Objective Leptin, a hormone secreted by adipocytes, plays a crucial role in regulating energy balance. Estrogen, like leptin, reduces food intake and adiposity while increasing energy expenditure in animals and humans of both sexes through its actions in the central nervous system. We reviewed the literature for studies of the effect of exogenously administered estrogen on serum leptin concentrations and adiposity in women. Methods Using PubMed/MEDLINE, we searched for studies of hormone therapy that enrolled healthy postmenopausal women. Studies were further evaluated to determine if leptin and adiposity were monitored both at baseline and throughout a treatment period of at least two months. Results Twenty articles met inclusion criteria. We found no consistent effect of exogenous estrogen on serum leptin concentrations, adiposity, or weight gain. Conclusion Despite suggestive data from animal studies, current literature does not provide compelling evidence that estrogen therapy attenuates weight gain, alters circulating leptin levels, or improves leptin action in postmenopausal women.