Objective: To determine the long-term effects of estrogen replacement therapy on sex hormone binding globuline (SHBG) and free testosterone (fT) levels in surgical postmenopausal women. Study Design: Forty patients with surgical menopause were enrolled in this prospective study. The women were randomly divided into two groups. The first group received oral therapy (continuous conjugated equine estrogens (CEE) - 0.625 mg per day) and the second group received transdermal therapy (patches delivering continuous 17 beta -estradiol (E2) - 0.05 mg per day). Serum SHBG and fT levels were determined at baseline and after first and second years of treatment. Two-way repeated measures analysis of variance with Bonferroni adjusted post-hoc test and unpaired-t-test were performed for statistical analysis with SPSS program. Results: Serum SHBG levels increased significantly with oral CEE after first year of treatment (P < 0.05) and remained at this level for the next year. Transdermal therapy did not affect SHBG levels after first and second years (P < 0.05). Serum fT levels did not change significantly in either group at the end of the first or second years (P < 0.05) although there was a significant difference between the groups after 2 years (P < 0.05). Conclusion: Oral conjugated estrogens increased SHBG levels during therapy. This effect may balance the increased estrogen and androgen stimulation on breast tissue and may be more beneficial to the cardiovascular system in postmenopausal women. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.