It is now clear that estrogen intervention reduces bone loss in postmenopausal osteoporosis. The aim of this study was to investigate whether the route of estrogen administration or addition of progesterone changes this positive effect. Transdermal estrogen (T-E), oral estrogen (E), and oral estrogen plus progestogen (E-P) were administered to 15, 18, and 17 postmenopausal women, respectively, who all had normal bone mineral density (BMD) before hormone replacement therapy (HRT). Calcium (500 mg/day) was routinely added to all HRT regimens. The BMD of the lumbar spine (L2-L4) was measured initially and at the end of the first and second years of treatment. The paired-sample t test, independent-sample t test, and Pearson correlation analysis were used for the statistical evaluation. The initial BMD measurements and the values at the end of the first and second years of the therapy were not significantly different either within or among the groups (P > 0.05). These results indicate a similar therapeutic value of each HRT regimen in the prevention of bone loss in postmenopausal women.