A proof of concept that experience-based management of endometriosis can complement evidence-based guidelines.

Background: Management of endometriosis should be based on the best available evidence. The pyramid of evidence reflects unbiased observations analysed with traditional statistics. Evidence-based medicine (EBM) is the clinical interpretation of these data by experts. Unfortunately, traditional statistical inference can refute but cannot confirm a hypothesis and clinical experience is considered a personal opinion. Objectives: A proof of concept to document clinical experience by considering each diagnosis and treatment as an experiment with an outcome, which is used to update subsequent management. Materials and Methods: Experience and knowledge-based questions were answered on a 0 to 10 visual analogue scale (VAS) by surgery-oriented clinicians with experience of > 50 surgeries for endometriosis. Results: The answers reflect the collective clinical experience of managing >10.000 women with endometriosis. Experience-based management was overall comparable as approved by >75% of answers rated ≥ 8/10 VAS. Knowledge-based management was more variable, reflecting debated issues and differences between experts and non-experts. Conclusions: The collective experience-based management of those with endometriosis is similar for surgery-oriented clinicians. Results do not conflict with EBM and are a Bayesian prior, to be confirmed, refuted or updated by further observations. What is new?: Collective experience-based management can be measured and is more than a personal opinion. This might extend EBM trial results to the entire population and add data difficult to obtain in RCTs, such as many aspects of surgery.

Validation of a clinical tool for vestibular trophism in postmenopausal women.

OBJECTIVE: This study aimed to develop and validate a clinical tool to assess vestibular trophism in women with genitourinary syndrome of menopause (GSM). METHODS: In this cross-sectional study, the principal investigator's center and three external reviewers assessed the vestibular images of postmenopausal women using a multi-item tool defined as vestibular trophic health (VeTH), which assessed five criteria: petechiae, pallor, thinning, dryness and redness. Dryness, dyspareunia, vulvar pain and the Vaginal Health Index (VHI) were also evaluated. RESULTS: Analysis of the intraclass correlation coefficient (0.76; confidence interval 0.62-0.82) and Cronbach's alpha coefficient (0.78; confidence interval 0.64) indicated an inter-rater reliability and reproducibility of VeTH in the 70 women enrolled in the study. The observed covariance between a high VeTH score and the symptom severity demonstrated a significant correlation, which was not evident between VeTH and the total VHI score. CONCLUSIONS: The vulvar vestibule is the main location of genital tenderness, primarily responsible for burning/pain and entry dyspareunia because of its capacity to develop an excess of nociceptors upon sexual hormone deprivation. Our study indicated that VeTH can be a reproducible tool for the morphological classification of vestibular trophism and bears a significant correlation with the severity of the symptoms.

Vaginal biological and sexual health--the unmet needs.

The vagina is a most neglected organ. It is usually clinically considered with a minimalistic view, as a 'connecting tube' for a number of physiologic functions: passage of menstrual blood, intercourse, natural conception and delivery. Unmet needs include, but are not limited to, respect of vaginal physiologic biofilms; diagnosis and care of the optimal tone of the levator ani, which surrounds and partly support it; care of its anatomic integrity at and after delivery and at pelvic/vaginal surgery; care of long-term consequences of pelvic radiotherapy; long-term care of the atrophic changes it will undergo after the menopause, unless appropriate, at least local, estrogen therapy is used; appreciation and respect of its erotic meaning, as a loving, receptive, 'bonding' organ for the couple. The vaginal erotic value is key as a non-visible powerful center of femininity and sexuality, deeply and secretly attractive in terms of taste, scent (together with the vulva), touch and proprioception. The most welcoming when lubrication, softness and vaginal orgasm award the woman and the partner with the best of pleasures. Prevention of sexual/vaginal abuse is a very neglected unmet need, as well. Who cares?

[Menstruation, inflammation and comorbidities: implications for woman health]. / Mestruazione, inflammazione e comorbilità: implicazioni per la salute della donna.

