Increasing evidence from studies in experimental animals and men show that dietary intake of fat especially animal fat is associated with increased risk of development and growth of carcinoma of the prostate (CaP). We have shown in our recently completed study that in white men changing their customary diet (37.9 plus or minus 1.0% energy from fat, 19 plus or minus 1 g fiber per day) to a low-fat, high-fiber diet (13.9 plus or minus 0.3% energy from fat, 32 plus or minus 1 g fiber per day) significantly decreased their serum testicular and adrenal androgens; urinary excretion rates of both testicular and adrenal androgens, and the production rate of testosterone.
The specific aim for this study is to verify in multiethnic groups that the decreases in serum androgens after diet modulation to a low fat diet are also reflected by decreases in intraprostatic androgens and changes in their metabolism resulting in increased 5 alpha reduced androgens. To address the specific aim we will recruit patients presenting to the Urology clinics with elevated serum PSA and or/abnormal digital rectal examination where a routine transrectal ultrasound guided prostate biopsy is indicated. Prostate samples not used for pathological diagnosis will be stored. Subjects whose biopsies show no evidence of CaP and have a persistently elevated PSA will require a repeat biopsy 8 to 12 months later. These subjects will be eligible for the study if they customarily consume a high-fat diet and will have serum/urine androgen levels measured. They will be randomized to continue on their customary high-fat diet or to diet modulation on an isocaloric low fat-high fiber diet (<15% of total calories as fat/ 25 to 35 g fiber a day) for eight weeks. After diet study, serum and androgen levels will be measured on the day before their scheduled second biopsy. All subjects will return for weekly clinic visits to ensure compliance with customary or low fat diet. The biopsies before and after diet modulation will be used for measurement of intraprostatic androgen levels and androgen metabolic enzyme activities including 5 alpha reductase, 3alpha/beta hydroxysteroid oxi/reductase and 17 beta hydroxysteroid dehydrogenase. The proposed study will provide unequivocal evidence to answer whether reduction in dietary fat will result in significant changes in intraprostatic androgens and enzyme activities. Small but significant decreases in intraprostatic androgen may create an unfavorable macroenvironment which over protracted time may slow or prevent the development and growth of CaP. The results will provide the important missing link between diet fat and CaP growth and development.
| Wang, Christina; Catlin, Don H; Starcevic, Borislav et al. (2004) Testosterone metabolic clearance and production rates determined by stable isotope dilution/tandem mass spectrometry in normal men: influence of ethnicity and age. J Clin Endocrinol Metab 89:2936-41 |
| Wang, Christina; Catlin, Don H; Demers, Laurence M et al. (2004) Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 89:534-43 |
| Wang, Christina; Swerdloff, Ronald S (2002) Should the nonaromatizable androgen dihydrotestosterone be considered as an alternative to testosterone in the treatment of the andropause? J Clin Endocrinol Metab 87:1462-6 |
