Anti-androgenic action by red clover-derived dietary isoflavones reduces non-malignant prostate enlargement in aromatase knockout (arko) mice

Background Red clover (RC)‐derived dietary isoflavones have been implicated as potential preventative agents for the development and prevalence of non‐malignant prostate diseases. This study investigated whether dietary isoflavones inhibit prostate growth in vivo in the aromatase knock‐out (ArKO) mouse that exhibits lifelong elevation of androgens leading to prostate enlargement. Methods Adult (11‐week‐old) wild‐type (WT) and ArKO mice were fed on protein matched isoflavones free (IF) and RC (isoflavone rich) diets for 28 days. Individual prostate lobes and testes were weighed and collected for histological analysis and serum androgens were measured. Responses were compared to castration and estrogen administration to ArKO mice to determine the mechanism of action. Results ArKO mice fed on IF diet exhibited enlarged prostate lobes and elevated serum androgens compared to WT mice. Following 28 days of RC diet, ArKO VP, AP, and SV weights were reduced to WT weights, although testis and body weights remained unaltered. Stereological analysis of VPs revealed a reduction in all components of the tissue, particularly the lumen. The RC diet reduced ArKO serum testosterone and dihydrotestosterone to WT levels. In comparison to castration and estrogen administration, the dietary isoflavones were shown to be anti‐androgenic rather than weakly estrogenic, mimicking responses observed in the castrated ArKO, rather than estrogen treated ArKOs. Conclusions This study demonstrates that RC‐derived isoflavones have a significant effect on prostatic growth, and are capable of reducing the enlarged non‐malignant prostate phenotype of the adult ArKO mouse, by acting as anti‐androgenic agents rather than weak estrogenic substances. Prostate 56: 54–64, 2003. © 2003 Wiley‐Liss, Inc.