Menstruation is the genital sign of systemic endocrine events. Heterogeneity of perimenstrual symptoms is associated with levels of inflammation, triggered by the fall of estrogens at genital and systemic level. Aim of the review is to concisely analyze the evidence on: 1) genital and systemic endocrine and inflammatory events associated with periods and perimenstrual symptoms; 2) rationale of intervention to reduce their intensity and impact on women's lives. This review of the literature, selected with a clinical perspective, supports the inflammatory basis of the menstrual event, triggered by the estrogens' and progesterone' fall. Moreover, the review analyzes the endocrine and inflammatory basis of perimenstrual pelvic and extrapelvic symptoms such as: menstrual pain, menstrual irregularities, premenstrual syndrome, gastrointestinal symptoms, catamenial headache, depression, perimenstrual myalgia, joint pain, allergies and asthma, heavy menstrual bleeding, associated ironless anemia, brain and behavioral consequences. Inflammation, with increase of cytokines and other markers, is modulated by the degranulation of mast cells at the basal level of the endometrium, in the blood, in all the organs where mast-cell are already activated from local pathologies and within the brain. The shift of inflammation from physiological to a pathologic intensity increases the severity of perimenstrual symptoms. Symptoms persist, moderately attenuated, also during the hormone free interval (HFI) in contraception. The HFI reduction from seven to two days significantly reduces menstrual inflammation and associated symptoms.

Contraception containing estradiol valerate and dienogest--advantages, adherence and user satisfaction.

UNLABELLED: The contraceptive pill containing estradiol valerate and dienogest meets women's requests for: a more natural contraceptive, that is reliable and easy to use, with positive cosmetic effects; less intense and shorter bleeding, reduced anaemia and increased vital energy; reduced dysmenorrhoea and all the specific cycle-related symptoms linked to a drop in oestrogen and the related systemic inflammation, the result of a hormone free interval (HFI) of just two days; with a good impact on sexuality and overall well-being, all associated with a high level of efficacy: (uncorrected Pearl Index: 0.79; corrected: 0.42). BACKGROUND: Women would prefer more natural hormonal contraception, with high reliability, good tolerability, a simple dosing schedule and possibly some health advantages. AIM: To evaluate what the pill containing estradiol valerate and dienogest can offer women and the best way to communicate this opportunity, after 4 years of growing clinical use. METHOD: A review of literature plus the Author's clinical experience. RESULTS: The new pill containing estradiol valerate and dienogest may satisfy women's need for: a more natural hormonal contraceptive with a low hormone dosage, high reliability and good tolerability; a simple dosing schedule (one pill per day for 28 days); a positive cosmetic effect on the skin; lighter and shorter withdrawal bleeding, improved anaemia, less fatigue and higher vital energy; reduced dysmenorrhoea and a dramatic reduction in all symptoms thanks to a shorter Hormone Free Interval (HFI) of just two days. The new pill is an option for all women taking hormonal contraception who would like a more natural choice; for those who have never used hormonal contraception and may consider this new opportunity positively, for those who suffer from various menstrual symptoms, related inflammation ("a shorter HFI means much fewer or no symptoms") and, possibly for pre-menopausal women, an opportunity to combine excellent contraception with a definite improvement in their well-being. CONCLUSION: The pill containing estradiol valerate and dienogest is a contraceptive option that may satisfy women's demands for a more natural contraceptive while offering high reliability, good tolerability, a simple dosing schedule, lighter and shorter withdrawal bleeding, improved anaemia and a reduction in cycle-related symptoms thanks to a shorter Hormone Free Interval, and improved sexuality and general well-being. Communication should focus on women's priorities regarding contraception and their pursuit of a better quality of life while on OC.

[Recurrent cystitis and vaginitis: role of biofilms and persister cells. From pathophysiology to new therapeutic strategies]. / Cristiti e vaginitis recidivanti: ruolo dei biofilm e delle persister cells. Dalla fisiopatologia a nuove strategie terapeutiche.

Recurrent vaginitis and cystitis are a daily challenge for the woman and the physician. The recurrence worsens the symptoms' severity, increases comorbidities, both pelvic (provoked vestibulodynia, bladder pain syndrome, levator ani hyperactivity, introital dyspareunia, obstructive constipation, chronic pelvic pain) and cerebral (neuroinflammation and depression), increases health costs, worsens the quality of life. Antibiotics increase the risk of bacterial resistences and devastate the ecosystems: intestinal, vaginal and mucocutaneous. Pathogenic biofilms are the (still) neglected etiology of recurrences. Biofilms are structured communities of bacteria and yeasts, protected by a self-produced polymeric matrix adherent to a living or inert structures, such as medical devices. Biofims can be intra or extracellular. Pathogens live in a resting state in the deep biofilm layers as "persister cells", resistant to antibiotics and host defences and ready to re-attack the host. The paper updates the evidence on biofilms and introduces new non-antibiotic strategies of preventing and modulating recurrent vaginitis and cystitis.

