Sex steroid hormones have multiple effects on lipid metabolism. We investigated the association between two common single nucleotide polymorphisms of the estrogen receptor 2 gene (ESR2), 1082G> A and 1730A> G, and PROGINS polymorphism of the progesterone receptor gene (PGR) with lipoprotein levels in a cross-sectional study with 472 women of European descent. The women were classified into three subgroups according to hormonal status, premenopausal women (n= 187; mean age= 34±9.7 years), postmenopausal women exposed to hormone replacement therapy (HRT)(n= 118; 56±6.7 years) and postmenopausal women unexposed to HRT (n= 167; 58±9.8 years). The premenopausal and postmenopausal women exposed to HRT, both carriers of G/A genotype, exhibited LDL-C (P= 0.027 and 0.001, respectively) and T-chol levels (P= 0.035 and 0.001, respectively) lower than carriers of G/G genotype. This association was not observed in postmenopausal women unexposed to HRT. These results suggest that ESR2 1082G> A genotype may influence LDL-C levels in women with abundant estrogen levels, due to either endogenous or exogenous sources.