Women with Genitourinary Syndrome of Menopause Treated with Vaginal Estriol, Microablative Fractional CO2 Laser and Microablative Fractional Radiofrequency: A Randomized Pilot Study.

Objective: This pilot study intended to assess the feasibility of a large-scale randomized clinical trial designed to analyze the effectiveness of microablative fractional CO2 laser (CO2L) and microablative fractional radiofrequency (RF) compared with vaginal estriol (VE) as treatments for women with moderate-to-severe Genitourinary Syndrome of Menopause (GSM). Methods: Participants were randomized into VE, CO2L, or RF groups. In the VE group, women were required to use vaginal estriol cream for 14 days and then twice a week for 4 months. In the CO2L and RF groups, three energy therapies were administered at monthly intervals. Visual Analog Scale (VAS) for GSM symptoms, Female Sexual Function Index (FSF-I), Vaginal Health Index (VHI), and Nugent Score (NS) were analyzed before and 120 days after the beginning of the treatments. Pain scores were verified after each CO2L and RF session. Results: Thirty-four participants completed the study: 11 in the VE group, 11 in the CO2L group, and 12 in the RF group. No unexpected or serious adverse events were observed. We also verified that GSM symptoms, sexual function, and VHI significantly improved (p < 0.05) with no difference among the groups. NS did not show statistically significant difference before and after the treatments. Pain during RF application was associated with higher scores. Conclusions: The study is feasible and does not seem to have safety implications. Preliminary results suggest that CO2L and RF are good alternatives to VE for ameliorating clinical symptoms, FSF-I, and VHI in patients with GSM. Clinical Trial Registration number: NCT04045379.

Prevalencia de vaginosis bacteriana y factores asociados en veinte ciudades del Perú / Prevalence of bacterial vaginosis and associated factors in twenty peruvian cities

RESUMEN Objetivos. Determinar la prevalencia de vaginosis bacteriana (VB) y factores asociados en mujeres peruanas de 18 a 29 años de edad en 20 ciudades a partir de datos del proyecto PREVEN. Materiales y métodos. Estudio de tipo transversal, la definición de VB se realizó previa selección de una muestra de secreción vaginal en una lámina portaobjetos. Las láminas fueron teñidas usando la tinción Gram para ser observadas al microscopio usando el puntaje de Nugent, el diagnóstico de VB se aplicó a los puntajes 7-10. Se estimaron razones de prevalencias (RP) y sus intervalos de confianza al 95% (IC 95%) mediante el uso de modelos lineales generalizados. Resultados. Un total de 6322 mujeres contestaron la encuesta epidemiológica y proporcionaron muestras vaginales. La prevalencia de VB fue de 23,7% (IC95%: 22,6-24,7) y se asoció con tener un mayor número de parejas sexuales en los últimos 12 meses (RP: 1,22, IC 95%: 1,03-1,44, p=0,020; para dos parejas y RP: 1,46, IC 95%: 1,23-1,74, p<0,001 para tres o más parejas), no usar condón en la última relación sexual (RP: 1,16, IC 95%: 1,01-1,34, p=0,034), ser residente de la sierra (RP: 1,18, IC 95%: 1,05-1,31, p=0,004) y tener flujo vaginal anormal o con mal olor (RP: 1,20, IC 95%: 1,09-1,33, p<0,001). Conclusiones. La alta prevalencia de VB encontrada remarca la necesidad de fortalecer los servicios de salud para la detección y tratamiento de esta condición.

ABSTRACT Objetives. To determine the prevalence of bacterial vaginosis (BV) and associated factors among 18-29-year-old women in 20 Peruvian cities using PREVEN project data. Materials and Methods. In this cross-sectional study, BV was defined using previously provided vaginal discharge samples on slides, which were Gram stained and observed under a microscope to determine the Nugent scores. A BV diagnosis was applied to samples with scores of 7-10. Prevalence ratios (PR) and 95% confidence intervals (95% CI) were estimated using generalized linear models. Results. A total of 6,322 women participated in the epidemiological survey and provided vaginal swabs. The prevalence of BV was 23.7% (95% CI: 22.6-24.7) and was associated with a greater number of sexual partners in the last 12 months (PR: 1.22, 95% CI: 1.03-1.44, p=0.020 for two partners; PR: 1.46, 95% CI: 1.23-1.74, p<0.001 for three or more partners), not using a condom during last intercourse (PR: 1.16, 95% CI: 1.01-1.34, p=0.034), being a sierra resident (PR: 1.18, 95% CI: 1.05-1.31, p=0.004), and having abnormal vaginal discharge or a bad smell (PR: 1.20, 95% CI: 1.09-1.33, p<0.001). Conclusions. The high prevalence of BV highlights the need to strengthen health services aimed at the detection and treatment of this condition.

