The endogenous estrogen 17beta-estradiol can be metabolized to 16alpha-hydroxyestrone (16alpha OHE1) or 2-hydroxyestrone (2OHE1). In contrast to 2OHE1, 16alpha OHE1 is highly estrogenic and has been found to enhance the proliferation of estrogen-sensitive breast cancer cells in culture. It has been hypothesized that shifting the metabolism of 17beta-estradiol toward 2OHE1 and away from 16alphaOHE1 could decrease the risk of estrogen-sensitive cancers, such as breast cancer. In a small clinical trial, increasing cruciferous vegetable intake of healthy postmenopausal women for four weeks increased urinary 2OHE1:16alpha OHE1ratios, suggesting that high intakes of cruciferous vegetables can shift estrogen metabolism.
Cruciferous vegetables are a rich source of glucosinolates and their hydrolysis products, including indoles and isothiocyanates, and high intake of cruciferous vegetables has been associated with lower risk of lung and colorectal cancer in some epidemiological studies. Glucosinolate hydrolysis products alter the metabolism or activity of sex hormones in ways that could inhibit the development of hormone-sensitive cancers, but evidence of an inverse association between cruciferous vegetable intake and breast or prostate cancer in humans is limited and inconsistent. Organizations such as the National Cancer Institute recommend the consumption of five to nine servings of fruits and vegetables daily, but separate recommendations for cruciferous vegetables have not been established. Isothiocyanates and indoles derived from the hydrolysis of glucosinolates, such as sulforaphane and indole-3-carbinol (I3C), have been implicated in a variety of anticarcinogenic mechanisms, but deleterious effects also have been reported in some experimental protocols, including tumor promotion over prolonged periods of exposure. Epidemiological studies indicate that human exposure to isothiocyanates and indoles through cruciferous vegetable consumption may decrease cancer risk, but the protective effects may be influenced by individual genetic variation (polymorphisms) in the metabolism and elimination of isothiocyanates from the body. Cooking procedures also affect the bioavailability and intake of glucosinolates and their derivatives. Supplementation with I3C or the related dimer 3,3'-diindolylmethane (DIM) alters urinary estrogen metabolite profiles in women, but the effects of I3C and DIM on breast cancer risk are not known. Small preliminary trials in humans suggest that I3C supplementation may be beneficial in treating conditions related to human papilloma virus infection, such as cervical intraepithelial neoplasia and recurrent respiratory papillomatosis, but larger randomized controlled trials are needed.