Menopausia quirúrgica en pacientes con mutación BRCA, el papel de la terapia hormonal / Surgical Menopause in Patients with BRCA Mutation, the Role of Hormone Therapy

Introducción: las mujeres con mutación BRCA1/2 (mBRCA) tienen un riesgo aumentado de desarrollar cáncer de mama (CM) y ovario (CO). La salpingo-oforectomía bilateral (SOB) se asocia con la reducción del riesgo del 80% para CO y un 50% para CM. Se recomienda realizarla entre los 35 y 40 años. Como consecuencia se produce una menopausia prematura, con un impacto negativo sobre la calidad de vida por la presencia de síntomas climatéricos, aumento del riesgo de enfermedad cardiovascular, osteoporosis y riesgo de alteración cognitiva. La terapia hormonal (THM) es el tratamiento más eficaz para la prevención de estos síntomas. Estado del arte: distintos estudios han demostrado un mayor riesgo de CM en mujeres posmenopáusicas que reciben THM en particular con terapia combinada, estrógeno + progesterona (E+P). Según el metanálisis de Marchetti y cols., en las mujeres portadoras de mBRCA que recibieron THM, no hubo diferencias en el riesgo de CM comparando E solo con E+P. En el estudio de Kotsopoulos, incluso se encontró un posible efecto protector en aquellas que usaron E solo. Otro estudio en portadoras sanas demostró que, en las mujeres menores de 45 años al momento de la SOB, la THM no afectó las tasas de CM. Sin embargo, en las mujeres mayores de 45 años, las tasas de CM fueron más altas. Como el esquema de E+P se asocia con un mayor riesgo relativo (RR) de CM, las dosis de progestágenos utilizados se deberían limitar, eligiendo derivados naturales de progesterona, de uso intermitente para disminuir la exposición sistémica. Según diferentes guías internacionales, a las portadoras de mBRCA sanas que se someten a una SOB se les debe ofrecer THM hasta la edad promedio de la menopausia. Conclusión: la menopausia prematura disminuye la expectativa de vida; es por ello que una de las herramientas para mejorar y prevenir el deterioro de la calidad de vida es la THM. El uso de THM a corto plazo parece seguro para las mujeres portadoras de mBRCA que se someten a una SOB antes de los 45 años, al no contrarrestar la reducción del riesgo de CM obtenida gracias a la cirugía. (AU)

Introduction: women with BRCA1/2 (mBRCA) mutation have an increased risk of developing breast (BC) and ovarian (OC) cancer. Bilateral salpingo-oophorectomy (BSO) is associated with an 80% risk reduction for OC and 50% for BC. The recommended age for this procedure is 35 to 40 years. The consequence is premature menopause, which hurts the quality of life due to the presence of climacteric symptoms, increased risk of cardiovascular disease, osteoporosis, and a higher risk of cognitive impairment. Hormone therapy (MHT) is the most effective treatment for preventing these symptoms. State of the art: different studies have shown an increased risk of BC in postmenopausal women receiving MHT, particularly with combined therapy, estrogen + progesterone (E+P). According to the meta-analysis by Marchetti et al., in women carrying mBRCA who received MHT, there was no difference in the risk of BC compared to E alone with E+P. In the Kostopoulos study, there was also a possible protective effect in those who used E alone. Another study in healthy carriers showed that in women younger than 45 years at the time of BSO, MHT did not affect BC rates. However, in women older than 45 years, BC rates were higher. As the E+P scheme is associated with a higher RR of BC, the doses of progestogens should be limited, choosing natural progesterone byproducts of intermittent use to decrease systemic exposure. According to various international guidelines, healthy mBRCA carriers undergoing BSO should be offered MHT until the average age of menopause. Conclusion: premature menopause decreases life expectancy, which is why one of the tools to improve and prevent deterioration of quality of life is MHT. Short-term use of MHT appears safe for women with mBRCA who undergo BSO before age 45 as it does not counteract the reduction in the risk of MC obtained by surgery. (AU)

Perda gestacional de repetição e o papel dos progestagênios: evidências atuais / Recurrent pregnancy loss and the role of progestagens: current evidence