[Short-course treatment of vulvovaginal candidiasis: comparative study of fluconazole and intra-vaginal fenticonazole]. / Il trattamento "short course" della candidosi vulvovaginale acuta: studio comparativo tra il fluconazolo ed il fenticonazolo intravaginale.

AIM: The aim of this paper was to compare the efficacy of fluconazole 150 mg and intra-vaginal fenticonazole 600mg in short-course treatment of the acute episode of vulvovaginal candidiasis (VVC). METHODS: In a prospective study, 80 patients with clinical and mycological (SavvyCheck™ test) confirmed VVC were enrolled and divided randomly in two groups. Forty patients received oral fluconazole (150 mg), whereas 40 patients received intra-vaginal tablet fenticonazole (600 mg). Two sequential doses of azole agents were given 3 days apart (short-course treatment). Second and third visits were done for all patients seven and 30±5 days after treatment. RESULTS: At the second visit, 31 patients (77.5%) were cured clinically (Sobel score <4) in fluconazole group and 32 patients (80%) in fenticonazole group (P=0.876). The vulvovaginal pruritus was reduced in lower time in fenticonazole patients than in fluconazole group (mean 2.3 days versus 4.5 days, P=0.047). At the third visit, three patients in fluconazole group and two patients in fenticonazole group had clinical sign of VVC. CONCLUSION: Fluconazole and intravaginal fenticonazole are both effective to cure symptoms of VVC but fenticonazole appears to reduce the pruritus in less time.

The recurrent vulvovaginal candidiasis: proposal of a personalized therapeutic protocol.

Background. Recurrent vulvovaginal candidiasis (RVC) is an increasing challenge in clinical practice. Objective. The purpose of this study was to reduce the episodes of RVC through the intake of fluconazole 200 mg/dose with a personalized regimen at growing administration intervals with a probiotic. Method. 55 patients received a 200 mg fluconazole as an induction dose for 3 alternate days. Symptoms resolution after 10-14 days made the patients eligible to continue with a maintenance therapy of fluconazole weekly for one month, followed by 200 mg after 10, 15, 20 and 30 days. Patients were allowed to move on to the next level of maintenance therapy only if they were symptom free. Patients were also given a probiotic with Beta Glucan and Echinacea Purpurea. Results. Among the 55 patients enrolled, four (7%) have withdrawn after the induction phase. 51 patients completed the whole therapeutic maintenance period, and eight (15,6%) experienced a recurrence before the end of the therapy. Five women (9,8%) relapsed (two after 2 months and three after 6 months). Conclusion. The positive results of our study prove the effectiveness of an individualized protocol for a rather short period, with a slowly decreasing administration of fluconazole + probiotic.

Correlates of sexual functioning in Italian menopausal women.

OBJECTIVES: To analyze the sexuality of Italian menopausal women. DESIGN: Cross-sectional study. POPULATION: Menopausal women consecutively observed during the study period in menopause clinics. METHODS: Women were interviewed about their current and premenopausal sexual activity: sexual intercourse frequency and self-rated sexual desire, capacity for orgasm and sexual satisfaction were recorded. Women were defined as having poor sexual functioning if they had one or less sexual intercourses per week or answered 'absent/poor' to the questions about the sexual domains. RESULTS: Oral hormone therapy (HT) use (odds ratio (OR) 0.43 for desire, 0.54 for orgasm and 0.56 for overall sexual satisfaction, all p < 0.001) and transdermal HT (OR 0.38, 0.53 and 0.53, respectively, all p < 0.001) were significantly associated with lower risk of poor sexual functioning. Higher physical and mental component scores (PCS and MCS, range 0-100) of the Short Form-12 are inversely related to poor sexual functioning (OR by point 0.96, 0.95, 0.95 for PCS and 0.96, 0.96 and 0.95, for MCS, respectively, all p < 0.001). Pain during and symptoms after sexual intercourse were significantly related to desire (OR 1.96 and 1.78, respectively), orgasm (OR 2.22 and 2.06, respectively) and sexual satisfaction (OR 2.02 and 1.79, respectively). The partner's health problems were associated with low sexual intercourse frequency (OR 4.18, p < 0.001) and absent/poor overall satisfaction (OR 2.61, p < 0.001). CONCLUSIONS: This study shows that, in menopausal Italian women attending menopause clinics, sexual function is associated with the quality of sexual life in reproductive age, partner's health status, current quality of life, HT and occurrence of pain during and symptoms after sexual intercourse.

