Incorporating microbiota data into epidemiologic models: examples from vaginal microbiota research.

PURPOSE: Next generation sequencing and quantitative polymerase chain reaction technologies are now widely available, and research incorporating these methods is growing exponentially. In the vaginal microbiota (VMB) field, most research to date has been descriptive. The purpose of this article is to provide an overview of different ways in which next generation sequencing and quantitative polymerase chain reaction data can be used to answer clinical epidemiologic research questions using examples from VMB research. METHODS: We reviewed relevant methodological literature and VMB articles (published between 2008 and 2015) that incorporated these methodologies. RESULTS: VMB data have been analyzed using ecologic methods, methods that compare the presence or relative abundance of individual taxa or community compositions between different groups of women or sampling time points, and methods that first reduce the complexity of the data into a few variables followed by the incorporation of these variables into traditional biostatistical models. CONCLUSIONS: To make future VMB research more clinically relevant (such as studying associations between VMB compositions and clinical outcomes and the effects of interventions on the VMB), it is important that these methods are integrated with rigorous epidemiologic methods (such as appropriate study designs, sampling strategies, and adjustment for confounding).

[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.

Using longitudinal profiles to characterize women's symptoms through midlife: results from a large prospective study.

OBJECTIVE: The aims of this study were to identify groups of symptoms experienced by women during midlife and to determine the main profiles or trajectories for each of these symptom groups through the menopausal transition. METHODS: The study uses data from the middle-aged cohort of women from a large community-based longitudinal study. Groups or patterns of symptoms are determined using factor analysis. Latent class analysis based on age and age at menopause is used to identify profiles for each of the symptom patterns. RESULTS: Of the four symptom patterns identified, "somatic," "urogynecological," and "physical" symptoms have a constant profile through midlife. Vasomotor symptoms vary through menopause: 11% of women have the "early severe" profile of symptoms that begin at premenopause, whereas 29% have the "late severe" profile, with symptoms peaking during postmenopause and persisting more than a decade after menopause. The remaining women with the "moderate" or "mild" profiles report occasional symptoms that tend to peak around menopause. CONCLUSIONS: Identifying the profile of vasomotor symptoms could help health professionals to tailor their advice to women going through menopause.

Vaginal pH-balanced gel for the control of atrophic vaginitis among breast cancer survivors: a randomized controlled trial.

OBJECTIVE: To estimate the effects of vaginal pH-balanced gel on vaginal symptoms and atrophy in breast cancer survivors treated with chemotherapy or endocrine therapy. METHODS: This was a randomized, double-blind, placebo-controlled study. Breast cancer survivors who experienced menopause after chemotherapy or endocrine therapy were voluntarily enrolled and randomly administered vaginal topical pH-balanced gel or placebo three times per week for 12 weeks. Vaginal dryness and dyspareunia were measured by visual analog scale, vaginal health index, and vaginal pH. The endometrium and ovary were evaluated by transvaginal ultrasonography. RESULTS: Among 98 enrolled women, 86 completed the treatment (n=44 and n=42 for the pH-balanced gel group and placebo group, respectively). Vaginal dryness and dyspareunia improved more in the pH-balanced gel group than in the placebo group (baseline mean 8.20 compared with end-point mean 4.23 [P=.001] and 8.23 compared with 5.48 [P=.040], respectively). Vaginal pH-balanced gel reduced the vaginal pH (gel: baseline mean 6.49 compared with end-point mean 5.00; placebo: 6.22 compared with 5.69 [P<.001]), and enhanced vaginal maturation index (gel: 45.5 compared with 51.2; placebo: 46.4 compared with 47.9 [P<.001]) and vaginal health index (gel: 15.8 compared with 21.1; placebo 14.3 compared with 16.98 [P=.002]). There was no significant difference in adverse effects between the two groups except for mild irritation at the early time of pH-balanced gel administration. CONCLUSION: Vaginal pH-balanced gel could relieve vaginal symptoms and improve vaginal health in breast cancer survivors who have experienced menopause after cancer treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00607295. LEVEL OF EVIDENCE: I.

Atrophic vaginitis: signs, symptoms, and better outcomes.

