Estrogen receptors (ER) are expressed not only in the reproductive system and ovaries but also in some other tissues, including the adrenal gland. The purpose of this study was to assess the association between the estrogen receptor (ER) alpha gene polymorphisms XbaI and PvuII and circulating levels of androstenedione, a precursor of sex-steroids synthetized in the ovary and adrenal. After adjustment for years since menopause, body mass, and dehydroepiandrosterone (DHEA) levels, a highly significant relationship was demonstrated between androstenedione and XbaI or PvuII polymorphisms, the highest levels of the hormone being found in the xx and pp genotypes (P<0.05 as compared to XX or PP, ANCOVA followed by least significant difference (LSD) multiple comparisons). This suggests that the ER genotype may determine the function of the sex-steroid system not only at the receptor level but also at the level of hormone synthesis. The pathogenetic role of this association in diseases related to menopause, such as osteoporosis, remains to be determined.