Equol Is a Novel Anti-Androgen that Inhibits Prostate Growth and Hormone Feedback1

Abstract

Equol (7-hydroxy-3[4'hydroxyphenyl]-chroman) is the major metabolite of the phytoestrogen daidzein, one of the main isoflavones found abundantly in soybeans and soy foods. Equol may be an important biologically active molecule based on recent studies demonstrating that equol can modulate reproductive function. In this study, we examined the effects of equol on prostate growth and LH secretion and determined some of the mechanisms by which it might act. Administration of equol to intact male rats for 4-7 days reduced ventral prostate and epididymal weight and increased circulating LH levels. Using binding assays, we determined that equol specifically binds 5alpha-dihydrotestosterone (DHT), but not testosterone, dehydroepiandrosterone, or estrogen with high affinity. Equol does not bind the prostatic androgen receptor, and has a modest affinity for recombinant estrogen receptor (ER) beta, and no affinity for ERalpha. In castrated male rats treated with DHT, concomitant treatment with equol blocked DHT's trophic effects on the ventral prostate gland growth and inhibitory feedback effects on plasma LH levels without changes in circulating DHT. Therefore, equol can bind circulating DHT and sequester it from the androgen receptor, thus altering growth and physiological hormone responses that are regulated by androgens. These data suggest a novel model to explain equol's biological properties. The significance of equol's ability to specifically bind and sequester DHT from the androgen receptor have important ramifications in health and disease and may indicate a broad and important usage for equol in the treatment of androgen-mediated pathologies.

Age-stratified serum levels of isoflavones and proportion of equol producers in Japanese and Korean healthy men

“…11,12 Equol and isoflavones have a binding affinity estrogen receptor b. 13,14 Additionally, equol can bind sex hormone-binding globulin 15,16 and 5a-dihydrotestosterone 14 and inhibit the growth of prostate cells in vitro and in vivo. 14,17 Therefore, equol can act as an anti-androgen and inhibit the development of sex hormone-dependent tumors such as breast cancer and prostate cancer.…”

“…13,14 Additionally, equol can bind sex hormone-binding globulin 15,16 and 5a-dihydrotestosterone 14 and inhibit the growth of prostate cells in vitro and in vivo. 14,17 Therefore, equol can act as an anti-androgen and inhibit the development of sex hormone-dependent tumors such as breast cancer and prostate cancer. 14 In our previous study, we demonstrated that the proportion of equol producers was significantly smaller in the patient group with prostate cancer than in the cancer-free control group and that this proportion was significantly smaller in patients with poorly differentiated adenocarcinoma than in those with well or moderately differentiated adenocarcinoma.…”

“…14,17 Therefore, equol can act as an anti-androgen and inhibit the development of sex hormone-dependent tumors such as breast cancer and prostate cancer. 14 In our previous study, we demonstrated that the proportion of equol producers was significantly smaller in the patient group with prostate cancer than in the cancer-free control group and that this proportion was significantly smaller in patients with poorly differentiated adenocarcinoma than in those with well or moderately differentiated adenocarcinoma. 18 Moreover, the serum isoflavone levels and the proportions of equol producers are very low among American men when compared with Japanese and Korean men.…”

Effect of forage on the content of phyto-oestrogens in bovine milk

“…Studies have shown that only 30% to 50% of the population is capable of producing equol from daidzein (Lampe et al, 1998;Rowland et al, 2000). Equol is superior to other isoflavones in its antioxidant activity (Arora et al, 1998), has greater affinity to the oestrogen receptors than its precursor daidzein (Setchell et al, 2002) and can bind 5a-dihydrotestosterone, thereby hindering its binding to the androgen receptor, thus altering growth and physiological hormone responses that are regulated by androgens (Lund et al, 2004). Therefore, milk with a high concentration of equol may be interesting as a dietary source of equol if the beneficiary effects of equol are confirmed.…”

Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta‐analysis of individual participant data from seven prospective studies including 2,828 cases and 5,593 controls

“…In vitro and animal studies have shown that equol has anti‐androgenic and anti‐proliferative properties in the prostate,30, 32 but its role in humans remains unclear. Equol production varies between individuals, and the term equol‐producers refers to people who produce equol after consuming isoflavones; therefore it may be possible that the health benefits of soya‐based diets are greater in equol‐producers than in equol non‐producers 33…”