Combined oral estradiol valerate-norethisterone treatment over three years in postmenopausal women. 1. Clinical aspects and endometrial histology

The aim of this study was to determine the medium-term safety and efficacy of once-daily, oral estradiol valerate 2 mg with norethisterone 0.7 mg on menopausal symptoms, bleeding incidence, endometrial pathology, adverse events and other clinical parameters. A three-year, single-center, open study was performed. Women with menopausal symptoms and > or = 6 months since the last spontaneous menstrual period were recruited. Patients were assessed using questionnaires and daily records of bleeding incidence and severity. Adverse events were recorded at each visit and endometrial histopathology was determined at baseline and annually. There were 206 patients at entry and 133 completers at the end of year 3. Menopausal symptoms showed significant improvements within 4 months (p < 0.0001 compared with baseline). By the end of month 4, 79.9% of patients had stopped bleeding. The mean number of days bleeding per month declined from 2.8 (month 1) to 1.1 (month 12). Significantly less bleeding was observed in patients who were > or = 2 years postmenopausal. No abnormalities in endometrial histology were found. Bleeding and breast tenderness were the commonest adverse events. Twenty-four patients experienced serious adverse events although no definite relationship to drug therapy was considered likely. We therefore conclude that the oral combination of estradiol valerate 2 mg and norethisterone 0.7 mg given daily and continuously leads to amenorrhea and symptom alleviation in the majority of patients and is well tolerated.