Proposal of a new cutoff for Nugent criteria in the diagnosis of bacterial vaginosis.

OBJECTIVES: Treatment for lower genital tract infections is the major demand for gynecological services in public and private health centers in Brazil. The aims of this study were to evaluate the diagnostic resources proposed by Amsel, comparing them with the microflora evaluation by the Nugent score and thus propose a new cutoff point in this rating score, showing the complementarity of both diagnostic criteria. METHODS: A total of 136 female patients aged between 18 and 69years were evaluated and had their vaginal discharge samples collected. RESULTS: Diagnosis based on the isolated analysis of the Amsel's criteria may lead clinicians to apply inadequate treatment techniques. When patients were evaluated according to the Amsel criteria, it was seen that the presence of clue cells had a higher Kappa index in the vaginosis diagnosis; when patients were distributed according to the Nugent criteria in relation to each Amsel criterion, it was observed that clue cells differentiate positive patients more efficiently than the Nugent criteria. In the proposed cutoff point, the identification of clue cells complied with pH alterations. It also complied with the positive Nugent score (≥7). However, when clue cells were analyzed by both Amsel and Nugent methods, the diagnostic conclusion was reached once this was the parameter with a higher Kappa value. CONCLUSION: The Amsel method could be used as a screening tool whereas the Nugent score could serve as a confirmatory resource of diagnosis, considering a new assessment cutoff point (negative 0-6 and positive ≥7).

Validez y reproducibilidad del sistema de puntuación de Nugent para el diagnóstico de vaginosis bacteriana en mujeres embarazadas / Accuracy and reliability of the Nugent Score System for diagnosis of bacterial vaginosis in pregnant women

Antecedentes: La vaginosis bacteriana se encuentra entre 15 a 20 por ciento de las mujeres embarazadas y el método rutinario para diagnosticarla es el estudio del flujo vaginal aplicando los criterios de Amsel. Sin embargo, existen otros métodos diagnósticos como el sistema de Nugent, que ha mostrado adecuada validez a menor costo. Objetivo: Evaluar la validez y reproducibilidad del sistema de Nugent para el diagnóstico de vaginosis bacteriana en embarazadas. Método: Estudio de evaluación de pruebas diagnósticas. Se estudiaron 100 mujeres con embarazo de bajo riesgo. A cada paciente se le tomaron dos muestras de secreción de flujo vaginal y tres evaluadores examinaron cada muestra. Se evaluó la validez de los criterios de Nugent comparándolos con los de Amsel (prueba de oro) y se obtuvo el mejor punto de corte usando la curva del receptor-operador (ROC), para calcular la sensibilidad, especificidad y valores predictivos. La reproducibilidad se midió con el coeficiente Kappa. Resultados: El promedio de edad fue 25,6 años y edad gestacional 23 semanas. Un 19 por ciento había tenido infección vaginal previamente. La prevalencia actual de vaginosis bacteriana fue 16 por ciento (IC95 por ciento: 9,43 por ciento; 24,67 por ciento). El área bajo la curva ROC fue 0,98 (IC95 por ciento: 0,95; 1,00). La sensibilidad fue 1,00 (IC95 por ciento: 0,77; 1,00), especificidad 0,96 (IC95 por ciento: 0,90; 0,99), valor predictivo positivo 0,82 (IC95 por ciento: 0,57; 0,96) y valor predictivo negativo 1,00 (IC95 por ciento: 0,95; 1,00). Conclusión: El sistema de Nugent para el diagnóstico de vaginosis bacteriana en embarazadas es una prueba válida y reproducible para implementar rutinariamente durante el control prenatal.

