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

Objective To determine whether there is a dose-response effect of perc utaneous 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 reques ted oestrogen replacement therapy were randomised to receive 25 mg, 50 mg, or 75 mg oestradiol implants. The bone mineral density changes we re compared with a control group of 15 untreated women. Main outcome m easures Dual energy X-ray absorptiometry using Hologic 1000 QDR before treatment and after one year of treatment. Plasma oestradiol and foll icle stimulating hormone levels before treatment and after one year. R esults There were significant correlations between the plasma oestradi ol levels and the percentage increase in bone density at the lumbar sp ine, 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 g roup, 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 ei ther the 50 mg or 75 mg oestradiol groups lost bone from these sites. Conclusions Oestradiol implants resulted in a wide range of circulatin g oestradiol levels with each of the doses used. There was a significa nt 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 pmo l/l.