Effects on Serum Hormone Concentrations after a Dietary Phytoestrogen Intervention in Patients with Prostate Cancer: A Randomized Controlled Trial

Abstract

Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERβ) and modulating several hormones. We primarily aimed to investigate the effect of a phytoestrogen intervention on hormone concentrations in blood depending on the ERβ genotype. Patients with low and intermediate-risk prostate cancer, scheduled for radical prostatectomy, were randomized to an intervention group provided with soybeans and flaxseeds (∼200 mg phytoestrogens/d) added to their diet until their surgery, or a control group that was not provided with any food items. Both groups received official dietary recommendations. Blood samples were collected at baseline and endpoint and blood concentrations of different hormones and phytoestrogens were analyzed. The phytoestrogen-rich diet did not affect serum concentrations of testosterone, insulin-like growth factor 1, or sex hormone-binding globulin (SHBG). However, we found a trend of decreased risk of increased serum concentration of estradiol in the intervention group compared to the control group but only in a specific genotype of ERβ (p = 0.058). In conclusion, a high daily intake of phytoestrogen-rich foods has no major effect on hormone concentrations but may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERβ.

Keywords: estradiol; insulin-like growth factor 1; isoflavones; lignans; phytoestrogens; prostate cancer; sex hormone-binding globulin; testosterone.

Figure 1

Design of the PRODICA (the impact of DIet and individual genetic factors on tumor proliferation rate in men with PROstate CAncer) study. During the inclusion meeting, participants were randomized to an intervention or a control group, filled out a questionnaire, and blood samples were collected. A similar questionnaire was filled out and blood samples were collected again within seven days before the time of surgery. The intervention was intended to last approximately 6 weeks.

Figure 2

Chemical structures of the analyzed phytoestrogens in the study. Collected with permission from PubChem, URL: pubchem.ncbi.nlm.nih.gov [29].

Figure 3

Flowchart of the PRODICA study.

Figure 4

Boxplots showing plasma concentrations of different phytoestrogens (nmol/L) in the intervention- (n = 51) and control groups (n = 54) in patients with prostate cancer at baseline and endpoint. (A) Plasma concentrations of lariciresinol, secoisolariciresinol, and glycitein. (B) Plasma concentrations of enterolactone, enterodiol, and equol. (C) Plasma concentrations of daidzein and genistein. Concentrations of secoisolariciresinol, glycitein, enterolactone, enterodiol, equol, daidzein, and genistein were statistically significantly higher in the intervention group compared to the control group at the endpoint. The Mann–Whitney U test was used to test differences between groups.