Therapeutic options for postmenopausal female sexual dysfunction.

BACKGROUND: Female sexual dysfunction (FSD) is a multidimensional problem combining biological, psychological and interpersonal elements of multiple etiologies. Menopause-related sexual dysfunction may not be reversible without therapy. Hormonal deficiency does not usually decrease in severity over time. Many options are available for the successful treatment of postmenopausal FSD. OBJECTIVE: To review the pharmacological and non-pharmacological therapies available for postmenopausal FSD, focusing on practical recommendations for managing postmenopausal women with sexual complaints, through a literature review of the most relevant publications in this field. PSYCHOSOCIAL THERAPY: This type of therapy (basic counselling, physiotherapy and psychosexual intervention) is considered an adaptable step-by-step approach for diagnostic and therapeutic strategies, normally combined with biomedical interventions to provide optimal outcomes. PHARMACOLOGICAL THERAPY: For postmenopausal FSD, many interventional options are now available, including hormonal therapies such as estrogens, testosterone, combined estrogen/testosterone, tibolone and dehydroepiandrosterone. CONCLUSIONS: Menopause and its transition represent significant risk factors for the development of sexual dysfunction. FSD impacts greatly on a patient's quality of life. Consequently, it is receiving more attention thanks to the development of effective treatments. Non-pharmacological approaches should be used first, focusing on lifestyle and psychosexual therapy. If required, proven effective hormonal and non-hormonal therapeutic options are available.

[Perception of chronic pelvic pain in women: predictors and clinical implications].

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.

Are subjects with erectile dysfunction aware of their condition? Results from a retrospective study based on an Italian free-call information service.

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 computer-assisted 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.

Etiology and diagnosis of coital pain.

Coital pain is the leading symptom of two major sexual disorders, dyspareunia and vaginismus. According to the new International Classification on Female Sexual Disorders they are included under the category of "Sexual Pain Disorders". Dyspareunia has long been considered to be psychogenic. On the contrary, it has solid biological bases: location of pain and its characteristics are the strongest predictors of its organicity. Biological factors include hormonal, inflammatory, muscular, iatrogenic, neurologic, vascular, connective and immunitary causes. A specific pathology of pain is in play when the meaning of pain shifts from the "nociceptive" domain, when it signals an ongoing tissue damage, to the "neuropathic" dimension, when pain is generated within the pain system itself, with increased peripheral input and/or lowered central pain threshold, as happens in chronic vulvar vestibulitis. Vaginismus, with its associated defensive contraction of perivaginal muscles when intercourse is attempted, is credited to be the pelvic expression of a more general muscular defense posture, associated with a variable phobic attitude towards coital intimacy. Vaginismus may prevent intercourse in the most severe degrees, whilst in the milder ones it becomes a cause of dyspareunia. Psychosexual factors--loss of libido and arousal disorders, associated with, or secondary to, sexual pain related disorders--may contribute to the worsening of coital pain over time, alone or when associated to couple problems. The clinical approach should aim at diagnosing biological, psychosexual and context-dependent etiologies. The psychobiology of the experience of sexual pain needs to be addressed in a comprehensive, integrated and patient-centered perspective.

The challenge of sexual medicine for women: overcoming cultural and educational limits and gender biases.

