HERITABILITY OF THE SYMPTOMS OF BENIGN PROSTATIC HYPERPLASIA AND THE ROLES OF AGE AND ZONAL PROSTATE VOLUMES IN TWINS A. WAYNE MEIKLE, ARUNA BANSAL, DARRELL K. MURRAY, ROBERT A. STEPHENSON, AND RICHARD G. MIDDLETON ABSTRACT Objectives. Both benign prostatic hyperplasia and lower urinary tract symptoms (LUTS) have been shown to increase with age in men, but a causal relationship between prostate volume and symptoms has not been established. This study had two aims, to investigate the inter-relationships of age, symptoms, and various zonal measurements in the prostate and to assess the impact of heritable influences on symptom score. Methods. Eighty-three monozygotic twin pairs and 83 dizygotic twin pairs were studied to determine age and LUTS as assessed by the American Urological Association symptom score. Their prostate volumes (total, transition zone, and peripheral zone) were measured by transrectal ultrasound. Results. There was significant evidence of pairwise correlation between transition zone and symptom score (P = 0.04) and between age and symptom score (P = 0.03). Age also showed significant correlation with all volume measurements. Heritability appears to account for 82.6% of the variability in symptom score in men older than 50 years. Conclusions. This study provides evidence that age and transition zone volume play a role in LUTS, but also that their influence is not strong. Estimates of heritability suggest that hereditary factors contribute sub- stantially to LUTS. UROLOGY 53: 701–706, 1999. © 1999, Elsevier Science Inc. All rights reserved. B enign prostatic hyperplasia (BPH) is associated with aging in men who have functionally nor- mal androgen synthesis and responsiveness. The causal relationship between BPH and symptoms of voiding dysfunction in aging men is unresolved. We recently reported that enlargement of the pe- ripheral zone (PZ) gradually increases between the ages of 25 and 75 years. In contrast, the transition zone (TZ) enlarges more rapidly in men after 50 years of age. 1,2 This suggests that factors regulating PZ growth differ from those regulating TZ growth. Prostate voiding symptoms may be related to growth of the TZ. Although men with higher tes- tosterone concentrations had smaller TZ volumes than those with lower concentrations, men with higher prostate symptom scores had larger TZ vol- umes than those with lower scores. 2 It has long been presumed that BPH in aging men causes lower urinary tract symptoms (LUTS). In recent years, however, this causal relationship be- tween prostate enlargement and LUTS has been blurred. 1–7 The associations among prostate en- largement, symptoms, and urinary flow rates have been relatively weak. 1–8 Further challenge of these associations came from the observations that LUTS may be improved more by agents affecting smooth muscle contraction of the urethra and bladder than by agents that reduce prostate volume. 9 –12 In men, the TZ wraps around the prostatic ure- thra and enlarges more after 50 years of age than the PZ. 1,2,13–15 Thus, although total prostate vol- ume (TV) may not correlate well with LUTS, it has been presumed that the TZ enlargement may be more important than the TV. 5,6,16 As men age, en- largement of the TZ occurs at a time in life when investigators have reported a worsening of symp- tom scores. Although men with larger TZ volumes had higher LUTS scores than those with smaller TZ volumes, the association was relatively weak. 1,2,4,6 This study was supported in part by grants DK-45760, DK-43344, and RR-00064 from the National Institutes of Health USPHS. From the Departments of Medicine, Medical Informatics, and Urology, University of Utah School of Medicine, Salt Lake City, Utah Reprint requests: A. Wayne Meikle, M.D., Department of Med- icine, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, UT 84132 Submitted: July 16, 1998, accepted (with revisions): October 1, 1998 ADULT UROLOGY © 1999, ELSEVIER SCIENCE INC. 0090-4295/99/$20.00 ALL RIGHTS RESERVED PII S0090-4295(98)00569-X 701