OR22-5 Dietary Fat Modulate Androgen Metabolism in the Human Prostate

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR22-Male Reproductive Hormones: Effects on Fertility and Beyond
Translational
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 12:15 PM
Room 104 (Moscone Center)
Christina CL Wang*1, Heinrich Vierhapper2, Peter J Nowotny3, Andrew Leung4, Thomas Vandergast5, Rachelle Bross6, Peter Christenson7, Laura Hull6, Jacob Rajfer8, Robert Sinow9, Samuel French10, Luciano Barajas10 and Ronald S. Swerdloff11
1Harbor - UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, 2University of Vienna, Vienna, Austria, 3University of Vienna, Wien, Australia, 4Los Angeles Biomedical Research Insititute at Harbor-UCLA Medical Center, Torrance, 5Kaiser Permanente South Bay Medical Center, Harbor City, 6Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, 7Los Angeles Biomeidcal Research Institute at Harbor-UCLA Medical Center, Torrance, 8Harbor-UCLA Med Ctr, Torrance, CA, 9Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, 10Harbor-UCLA Medical Center and Los Angeles Biomedical Research Center, Torrance, 11Harbor - UCLA Med Ctr and Los Angeles Biomedical Research Institute, Torrance, CA
Context: Epidemiological studies showed that dietary fat is associated with risk of development of prostate cancer (PCa). We have previously shown that low fat diet lowers serum and urinary androgens in middle aged men.

Objective and Main Outcome Measures: We determined, before and after high and low fat diet modulation, changes in the conversion of T to 5α- and 5β-diols and androgen levels in prostatic tissues obtained at biopsy in men with elevated PSA but without evidence of PCa on first biopsy.

Design, Setting, Participants and Methods: 56 men (mean age 60±1 years) with elevated serum PSA but without PCa on initial biopsy who were usually taking a high fat diet participated in the study. 30 subjects were randomized to take a diet mimicking their home diet (>30% calories as fat) and 26 to a diet containing 10 to 15% of total calories from fat and 25 to 35 g fiber/day for 8 weeks. Clinically indicated prostate biopsies were performed before and after diet modulation because of a persistent elevated PSA. Conversion of T to the 5α- and 5β-reduced metabolites and prostate androgens were measured by GC-MS using established methods.

Results: Conversion of T to DHT and 5α,3α-diol were increased from baseline after both high and low fat diet groups without between group differences. Conversion of T to 5α,3β-diol (p=0.04) and the 5β,3α-diols  (p=0.04) were only increased with low fat diet. Serum androgens were very low or non-detectable in many biopsies, but prostatic 5β,3α-diol levels decreased after high fat diet but increased with low fat diet and the difference between the two groups were significant (p=0.01).

Conclusions: Conversion of T to DHT and 5α, 3α-diol was increased with both diets. Low fat diet significantly induced conversion of T to less active 5α,3β- and 5β, 3α-diols metabolites. This suggests diet modulation may affect androgen metabolism to form less active metabolites in the prostate.

Abbreviations: T=testosterone, DHT = 5α dihydrotestosterone, 5α,3α-diol= 5α,3α-androstanediol, 5α,3β-diol= 5α,3β-androstanediol, 5β,3α-diol= 5β,3α-androstanediol, and 5β,3β-diol= 5β3β-androstanediol. GC-MS= gas chromatography-mass spectrometry.

Disclosure: JR: Investigator, Allergen. Nothing to Disclose: CCW, HV, PJN, AL, TV, RB, PC, LH, RS, SF, LB, RSS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: 5RO1 DK061006