COMBINED ORAL ESTRADIOL VALERATE-NORETHISTERONE TREATMENT OVER 3 YEARS IN POSTMENOPAUSAL WOMEN - 1 - CLINICAL ASPECTS AND ENDOMETRIAL HISTOLOGY

The aim of this study was to determine the medium-term safety and effi cacy of once-daily, oral estradial valerate 2 mg with norethisterone 0 .7 mg on menopausal symptoms, bleeding incidence, endometrial patholog y, adverse events and other clinical parameters. A three-year single-c enter, open study was performed. Women with menopausal symptoms and gr eater than or equal to 6 months since the last spontaneous menstrual p eriod 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 a t baseline and annually. There were 206 patients at entry and 133 comp leters at the end of year 3. Menopausal symptoms showed significant im provements within 4 months (p < 0.0001 compared with baseline). By the end of month 4, 79.9% of patients had stopped bleeding. The mean numb er of days bleeding per month declined from 2.8 (month 1) to 1.1 (mont h 12). Significantly less bleeding was observed in patients who were 1 2 years postmenopausal. No abnormalities in endometrial histology were found. Bleeding and breast tenderness were the commonest adverse even ts. Twenty-four patients experienced serious adverse events although n o definite relationship to drug therapy was considered likely. We ther efore conclude that the oral combination of estradiol valerate 2 mg an d norethisterone 0.7 mg given daily and continuously leads to amenorrh ea and symptom alleviation in the majority of patients and is well tol erated.