Previous exposure to hormone replacement therapy and confounders in metabolic studies.

OBJECTIVE: The quantity of intra-abdominal fat is highly associated with the development of diabetes mellitus. We sought to determine whether recent hormone replacement therapy (HRT) use modifies central fat and insulin sensitivity in postmenopausal women compared with women who had never used HRT. DESIGN: We measured intra-abdominal fat, subcutaneous abdominal fat, and sagittal diameter at the L4-L5 vertebral disc space using computed tomography imaging. Total body fat and fat-free mass were measured using dual energy x-ray absorptiometry. Insulin sensitivity was assessed using the euglycemic hyperinsulinemic clamp technique in 42 nonobese postmenopausal women, age 51 +/- 4 years (12 recent HRT users plus 30 never-users). All women who were taking HRT discontinued it for 2 months before the study. RESULTS: After statistical adjustment for age, previous use of HRT was associated with decreased intra-abdominal fat (72 +/- 34 cm2) compared with no HRT use (96 +/- 33 cm2; p = 0.05). This difference remained significant after adjustment for time since menopause. When previous HRT users were compared with nonusers, there were no differences in subcutaneous abdominal fat, sagittal diameter, fat-free mass, total fat, insulin sensitivity, or body weight. CONCLUSIONS: Recent HRT use is associated with lower intra-abdominal fat in nonobese, early postmenopausal women. This finding suggests a carry-over effect of HRT on intra-abdominal fat. Recent HRT use does not seem to be associated with differences in glucose disposal.