Evolución del estrógeno en la anticoncepción hormonal combinada: del etinilestradiol al estetrol pasando por el estradiol / Evolution of oestrogen in combined hormonal contraception: From ethinylestradiol to estetrol via estradiol

El objetivo de este artículo ha sido el de analizar las evidencias disponibles sobre la eficacia y la seguridad de un nuevo anticonceptivo oral que contiene estetrol (E4) y drospirenona (DRSP). Para ellos se ha efectuado una revisión de la literatura que ha incluido los estudios publicados sobre esta nueva formulación anticonceptiva. Los ensayos clínicos en fase 2 y fase 3 realizados han puesto de manifiesto que la combinación E4 15mg/DRSP 3mg es eficaz para evitar el embarazo, es bien aceptada por las mujeres y no produce cambios de significado clínico en los parámetros de la coagulación. Para confirmar los resultados obtenidos en los ensayos en fase 2 y 3, es necesario un estudio en fase 4 que ponga de manifiesto el comportamiento de este nuevo anticonceptivo en la vida real.(AU)

The objective of this article was to analyse the available evidence on the efficacy and safety of a new oral contraceptive containing estetrol (E4) and drospirenone (DRSP). We conducted a literature review that included published studies on this new contraceptive formulation. Phase 2 and phase 3 clinical trials have shown that the E4 15mg/DRSP 3mg combination is effective in preventing pregnancy, is well accepted by women, and does not produce clinically significant changes in coagulation parameters. To confirm the results obtained in phase 2 and 3 trials, a phase 4 study is necessary to reveal the behaviour of this new contraceptive in real life.(AU)

Efectos de la terapia hormonal con drospirenona / 17 ß - estradiol sobre los parámetros del síndrome metabólico en posmenopáusicas / Effects of hormone therapy with drospirenone / 17 ß - estradiol on the parameters of the metabolic syndrome in postmenopausal women

Evaluar los efectos de la terapia hormonal (TH) con Drospírenona (DRSP)/17 ß -estradiol (E2), sobre los parámetros del Síndrome Metabólico (SM) en pacientes postmenopáusicas. Métodos: Investigación comparativa y aplicada, con diseño cuasi experimental, de casos y controles a simple ciego, prospectivo y de campo; realizada en la Consulta de Ginecología. Hospital "Dr. Manuel Noriega Trigo". San Francisco, Estado Zulia. Venezuela. Participaron 120 mujeres separadas al azar para recibir la combinación DRSP/E2 (Grupo A) o un placebo (Grupo B). Se evaluaron los componentes del SM antes y posterior a 6 meses de haber recibido la TH. Resultados: Se encontró una alta prevalencia de SM en ambos grupos antes de recibir el tratamiento (53,3% y 48%; grupo A y B respectivamente). Posterior al tratamiento, DRSP/E2 al compararse con un placebo, redujo significativamente tanto la prevalencia del SM como el riesgo de padecerlo (21,7% versus 48,3%, OR [IC95%]= 0,29 [0,13-0,65]; p < 0.001), con reducción significativa (p< 0.001) de la hipertensión arterial, glicemia basal alterada, hipertrigliceridemia y obesidad central; además de una reducción significativa de los síntomas vasomotores, síntomas psicológicos e incontinencia urinaria (p< 0.001). En el grupo B la prevalencia del SM se mantuvo sin cambios, salvo para la glicemia basal alterada y los síntomas vasomotores y psicológicos que mostraron una reducción significativa (p< 0.001). Conclusión: DRSP/E2 (2mg/1 mg) demostró ser eficaz luego de 6 meses de tratamiento tanto para el control de los parámetros que definen al SM; con pocos y leves efectos indeseados(AU)

