Data from laboratory and epidemiologic studies support a relationship between endogenous
hormones and the increased risk of several female
cancers. In epidemiologic studies, consistent associations have been observed between risk of breast, ovarian and
endometrial cancers and reproductive and hormonal risk factors such as high postmenopausal body mass index (BMI) and postmenopausal
hormone use, which suggest the importance of endogenous
hormones in the etiology of these diseases. The relationship between circulating
estrogen levels in postmenopausal women and the risk of
breast cancer is well established, with an approximately 2-fold higher risk among women in the top 20-25% (versus bottom 20-25%) of levels. However, data evaluating the relationship between endogenous
estrogens and premenopausal
breast cancer risk are more limited and less consistent. Two studies to date have evaluated the relationship between circulating
estrogens and
breast cancer risk by menstrual cycle phase at blood collection and only one study has examined this relationship by menopausal status at diagnosis. Three prospective studies have evaluated circulating
estrogen levels and
endometrial cancer risk in postmenopausal women, with consistent strong positive associations reported (with relative risks of 2-4 comparing high versus low
hormone levels), while this relationship has not been studied in premenopausal women. Compared to breast and
endometrial cancers, reproductive and hormonal characteristics such as postmenopausal
hormone use are generally weaker and less consistent risk factors for
ovarian cancer, and the only small prospective study conducted to date indicated a non-significant positive relationship between circulating
estrogen levels and
ovarian cancer risk. In this review, we summarize current evidence and identify key areas to be addressed in future epidemiologic studies of endogenous
estrogens and the risk of breast, endometrial, and
ovarian cancers.