THE DOSE-RESPONSE OF PERCUTANEOUS ESTRADIOL IMPLANTS ON THE SKELETONS OF POSTMENOPAUSAL WOMEN

Objective To determine whether there is a dose-response effect of percutaneous oestradiol implants on the skeletons of postmenopausal women using a range of doses available in clinical practice. Design One year randomised study. Subjects Forty-five postmenopausal women who requested oestrogen replacement therapy were randomised to receive 25 mg, 50 mg, or 75 mg oestradiol implants. The bone mineral density changes were compared with a control group of 15 untreated women. Main outcome measures Dual energy X-ray absorptiometry using Hologic 1000 QDR before treatment and after one year of treatment. Plasma oestradiol and follicle stimulating hormone levels before treatment and after one year. Results There were significant correlations between the plasma oestradiol levels and the percentage increase in bone density at the lumbar spine, the total hip, the femoral neck, and the trochanter. The median (range) plasma oestradiol level was 327 pmol/l (114-853) in the 25 mg group, 358 pmol/l (220-957) in the 50 mg group and 518 pmo1/1 (167-828) in the 75 mg group. Three women who lost a significant amount of bone from the clinically relevant sites in the 25 mg oestradiol group all had plasma oestradiol levels below 300 pmol/l. None of the women in either the 50 mg or 75 mg oestradiol groups lost bone from these sites. Conclusions Oestradiol implants resulted in a wide range of circulating oestradiol levels with each of the doses used. There was a significant relation between plasma oestradiol levels and the increases in bone density at both the lumbar spine and the proximal femur. None of the women lost bone density at the clinically important sites of the spine and femoral neck if their plasma oestradiol levels were above 300 pmol/l.