17beta-estradiol (1 mg/day) continuously combined with dydrogesterone (5, 10 or 20 mg/day) increases bone mineral density in postmenopausal women

Abstract

Although the minimal dose of 17beta-estradiol in hormone replacement regimens was originally considered to be 2 mg/day, it is now increasingly accepted that a lower dose of 1 mg/day is effective in protecting women from the detrimental effects of the menopause. A 1-year, multicentre, double-blind, randomised study was conducted in 214 healthy postmenopausal women in order to assess the effect of 17beta-estradiol (1 mg/day) continuously combined with dydrogesterone (5, 10 or 20 mg/day) in preventing bone loss. Bone mineral density (BMD) was evaluable in 177 women who completed the study. In all women, a statistically significant increase from baseline in lumbar vertebrae (L2-L4) BMD was seen after 6 months ( + 2.4%; p < 0.01); this increase was somewhat greater after 12 months ( + 3.6%; p < 0.01). Similar effects were seen in the hip. After 6 months, BMD in the femoral neck, Ward's triangle and trochanter had increased by 0.20% (not significant [n.s.]), 0.32% (n.s.) and 1.08% (p < 0.01), respectively, compared with baseline. Greater increases were again seen after 12 months ( + 1.16%, + 1.62% and + 2.83%, respectively), all of which were statistically significant (p < 0.01) compared with baseline. The change in BMD from baseline did not differ significantly between the three dydrogesterone dosages for either L2-L4 or hip. All dosages were well-tolerated and amenorrhoea was achieved in over 70%. In conclusion, 17beta-estradiol (1 mg/day) continuously combined with dydrogesterone (5, 10 or 20 mg/day) results in a significant increase in lumbar vertebrae and hip BMD in postmenopausal women. The lower dose of oestrogen and the avoidance of cyclical bleeding make this a particularly suitable regimen for the prevention and treatment of osteoporosis in older women.