Objetivo: Discutir o uso dos progestagênios em mulheres com perda gestacional de repetição (PGR) sem causa aparente, abordando tipos de progestagênios e resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publicados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando-se os seguintes descritores: "progesterone", "dydrogesterone", "recurrent pregnancy loss" e "recurrent abortion". Resultados: Duas grandes metanálises encontraram uma redução da taxa de abortamento e aumento da taxa de nascidos vivos com o uso do progestágeno sintético em pacientes com PGR inexplicada, porém essa conclusão foi contestada em uma metanálise mais recente. Entretanto, a progesterona vaginal micronizada poderia aumentar a taxa de nascidos vivos em mulheres com ameaça de aborto e com história de um ou mais abortos anteriores (risco relativo [RR]: 1,08, intervalo de confiança [IC] de 95%: 1,02-1,15). O benefício foi maior no subgrupo de mulheres com três ou mais perdas anteriores. Conclusão: Ainda restam dúvidas sobre o uso de "progesterona" nas pacientes com PGR inexplicada. Sua administração deve ser discutida individualmente com cada mulher, levando-se em conta especialmente a idade materna, o número de abortos prévios e a história de sangramento na gestação em curso, evitando-se tratamentos que trazem custos e não são isentos de efeitos colaterais.(AU)

Objective: To discuss the use of progestins in women with recurrent pregnancy loss (RPL) with no apparent cause, addressing types of progestins, and results of clinical trials, systematic reviews, and meta-analyses. Methods: This is a non-systematic review of articles published in the PubMed, Cochrane, SciELO electronic databases in the last five years, using the following descriptors: "progesterone", "dydrogesterone", "recurrent pregnancy loss", and "recurrent abortion". Results: Two large meta-analyses found a reduction in the rate of miscarriage, and an increase in the rate of live births with the use of synthetic progestin in patients with unexplained RPL, but this conclusion was challenged in a more recent meta-analysis. However, micronized vaginal progesterone could increase the rate of live births in women with a threatened miscarriage and a history of one or more previous miscarriages (RR: 1.08, 95% CI: 1.02-1.15). The benefit was greatest in the subgroup of women with three or more previous losses. Conclusion: There are still doubts about the use of "progesterone" in patients with unexplained RPL. Its administration should be discussed individually with each woman, taking into account especially the maternal age, number of previous abor tions, and history of bleeding during pregnancy, avoiding treatments that bring costs and are not free from side effects.(AU)

Parto pré-termo espontâneo sem rotura de membranas: intervenções para evitar o parto pré-termo / Spontaneous preterm birth without rupture of membranes: interventions to prevent preterm birth

A prematuridade é uma síndrome com múltiplos fatores de risco e cuja causa permanece desconhecida, mas, independentemente da etiologia, a parturição converge para uma via final comum de esvaecimento, dilatação e encurtamento do colo uterino. Do ponto de vista hormonal, o responsável por esse processo é a progesterona. A prevenção de quadros de prematuridade pode basear-se em tratamentos medicamentosos como a administração diária de comprimidos de progesterona; intervenções cirúrgicas para a contenção da cérvice uterina com fios inabsorvíveis mantidos até o termo, a cerclagem cervical; e o pessário cervical, dispositivo de silicone que envolve e inclina o colo uterino, evitando sua abertura. Para propor qualquer intervenção profilática ou terapêutica, a avaliação ultrassonográfica via transvaginal no segundo trimestre gestacional desempenha papel crucial. Apresentamos neste terceiro e último artigo da série sobre parto pré-termo espontâneo as intervenções terapêuticas e o rastreamento do colo uterino.(AU)

Preterm birth is a syndrome with multiple risk factors, with unknown etiology. Parturition converges to a final path with uterine cervix effacement, dilation and shortening and progesterone is the hormone responsible for this process. Preterm birth prevention relies on daily administration of progesterone pills; cerclage as a surgical intervention; or cervical pessary, a vaginal silicone device that enfolds and deflects the cervix, avoiding its opening. To propose any of these interventions it is crucial to evaluate the cervix during the second trimester by transvaginal ultrasound. Here, in the third and last article regarding preterm birth without membrane disruption, we present therapeutic interventions and ultrasound screening.(AU)

Progesterona para el tratamiento del trauma craneoencefálico grave: una revisión sistemática y metaanálisis / Progesterone to treat severe traumatic brain injury: a systematic review and meta-analysis / Progesterona para o tratamento do traumatismo crânio-encefálico grave: revisão sistemática e meta-análise