To assess the effects of hormone therapy (HT) with drospirenone (DRSP)/17 ß -estradiol (E2) on the parameters of the metabolic syndrome (MS) in postmenopausal patients. Methods: We performed a comparative and applied research, with quasiexperimental, case-control, single-blind, prospective and field design. The study was realized in the Gynecology consultation. Hospital "Dr. Manuel Noriega Trigo". San Francisco, Estado Zulia. Venezuela. 120 women were included, they were separated to receive either the combination DRSP/E2 (Group A) or placebo (Group B). We assess MS components before and ather 6 months of receiving HT. Results: We found a high prevalence in both groups before receiving treatment (53.3% and 48%, group A and B respectively). A ther treatment, DRSP/E2 when compared to placebo, significantly reduced both the prevalence of MS as the risk of setting it (21.7% versus 48.3%, OR [95%] = 0.29 [0.13-0.65] p <0.001), with a significant reduction (p <0.001) of hypertension, impaired fasting glucose, hypertriglyceridemia, central obesity; and a significant reduction in vasomotor symptoms, psychological symptoms and urinary incontinence (p <0.001). In group B the prevalence of MS was unchanged, except for impaired fasting glycemia and vasomotor and psychological symptoms showed a significant reduction (p <0.001). Conclusion: DRSP/E2 (2mg /1mg), proved to be effective a ther 6 months of treatment both for the control of the parameters that define the SM, with few and mild side effects(AU)

Cálculo del Índice de Pearl de etinilestradiol 30 mcg/drospirenona 3 mg (Genesa®)

Objetivo: Calcular el índice de Pearl de Genesa® en mujeres venezolanas. Métodos: Estudio fase IV, prospectivo y abierto. Las pacientes recibieron etinilestradiol 30 mcg / drospirenona 3 mg (Genesa®): un comprimido diario desde el primer día de la menstruación por 21 días; descanso de siete días y reinicio el día ocho. Resultados: Se ingresaron al estudio 115 pacientes, se obtuvo un índice de Pearl de 0,98. Los efectos adversos fueron: un embarazo, incremento de peso, retención de líquidos, náuseas, manchas en la piel. Conclusiones: Etinilestradiol 30 mcg/drospirenona 3 mg (Genesa®) presenta un adecuado índice de Pearl en mujeres venezolanas.

Objective: To calculate the Pearl index of Genesa® in Venezuelan women. Methods: Phase IV prospective and open study. Patients received ethinylestradiol 30 mcg / drospirenone 3 mg (Genesa®): one tablet daily from the first day of menstruation for 21 days; seven-day break and restart the eighth day. Results: 115 patients were admitted to the study, a Pearl index of 0.98 was obtained. Most common side effects: one pregnancy, weight gain, fluid retention, nausea, skin blemishes. One patient discontinued treatment for adverse effects (vomiting and nausea). Conclusions: Genesa® presents an adequate Pearl Index in Venezuelan woman.

Efecto de la terapia hormonal combinada (drospirenona / 17 β -estradiol) sobre el peso corporal en posmenopáusicas

Objetivo: Comparar los efectos de la terapia hormonal combinada (drospirenona /17 β-estradiol) versus un placebo sobre el peso corporal u otras variables antropométricas en pacientes posmenopáusicas asistidas en la consulta ginecológica del Hospital “Dr. Manuel Noriega Trigo”, Estado Zulia, Venezuela. Métodos: Estudio cuasi-experimental, de casos y controles, aleatorio, a simple ciego, en el cual participaron 120 mujeres posmenopáusicas, divididas en dos grupos para recibir una dosis diaria durante 6 meses de una terapia hormonal combinada (grupo A; drospirenona 2 mg/ 17 β-estradiol 1 mg) o un placebo (grupo B). Se evaluaron tanto el peso corporal como el índice de masa corporal, circunferencia abdominal e índice de cintura cadera, antes y al final del tratamiento. Resultados: Se evidenció que en el grupo que recibió la terapia hormonal hubo una reducción de alrededor de 3 kg en la media del peso corporal luego de 6 meses de tratamiento (79,80±9,35 vs. 76,33±8,36; P< 0,001); asimismo, una reducción significativa en el índice de masa corporal (30,12±2,02 vs. 28,72±1,79; P< 0,001), circunferencia abdominal (120,10±14,73 vs. 110,10±14,00; P< 0,001) y en el índice cintura cadera (0,87±0,04 vs. 0,84±0,07; P< 0,05). En el grupo que recibió un placebo no hubo modificaciones significativas en estas variables. Conclusiones: La terapia hormonal con drospirenona /17 β-estradiol se asoció con una reducción significativa del peso corporal, índice de masa corporal, circunferencia abdominal e índice cintura cadera luego de 6 meses de tratamiento en posmenopáusicas; con pocos o leves efectos adversos.

