Manejo do sangramento inesperado em usuárias de métodos contraceptivos hormonais: revisão das recomendações atuais / Management of unscheduled bleeding in women using hormonal contraceptive: review of current recommendations

Os objetivos desta revisão foram identificar e analisar as principais recomendações atuais relativas ao manejo do sangramento inesperado em usuárias de anticoncepcional hormonal. Foram revisadas as principais diretrizes publicadas nos últimos dez anos. Quatro bases de dados eletrônicas foram consultadas (Medline, LILACS, Scielo, CINAHL®). De um total inicial de 14.130 citações, 14 foram selecionadas para inclusão. As principais recomendações sugerem que as mulheres que optam por métodos hormonais devem ser orientadas quanto à possibilidade da ocorrência de sangramentos inesperados. Tais sangramentos podem desaparecer espontaneamente com a persistência no uso do método. Na maioria das vezes, esta intercorrência não afeta a eficácia anticonceptiva do método, e recomenda-se não criar a expectativa de que irá ocorrer amenorreia na vigência do uso de métodos contraceptivos hormonais. Esta revisão pode ser útil na prática clínica, dada a importância do tema e a frequência desse tipo de queixa nos ambulatórios de tocoginecologia

The objectives of this review were to identify and analyze the main current recommendations on the management of unscheduled bleeding in women using hormonal contraceptives. The main guidelines published during the last ten years were reviewed. Four electronic databases were consulted (Medline, LILACS, Scielo, CINAHL®). From the total of 14,130 citations, 14 were selected for inclusion. The main recommendations suggest that women using hormonal contraceptives should be informed about the possible occurrence of unscheduled bleeding. This bleeding may disappear spontaneously with the persistent use of the method. Most of the time this event do not affect the contraceptive effectiveness of the method, and women should not expect the amenorrhea during the use of hormonal contraceptive methods. This review can be useful for clinical practice, considering the importance of this topic and the frequency of this kind of complaint in tocogynecology clinics

Sangramento durante a anticoagulação oral: alerta sobre um mal maior / Sangrado durante la anticoagulación oral: alerta sobre un mal mayor / Bleeding during oral anticoagulant therapy: warning against a greater hazard

FUNDAMENTO: Sangramento é uma das grandes preocupações em pacientes sob anticoagulação oral. OBJETIVO: Investigar causas determinantes do sangramento em usuários de anticoagulante oral. MÉTODOS: Foram acompanhados prospectivamente, por 48 ± 7,2 meses, 360 pacientes com fibrilação atrial (FA), todos em uso de anticoagulante oral (ACo) com INR-alvo de 2,0-3,5, avaliados em média a cada 30 dias. Os pacientes foram investigados quanto à presença de patologia associada que levasse a sangramento. RESULTADOS: Participaram deste estudo 338 pacientes. Desses, 210 (62,13 por cento) eram do sexo feminino. A estenose mitral estava presente em 218 pacientes (64,4 por cento), a prótese biológica mitral em 64 (18,9 por cento) e a insuficiência da valva mitral em 56 (16,5 por cento). O sangramento ocorreu em 65 pacientes (19,2 por cento) e de forma grave em 7 (10 por cento). Em 38/65 pacientes (58,5 por cento), identificou-se nova doença associada, facilitadora do sangramento. Em 100 por cento dos pacientes com sangramento na faixa terapêutica, foi encontrada doença associada, contra 49,05 por cento de diagnóstico de doenças associadas naqueles com INR > 3,5 (p = 0,001). CONCLUSÃO: O diagnóstico de doença local associada ao sangramento foi frequente entre os medicados com anticoagulante oral (58,5 por cento). Houve associação entre sangramento com INR na faixa terapêutica (INR 2,0-3,5) e diagnóstico de patologia predisponente a sangramento (p < 0,001). Em pacientes em uso de anticoagulante oral que apresentam sangramento, é mandatória a investigação da causa, sobretudo se a INR estiver na faixa terapêutica.