Resumen: Objetivo: revisar sistemáticamente la evidencia sobre la administración de progesterona tras un trauma craneoencefálico grave en adultos y su relación con mortalidad y pronóstico neurológico. Criterios de inclusión: ensayos clínicos aleatorizados que incluyan a pacientes adultos mayores de 18 años, haber sufrido un traumatismo craneal grave (Glasgow <8), donde se compare la administración de progesterona vs grupo control (placebo o no administración). Método: se realizó la búsqueda en las siguientes bases de datos: MEDLINE, the Central Register of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injuries group y lista de referencia de los artículos. Resultados: no hubo reducción de la mortalidad comparado con el grupo control (RR 0,93, IC95% 0,79-1,10 p= 0,41), no hubo diferencias entre progesterona y el grupo control en desenlaces neurológicos positivos ni negativos (RR 1,07, IC95% 0,97-1,17 p= 0,20; RR 0,94, IC 95% 0,81-1,08 p= 0,27), respectivamente. Conclusiones: no se encontró evidencia respecto a que la administración de progesterona posterior a un traumatismo craneoencefálico reduzca la mortalidad o mejore desenlaces neurológicos, aunque se necesitan más estudios de buena calidad para extraer conclusiones definitivas.

Summary: Objective: to systematically review evidence on the administration of progesterone after a traumatic brain injury in adults and its relationship with mortality and neurological head prognosis. Inclusion criteria: randomized clinical trials that include: patients older than 12 years old, having had an injury (Glasgow <8), comparing the administration of Progesterone versus the control group (placebo or no administration). Methods: we searched the following databases: MEDLINE, the Central Register of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injury Group and reference list of articles. Results: there was no reduction in mortality in patients in the control group (RR 0.93, 95% CI 0.79-1.10 p = 0.41), there were no differences between progesterone and the control group in favorable or adverse neurological outcomes (RR 1.07, 95% CI: 0.97-1.17 p = 0.20, RR 0.94, 95% CI: 0.81 -1,08 p= 0.27), respectively. Conclusions: there is no evidence that the administration of progesterone after a traumatic brain injury reduces or improves neurological results, although further good quality studies are required to obtain conclusive results.

Resumo: Objetivo: realizar uma revisão sistemática da evidência sobre a administração de progesterona depois de traumatismo crânio-encefálico grave em adultos e sua relação com a mortalidade e o prognóstico neurológico. Critérios de inclusão: ensaios clínicos aleatorizados que incluam: pacientes adultos maiores de 18 anos, haver sofrido um traumatismo craniano grave (Glasgow <8) donde se compare a administração de progesterona versus grupo controle (placebo ou não administração). Métodos: foi feita uma pesquisa bibliográfica nas seguintes bases de dados: MEDLINE, Central Register of Controlled Trials (CENTRAL), PubMed, HINARI, EMBASE, Cochrane Injuries Group e nas referências bibliográficas dos artigos. Resultados: não foi observada uma redução da mortalidade comparada com o grupo controle (RR 0,93, IC del 95%: 0,79-1,10 p= 0,41), não foram observadas diferenças entre o grupo que recebeu progesterona e o grupo controle nos resultados neurológicos positivos ou negativos (RR 1,07, IC del 95%: 0,97-1,17 p= 0,20; RR 0,94, IC del 95%: 0,81-1,08 p= 0,27), respectivamente. Conclusões: não se encontrou evidência de que a administração de progesterona depois de um traumatismo crânio-encefálico reduza a mortalidade ou melhore os resultados neurológicos embora novos estudos de boa qualidade sejam necessários para chegar a conclusões definitivas.

Reducción embrionaria en embarazo gemelar / Embryo reduction in twin pregnancy

La reducción embrionaria es la interrupción selectiva del desarrollo de uno o varios fetos en el primer trimestre del embarazo. El embarazo gemelar se presenta aproximadamente en uno de cada 100 nacimientos y se considera como una entidad con alto riesgo materno y fetal. Los embarazos múltiples tienen un impacto mayor en los sistemas de salud, debido a la mayor frecuencia de complicaciones. La rotura prematura de membranas causa aproximadamente el 40 por ciento de los partos pretérmino y, como consecuencia, aportan un 10 por ciento de la mortalidad perinatal según la Sociedad Española de Ginecología y Obstetricia. En este caso clínico se observó que una actitud expectante con los pertinentes controles ecográficos (índice del líquido amniótico), analíticos (recuento leucocitario y reacción en cadena de la polimerasa) y clínicos (frecuencia cardiaca y temperatura) pueden llevar a una buena evolución posnatal que justificó al menos en esta ocasión, una actitud conservadora(AU)

