Glucose metabolism, lipid metabolism, and cardiovascular risk factors in adult Turner's syndrome. The impact of sex hormone replacement

Abstract

OBJECTIVE: To examine glucose metabolism, blood pressure, physical fitness, and lipid metabolism in adult untreated women with Turner's syndrome compared with a group of normal women and to examine the effects of female sex hormone substitution on these factors. RESEARCH DESIGN AND METHODS: A total of 26 patients with Turner's syndrome were examined before and during sex hormone replacement with 17 beta-estradiol and norethisterone, and an age-matched control group (n = 24) was examined once. A frequently sampled intravenous glucose tolerance test was applied with minimal model assessment. We also performed an oral glucose tolerance test, measurement of 24-h ambulatory blood pressure, and assessment of physical fitness and lipid metabolism. RESULTS: Insulin sensitivity (SI) and glucose effectiveness (SG) were similar in Turner's syndrome patients and control subjects, whereas the acute insulin response (P = 0.03) was lower in Turner's syndrome patients, and no change was seen during sex hormone treatment. Abnormal glucose tolerance was found in 50% of Turner's syndrome patients before and 78% during treatment with sex hormones. Fat-free mass (FFM; P = 0.0005) and physical fitness (P = 0.002) were lower in Turner's syndrome subjects compared with control subjects. During treatment, an increase in FFM (P = 0.001) and physical fitness (P = 0.02) was seen in Turner's syndrome patients. Blood pressure was increased in Turner's syndrome, and a decrease was seen in diastolic blood pressure during treatment with sex hormones. CONCLUSIONS: Turner's syndrome is associated with glucose intolerance, diminished first-phase insulin response, elevated blood pressure, reduced FFM, and physical fitness. Sex hormone administration causes a deterioration in glucose tolerance, increases FFM and physical fitness, and has beneficial effects on blood pressure. The deleterious effect on glucose tolerance may be mediated by norethisterone, a gestagen known to have androgenic effects.