Effect of postmenopausal oestradiol and dydrogesterone therapy on lipoproteins and insulin sensitivity,secretion and elimination in hysterectomised women

OBJECTIVES: To investigate in depth the metabolic effects of oestradiol-17 beta both alone and in combination with the progestagen dydrogesterone. METHODS: Fifteen hysterectomised postmenopausal women were studied before treatment and after 24 weeks taking oestradiol-17 beta alone (2 mg per day), then following a further 6 (oestrogen-alone phase) and 12 (oestrogen plus progestagen phase) weeks with inclusion of dydrogesterone (10 mg per day for days 17-28 of each 28 day cycle). Measurements at each visit included fasting serum lipid and lipoprotein concentrations, insulin sensitivity, secretion and elimination by modelling analysis of intravenous glucose tolerance test glucose, insulin and C-peptide concentrations, body fat distribution by dual-energy X-ray absorptiometry (DXA) and arterial function by carotid artery ultrasound. RESULTS: Significant reductions were seen throughout in total and LDL cholesterol. The net reductions in total and LDL cholesterol by the end of the study were 5.8% (P<0.05) and 18.4% (P<0.001), respectively. HDL and HDL subfraction cholesterol concentrations rose during treatment with oestradiol alone, the rise being primarily in the HDL(2) subfraction (+21.6%, P<0.001). Fasting serum triglycerides rose 30% on oestradiol treatment. These increases were unaffected by the addition of dydrogesterone. Insulin sensitivity, secretion and elimination, body fat distribution and arterial function were not significantly affected at any stage of the therapy. CONCLUSIONS: The small study sample and high variability in measures of glucose and insulin metabolism may have contributed to the absence of the expected significant improvement in these parameters. Orally administered oestradiol had beneficial effects on total, LDL and HDL cholesterol which were unaffected by the addition of dydrogesterone.