Embryonic reduction is the selective interruption of the development of one or several fetuses in the first trimester of pregnancy. Twin pregnancy occurs in approximately one in every 100 births. It is considered an entity with high maternal and fetal risk. Multiple pregnancies have greater impact on health systems due to the higher frequency of complications. Premature rupture of membranes causes approximately 40 percent of preterm births and, consequently, it contributes 10 percent of perinatal mortality according to the Spanish Society of Gynecology and Obstetrics. In this clinical case it was observed that an expectant attitude with the relevant ultrasound (index of amniotic fluid), analytical (leukocyte count and polymerase chain reaction) and clinical (heart rate and temperature) controls can lead to good postnatal evolution, justified at least on this occasion, a conservative attitude(AU)

Use of human intravaginal tampon embedded with natural progesterone induces synchronous estrus in Santa Inês ewes / Uso de tampão intravaginal humano embebido com progesterona humana para indução e sincronização de estro em ovelhas Santa Inês

Este estudo avaliou a eficiência de três protocolos de indução de estro síncronizado em ovelhas da raça Santa Inês. Vinte e quatro ovelhas adultas foram equitativamente distribuídas em três grupos, de acordo com ordem de parto, peso corporal (kg) e escore da condição corporal. As ovelhas receberam implante vaginal de progesterona natural por seis dias mais 37,5µg de d-cloprostenol laterovulvar e 300UI de eCG i.m., 24 horas antes da remoção do dispositivo. Ovelhas controle receberam CIDR330mg de progesterona, e as demais receberam dispositivo absorvente intravaginal humano, tamanho mini, embebido com 200 (OB200) ou 400mg (OB400) de progesterona. Coletas de sangue foram feitas nos momentos D0 (antes da inserção dos dispositivos), D0+6h e diariamente, até um dia após retirada do dispositivo (D7). A progesterona (ng/mL) foi semelhante (P>0,05) em todos os tratamentos ao longo do período experimental, exceto no dia da remoção do dispositivo, quando as ovelhas controle (2,5±0,3) tiveram progesterona superior (P<0,05) às ovelhas OB200 (0,6±0,1) e OB400 (1,2±0,4). O percentual de animais em estro (100,0, 62,5 e 100,0%) foi semelhante (P>0,05) e o intervalo para o estro (46,3±3,9a, 26,4±4,5b e 31,2±5,8a,b) foi diferente (P<0,05) entre os animais dos grupos controle, OB200 e OB400, respectivamente. A taxa de concepção das ovelhas foi de 50,0% (4/8) para cada grupo (P>0,05). Dispositivos humanos e fonte de progesterona podem ser usados para induzir o estro sincronizado em ovelhas Santa Inês.(AU)

Prevención de parto pretérmino / Prevention of preterm delivery

Resumen Tradicionalmente, el parto pretérmino se considera aquel que ocurre después de las 20 semanas y antes de completar las 37 semanas de gestación; sin embargo, esta definición está siendo reevaluada. Actualmente, el parto pretérmino constituye la primera causa de mortalidad infantil en países desarrollados y aumenta significativamente su morbilidad. Debido a ello, es de suma importancia determinar sus factores predisponentes, con el objetivo de detectar a las madres en riesgo y consecuentemente, evitar este desenlace. Existen muchos factores de riesgo conocidos para parto pretérmino y algunos de estos son: parto pretérmino previo, longitud cervical corta, características demográficas, antecedente de cirugía cervical, sangrado vaginal durante primer trimestre, obesidad, infecciones, tabaquismo, bajo peso preconcepcional, abuso de sustancias y periodo intergenésico corto. Algunas medidas de prevención de parto pretérmino efectivas pueden ser: mejor control prenatal, tratamiento antibiótico de ciertas infecciones genitales y en las pacientes con ruptura prematura de membranas, tratamiento de bacteriuria asintomática, la suplementación con progesterona en pacientes con parto pretérmino previo o sin antecedente pero con longitud cervical muy corta antes de la semana 24 de gestación, el cerclaje en mujeres con antecedente de parto pretérmino previo menor a 34 semanas y longitud cervical menor a 25 mm antes de las 24 semanas de gestación, el uso de pesario en pacientes asintomáticas sin antecedentes de parto pretérmino con diagnóstico incidental de cérvix corto a las 18-22 semanas, la suplementación con zinc en mujeres de bajos ingresos y mala nutrición, y finalmente, el aumento de intervalo intergenésico a más de 12 meses.

