Modulation of Estrogen Chemical Carcinogenesis by Botanical Supplements used for Postmenopausal Women's Health

Abstract

Breast cancer risk has been associated with long-term estrogen exposure including traditional hormone therapy (HT, formally hormone replacement therapy). To avoid traditional HT and associated risks, women have been turning to botanical supplements such as black cohosh, red clover, licorice, hops, dong gui, and ginger to relieve menopausal symptoms despite a lack of efficacy evidence. The mechanisms of estrogen carcinogenesis involve both hormonal and chemical pathways. Botanical supplements could protect women from estrogen carcinogenesis by modulating key enzymatic steps [aromatase, P4501B1, P4501A1, catechol-O-methyltransferase (COMT), NAD(P)H quinone oxidoreductase 1 (NQO1), and reactive oxygen species (ROS) scavenging] in estradiol metabolism leading to estrogen carcinogenesis as outlined in Figure 1. This review summarizes the influence of popular botanical supplements used for women's health on these key steps in the estrogen chemical carcinogenesis pathway, and suggests that botanical supplements may have added chemopreventive benefits by modulating estrogen metabolism.

Figure 1

Seven key steps in estradiol metabolism leading to increased cancer risk and how botanical compounds and/or extracts can influence the enzymes. 1) Inhibition of aromatase with licorice [20], hops [21,22], and mixed results with red clover [17,18]. 2) CYP1B1 inhibition with hops [29], red clover [30], and induction with black cohosh [27,28]. 3) Inhibition of CYP1A1 with hops [29] and an induction with black cohosh [27,28], licorice [36], while red clover has been shown to increase CYP1A1 [34] and decrease CYP1A1 [35]. 4) COMT has been inhibited by red clover [35,38]. 5) NQO1 was induced by black cohosh [40], licorice [–45], hops [46,47], dong gui [48], ginger [49] with mixed results from red clover [35,41,42]. 6) GST was increased by licorice [44,45,50] and ginger [51,52] and inhibited by dong gui [53]. 7) ROS were scavenged by all the botanicals in this review; black cohosh [55], licorice [–58], and ginger [59] with weak antioxidant activity from red clover [60], hops [46], and dong gui [48].