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To verify the effects of hypoestrogenism and replacement therapy on body mass index (BMI) and leptin in ovariectomized women.We conducted a longitudinal study on 56 women undergoing abdominal bilateral ovariectomy divided into three groups: 19 untreated controls, 18 scheduled to receive 17β-estradiol, and 19 on raloxifene starting 15 days after surgery. Height, weight, and BMI were recorded on the day of surgery, 5 and 15 days later, and then after 6 months. Leptin and estradiol concentrations were determined by radioimmunoassay on the day of surgery, days 1, 5, and 15, and 6 months after.Leptin levels rose significantly on the day after surgery [median (range): 18.2 (9.8–25.0), 12.5 (9.1–20.9), and 20.5 (12.9–24.5);P < 0.01 v basal] and returned to values similar to baseline on day 5 in all groups. Six months later, controls showed significantly higher leptin levels in comparison with both treated women and basal values [median (range): 19.7 (10.4–22.8), 11.0 (7.6–16.9), and 13.5 (9.1–14.8) ng/ml;P < 0.01). Estradiol levels decreased in all groups, reaching statistical significance 5 days after surgery (P < 0.01 v basal). A significant rise was observed 6 months after surgery in women treated with estrogens (P < 0.01). Six months after surgery, BMI increased in untreated controls in comparison with treated women and baseline, although not significantly.The absence of modifications in leptin on days 5 and 15 after ovariectomy suggests that, in humans, estrogens may not exert an important effect on leptin secretion. After 6 months, replacement therapy maintained leptin levels and BMI was unmodified, whereas untreated controls showed a significant increase in leptin and a trend toward higher BMI, suggesting that replacement therapy may prevent changes in fat distribution and in leptin levels.