Abstract Preterm delivery is traditionally known as birth that occurs after 20 weeks and before completing 37 weeks of gestation; however, this definition is being reevaluated. In developed countries, preterm delivery is the primary cause of children mortality and it significantly increases their morbidity. It is fundamental to determine its predisposing factors, in order to detect mothers at risk and consequently, avoid this adverse outcome. Some of the known risk factors for preterm delivery are: short cervical length, demographic characteristics, history of cervical surgery, previous preterm delivery, vaginal bleeding during the first trimester, obesity, infections, smoking, low preconceptional weight, substance abuse, and short interpregnancy interval. On the other hand, some effective prevention measures may include: better prenatal control, antibiotic treatment for certain genital infections, in patients with premature rupture of membranes, and asymptomatic bacteriuria; supplementation of progesterone in patients with or without history of previous preterm delivery, but with very short cervical length before the 24th week of gestation, use of cervical cerclaje in women with history of preterm delivery before 34 weeks and cervical length less than 25 mm at 24 weeks of gestation, use of pessary in asymptomatic women without history of preterm delivery with incidental diagnosis of short cervix at 18-22 weeks of gestation, zinc supplementation in women with low income and malnutrition, and finally, interpregnancy interval longer than 12 months.

Prevención de parto prematuro en gemelar: ¿qué hay de nuevo? / Premature birth prevention in twin: what's new?

La incidencia del embarazo gemelar ha aumentado en todo el mundo de manera significativa en los últimos años. Uno de los principales problemas asociados es la prematurez, la cual afecta prácticamente al 50% de los embarazos gemelares, y es la causa única más importante de morbilidad y mortalidad perinatal. En este contexto cobran cada vez mas importancia las medidas de prevención del parto prematuro. En el embarazo único, existe evidencia sólida para recomendar el uso de múltiples estrategias de prevención, con resultados alentadores. En gestaciones múltiples en cambio, la información es menor y los resultados menos prometedores. Este articulo tiene como objetivo revisar la evidencia disponible sobre diferentes técnicas de prevención del parto prematuro en embarazos gemelares.

The incidence of twin pregnancy has increased significantly worldwide in recent years. One of the main associated problems is prematurity, which affects almost 50% of twin pregnancies, and is the single most important cause of perinatal morbidity and mortality. In this context, measures of prevention of preterm delivery are becoming increasingly important. In single pregnancy, there is strong evidence to recommend the use of multiple prevention strategies, with encouraging results. In multiple gestations, the information is smaller and the results less promising. This article aims to review available evidence on different techniques for preventing preterm birth in twin pregnancies.

Vaginal progesterone on the prevention of preterm birth and neonatal complications in high risk women: a randomized placebo-controlled double-blind study

Background: Preterm birth is the major cause of neonatal mortality and morbidity

Objective: The aim of this study was to evaluate the effect of prophylactic vaginal progesterone on decreasing preterm birth rate and neonatal complications in a high-risk population

Materials and Methods: A randomized, double-blind, placebo-controlled study was performed on 100 high-risk singleton pregnancies. Vaginal suppository progesterone [400 mg] or placebo was administered daily between 16-22 wks to 36 wks of gestation. Progesterone [n=50] and placebo [n=50] groups were compared for incidence of preterm delivery and neonatal complications

Results: The preterm birth rate was 52%. Preterm birth rate before the 37 wks of gestation [68% vs. 36%: RR=1.89, 95% CI: 1.25-2.86] and also before the 34 wks of gestation [42% vs. 18%: RR=2.33, 95% CI: 1.19-4.58] in placebo group was significantly higher than progesterone group. Our study also showed that the administration of vaginal progesterone was associated with a significant reduction in the risk of birth weight

Conclusion: Prophylactic vaginal progesterone reduced the rate of preterm delivery, the risk of a birth weight

A utilização da progesterona natural micronizada em gestações gemelares na prevenção do trabalho de parto prematuro / Use of natural micronized progesterone in the prevention of preterm labor in twin pregnancies

Com o objetivo de determinar a eficácia da progesterona natural micronizada em gestações gemelares para a profilaxia do trabalho de parto prematuro, foi avaliada uma coorte histórica de 43 mulheres com gestações gemelares. As gestantes foram divididas em dois grupos: usuárias da progesterona (Grupo 1) e não usuárias da progesterona (Grupo 2). O medicamento foi administrado na dosagem de 200 mcg por via vaginal, a partir de 20 semanas de gestação. Das 43 gestações estudadas, 20 foram tratadas com a progesterona. Não houve associação entre uso da progesterona e época do parto, de forma que o uso da progesterona natural micronizada não impediu o parto prematuro (p = 0,87). Portanto, a progesterona natural micronizada não reduziu a frequência do trabalho de parto prematuro em gestações gemelares...

