ObjectiveThe androgenic effect of progestogen, necessary in early postmenopausal hormone replacement therapy (HRT), may adversely affect insulin sensitivity as well as body fat distribution and thereby increase the cardiovascular risk profile. The impact of HRT with sequential combined oral 17&bgr;-estradiol and norethisterone acetate on insulin sensitivity and body composition in early menopause has not been studied.DesignA randomized single blind placebo-controlled 6-month study of sequential combined 17&bgr;-estradiol norethisterone acetate on insulin sensitivity and body composition was carried out. Thirty fit healthy postmenopausal women were enrolled and completed this 6-month study. Body composition was measured by dual-energy x-ray absorptiometry scanning, and insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp. Studies were undertaken at baseline and after 6 months of therapy. The studies were performed during the estrogen-only phase of therapy.ResultsAll women demonstrated a degree of decreased insulin sensitivity that was not modified by 6 months of hormone replacement therapy. Body composition remained unchanged over 6 months. There was no alteration in total body fat or the distribution of body fat. The percentage of central abdominal fat (android) was not altered.ConclusionSix months of HRT with sequential combined oral 17&bgr;-estradiol norethisterone acetate does not have an adverse effect on insulin sensitivity and does not promote an increase in weight or the more android distribution of body fat, which could contribute to the increased cardiovascular risk profile that is evident in postmenopausal women.