Benign prostatic hyperplasia (BPH) is the most common neoplasm diagnosed in men of the United States and causes considerable morbidity and mortality. Prostate size varies considerably among normal aging men. Enlargement of the transitional zone that is primarily responsible for urethral obstruction also varies considerably. Although its cause is unknown, there is evidence that endocrine, genetic and environmental factors are all important in its pathogenesis. We have established that hereditary and environmental factors influence the variation in sex hormone levels in male twins. We hypothesize that prostate size, shape, and nodularity and residual urine volume are affected by endocrine, genetic and environmental factors. We propose to conduct studies of these factors in 120 monozygotic and 120 dizygotic male twin pairs between the ages of 25 to 75 years. A questionnaire will obtain data on demographic factors, medical history, sexual development, diet, and symptoms of urinary obstruction. Rectal examination, transrectal ultrasound (which will measure size of the transitional zone and total prostate size and residual urine volume), and anthropometry will be done by the team. Plasma sex steroids, insulin, and prostate specific antigen will be measured by immunoassays. Hereditary, endocrine, and environmental influences on prostate size and shape and residual urine volume will be assessed with the twin model. Multiple linear regression will be used to ascertain the relationships among the variables measured and prostate morphometrics, symptoms, and residual urine volume. This study will be the first to examine both hereditary and environmental factors in the pathogenesis of BPH. It is made possible because of cooperative population for the study and the combined efforts of the investigative team.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK045760-01
Application #
3247280
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1992-09-30
Project End
1996-09-29
Budget Start
1992-09-30
Budget End
1993-09-29
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Gunawardena, K; Murray, D K; Meikle, A W (2000) Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis. Prostate 44:287-95
Bansal, A; Murray, D K; Wu, J T et al. (2000) Heritability of prostate-specific antigen and relationship with zonal prostate volumes in aging twins. J Clin Endocrinol Metab 85:1272-6
Meikle, A W; Bansal, A; Murray, D K et al. (1999) Heritability of the symptoms of benign prostatic hyperplasia and the roles of age and zonal prostate volumes in twins. Urology 53:701-6
Meikle, A W; Swope, R E; Yin, D Y et al. (1999) Transforming growth factor beta-1 and beta-2 and type II receptor functional regulation of ALVA-101 human prostate cancer cells. Metabolism 48:1075-81
Wilson, D E; Meikle, A W; Boike, S C et al. (1998) Bioequivalence assessment of a single 5 mg/day testosterone transdermal system versus two 2.5 mg/day systems in hypogonadal men. J Clin Pharmacol 38:54-9
Ramirez, M E; McMurry, M P; Wiebke, G A et al. (1997) Evidence for sex steroid inhibition of lipoprotein lipase in men: comparison of abdominal and femoral adipose tissue. Metabolism 46:179-85
Meikle, A W; Stephenson, R A; Lewis, C M et al. (1997) Effects of age and sex hormones on transition and peripheral zone volumes of prostate and benign prostatic hyperplasia in twins. J Clin Endocrinol Metab 82:571-5
Meikle, A W; Arver, S; Dobs, A S et al. (1997) Prostate size in hypogonadal men treated with a nonscrotal permeation-enhanced testosterone transdermal system. Urology 49:191-6
Arver, S; Dobs, A S; Meikle, A W et al. (1997) Long-term efficacy and safety of a permeation-enhanced testosterone transdermal system in hypogonadal men. Clin Endocrinol (Oxf) 47:727-37
Meikle, A W; Arver, S; Dobs, A S et al. (1996) Pharmacokinetics and metabolism of a permeation-enhanced testosterone transdermal system in hypogonadal men: influence of application site- -a clinical research center study. J Clin Endocrinol Metab 81:1832-40

Showing the most recent 10 out of 15 publications