A historical cohort of 43 women with twin pregnancies were assessed to determine the effectiveness of natural micronized progesterone in twin pregnancies for the prophylaxis of preterm labor. The women were divided into two groups: progesterone users (Group 1) and non-users of progesterone (Group 2). The drug was administered at a dose of 200 mcg vaginally, from 20 weeks of gestation. Of the 43 pregnancies studied, 20 were treated with progesterone. There was no association between use of progesterone and delivery time, so that the use of natural micronized progesterone did not prevent preterm birth (p = 0.87). Therefore, natural micronized progesterone did not reduce the frequency of preterm birth in twin pregnancies...

Efectividad del tratamiento de la amenaza de parto pretérmimo con progesterona natural micronizada / Effectiveness of treatment of threatened labor preterm micronized natural progesterone

Objetivo: Evaluar la efectividad de la progesterona natural micronizada administrada vía oral y del fenoterol administrado vía endovenosa, en el tratamiento de las pacientes con diagnóstico de amenaza de parto pretérmino. Métodos: Estudio experimental tipo ensayo terapéutico en pacientes que acudieron al Hospital Universitario de Caracas. Resultados: 15 pacientes del grupo estudio con progesterona presentaron resultados satisfactorios (X² = 155,837, df = 18); del grupo control, 13 pacientes con resultados satisfactorios (X² = 133,093, df = 18). La efectividad absoluta en el grupo de estudio fue de 0,68 contra 0,59 del grupo control (X² = 0,393; df = 1; P < 0,531). Conclusiones: Los tratamientos con progesterona natural micronizada y fenoterol demostraron ser inhibitorios de la dinámica uterina, a partir de la segunda hora de iniciado el tratamiento, evitando su progreso hacia trabajo de parto en un 90 %. La progesterona natural micronizada es efectiva en el tratamiento de la amenaza de parto pretérmino y se debe considerar su uso como alternativa terapéutica.

Objective: To evaluate the effectiveness of micronized natural progesterone administered orally and intravenously administered fenoterol in the treatment of patients with a diagnosis of preterm labor. Method: The type of therapeutic trial in patients attended at the Hospital Universitario de Caracas. Results: 15 patients in the progesterone study showed satisfactory results (X² = 155.837 df = 18); the control group, 13 patients with satisfactory results (X² = 133.093 df = 18). The absolute effectiveness in the study group was 0.68 against 0.59 in the control group (X² = 0.393 df = 1, P < 0.531). Conclusions: Treatment with micronized natural progesterone and fenoterol proved inhibitory uterine dynamics from the second hour of starting treatment preventing its progress toward labor by 90 %. The micronized natural progesterone is effective in the treatment of preterm labor and should be considered as an alternative therapeutic use.

Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. .

The putative role of ovary removal and progesterone when considering the effect of formaldehyde exposure on lung inflammation induced by ovalbumin

OBJECTIVE: Formaldehyde exposure during the menstrual cycle is known to affect the course of allergic lung inflammation. Because our previous data demonstrated that formaldehyde combined with an ovariectomy reduced allergic lung inflammation, we investigated the putative role of ovary removal and progesterone treatment when considering the effect of formaldehyde on allergic lung inflammation. METHOD: Ovariectomized rats and their matched controls were exposed to formaldehyde (1%, 3 days, 90 min/day) or vehicle, and immediately after exposure, the rats were sensitized to ovalbumin by a subcutaneous route. After 1 week, the rats received a booster by the same route, and after an additional week, the rats were challenged with ovalbumin (1%) by an aerosol route. The leukocyte numbers, interleukin-10 (IL-10) release, myeloperoxidase activity, vascular permeability, ex vivo tracheal reactivity to methacholine and mast cell degranulation were determined 24 h later. RESULTS: Our results showed that previous exposure to formaldehyde in allergic rats decreased lung cell recruitment, tracheal reactivity, myeloperoxidase activity, vascular permeability and mast cell degranulation while increasing IL-10 levels. Ovariectomy only caused an additional reduction in tracheal reactivity without changing the other parameters studied. Progesterone treatment reversed the effects of formaldehyde exposure on ex vivo tracheal reactivity, cell influx into the lungs and mast cell degranulation. CONCLUSION: In conclusion, our study revealed that formaldehyde and ovariectomy downregulated allergic lung inflammation by IL-10 release and mast cell degranulation. Progesterone treatment increased eosinophil recruitment and mast cell degranulation, which in turn may be responsible for tracheal hyperreactivity and allergic lung inflammation. .

