Dosage of estradiol, bone and body composition in Turner syndrome: a 5 year randomized controlled clinical trial

OBJECTIVE: Reduced bone mineral density (BMD) is seen in Turner syndrome (TS) with an increased risk of fractures, and body composition is characterized by increased body fat and decreased lean body mass. To evaluate the effect of two different doses of oral 17ß-estradiol in young TS women on bone mineral density (BMD), biochemical markers of bone turnover, and body composition with the hypothesis of a positive effect of the higher dose.

DESIGN: A double-blind 5-year randomized controlled clinical trial. 20 young TS women participated. Inclusion criterions were diagnosis of TS, age 15-25 years, and current treatment with 2 mg oral estradiol daily.

METHODS: The low-dose (LD) group was administered 2 mg 17ß-estradiol/day orally and placebo, the high-dose (HD) group was administered 2+2 mg 17ß-estradiol/day orally. Main outcome measures were whole body and regional bone mineral density (BMD), lean body mass (LBM), fat mass (FM) measured yearly be DXA-scan and resorptive and formative bone markers in serum.

RESULTS: BMD, whole body and regional, increased over time with an attenuation towards the end of the study, and bone turnover markers decreased over time, both with no differences between the treatment groups (P=0.2-0.9). LBM increased significantly more in the HD group (P=0.02). FM remained stable in both groups.

CONCLUSIONS: A steady increase in BMD over time in TS was found similar to healthy young women. The higher estrogen dose did not differentially affect BMD or bone markers. The positive effect on body composition may have long ranging health benefits in TS.