency of 1.7/week. Patients and partners reported prosthetic erections as excellent, satisfactory or poor in 96 (48%), 100 (50%) and 4 (2%) cases, and in 20 (17%), 80 (66%) and 20 (17%) cases, respectively. Postoperative sexual activity was considered excellent, satisfactory or poor by 140 (70%), 44 (22%) and 16 (8%) patients and by 34 (28%), 81 (68%) and 5 (4%) partners, respectively. Reasons for patients’ complaints included postoperative penile shortening in 60 (30%) cases and poor glandular engorgement in 40 (20%) cases. Partners’ main complaint was unnaturalness of the prosthetic erection, a factor reported by 30 (25%) subjects. Complications requiring surgical exploration included infection in 12 patients (6%) and mechanical failure in 8 patients (4%). Kaplan–Meier estimates demonstrated significantly decreased mechanical survival for the Ultrex type of cylinders compared to the CX type of cylinders.Conclusions:AMS three–piece inflatable implants provide an overall patient and partner satisfaction rate of 92 and 96%, respectively. However, postoperative penile shortening and poor glandular engorgement were the causes of some complaints among the patient population as well as the unnaturalness of prosthetic erection among female partners. In the long–term, mechanically speaking, CX cylinders seem to be more reliable than the Ultrex ones.

In this article, the development of a novel voltammetric system for real‐time, high spatial resolution trace element concentration profile measurements at the sediment‐water interface, or other interfaces, is reported. The heart of this system is a novel gel‐integrated Hg‐plated Ir‐based 64 individually addressable microsensor arrays. The gel membrane minimizes fouling problems and insures high stability of the Hg semidrops. Measurements were performed simultaneously over the 64 lines using a powerful multiplexing system and a single potentiostat. The voltammetric probe and sensor have been described in detail. This voltammetric system has been characterized by running both cyclic voltammetry (CV) in hexacyanoferrate(III) solution using the gel‐integrated Ir‐based microsensor and square‐wave anodic stripping voltammetry (SWASV) in Pb(II) and Cd(II) solution using the gel‐integrated Hg‐plated Ir‐based microsensor. The results showed that reproducible and reliable simultaneous measurements can be obtained over the 64 individually addressable lines even with fast dynamic techniques such as SWASV. Moreover, theoretical and experimental data were in good agreement. Profiling capability has also been demonstrated.

This article describes a novel voltammetric in‐situ profiling system (VIP System) for continuous, real‐time monitoring of trace elements in fresh and seawater down to 500 meter depth. The VIP System has been designed using advanced microprocessor and telemetry technology. The heart of the submersible voltammetric probe is a Hg‐plated Ir‐based microsensor covered with an antifouling gel membrane. This gel integrated microsensor allows direct voltammetric measurements of trace metals in complex media without physical and chemical interferences of the test solution. A detailed description of the system is given and examples of environmental applications are reported for in‐situ trace metal monitoring in oxygen saturated seawater as well as for in‐situ profiling of MnIIin anoxic lake water. The results indicate that the VIP System is robust and reliable and that in‐situ measurements of mobile fraction of trace metals can be achieved down to very low concentration levels (ca. 5 ppt).

AbstractVulval pain can be an especially distressing problem. It is a more frequent symptom than was previously recognized. Patients suffering from vulval pain may present directly to a wide range of health care professionals, including sexual therapists. On the other hand, the complaint of vulval pain may come to light when a woman presents with a sexual or relationship problem; in such a situation vulval pain may be the cause or the result of the sexual or relationship problem. All patients complaining of vulval pain should be properly examined and appropriate treatment instigated. Sometimes a multidisciplinary approach is required.

Objective: Vulvovaginal health is important to women's overall health, fertility, sexuality, self-perception, self-confidence and intimacy. It is important to identify the existing perceptions and levels of knowledge about intimate care practices from women in different countries, and with different cultures, religions, and perspectives to help women overcome barriers to optimal intimate care.

Flank incisions may be associated with flank hernias, which may be complicated by incarceration and strangulation. Furthermore, they may be the cause of significant patient dissatisfaction with the surgical outcome. To avoid an open surgical procedure with its associated morbidity for hernia repair we describe a novel laparoscopic technique for repairing flank hernias with minimal morbidity and an excellent outcome.

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