Atrophic vaginitis is a common finding in women with low estrogen states. Many women believe their symptoms are expected signs of aging. NPs can provide therapeutic options to improve vaginal health and quality of life. This article reviews physiology, clinical manifestations, signs, symptoms, and treatment methods for atrophic vaginitis.

Desquamative inflammatory vaginitis as a manifestation of vitamin D deficiency associated with Crohn disease: case reports and review of the literature.

Desquamative inflammatory vaginitis (DIV) is a chronic disorder associated with yellow vaginal discharge, vulvovaginal burning and pruritus, and dyspareunia. The cause of DIV is unknown; however, infectious, hormonal, and inflammatory etiologies have been proposed. In this series, we observe the association of DIV and vitamin D deficiency by reporting 4 cases of women with DIV and vitamin D deficiency associated with Crohn disease. We further show that the DIV symptoms resolve when the circulating concentrations of 25-hydroxyvitamin D (25-HD) returned to normal. These data provide further support for the notion that DIV can be associated with vitamin D deficiency and DIV symptoms reflect altered vaginal mucous membrane function.

Atrophic vaginitis.

With the loss of estrogen that occurs with menopause, physiologic and structural changes occur within the vulvovaginal mucosa that lead to a condition commonly called atrophic vaginitis. Although mild genital changes occur in most women, 10-47% of postmenopausal women will develop one or more debilitating symptoms that include vulvovaginal dryness, dyspareunia, vulvar itching or pain, recurrent urinary tract infections, as well as abnormal vaginal discharge. Topical estrogen replacement therapies reverse these mucosal changes and are effective treatments for the symptoms of atrophic vaginitis. Vaginal moisturizers and lubricants also provide symptomatic relief for vaginal dryness and dyspareunia, respectively.

Genitourinary symptoms in the menopausal transition.

Irregular uterine bleeding is a common symptom among women in the menopausal transition. Women commonly transition from having regular cycles to having irregular cycles before the final menstrual period. In late perimenopause, anovulation becomes more common, leading to skipped menstrual cycles. Low-dose oral contraceptive pills are effective in decreasing the amount of menstrual blood loss and improving menstrual cycle regularity. It is unclear whether menorrhagia is associated with normal perimenopausal hormonal changes. Studies to date have failed to correlate menorrhagia with hormonal levels and pathology within the uterus. Because of the common association between uterine pathology and menorrhagia, this is an important area for future studies. Vaginal dryness is a common symptom, particularly in late perimenopause. The association between vaginal dryness and low estrogen levels is clear. Estrogen-based hormone replacement therapy is effective in treating this symptom. Locally released estrogen therapy may be preferred over systemic therapy because of lower systemic estradiol levels, reduced side effects, and high efficacy. The long-term safety of these products, particularly in women with a history of breast cancer, requires more study. The prevalence of incontinence increases as women age, but it is unclear whether the menopausal transition is an independent risk factor. Incontinence is a frequent complaint among women in the menopausal transition. In postmenopausal women, hormone therapy (HT) appears to be ineffective in preventing or improving the symptoms of incontinence. Further study of HT, including locally applied estrogens for the common symptom of incontinence, are needed in women in the menopausal transition.

Corrimento vaginal / Genital discharge

Os autores fazem uma revisão bibliográfica sobre as causas mais comuns do corrimento vaginal, com ênfase nas três principais etiologias vivenciadas na prática médica, objetivando a abordagem de aspectos como patogenia, manifestações clínicas, diagnóstico e tratamento

Paecilomyces lilacinus vaginitis in an immuno-competent patient.

Paecilomyces lilacinus, an environmental mold found in soil and vegetation, rarely causes human infection. We report the first case of P. lilacinus isolated from a vaginal culture in a patient with vaginitis.

Sexually transmitted diseases other than human immunodeficiency virus infection in older adults.

Sexually active older adults may engage in activities that put them at risk for sexually transmitted diseases (STDs). A brief review of the main STDs among older adults, including the epidemiology, clinical presentations, and diagnosis of and treatment recommendations for such STDs, is presented.

Vaginitis due to Candida krusei: epidemiology, clinical aspects, and therapy.

