A one-year randomized double-blind, multicentre study to evaluate the effects of an oestrogen-reduced, continuous combined hormone replacement therapy preparation containing 1 mg oestradiol valerate and 2 mg dienogest on metabolism in postmenopausal women

The objectives were to evaluate the impact of an oestrogen-reduced continuous combined hormone replacement therapy preparation containing 1 mg oestradiol valerate (1EV) and 2 mg dienogest (2DNG) on metabolism. In a randomized double-blind study 1EV/2DNG was compared with a reference preparation containing 1 mg 17s-oestradiol and 0.5 mg norethisterone acetate (E2/NETA). For the primary variable i.e. the ratio of HDL cholesterol (week 52 to baseline) at least 98 case evaluations were planned. Secondary variables were other lipid parameters haemostasis factors and carbohydrate metabolism. After 1 year of treatment the mean HDL cholesterol levels had decreased by 4.5 +or- 14.8% in the 1EV/2DNG group and by 6.1 +or- 13.9% in the E2/NETA group (treatment difference NS). The ratio of HDL cholesterol (week 52 to baseline) was 0.944 for 1EV/2DNG and 0.929 for E2/NETA (geometric means). The primary efficacy variable the ratio of the geometric means of the two treatments (1EV/2DNG/E2/NETA) was 1.016 with a lower one-sided 95% confidence limit of 0.973 which was clearly above the prespecified non-inferiority bound of 0.85 (p-value < 0.001). HDL2 cholesterol increased by 0.3 +or- 34.4% (1EV/2DNG) and decreased by 6.2 +or- 34.3% (E2/NETA; treatment difference NS); HDL3 cholesterol decreased by 4.4 +or- 19.9% (1EV/2DNG) and 8.2 +or- 17.7% E2/NETA; treatment difference NS). Changes in the haemostasis and carbohydrate variables were very similar in both treatment groups. This study provides evidence that a new oestrogen-reduced HRT preparation containing 1 mg oestradiol valerate and 2 mg dienogest has no major impact on lipid variables. Minimal changes were seen in haemostatic and carbohydrate variables. (authors)