Studies evaluating the effect of estrogen replacement therapy (ERT) on leptin levels are contradictory. The aim of this study was to investigate effects of bilateral ovariectomy and ERT on serum leptin levels and anthropometric measurements as well as interaction among leptin, sex hormone binding globulin (SHBG), and insulin like growth factor-I (IGF-I) in premenopausal women after bilateral ovariectomy. Twenty-four premenopausal women who undergo bilateral overiectomy were divided into two groups based on whether they received hormonal treatment postoperatively. The studied parameters were evaluated in both groups preoperatively and during the fourth and eighth weeks postoperatively. Serum leptin, testosterone, prolactin, insulin, IGF-1 levels, BMI, HOMA-IR, and waist-to-hip ratio values did not change in both groups at all times. In the estradiol group, serum SHBG concentrations were significantly higher on weeks 8 compared with control group and basal values (p = 0.03 and 0.014, respectively). Leptin levels showed a positive linear correlation with BMI in all groups and at all times evaluated (r = 0.80, p < 0.01 for controls and r = 0.62, p < 0.01 for women treated with 17 beta-estradiol) and with insulin in estradiol group on weeks 4 (r = 0.755, p < 0.05). No correlation was found between leptin and estradiol, testosterone, prolactin, SHBG, IGF-1 levels, and anthropometric variables at all times. Leptin levels do not show modification 8 weeks after bilateral ovariectomy and under ERT, suggesting that estrogens do not have a stimulatory action on leptin in humans. Although needing confirmation by a longer study, our findings suggest that IGF-I system and SHBG did not regulate leptin and vice versa and ERT do not have any effect on leptin, SHBG, and IGF-I.