Women's sexuality is multifactorial, rooted in biological, psychosexual and context-related factors, correlated not only to the couple concerned, but also to family and socio-cultural issues. Female sexual identity, sexual function and sexual relationship interact to give female sexual health its full meaning or, on the contrary, its problematic profile. Women's sexuality is discontinuous throughout the life cycle and is dependent on personal, current contextual and relationship variables as well as historical factors. Female sexual dysfunctions (FSD) occur along a continuum from dissatisfaction (with or without significant distress) to complete dysfunction (with or without significant distress). Sexual problems reported by women are not discrete and often co-occur, co-morbidity being one of the leading characteristics of female sexual dysfunctions. Socio-cultural factors may modulate the expression and complaining modality, i.e. wording of a sexual disorder. The meaning of sexual intimacy is to be understood, as it is indeed a strong modulator of the sexual response and of the quality of satisfaction the woman experiences, besides being the simple adequacy of the sexual function. Quality of feelings for the partner and the partner's health and sexual problems may further contribute to FSD. To improve women's sexual health, physicians should receive a formal training in sexual medicine both in the general medical training and in the speciality course; should become competent in the first level medical diagnosis of FSD; have an interdisciplinary approach and acknowledge the socio-cultural and context-dependent differences in FSD etiology and wording.

Definitions of women's sexual dysfunction reconsidered: advocating expansion and revision.

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 fullfilment 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.

Clinical approach to dyspareunia.

Dyspareunia needs to be addressed from an integrated patient-centered perspective. This review analyzes the organic causes of pain during intercourse. Factors that are often underevaluated in the clinical setting include hormonal, inflammatory, muscular, iatrogenic, neurologic, vascular, connective, and immunitary causes. Psychosexual factors, such as vaginismus, loss of libido, arousal disorders and sexual pain-related disorders, often overlap. A preliminary clinical approach aimed at integrating different biological and psychosexual etiologies in a comprehensive manner is discussed in this article.

Vulvodynia: the challenge of "unexplained" genital pain.

Vulvodynia is a clinical syndrome that may include unexplained vulvar pain, sexual dysfunction, and psychological disability. It is a multifactorial syndrome that should be diagnosed, if possible, with an intradisciplinary approach. This article discusses the diagnosis and treatment of vulvodynia, starting with a summary of the complex nervous system within the pelvis. Different clinical pictures and different subtypes of the syndrome have been described in order to identify the etiologic aspects that are essential for diagnosis and subsequent treatment. Clinical evaluation should stress attention to detailed "pain-mapping" and evaluation of past and present history. The gynecological examination should be an overall patient evaluation, incorporating global physical impression, change in posture due to pain and careful examination of the pelvic floor. Examination of the pelvic floor is frequently omitted. Leading to an incorrect diagnosis of psychogenic pain. Such a misdiagnosis can result in the dismissal of appropriate treatment. Proper evaluation requires a comprehensive, multidisciplinary approach that includes medical, rehabilitative, and psychological issues.

Cardioprotective effects of ovarian hormones and the HERS in perspective.

The increased population of women in menopause living in the industrialized countries is associated with an increase of diseases which are dependent or facilitated by a state of estrogen deficiency such as cardiovascular and cerebrovascular diseases. Several studies have shown that estrogen replacement therapy reduces the occurrence of coronary and may be of cerebrovascular disease by nearly 50% in treated women compared to non-users. These findings are supported by the evidence that estrogens have a beneficial effect on cholesterol metabolism and deposition, contributing to the inhibition of atherosclerotic plaque formation in arterial walls as well as a direct effect on the vessel wall. Progestins may, in some cases, counteract the beneficial effect of estrogens upon cardiovascular functions. More androgenic progestins may have a detrimental effect upon vascular reactivity while less androgenic progestins seem not to reduce the beneficial effect of estrogens. Of interest, continuous combined administration of hormone replacement therapy seem to be preferable for women with coronary artery disease or for those with increased cardiovascular risk. Case-control and cohort studies have shown that estrogen progestin therapy is associated with a significant reduction of cardiovascular mortality and morbidity. The HERS study has added critical data regarding the cardioprotective effect of hormone replacement therapy in elderly women with proven coronary artery disease. Because of the several methodological and statistical flaws of the HERS study, further studies are warranted to evaluate the effect of hormone replacement therapy on cardiovascular prognosis. Large scale randomized studies will evaluate the effect of estrogen and estrogen-progestin replacement therapy upon cardiovascular events in menopausal women. Until completion of these studies hormone replacement therapy in women with increased cardiovascular risk should be seen with no enthusiasm but also with no fear.