Twelve women with vaginal Candida krusei infection were evaluated. In vitro antifungal susceptibility testing and molecular typing were performed. Patients infected with C. krusei frequently had refractory vulvovaginal signs and symptoms that were otherwise indistinguishable from vaginitis due to other yeasts. Patients were 32-63 years old and had previously received multiple courses of antimycotic agents, including fluconazole and miconazole. The most active azole in vitro was clotrimazole, with a 90% minimum inhibitory concentration of 0.25 microg/mL. Four of 6 patients treated with boric acid had clinical and mycological cure. Two dominant genotypes of C. krusei were identified via contour-clamped homogenous electrical field analysis. No major genotypic change was observed in successive isolates from the same patient in most cases, suggesting that these refractory cases were relapses. C. krusei is a rare but important cause of refractory vaginitis and is unique because of its intrinsic resistance to fluconazole.

Vaginitis: case reports and brief review.

Vaginitis is the most frequently gynecologic diagnosis encountered by physicians who provide primary care to women. Accurate diagnosis can be elusive, complicating treatment. Most experts believe that up to 90% of vaginitis cases are secondary to bacterial vaginosis, vulvo-vaginal candidiasis, and trichomoniasis. The diagnosis of vaginitis is based on the patient's symptoms, the physical examination, the findings of microscopic examination of the wetmount and potassium hydroxide (KOH) preparations, and the results of the pH litmus test. Additional cultures and testing may be needed for difficult-to-diagnose cases.

[A new method for self assessment of the pH value of vaginal secretions using an indicator-coated panty liner--initial preliminary report]. / Neue Methode zur Selbstbestimmung des pH-Wertes des Scheidensekretes mittels indikatorbeschichteter Slipeinlagen--Erste vorläufige Mitteilung.

BACKGROUND: The measurement of the pH-value in the secretions of the vagina is one of the most important early diagnostic methods to recognize disturbances of the vaginal milieu in order to prevent the very early premature deliveries. Up to now, within the framework of a prenatal care program, the acidity of the vagina was assessed by the women themselves "invasively" by introduction of a special indicator device (pH-strips or disposable pH-measuring gloves). Now we have developed a possibility to assess the pH-value just by simple inspection of an indicator coated panty liner, which is worn for a couple of hours. The results can be assessed by comparing the color of the indicator with a standard scale. RESULTS: It was possible to assess the pH in 77% of 133 parallel measurements comparing the pH of the vagina and of the indicator coated panty liner in 19 pregnant women. An agreement of the two methods for pH-determination was found in 66%. CONCLUSIONS: These results are encouraging and further investigation in larger series of cases are in progress.

A comparative study of the effects of an estradiol-releasing vaginal ring combined with an oral gestagen versus transdermal estrogen combined with a levonorgestrel-releasing IUD: clinical findings and endometrial response.

OBJECTIVE: Our purpose was to compare the effects of a new estradiol-releasing vaginal ring with an oral progestin versus the efficacy, safety and acceptability of an intrauterine device releasing levonorgestrel combined with estradiol, delivered transdermally from a patch. Climacteric symptoms, bleeding pattern, and endometrial histologic features were studied. MATERIALS AND METHODS: Fifty-six parous, postmenopausal women with urogenital symptoms were allocated to two groups for 1 year" 28 women receiving estradiol by a vaginal ring (2 mg/3 months) and an oral progestin for 7 days every month and 28 women receiving a continuous transdermal daily dose of 50 micrograms of estradiol with a levonorgestrel-releasing (20 micrograms/day) intrauterine device inserted. All the patients were subjected to vaginosonographic examination followed by thorough pathological examination of uterine curetting samples. RESULTS: A mean endometrial thickness (double layer) of 2.9 and 3.0 mm, respectively, was found to be predictive of normal endometrium. Both treatment regimens effectively relieved urogenital symptoms. Endometrial proliferation was not observed. CONCLUSIONS: Treatment of urogenital symptoms in postmenopausal women with these two forms of hormone replacement therapy was shown to be an effective and safe method, exhibiting possible advantages over other methods of treatment.

