In a prospective, randomized clinical study 77 women were assigned randomly to receive sequential hormone therapy with either conventional oral conjugated equine estrogens (0.625 mg) with the addition on 14 of the 28 days of oral medroxyprogesterone acetate (5 mg) or natural E(2) gel (1.5 mg) with oral micronized P (200 mg) on 14 of the 28 days of each cycle. Because oral conjugated equine estrogens-medroxyprogesterone acetate induced a highly significant increase in breast cell proliferation in contrast to percutaneous E(2)-oral P with a difference between therapies approaching significance, the former therapy has a marked impact on the breast whereas natural percutaneous E(2)-oral micronized P has not. ; Peer reviewed