Predição e prevenção do parto pré-termo espontâneo / Prediction and prevention of spontaneous preterm birth

A incidência de parto pré-termo varia de 7-12% de todas as gestações e o nascimento prematuro é das principais causas de morbimortalidade neonatal, responsável por mais de três quartos das mortes neonatais, quando malformações congênitas são excluídas. Várias estratégias são adotadas com o objetivo de reduzir as taxas de partos prematuros, incluindo a identificação de fatores de risco e o uso profilático de progesterona. Destacam-se, entre as principais ações da progesterona, o efeito relaxante sobre a musculatura uterina, a capacidade de bloquear os efeitos da ocitocina, o efeito anti-inflamatório e imunossupressor. O uso de progesterona exógena reduz as taxas de prematuridade em pacientes com risco de parto prematuro, tal como história prévia de parto prematuro, e colo uterino curto demonstrado pela ultrassonografia transvaginal no segundo trimestre de gestação. Esta revisão objetiva, inicialmente, evidenciar aspectos importantes a serem abordados na assistência ambulatorial e, posteriormente descrever as principais ações preditivas e preventivas do nascimento prematuro disponíveis na assistência obstétrica.

Incidence of preterm delivery ranges from 7-12% of all gestations and premature birth is one of the main causes for newborn morbimortality. It is responsible for over three quarters of neonatal deaths, minus congenital malformations. Several strategies can be adopted to reduce premature delivery rates, including risk factor identification and prophylactic use of progesterone. Among the main actions of progesterone is its relaxingeffect upon uterine muscles, the ability to block the effects of cytokin, and its antiinflammatory and immunosuppresive effects. The use of exogenous progesterone reduces the rates of prematurity for patients under risk of premature delivery, such as those with a history of premature deliveries, and short cervix as revealed by transvaginal ultrasound in the second quarter of pregnancy. This review aims to highlight important aspects tobe considered in the outpatient clinic and describe the main predictive and preventive actions of premature birth available in obstetric care.

Clorhidrato de isoxuprina endovenoso o progesterona vaginal en la amenaza de parto pretérmino / Intravenous isoxuprin clorhidrate or vaginal progesterone in treathened preterm labor

El objetivo fue comparar la eficacia del clorhidrato de isoxuprina endovenoso o la progesterona vaginal en la amenaza de parto pretérmino en la Maternidad “Dr. Nerio Belloso”. Hospital Central “Dr. Urquinaona”, Maracaibo, Estado Zulia. Se Seleccionaron 82 embarazadas con edad gestacional entre 24 y 34 semanas y diagnóstico de amenaza de parto pretérmino para recibir progesterona vaginal (grupo A; n=41) o clorhidrato de isoxuprina endovenoso (grupo B; n=41). Se evaluaron tiempo de cese de las contracciones y los efectos adversos maternos. El promedio de edad gestacional de las pacientes al momento del inicio del tratamiento fue de 31.7 ± 2.1 semanas en el grupo A y 32.4 ± 2.4 semanas en el grupo B (P=ns). En las primeras 24 horas de tratamiento clorhidrato de isoxuprina fue más efectivo que la progesterona vaginal con una tocólisis efectiva (26,8% en el grupo A y en 61.0% en el grupo B, p<0.05). Sin embargo, después de 7 días de tratamiento, 73.2% de las pacientes del grupo A y 36.6% de las pacientes en el grupo B aún permanecían sin contracciones (P<0.05). El retraso del parto más allá de las 34 semanas se logro en 80.5% de las pacientes en el grupo A y 26.8% de las pacientes grupo B (P<0.05). La cefalea fue el efecto adverso más frecuente en el grupo de pacientes del grupo A. La progesterona vaginal es más efectiva que el clorhidrato de isoxuprina endovenoso en el tratamiento de la amenaza de parto pretérmino.