Objective: To compare the effects of combined hormonal therapy (drospirenone/17 β-estradiol) versus a placebo on body weight and other anthropometric variables in postmenopausal women assisted in the gynecology consultation at the Hospital “Dr. Manuel Noriega Trigo”, in Zulia state, Venezuela. Methods: A quasi-experimental, case control, randomized, single blind study, which involved 120 postmenopausal women, divided into two groups to receive a daily dose for 6 months of combined hormone therapy (group A; drospirenone 2 mg/ 17 β-estradiol) or placebo (group B). We evaluated body weight, body mass index, waist circumference and waist-hip ratio, before and at the end of treatment. Results: We showed that in the group receiving hormonal therapy with drospirenone / 17 β-estradiol was a reduction of about 3 kg in mean body weight after 6 months of treatment (79,80 ± 9,35 vs. 76,33 ± 8,36; P <0,001); and a significant reduction in body mass index (30,12 ± 02,02 vs. 28,72 ± 1,79; P <0,001), abdominal circumference (120,10 ± 14,73 vs. 110,10 ± 14,00; P <0,001) and waist hip (0,87 ± 0,04 vs. 0,84 ± 0,07; P <0;05). In the group receiving a placebo had no significant changes in these variables. Conclusions: Hormonal therapy with drospirenone / 17 β-estradiol was associated with a significant reduction in body weight, body mass index, waist circumference and waist-hip ratio after 6 months of treatment in postmenopausal women, with few or mild side effects.

Effects of hormone therapy on the endometrium in postmenopausal women: a one year randomized trial of low dose oral estradiol in association with a levonorgestrel-releasing intrauterine system or drospirenone / Efeitos da terapia hormonal no endométrio de mulheres na pós-menopausa: estudo clínico randomizado por um ano com estradiol oral em baixa dosagem em associação com sistema intrauterino com levonorgestrel ou drospirona

To compare the endometrial effects and uterine bleeding patterns associated with treatment using (1) levonorgestrel-releasing intrauterine system (LNG-IUS) and estradiol (1 mg/day, p.o.) or (2) orally administered drospirenone (2 mg/day) andestradiol (1 mg/day). METHODS: thirty-four patients (aged 52.53 ± 4.44 in the LNG-IUS group and 53.15 ± 4.018 in the DRSP group) were randomized. The severity of menopausal symptoms was evaluated using the Kupperman index every three months. Transvaginal ultrasound, hysteroscopy and histological evaluation were repeated after 12 months. During this period, patients kept menstrual calendars. All categorical variables were described as percentages. Variables were tested for normal distribution and Student's t test was applied for independent samples and ANOVA forrepeated measures when appropriate. Data were considered to be significant when p<0.05. RESULTS: slight vaginal bleeding was reported in the first month of treatment by 53.3 percent of patients from the LNG-IUS/estradiol group compared with 7.7 percent of patients from the drospirenone/estradiol group. There were no differences in endometrial thickness between the two groups throughout the study period. End-of-study histological findings showed atrophic endometrium in 53.3 percent of patients in the LNG-IUS/estradiol group compared with 76.9 percent of patients in the drospirenone/estradiol group. CONCLUSIONS: our results suggest good endometrial protection with both HT regimens...

