Dose effects of oral estradiol on bone mineral density in Japanese women with osteoporosis

Abstract

Objectives This 2-year study compared 0.5 and 1.0 mg oral estradiol (E2), with or without levonorgestrel (LNG), for the treatment of postmenopausal osteoporosis in Japanese women.Methods Japanese women with osteoporosis after natural menopause or bilateral oophorectomy were randomized to receive E2 0.5 or 1.0 mg/day with LNG 40 μg as required, or placebo, for 52 weeks. Women treated with E2 in the first year continued therapy at the same doses in the second year. Efficacy, safety and pharmacokinetics were assessed.Results There were 73 women randomized to E2 0.5 mg, 157 to E2 1.0 mg and 79 to placebo. Lumbar bone mineral density at 52 weeks increased significantly more with E2 1.0 mg (p < 0.001) and 0.5 mg (p < 0.001) than with placebo (no change). After 2 years, a 10% increase in bone mineral density with E2 1.0 mg was significantly greater than with E2 0.5 mg (8%; p = 0.008). E2 was associated with an acceptable safety and tolerability profile, with slightly more adverse events with E2 1.0 than 0.5 mg. Serum E2 concentration increased in a dose-dependent manner.Conclusion This study showed that E2, at both 1.0 mg and 0.5 mg doses, was effective in increasing bone mineral density with an acceptable safety and tolerability profile in Japanese postmenopausal women with osteoporosis but that the bone mineral density response was higher with the 1.0 mg dose.