The effects of sequential combined oral 17 beta-estradiol norethisterone acetate on insulin sensitivity and body composition in healthy postmenopausal women: a randomized single blind placebo-controlled study

Objective: The androgenic effect of progestogen, necessary in early postmen opausal hormone replacement therapy (HRT), may adversely affect insulin sen sitivity as well as body fat distribution and thereby increase the cardiova scular risk profile. The impact of HRT with sequential combined oral 17 bet a -estradiol and norethisterone acetate on insulin sensitivity and body com position in early menopause has not been studied. Design: A randomized single blind placebo-controlled 6-month study of seque ntial combined 17 beta -estradiol norethisterone acetate on insulin sensiti vity and body composition was carried out. Thirty fit healthy postmenopausa l women were enrolled and completed this 6-month study. Body composition wa s measured by dual-energy x-ray absorptiometry scanning, and insulin sensit ivity was measured using the euglycemic hyperinsulinemic clamp. Studies wer e undertaken at baseline and after 6 months of therapy. The studies were pe rformed during the estrogen-only phase of therapy. Results: All women demonstrated a degree of decreased insulin sensitivity t hat was not modified by 6 months of hormone replacement therapy. Body compo sition remained unchanged over 6 months. There was no alteration in total b ody fat or the distribution of body fat. The percentage of central abdomina l fat (android) was not altered. Conclusion: Six months of HRT with sequential combined oral 17 beta -estrad iol norethisterone acetate does not have an adverse effect on insulin sensi tivity and does not promote an increase in weight or the more android distr ibution of body fat, which could contribute to the increased cardiovascular risk profile that is evident in postmenopausal women.