Comparar os efeitos endometriais e no padrão de sangramento uterino de tratamento com (1) sistema intrauterine com levonorgestrel (SIU-LNG) e estradiol (1 mg/dia, v.o.) ou (2) associação oral de drospirenona (DRSP) (2 mg/dia) e estradiol (1 mg/dia). MÉTODOS: trinta e quatro pacientes (idade 52,53 ± 4,44 grupo SIU-LNG e 53,15 ± 4,018 grupo DRSP)foram randomizadas. A gravidade dos sintomas menopausais foi avaliado pelo índice de Kupperman a cada três meses. Ultrassom transvaginal, histeroscopia e avaliação histológica foram repetidos após 12 meses. Durante este período, as pacientes fizeram registros em calendários menstruais. Todas as variáveis categóricas foram descritas como porcentagens. Variáveis foram testadas para distribuição normal e teste t de Student para amostras independents e ANOVA para medidas repetidas foram utilizados quando apropriado. Significância estatística foi considerada para p<0.05. RESULTADOS: leve sangramento vaginal foi relatado no primeiro mês de tratamento por 53,3 por cento das pacientes do grupo SIU-LNG/estradiol vs. 7,7 por cento das pacientes do grupo drospirenona/estradiol. Não houve diferença na espessura endometrial entre os grupos durante o periodo do estudo. Os achados histológicos ao final do estudo motraram endométrio atrófico em 53,3 por cento das pacientes no grupo SIU-LNG/estradiol vs. 76,9 por cento das pacientes no grupo drospirenona/estradiol. CONCLUSÕES: nossos resultados sugerem boa proteção endometrial com ambos os tratamentos de terapia hormonal...

Simultaneous determination of ethinyl estradiol and drospirenone in oral contraceptive by high performance liquid chromatography

A simple, rapid, economical and reliable high performance liquid chromatographic method has been developed and successfully applied in simultaneous determination of ethinyl estradiol and drospirenone in coated tablets. The HPLC method was performed on a LiChroCART® 100RP column (125x4 mm i.d., 5 µm) with acetonitrile:water 50:50 (v/v) as mobile phase, pumped at a flow rate of 1.0 mL.min-1. The fluorescence detection for ethinyl estradiol was made at λex= 280 nm and λem= 310 nm and a UV detection for drospirenone was made at 200 nm. The elution time for ethinyl estradiol and drospirenone were 4.0 and 5.7 min, respectively. The method was validated in accordance to USP 34 guidelines. The proposed HPLC method presented advantages over reported methods and is suitable for quality control assays of ethinyl estradiol and drospirenone in coated tablets.

Um método simples, rápido, econômico e confiável foi desenvolvido empregando a cromatografia líquida de alta eficiência para a determinação simultânea de etinilestradiol e drospirenona em comprimidos revestidos. O método foi realizado utilizando coluna LiChroCART® 100RP (125 x 4 mm d.i., 5 µm), a fase móvel constituída de acetonitrila:água, 50:50 (v/v) com vazão de 1,0 mL.min-1. A detecção foi realizada empregando fluorescência em λex= 280 nm e λem= 310 nm para o etinilestradiol e na região de UV em 200 nm para a drospirenona. O etinilestradiol e a drospirenona tiveram tempo de retenção de 4,0 e 5,7 min, respectivamente. O método foi validado de acordo com as diretrizes da USP 34. O método proposto apresentou vantagens sobre os relatados na literatura e pode ser considerado adequado para o controle de qualidade do etinilestradiol e da drospirenona em comprimidos revestidos.

Avaliação hemodinâmica e da função endotelial em mulheres jovens normotensas em uso de anticoncepcional hormonal combinado oral contendo drospirenona / Assessment of hemodynamic and endothelial function in normotensive young women using a combined hormonal oral contraceptive containing drospirenone

Importância. Anticoncepcionais hormonais combinados orais (AHCO) podem levar ao aumento do risco da doença cardiovascular, que pode estar associado a alterações na pressão arterial e na função endotelial. Objetivos. O objetivo deste estudo foi avaliar o impacto do uso de AHCO contendo 20 mg de etinilestradiol (EE) e 3 mg de drospirenona (DRSP) por mulheres jovens normotensas sobre a função endotelial arterial, pressão arterial sistólica (PAS, mmHg) e diástólica (PAD, mmHg), frequência cardíaca (FC, bpm), débito cardíaco (DC, L/min), e sobre a resistência periférica total (RPT, NU). Métodos. Setenta e uma mulheres jovens saudáveis com idade média de 29 ± 1 ano foram avaliadas. Quarenta e três foram analisadas antes da introdução do AHCO e ao final de 6 meses de uso (grupo-caso) e vinte e oito, não usuárias de nenhum método hormonal de contracepção, foram avaliadas quanto aos mesmos parâmetros no mesmo intervalo de tempo (grupo-controle). Resultados. Não se observaram mudanças significantes na função endotélio-dependente (VMF%) e independente (VIE%) e nas medidas de PAS, PAD, FC, DC e da RPT com o uso do AHCO (p> 0,05 para todas as variáveis). Não houve variações significantes nestes parâmetros no grupo-controle. Conclusão: O uso desta formulação de AHCO não causou alterações deletérias na reatividade vascular, e nas variáveis hemodinâmicas em mulheres jovens normotensas.