BACKGROUND: Bleeding is one of the main concerns in patients undergoing oral anticoagulation therapy. OBJECTIVE: To investigate the determinant causes of bleeding in patients undergoing oral anticoagulant therapy. METHODS: A total of 360 patients with atrial fibrillation (AF) undergoing oral anticoagulant (ACo) therapy, with a target INR of 2.0-3.5, were followed prospectively for a period of 48 ± 7.2 months. The patients were evaluated on average every 30 days and were investigated regarding the presence of associated pathology that could lead to bleeding. RESULTS: A total of 338 patients participated in the present study. Of these, 210 (62.13 percent) were females. Mitral stenosis was present in 218 patients (64.4 percent), a mitral biological prosthesis in 64 (18.9 percent) and mitral valve failure in 56 (16.5 percent) patients. Bleeding occurred in 65 patients (19.2 percent), being severe in 7 (10 percent) patients. In 38/65 patients, a new associated disease was identified, which facilitated bleeding. An associated disease was identified in 100 percent of the patients with bleeding within the therapeutic range, against 49.05 percent of associated disease diagnosis in those with an INR > 3.5 (p=0.001). CONCLUSION: The diagnosis of a local disease associated to the bleeding was frequent among those patients undergoing oral anticoagulant therapy (58.5 percent). There was an association between bleeding with an INR within the therapeutic range (INR=2.0-3.5) and the diagnosis of a pathology predisposing to bleeding (p<0.001). It is mandatory to investigate the cause of bleeding in patients undergoing oral anticoagulant therapy, especially if the INR is within the therapeutic range.

FUNDAMENTO: El sangrado es una de las grandes preocupaciones en pacientes bajo anticoagulación oral. OBJETIVO: Investigar causas determinantes del sangrado en usuarios de anticoagulante oral. MÉTODOS: Se realizó el seguimiento, prospectivamente, por 48 ± 7,2 meses, de 360 pacientes con fibrilación atrial (FA), todos en uso de anticoagulante oral (ACo) con INR-objetivo de 2,0-3,5, evaluados en promedio cada 30 días. Los pacientes se investigaron sobre la presencia de patología asociada que llevara al sangrado. RESULTADOS: Participaron en este estudio 338 pacientes. De ellos, 210 (62,13 por ciento) eran del sexo femenino. La estenosis mitral estaba presente en 218 pacientes (64,4 por ciento), la prótesis biológica mitral en 64 (18,9 por ciento) y la insuficiencia de la válvula mitral en 56 (16,5 por ciento). El sangrado ocurrió en 65 pacientes (19,2 por ciento) y de forma grave en 7 (10 por ciento). En 38/65 pacientes (58,5 por ciento), se identificó nueva enfermedad asociada, facilitadora del sangrado. En el 100 por ciento de los pacientes con sangrado en el intervalo terapéutico, se encontró enfermedad asociada, contra el 49,05 por ciento de diagnóstico de enfermedades asociadas en aquellos con INR > 3,5 (p = 0,001). CONCLUSIÓN: El diagnóstico de enfermedad local asociada al sangrado fue frecuente entre los medicados con anticoagulante oral (58,5 por ciento). Hubo asociación entre sangrado con INR en el intervalo terapéutico (INR 2,0-3,5) y diagnóstico de patología predisponente a sangrado (p < 0,001). En pacientes en uso de anticoagulante oral que presentan sangrado, es indispensable la investigación de la causa, sobre todo si la INR está en el intervalo terapéutico.

[Evaluation of bleeding patterns in postmenopausal women under continuous or sequential hormone therapy]

The improved uterine bleeding profile in postmenopausal women receiving hormone therapy likely enhance compliance with hormone replacement therapy. To compare the bleeding patterns in post menopausal women receiving continuous or sequential hormone therapy. This quasi-experimental clinical trial was performed on 44 healthy postmenopausal women < 65 years old with intact uterus who were presented for gynecologic examination at Bouali hospital in Tehran [Iran] during 2001-2002. The patients were divided into two groups marked as group I including postmenopausal women on oral replacement with estrogen conjugate 0.625 mg and medroxyprogesterone 2.5 mg daily, in a continuous combined fashion, and group II composed of post menopausal women on oral replacement with estrogen conjugate 0.625 mg daily and medroxyprogesterone 5 mg during the last 14 days of each month. The patients were followed up for one year. The data on bleeding patterns and their relationship with duration of menopause and body mass index were analyzed statistically using K[2] and Fisher exact tests. The mean menopause age was 53 +/- 4.7 and 45.2 +/- 2.2 years in group I and II, respectively. There was a significant difference between two groups, statistically [p< 0.001]. The mean menopause duration was 3.8 +/- 2.8 years in group I and 1.1 +/- 0.8 in group II with a statistically significant difference between two groups [p=0.01]. The difference in body mass index between two groups was insignificant, statistically. All women in group II [22/100%] were found to have amenorrhea after one years. Among the patients in group II, one [14.3%] suffered spotting, 5 [71.4%] with regular bleeding and 1 [14.3%] with amenorrhea following the same time period. The difference in bleeding patterns between two groups was shown to be statistically significant [p=0.000]. While unexpected vaginal bleeding in women using continuous combined HRT decreased after 1 year, the degree of bleeding among those using cyclic HRT remained unchanged