The objetive was to compare the efficacy of endovenous isoxuprine clorhidrate of vaginal progesterone in treathened preterm labor in the Maternidad “Dr. Nerio Belloso”. Hospital Central “Dr. Urquinaona”, Maracaibo. Estado Zulia. Eighty two patients with a gestational age between 24 and 34 weeks and treathened preterm labor were selected to receive vaginal progesterone (group A; n= 41) or endovenous isoxuprine clorhidrate (group B; n=41). Time of ceasing of uterine contractions and maternal adverse effects were evaluated. Mean gestational age of patients at beginning of treatment was 31.7 ± 2.1 weeks in group A and 32.4 ± 2.4 weeks in group B(P=ns). At the first 24 hours of treatment, isoxuprine clorhidrate was more effective than vaginal progesterone for effective tocolysis (26.8% in group A and 61.0% in group B, P<0.05). However, after 7 days of treatment, 73.2% of patients in group A and 36.6% of patients in group B still were without contractions (P<0.05). Delay of delivery beyond 34 weeks was achieved in 80.5% of patients in group A and 26.8% of patients in group B (P<0.05). Headache was the most frequent adverse effects in patients of group A. Vaginal progesterone is more effective than endovenous isoxuprine clorhidrate in the treatment of treathened preterm labor.

Progesterona para prevenção do parto prematuro / Progesterone for prevention of preterm delivery

Esta revisão, baseada em evidências, pretendeu analisar a utilização da progesterona na prevenção do parto prematuro. Foram apresentados os principais ensaios clínicos randomizados em gestações únicas ou gemelares que utilizaram a progesterona sintética por via intramuscular ou a progesterona natural pela via vaginal ou oral em gestações de risco para a prematuridade espontânea. Concluímos que há benefícios quanto ao uso da progesterona sintética e natural para prevenir o parto prematuro em gestações únicas com antecedente de prematuridade espontânea e no colo curto.

This review, based on evidence, aimed to examine the use of progesterone to preventing premature labor and presented the major randomized clinical trials in singleton or twin gestations using the synthetic progesterone by intramuscular and natural progesterone by vaginal or oral in high risk pregnancies for spontaneous prematurity. We concluded that there are benefits about the use of the synthetic progesterone and natural progesterone to prevent premature labor in single pregnancies with a history of spontaneous prematurity and in short cervix.

The effect of progesterone in the prevention of the chemically induced experimental colitis in rats / Efeito da progesterona na prevenção de colite experimental induzida quimicamente em ratos

PURPOSE: To study the effects of progesterone on an experimental colitis model. METHODS: Wistar albino rats were treated subcutaneously with 2mg/kg once a day during seven days Colitis was induced by intrarectal administration of 5mg trinitrobenzene sulfonic acid (TNBS). Disease activities, macroscopic and microscopic scores were evaluated. To determine the response provoked by progesterone we measured Colonic malondialdehyde (MDA), TNF alfa, IL-6 and Nitric oxide (NO) levels in addition to the MPO (Myeloperoxidase) and caspase-3 activities. RESULTS: Progesterone ameliorated significantly the macroscopic and microscopic scores. TNBS-induced colitis significantly increased the colonic MDA levels and caspase-3 activities in group 2 in comparison to the control group. The results of the study revealed a decline in MDA, NO, IL6 and TNF-α levels in the colon tissue and in blood due to progesterone therapy in group 3 when compared to the group 2, a significant improvement. Progesterone treatment was associated with decreased MDA, MPO, TNF alfa and caspase-3 activity. CONCLUSION: Progesterone therapy decreased oxidative damage in the colonic mucosa.

OBJETIVO: Investigar os efeitos da progesterona em um modelo de colite experimental. MÉTODOS: Ratos albinos Wistar foram tratados subcutaneamente com 2mg/kg por dia durante sete dias. A colite foi induzida por administração intrarretal de 5mg ácido sulfônico trinitrobenzeno (TNBS). Foram avaliadas as atividades da doença, escores macroscópicos e microscópicos Para determinar a resposta provocada pela progesterona foi medida no cólon os níveis de malondialdeído (MDA), TNF alfa, IL-6 e óxido nítrico (NO), além da atividade da MPO (Myeloperoxidase) e caspase-3. RESULTADOS: A progesterone melhorou significantemente os escores macroscópicos e microscópicos. A colite induzida pelo TNBS significantemente aumentou os níveis colônicos de MDA e a atividade da caspase-3 no grupo 2 em comparação com o grupo controle. Os resultados do estudo revelaram um declínio nos níveis de MDA, NO, IL6 e TNF-α no tecido colônico e no sangue devido à terapia com a progesterona no grupo 3 quando comparado ao grupo 2. O tratamento com a progesterona foi associado com decréscimo do MDA, MPO, TNF alfa e atividade da caspase-3. CONCLUSÃO: A terapia com progesterona decresce o dano oxidativo na mucosa do cólon.