Abstract only Changes in sex hormones with weight loss might have implications for breast cancer prevention and have not been examined extensively, particularly in African‐American (AA) women. We conducted a longitudinal study of 278 overweight/obese postmenopausal women (38% AA), not taking hormone therapy, who lost at least 4 kg after a 6‐month weight‐loss program. During the next 12 months, participants attempted to sustain weight loss. We evaluated percent change in serum estrone (E1), total estradiol (E2), testosterone, androstenedione, dehydroepiandrosterone sulfate and sex hormone‐binding globulin (SHBG) across the two phases using GEE. During the weight‐loss program, mean weight loss was 7.7 kg: E1 (−5.7%, P=0.006) and E2 (−9.9%, P< 0.001) decreased, SHBG (16.2%, P< 0.001) increased. During weight maintenance, weight increased on average 2.2 kg: E1 (−6.4%, P=0.003) and SHBG (−8.0%, P<0.0001) decreased. AA women experienced less change in estrogens (E1 0.6% vs. 1.2%, p‐interaction= 0.10, E2 1.1% vs. 1.9%, p‐interaction=0.04) and SHBG (0.9% vs. 1.6%, p‐interaction=0.006) per kg weight change than non‐AA. AA women also had significantly higher estrogen concentrations, independent of adiposity. Overweight/obese postmenopausal women who successfully lose and maintain weight have reductions in estrogens which may reduce breast cancer risk. The racial differences merit investigation.