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.

Key words:

• ESTRADIOL
• JAPANESE
• ORAL
• OSTEOPOROSIS
• POSTMENOPAUSAL

Acknowledgements

Editorial assistance was provided by Parexel MMS. Evaluation of bone findings was performed by Dr Toshitaka Nakamura (Department of Orthopedic Surgery, University of Occupational and Environmental Health, Fukuoka) and Dr Takami Miki (Osaka City University Medical School, Postgraduate School of Medicine, Geriatric Medicine, Osaka). Histopathology evaluation of endometrial biopsy was performed by Dr Alex Ferenczy (Department of Pathology, Jewish General Hospital and McGill University, Montreal, Canada) and Dr Atsuhiko Sakamoto (Department of Pathology, Kyorin University, Tokyo).

Conflict of interest  Professor Mizunuma and Professor Honjo previously acted as consultants to Bayer Schering Pharma.

Source of funding  This study was funded by former Nihon Schering KK, now part of Bayer Schering Pharma.