PIP: At the outpatient obstetric-gynecologic clinic of Areteion Hospital in Athens, Greece, 56 postmenopausal women, 48-76 years old and with signs and symptoms of estrogen deficiency-induced atrophic vaginitis, were randomly assigned to either the group using a silicon vaginal ring containing 2 mg micronized 17-beta- estradiol and oral medroxyprogesterone acetate for 7 days at the beginning of each month (group A) or the group using a combination of 50 mcg estradiol via a transdermal patch and a levonorgestrel-releasing IUD (group B). The women were using these regimens for 12 months. The purpose of the study was to compare the clinical and endometrial effects of the new vaginal ring with an oral progestin with those of the established hormone replacement regimen of transdermal estrogen and a levonorgestrel-releasing IUD. Vaginal ultrasound and pathologic examination of uterine curettage samples were used to determine endometrial effects. The urogenital complaints of all 56 women disappeared. The mean endometrial thickness before treatment was similar for both groups (2.9 mm for group A and 3 mm for group B) and was not significantly different than endometrial thickness after treatment (2.6 and 2.8 mm, respectively). Endometrial proliferation was not observed. The mean endometrial thickness at baseline predicted normal endometrium. After 3 months of treatment, vaginal bleeding patterns were similar in both groups. These findings confirm that both regimens effectively treat estrogen deficiency-induced urogenital disorders and do not increase the risk of endometrial proliferation.

Concordancia entre el diagnóstico clínico y paraclínico de las cervico-vaginitis más frecuentes / Concordance between the clinical and paraclinical diagnosis of the most frequent cervico-vaginitis

Se realizó un estudio multicéntrico (Hospital Universitario de San Ignacio, Hospital San José e Instituto Materno Infantil de Bogotá), seleccionando secuencialmente 301 pacientes de la consulta general de ginecología con o sin sintomatología de cervico-vaginitis que cumplieran los criterios de inclusión y de exclusión. El objetivo general del estudio fue establecer la concordancia entre el diagnóstico clínico de la secreción vaginal y el diagnóstico hecho mediante los exámenes para-clínico considerados como estándar de oro. Dentro de los objetivos específicos se consideraron establecer las cervico vaginitis tanto sintomáticas asintomáticas, establecer la sensibilidad y especificidad del examen clínico frente al método diagnóstico para cada germen en particular y establecer la frecuencia con que las cervico-vaginitis se presentan en nuestro medio. A cada paciente se le practicó inicialmente examen con especuloscopia realizando clínico correspondiente a los hallazgos encontrados, y posteriormente se le tomó muestra de flujo específicamente para Cultivo de Gardenerella vaginalis, Trichomona Vaginalis, Candida albicans, Neisseria gonorreae y prueba de ELISA para Clamydia trachomatis. (truncado 2500 caracteres)

Vaginitis: diagnosis and management.

The various conditions that give rise to vaginitis include specific and nonspecific entities, such as candidiasis, trichomoniasis, bacterial vaginosis, group B streptococcal vaginitis, purulent vaginitis, volvodynia, and vestibulitis. The patient with chronic vaginitis usually develops this condition because of a misdiagnosis. It is critical that patients who have chronic vaginitis be thoroughly evaluated to determine if there is a specific etiology and whether their condition is recurrent or persistent, or is a reinfection. This also must include obtaining a detailed history, beginning with the patient's best recollection of when she felt perfectly normal. The physician must have an understanding of a healthy vaginal ecosystem and what mechanisms are in place to maintain the equilibrium. The vaginal ecosystem is a complex system of micro-organisms interacting with host factors to maintain its equilibrium. The endogenous microflora consists of a variety of bacteria, which include aerobic, facultative and obligate anaerobic bacteria. These organisms exist in a commensal, synergistic or antagonistic relationship. Therefore, it is important to understand what factors control the delicate equilibrium of the vaginal ecosystem, and which factors, both endogenous and exogenous, can disrupt this system. It is also important for the physician to understand that when a patient has symptoms of vaginitis it is not always due to an infectious etiology. There are situations in which an inflammatory reaction occurs but the specific etiology may not be determined. Thus, it is important that the physician not rush through the history or the examination.

[Bacterial flora of the vagina and the effect of endogenous and exogenous factors on its changes]. / Flora bakteryjna pochwy i wplyw czynników egzo- i endogennych na jej zmiany.

The paper describes composition of the bacterial vaginal flora and its basic mechanisms enabling coexistence of different bacterial species residing in this region. A role of the dominant bacteria in maintaining stability of the microflora was stressed. Also various factors influencing ecological balance of the vaginal flora were presented.