The long-term effect of percutaneous and oral estrogen replacement therapy on soft tissue body composition was examined in a two-year, placebo-controlled study with 110 early postmenopausal women. The women were allocated to four treatment groups: (1) oral cyclical combination of estradiol valerate and cyproterone acetate, (2) oral placebo, (3) percutaneous 17 beta-estradiol, supplemented by oral progesterone during the second year, or (4) percutaneous placebo cream. Total-body lean body mass (LBM) and fat mass (FM) were measured by dual photon (153Gd) absorptiometry once a year, and the fat layer in the distal forearm (FATarm) was measured every 3 months by single photon (125I) absorptiometry. Both hormone therapies prevented an increase in FATarm, as observed in the placebo groups. A similar pattern was seen for FM, body weight, and skin-fold thickness (measured once a year by mechanical calipers), whereas LBM was unaffected by the therapy. Hormonal replacement therapy prevents the age-related increase in body fat observed after the menopause.