Background: The bacterial vaginosis is found in 15 percent to 20 percent of the pregnant women and the study of the vaginal discharge using the Amsel criteria is the usual method to diagnose it. However, there are other diagnostic methods like the Nugent Score System which has shown to be accurate and less expensive. Objective: To evaluate the accuracy and reliability of the Nugent Score System for diagnosing bacterial vaginosis in pregnant women. Methods: This is a study for evaluating medical tests. We studied 100 women who had a low risk pregnancy. Two samples of the vaginal discharge were taken in each woman and three masked evaluators examined each sample. The accuracy of the Nugent Score System was evaluated compare it with the Amsel criteria as a gold standard. To calculate the sensibility, specificity, positive predictive value, and negative predictive value of the Nugent Score System, we got the best cut point from the Nugent Score System using the receiver operator curve (ROC). The reliability was measured using the Kappa coefficient. Results: The average age was 25.6 years and the average gestational age was 23 weeks. A 19 percent of the women had had a vaginal infection previously. The current prevalence of bacterial vaginosis was 16 percent (95 percent CI: 9.43 percent; 24.67 percent). The ROC analysis showed an area under the curve of 0.98 (95 percent CI: 0.95; 1.00). The sensitivity was 1.00 (95 percent CI: 0.77; 1.00), the specificity 0.96 (95 percent CI: 0.90; 0.99), the positive predictive value 0.82 (95 percent CI: 0.57; 0.96), and the negative predictive value 1.00 (95 percent CI 0.95; 1.00). Conclusion: The Nugent Score System for diagnosing bacterial vaginosis in pregnant women is a valid and reproducible test for being implemented routinely during the prenatal care.

Balance del contenido vaginal en el diagnóstico diferencial de vaginosis-vaginitis: Reacción inflamatoria vaginal en embarazadas sintomáticas / Balance of vaginal content in vaginosis-vaginitis differential diagnosis: Vaginal inflammatory reaction in symptomatic pregnant women

El objetivo del trabajo fue validar el alto valor predictivo de BACOVA (Balance del contenido vaginal, disponible en www.fba.org.ar/proeco) en el diagnóstico microscópico diferencial de vaginosis bacteriana (VB) y vaginitis microbiana inespecífica (VMI). Fueron estudiadas 299 embarazadas sintomáticas. Se determinó por microscopía el Valor Numérico (Nugent) (VN), células guía (CG), morfotipos extraños (Mex), leucocitos por campo (Lpc), tricomonas (TV) y levaduras (LE) con lectura a 400X. Los resultados globales fueron: VN de 7 a 10, 16,4% del total de casos. BACOVA permitió diferenciar 11,7% de los casos con VN de 7 a 10, con reacción inflamatoria vaginal (RIV) menor de 10 Lpc, como casos típicos de BV. Con igual VN se detectó 4,7% de casos con RIV con más de 10 Lpc, compatibles con VMI. En sólo 7,3% de los casos de LE detectadas por microscopía (20,4% en total), se confirmó una RIV significativa. Hubo 2,7% del total de casos con RIV significativa, pH<4,5 y resultado negativo para el resto de los criterios estudiados. La determinación de la RIV, fue imprescindible, junto al VN, en el diagnóstico diferencial de VB y VMI. La RIV también es necesaria para establecer la significación clínica de la presencia de levaduras. BACOVA detecta casos con RIV significativa (2,7%), como único marcador, con pH inferior a 4,5, compatibles con infección del tracto genital superior.

This study was undertaken to demonstrate the high diagnostic predictive value of BACOVA (Balance of Vaginal Content, www.fba.org.ar/proeco) for bacterial vaginosis and microbial non specific vaginitis, in pregnant women primary health care. BACOVA including Nugent score (Gram 1000X) and leucocyte count (Wet mount and Giemsa, using 400X) was evaluated in 299 symptomatic pregnant women. Nugent score 7 to 10 was detected in 16.4%. Crossing Nugent value 7 to 10 with leucocytes counts shows that only 11.7% were below 10 leucocytes per field and 4.7% had a significant vaginal inflammatory response. Yeasts were detected in 20.4% but only in 7.2% of cases they show a significant association with vaginal inflammatory response. In 2.7% of the cases there was a significant vaginal inflammatory response, with pH below 4.5, VN from 0 to 3 and negative for TV, fishy odor, and exogenous microbial morphotypes. Simultaneous study of vaginal inflammatory response and Nugent score is mandatory in order to detect true cases of bacterial vaginosis (11.7%) from those of potential microbial non specific vaginitis (4.7%) (Donders' "aerobic vaginitis") Besides, vaginal inflammatory response became a strong criterion to define yeast vulvovaginitis (7.2%). Cases (2.7%) with score 0 to 3, negative for other criteria, with a high vaginal inflammatory response, are predictors of upper genital infections.

