One-year endometrial safety evaluation of a continuous combined transdermal matrix patch delivering low-dose estradiol-norethisterone acetate in postmenopausal women.

OBJECTIVE: To evaluate the safety and endometrial protection of low-dose transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) in terms of post-treatment incidence of endometrial hyperplasia/cancer after 1 year of treatment in postmenopausal women with intact uteri. METHODS: Patients were randomized to receive either transdermal E2/NETA (delivering daily doses of E2 25 microg and NETA 125 microg; applied every 3-4 days) or oral E2/NETA (E2 1mg and NETA 0.5 mg; given daily) in this open-label study. The primary variable was the incidence of endometrial hyperplasia/cancer based on endometrial biopsies; secondary variables included vaginal bleeding/spotting patterns, patch adhesion, safety and tolerability. RESULTS: Six hundred and seventy-seven patients were randomized (507 in the transdermal group and 169 in the oral group; one did not receive study drug) and >80% completed the study. There were no cases of endometrial hyperplasia or cancer in either group and the upper limit of the one-sided 95% confidence interval in the transdermal group was 0.85%. Over time, both treatments were associated with a decreasing frequency of spotting/bleeding days. The overall incidence of adverse events (AEs) was comparable in both groups, and the majority was mild-to-moderate in intensity. Breast tenderness was the most frequently reported AE (transdermal 19.9% versus oral 28.4%). AEs related to the gastrointestinal system were more frequent with oral E2/NETA, and episodes of spotting and bleeding were more frequent with transdermal E2/NETA. Local skin tolerability of the transdermal matrix system was good. CONCLUSIONS: Transdermal E2/NETA (25 and 125 microg) provided adequate endometrial protection in postmenopausal women when evaluated according to CPMP/CHMP criteria, achieved a high rate of amenorrhea, and was well tolerated.

Long-term darifenacin treatment for overactive bladder in patients aged 65 years and older: analysis of results from a 2-year, open-label extension study.

OBJECTIVES: This analysis evaluated the long-term safety, tolerability and efficacy of darifenacin, a muscarinic M3 selective receptor antagonist, in the treatment of overactive bladder (OAB) in patients > or = 65 years of age. METHODS: Patients who completed one of two 12-week, placebo-controlled, double-blind, feeder studies received once-daily (o.d.) treatment with darifenacin 7.5 mg for the first 2 weeks of the 2-year, open-label extension study. The dose could be subsequently adjusted (7.5 or 15 mg o.d.) according to need. Safety and tolerability were assessed, and efficacy variables/endpoints were evaluated from patient diary data. RESULTS: 214 patients (65-89 years) entered and 137 (64.0%) completed the 2-year extension study, amounting to 308 patient-years' drug exposure. Darifenacin was well tolerated with no new safety concerns. The most common adverse events (AEs) were dry mouth and constipation, which infrequently resulted in discontinuation (2.3% and 4.2%, respectively). Darifenacin produced significant improvements in OAB symptoms that were maintained over the 2-year period (median reduction from feeder-study baseline to 2 years: -11.0 [-83.7%] for incontinence episodes/week and -1.2 [-12.4%] for micturitions/day, both p < 0.05), with 44.4% patients achieving > or = 90% reduction in incontinence episodes at 2 years. CONCLUSIONS: Darifenacin demonstrated good tolerability and safety in older patients with OAB. The improvement in OAB symptoms was sustained throughout the 2-year extension, resulting in high treatment persistence rates. Results were comparable with those in the overall OAB population from this study, indicating that darifenacin treatment is effective and well tolerated irrespective of age.

Distúrbios urinários no climatério: avaliaçäo clínica e urodinâmica / Postmenopausal urinary disorders: clinical and urodynamic evaluation

Objetivos: avaliar a freqüência dos distúrbios urinários e a variaçäo dos parâmetros urodinâmicos segundo o tempo de pós-menopausa. Métodos: foram estudadas 242 mulheres menopausadas atendidas nos Setores de Climatério e de Uroginecologia e Cirurgia Vaginal da Disciplina de Ginecologia da Escola Paulista de Medicina, UNIFESP, que apresentavam queixas urinárias. As pacientes foram agrupadas segundo o tempo de pós-menopausa em: grupo A - até 4 anos; grupo B - de 5 a 9 anos e grupo C - mais de 10 anos. Todas foram submetidas a anamnese, exame ginecológico e estudo urodinâmico. Analisamos a freqüência de alteraçöes urinárias e a variaçäo dos parâmetros urodinâmicos, como volume urinário (VOL); tempo total de micçäo (TTM); fluxos urinário máximo (FMAX) e médio (FM); resíduo pós-miccional (RES); capacidade vesical primeiro desejo miccional (CVID); capacidade vesical máxima (CVM); pressäo máxima de fechamento uretral e comprimento funcional da uretra, com bexiga cheia e vazia (PMCH, PVM, CFUCH, CFV). Os dados foram analisados estatisticamente. Resultados: o diagnóstico clínico mais comum foi de incontinência urinária de esforço (IUE) nos três grupos, porém observou-se maior incidência de urgência miccional com o evoluir do tempo de pós-menopausa. Em relaçäo ao diagnóstico urodinâmico, 93,6 por cento, 84,6 por cento e 90,7 porcento, respectivamente, das pacientes dos grupos A, B e C apresentaram IUE, ao passo que 4,8 por cento, 13,5 por cento e 6,2 por cento revelaram instabilidade vesical. Houve diminuiçäo dos seguintes parâmetros urodinâmicos, segundo o tempo de pós-menopausa: TTM, FMAX e CVID, além de aumento do resíduo pós-miccional. Conclusöes: apesar da elvada incidência de sintomas urinários irritativos, como urgência incontinência, a IUE foi a principal afecçäo urinária nesta faixa etária.