Effects of low‐dose continuous combined hormone replacement therapy on glucose homeostasis and markers of cardiovascular risk in women with type 2 diabetes

Summary Background  Low-dose hormone replacement therapy (HRT) has attracted interest for the treatment of postmenopausal symptoms in diabetes because of concerns about increased risk of coronary heart disease (CHD) and stroke with conventional HRT containing conjugated equine oestrogens (CEEs) and medroxyprogesterone acetate (MPA). Objectives  We assessed the effects on glucose homeostasis and cardiovascular risk factors of continuous oral 17β oestradiol (1 mg) and norethisterone (0·5 mg) in postmenopausal women with type 2 diabetes. Design  Double-blind, randomized placebo-controlled trial. Assessments  Hyperinsulinaemic isoglycaemic clamp and cardiovascular risk factors were assessed before and after 3 months of treatment. Results  Twenty-eight women completed the study. HRT decreased fasting glucose compared with placebo [−9·4% with HRT vs.+2·3% for placebo, 95% confidence interval (CI) −23·2 to −0·3] and total cholesterol (−13·7 vs.+1·0%, 95% CI −22·4 to −3·1%) No significant effect was seen on metabolic clearance rate of glucose, glycated haemoglobin (HbA1c), triglycerides, high density lipoprotein (HDL)-cholesterol or C-reactive protein (CRP). Conclusions  In women with type 2 diabetes, low-dose HRT decreased fasting glucose and total cholesterol without detectable adverse effects on glucose clearance, triglycerides and CRP as reported with conventional HRT.