Prueba de supresión con Dexametasona 1mg en una población de individuos con normopeso, sobrepeso y obesidad: Estudio multicéntrico / The Overnight 1mg Dexamethasone Test in Healthy Subjects with Normal Weight, Overweight and Obesity: a Multicentric Study

La prueba de supresión con dexametasona-1mg oral nocturna evalúa la conservación del mecanismo de retroalimentación negativa normal ejercido por los glucocorticoides sobre el eje hipotálamo-hipófiso-adrenal (HH-A), siendo ampliamente utilizada en el algoritmo diagnóstico de sospecha de síndrome de Cushing (SC). Pero la concentración de cortisol sérico matinal postinhibición que define la supresiblidad normal ha sido motivo de controversia, con valores variables desde el original =5 ug/dl (=138 nmol/L) hasta una cifra =1,8 ug/dl (=50 nmol/L) últimamente. Asimismo, es controvertida la respuesta en la obesidad, donde está descripta una alteración del eje H-H-A. Por lo tanto, el Departamento de Suprarrenal de SAEM llevó a cabo este estudio multicéntrico con el objetivo de definir la concentración de cortisol sérico obtenida luego de la administración de dexametasona 1mg nocturna, en una población de sujetos sanos de nuestro país con peso normal; concomitantemente, se evaluaron individuos con sobrepeso y con obesidad simple para comparar su respuesta respecto de los sujetos normopeso. Se estudiaron 80 individuos sanos, 60 mujeres y 20 hombres, de 15 a 66 años de edad, que fueron divididos en tres grupos según el índice de masa corporal (IMC): Normopeso, IMC=19-24,9 kg/m2, n=39; Sobrepeso, IMC=25-29,9 Kg/m2, n=21; y Obesos, IMC = 30 kg/m2, n=20. Se administró dexametasona 1 mg vía oral a las 23 hs. y se determinó la cortisolemia a las 8hs. de la mañana siguiente. Las determinaciones se centralizaron en un solo laboratorio y fueron realizadas por el equipo de radioinmunoensayo (RIA) de DSL, sensiblidad analítica de 0,5 ug/dl. Paralelamente en 10 sujetos, se determinó la cortisolemia postinhibición en las mismas muestras con otro equipo analítico, RIA-DPC. Resultados: Los resultados de la cortisolemia postsupresión en los tres grupos estudiados se expresan como X± DS (rango): en el grupo normopeso fue de 2,10± 0,77 ug/dl (0,78-3,40); en el sobrepeso, 1,94± 0,66 ug/dl (0,962,90); y en los obesos, 1,86 ± 0,63 ug/dl (0,85-3,30), no observándose diferencias significativas entre los tres grupos estudiados (test de Kruskall Wallis Dunn, p=0,319). En los 10 sujetos cuyas muestras fueron simultáneamente analizadas por RIA-DSL y por RIA-DPC, se observaron marcadas diferencias en 8/10, siendo la mediana de cortisol sérico obtenida por RIA-DPC de 0,5µg/dl, significativamente menor a la obtenida por RIA-DSL, de 2,2 µg/dl (test de Wilcoxon, p=0,002). Conclusiones: Debemos destacar que este es el primer estudio multicéntrico que evalúa la respuesta a la inhbibición con dexametasona 1 mg en nuestro medio. En esta primera etapa, demostramos que una concentración de cortisol sérico post 1 mg de dexametasona oral nocturna = 3,4 µg/dl (= 93,8nmol/l), determinada por RIA-DSL, caracteriza la respuesta normal de nuestra población de sujetos sanos. Ello es independiente del peso corporal, ya que los sujetos con normopeso, sobrepeso y obesidad suprimieron a valores similares. No se observó falta de supresión en ningún caso estudiado. Por otra parte, dadas las marcadas diferencias de valores halladas en las mismas muestras cuando son analizadas por equipos diferentes de RIA, es fundamental referir los resultados al método y equipo utilizados y estandarizar las pruebas clínicas con la metodología específica empleada en cada laboratorio.