Relationship between progesterone receptor level in endometrium and bleeding pattern in depot medroxyprogesterone acetate users.

Bleeding disturbance is the major reason for discontinuation among depot medroxyprogesterone acetate (DMPA) users. However, the causes of progestin-induced bleeding are not well understood. The aim of the study was to examine the correlation between the occurrence of uterine bleeding and progesterone receptor (PR) levels in the endometrium. Forty-five matched pairs of age and body mass index in DMPA users with bleeding and amenorrhea were studied. The endometrial PR levels were evaluated. The PR score was assessed semi-quantitatively. Forty-two subject pairs met the criteria. There was no difference in serum estradiol and progesterone levels between the groups. No correlation between the number of bleeding days and PR score nor between the number of bleeding days and serum estradiol and progesterone level was detected. The stromal PR score in DMPA subjects with amenorrhea was significantly higher than those with bleeding (p < 0.05). By contrast, the PR score in glandular endometrium was not significantly different between the groups (p > 0.05). In conclusion, after a second dose of DMPA, subjects with amenorrhea had a higher stromal PR score than those with uterine bleeding.

Etinil estradiol y medroxiprogesterona ciclicos en mujeres climatericas: eficacia clínica y patrones de sangrado uterino / Ethynil estradiol and medioxiprogesterone in climateric women: clinical response and uterine bleeding

Se evalúa la eficacia clínica sobre el síndrome climatérico de un esquema de hormonoterapia sustitutiva cíclica, en un grupo de 40 mujeres con menopausia instalada, sintomatología moderada a severa y prueba de progesterona negativa. Cada ciclo consistió en la administración secuencial de 15 *g de etinil estradiol durante 21 días con el agregado de 10 mg de medroxiprogesterona acetato los últimos 10 días. Cada paciente recibió cuatro ciclos de tratamiento con intervalos de 7 días de descanso. Todas las mujeres experimentaron una significativa mejoría de su sintomatología, tanto de las crisis vasomotoras como del síndrome de acompañamiento, de acuerdo al índice de Blatt. El alivio sintomático se manifestó desde el primer ciclo terapéutico, observándose una progresiva reducción de los puntajes en los sucesivos ciclos. Los síntomas vasomotores experimentan un descenso más marcado y definido que el síndrome de acompañamiento. La respuesta clínica global fue calificada como favorable (respuestas excelentes y buenas) en el 97,5% de los casos. En todas las pacientes se evidenció una franca mejoría de su trofismo vaginal como consecuencia de la terapia. Estos resultados señalan que la dosis utilizada, de 15 *g diarios de etinil estradiol durante 21 días, sería suficiente para el alivio de la sintomatología climatérica, en un alto porcentaje de pacientes. La mayoría de las mujeres experimentó sangrados cíclicos como consecuencia de la terapia. El análisis de los patrones de sangrado mostró un franco predominio de los de tipo posterapéutico o por deprivación, que se inician despues de completado un ciclo de tratamiento; lo que sugiere que el agregado de 10 mg de acetato de medroxiprogesterona durante 10 días permitiría una adecuada oposición al efecto proliferativo estrogénico, induciendo una adecuada respuesta secretoria y la consiguiente descamación del endometrio

Rifampicin induced uterine bleeding.

A case of uterine bleeding after intake of rifampicin is reported in a 35-year-old female. Provocation test was also positive. The underlying mechanism whether it was a hypersensitivity phenomenon like fixed drug eruption or due to induction of uterine acyl-hydrolase enzyme, is not clear. Uterine bleeding has not been observed as a side-effect of rifampicin in the past.