Endocrine Abstracts

Cardiovascular disease is the major cause of mortality in women with Turner Syndrome(TS), and may be congenital or acquired. There is a high prevalence of risk factors for ischaemic heart disease(IHD) including hypertension, dyslipidaemia, diabetes and obesity. This oestrogen dose-ranging vascular physiology study compared women with TS (n=14) and 46,XX gonadal dysgenesis(GD) (n=11) to determine the relative contributions of oestrogen deficiency and genetics, and to assess the oestrogen-responsiveness of surrogate markers of IHD risk. Local Ethics Committee approval was obtained.

All women sequentially received for three periods of 12 weeks (three 28-day cycles) each: oral 17-beta oestradiol 1, 2 and 4mg daily, with dydrogesterone 10mg on days 15-28 of each cycle. Vascular physiology studies to assess augmentation index(AIx), pulse wave velocity(PWV), carotid intima-media thickness(IMT) and flow-mediated dilatation(FMD) were performed during week 10 of each respective dose, along with metabolic and anthropometric assessments.

Carotid IMT decreased in TS women with increasing oestrogen dose (0.63, 0.57, 0.56mm at 1,2 and 4mg oestradiol respectively,p=0.003). Similar changes were seen in 46,XXGD women(p=0.038). AIx, PWV and FMD, as well as blood pressure and anthropometric parameters did not change in either group with increasing oestrogen dose, while HDL cholesterol increased in both groups. Triglyceride concentrations increased in women with TS, while insulin concentrations and calculated HOMA decreased in 46,XXGD women.

Increasing oestrogen dose reduces carotid IMT, which correlates strongly with IHD risk, in women with TS and 46,XXGD. Oestrogen resistance does not appear to be a feature of TS in this respect, since both groups responded similarly. Arterial stiffness and endothelial function were unaffected by higher doses. Insulin sensitivity improved in 46,XXGD but not TS women.

In conclusion, higher doses of oestrogen may be beneficial in young oestrogen-deficient women to reduce risk of IHD. The absence of an increase in blood pressure or weight is reassuring.