The overnight oral dexamethasone test assesses the normal negative feedback of cortisol on the hypothalamic-pituitary-adrenal axis (H-P-A) 1. It is widely used in the screening of Cushing’s Syndrome (CS) 3,4,5. But the cut-off values for the normal response remains controversial: originally it was considered as 5 ug/dl and in the last years it was reported as 1.8 ug/dl 4. Likewise, there is no agreement about the suppression values in obesity, where a hyperactivity of the H-P-A axis has been reported. Therefore, the Adrenal Department of the Argentine Society of Endocrinology and Metabolism (SAEM) studied 80 healthy subjects recruited from ten hospitals of Buenos Aires in order to assess the normal response in our population. Sixteen women and twenty men, aged 15-66 years old (X = 39.2ys), were classified into three groups, according to their body mass index (BMI): normal weight, BMI- 19-24.9 kg/m2 (n= 39); overweight, BMI- 25-29.9 kg/m2 (n=21) and obese subjects, BMI> 30 kg/m2 (n=20). They had to be euthyroid and free of corticosteroid treatment, contraceptive pills, hormone replacement therapy, rifampicin and psychotropic drugs at the time of the study. Subjects referring drug abuse, alcoholism, depression, cardiovascular, and renal disorders and,obviously, adrenal diseases were excluded from the study. Dexamethasone 1mg per os was administered at 11p.m. and blood was withdrawn at 8 a.m. on the next morning to determine plasma cortisol concentration. Determinations were centralized in one laboratory and the RIA-DSL (Diagnostic System Laboratories-radioimmunoassay) was used. Additionally, in ten subjects plasma cortisol was also determined in the same blood samples by another radioimmunoassay kit, RIA-DPC (Diagnostic Products Corporation). The Kruskall-Dunn test was used to compare the plasma cortisol levels post-1mg dexamethasone among the three groups studied. In the 10 patients whose determinations were made in the same blood samples by two different RIA-kits (DSL and DPC),the Wilcoxon test was used to compare the results of plasma cortisol between RIA-DSL and RIA-DPC. Results: The results are expressed as X ± SD ug/dl (range). Plasma cortisol levels after 1mg-dexamethasone were: 2.10 ± 0.77 ug/dl ( 0.78- 3.40 ug/dl) in the normal weight goup; 1.94 ± 0.66 ug/dl (0.96-2.90) in the overweight group and 1.86 ± 0.63 ug/dl (0.85-3.30) in the obese subjects (Table I); no significant differences were observed among the three groups (p=0.319). According to these results, the cut-off value for plasma cortisol post-dexamethasone in the normal weight subjects was considered as = 3.4 ug/dl (93.8 nmol/L) using RIA-DSL. Similar suppression values were obtained in the overweight and obese subjects - 2.9 and 3.3 ug/dl, respectively. No false positive results were observed, either individually or in each group (Fig 1). In the 10 subjects whose blood cortisol was simultaneously determined in the same samples by RIA-DSL and RIA-DPC, the median for plasma cortisol was 2.2 ug/dl for the first and 0.5 ug/dl for the latter, respectively, with a significant difference between both RIA kits (p=0.002). (Table II). Conclusions: In this first stage, the present multicentric study shows that a plasma cortisol level post - 1mg dexamethasone suppression of = 3.4 ug/dl ( 93.8 nmol/L) defines our normal population response, with no significant differences among normal weight,overweight and obese subjects. Furthermore, we wish to point out that the cortisol values must be referred to the method and commercial kits used in each laboratory, since significant differences can be observed in the same blood samples when different kits are used, such as we and other authors have observed. We wish to remark the importance of our study, which is the first in its characteristics in Argentina. Furthermore, in a second stage, we plan to enlarge the sample number and to determine blood cortisol in the same samples by using different methods, in order to obtain a standardized cortisol suppression level. We also plan to study patients with confirmed CS and pseudocushing states in order to assess the sensitivity and specificity of the 1mg-dexamethasone suppression test in our population.