ESPE Abstracts (2015) 84 P-2-212

The Effect of High Dose Oral 17sz Estradiol on Bone Mineralization and Body Composition in Young Women with Turner Syndrome - A 5 Year Randomized Controlled Clinical Trial

Line Cleemanna, Kirsten Holma, Hanne Kobbernagelb, Bent Kristensenb, Sven Olaf Skoubyc, Andreas Emil Kryger Jensend,e & Claus Gravholtf,g

aDepartment of Pediatrics, Nordsjællands Hospital Hillerød, Hillerød, Denmark; bDepartment of Radiology, Nordsjællands Hospital Hillerød, Hillerød, Denmark; cDepartment of Gynecology and Obstetrics, Herlev University Hospital, Herlev, Denmark; dCenter of Research and Innovation, Nordsjællands Hospital Hillerød, Hillerød, Denmark; eDepartment of Public Health, University of Copenhagen, Copenhagen, Denmark; fDepartment of Endocrinology, Internal Medicine and the Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark; gDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

Background: Reduced bone mineral density (BMD) is seen in Turner syndrome (TS) with an increased risk of fractures and osteoporosis. Body composition in TS is characterised by increased body fat (FM) and decreased lean body mass (LBM), even with a normal BMI. Oestrogen replacement therapy for attaining and preserving normal bone mass is necessary in most TS girls. There is a potential role of age-specific estrogen doses, with lower doses used in the early puberty and higher doses at the end of adolescence. Oestrogen also affects the accrual and preservation of LBM positively.

Objective and aims: To evaluate the effect of two different doses of oral 17ß-oestradiol in young women with TS on BMD, bone markers, hormones related to bone metabolism, and body composition.

Method: A double-blind 5 year randomized controlled clinical trial. The lower-dose (LD) group took 2 mg 17ß-oestradiol/day orally and placebo. The higher-dose (HD) group took 2+2 mg 17ß-estradiol/day orally. 20 young TS women (19.2±2.5 years, range 16.0–24.9) participated. DXA scan (BMD, FM, LBM), CTX, PINP, BSAP, PTH, IGF1, and IGFBP3 were performed yearly.

Results: BMD increased over time with a tendency of attenuation towards the end of the study and bone markers decreased over time, both with no differences between the groups. IGF1 decreased in both groups. The rate of change of IGF1 was constantly lower in the HD group. LBM increased significantly in the HD group over time, whereas FM remained stable in both groups.

Conclusion: We show a distinct pattern of changes in BMD in TS over time with a steady increase in BMD in accordance with the findings in the general population of healthy young women. The higher estrogen dose did not affect BMD or bone markers. The positive effect on body composition may have long ranging health benefits in TS.

Funding: Novo Nordisk supplied the study medication.