Background: Combined oral contraceptives (COCs) may lead to a rise in cardiovascular disease risk, possibly associated with changes in blood pressure and endothelial function. Objective: The objective was to evaluate the impact of COC containing 20 mcg of ethinyl estradiol (EE) and 3 mg of drospirenone (DRSP) on the arterial endothelial function, systolic and diastolic blood pressure (SBP and DBP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) of normotensive young women. Methods: Of the 71 women in the study, 43 were evaluated before the introduction of COC and after 6 months of its use (case group) and 28, COC nonusers, were assessed for the same parameters at the same time interval (control group). Results: No significant changes in endothelium-dependent and -independent functions or in measures of SBP, DBP, HR, CO, and TPR caused by COC use were observed in the case group (P> 0.05 for all variables) or in the control group. Conclusion: These data suggest COC with 20 mcg EE and 3 mg DRSP does not alter arterial endothelial function or hemodynamic parameters in normotensive young women.

Experiencia piloto con el uso extendido de un anticonceptivo oral combinado de baja dosis de estrógeno / Extended use of an oral combined contraceptive pill with low estrogen dose: pilot experience

Objetivo: Evaluar en una experiencia piloto la aceptabilidad y bienestar de la usuaria, después de un periodo de 12 meses de un anticonceptivo hormonal combinado oral de baja dosis estrogénica, con modalidad de uso extendido de 84 píldoras activas consecutivas, seguidas de 7 días de placebo. Método: Se incorporan 25 mujeres voluntarias que usan una combinación de 20 ug de etinilestradiol + 3 mg de drospirenona, con un tiempo de uso de 12 meses. En calendario de registro diario se consignan los días de sangrado o goteo genital así como todo tipo de fármaco ingerido. Al término de los 12 meses se efectúa una encuesta respecto al grado de satisfacción con la posología recibida. Resultados: 13 usuarias (52 por ciento) cumplen los 12 meses de uso. Todas ellas manifiestan un alto grado de conformidad, destacando las ventajas de presentar periodos menstruales ocasionales, mejoría marcada en la sintomatología compatible con el síndrome de tensión premenstrual con el consiguiente incremento del bienestar general. Siete usuarias (28 por ciento) no terminan el estudio por razones médicas, siendo 6 de estas por alteraciones de los flujos rojos y en 5 casos (20 por ciento) se producen retiros no médicos. Conclusión: Esta experiencia, que es la primera con la formulación descrita, confirma en un porcentaje de usuarias las bondades adicionales reportadas en las experiencias previas con otros productos similares, respecto al uso extendido de anticoncepción hormonal oral en un grupo de mujeres que deseaban espaciar sus periodos menstruales.

Objetives: A pilot study designed in order to know about the acceptability of an oral combined contraceptive pill, with low estrogen dose used in an extended way of 84 consecutive days, followed by 7 days of no pills ingestion during a scheduled follow up of 1 year. Methods: 25 volunteers women were recruited among those which wants to use oral combined contraceptive pills and who accepted this extended way of use. Combined contraceptive pills contains each 20 ug of ethinylestradiol plus 3 mg of drosperinone. At admission women were provided with menstrual diary cards in order to check all bleeding days plus any extra pharmaceutical compound received. At the end of the 12 months follow up an interview was done in order to know women experiences and acceptability of this extended way of use. Results: 52 percent of women end the study at the scheduled 12 months use. All of them feel that the main advantages of these extended way of use were to have few menstrual periods and improving premenstrual symtomatology with better quality of life. 7 women (28 percent) did not finish the study because of medical reasons being due in 6 of these for bleeding disturbances. Conclusions: This report is pioneer with the use this hormone combination in this extended type way of use. Results confirm previous positive reports experiences using another similar hormonal compounds with this extended way of use in women who want to reduce the interval of their menstrual periods.