0021-972X/97/$03.00/0
Journal of Clinical Endocrinology and Metabolism
Copyright © 1997 by The Endocrine Society
Vol. 82, No. 2
Printed in U.S.A.
Effects of Age and Sex Hormones on Transition and
Peripheral Zone Volumes of Prostate and Benign
Prostatic Hyperplasia in Twins*
A. WAYNE MEIKLE, ROBERT A. STEPHENSON, CATHRYN M. LEWIS,
RICHARD G. MIDDLETON
AND
Departments of Medicine (A.W.M.), Urology (R.A.S., R.G.M.), and Medical Informatics (C.M.L.),
University of Utah School of Medicine, Salt Lake City, Utah 84132.
ABSTRACT
Benign prostatic hyperplasia has been shown to increase with age
and be influenced by sex hormones. The relationship between aging
and hormonal influences on growth of zones of the prostate is unresolved. We studied the relationship of age and sex hormones on volume of prostate zones in 214 male twins between 25 and 75 yr old.
Volumes of the total prostate (TV), transition zone (TZ), and peripheral zones (PZ) were measured using transrectal ultrasound, and sex
steroid concentrations were measured using RIA. Using transformed
data corrected for age, TV (r ⫽ 0.54, P ⬍ 0.00001), TZ (r ⫽ 0.58, P ⬍
0.00001), and PZ (r ⫽ 0.39, P ⬍ 0.00001) volumes increased with age.
However, the PZ volume rose more rapidly than the TZ before age 50,
and TZ showed a steeper increase after age 50 yr than the PZ volume.
The TZ, PZ, and ratio TZ/PZ correlated significantly (r ⫽ 0.87, 0.90,
and 0.52, respectively; P ⬍ 0.00001). After a TV exceeded 30 g, the rise
of the PZ became attenuated, and the slope of the TZ became steeper.
Age-adjusted sex hormone concentration was not evaluated in men
with larger prostate volumes. Men with American Urological Association symptom scores above 10 had significantly (P ⬍ 0.001) larger
total prostate volume (TV) and TZ volume, but not PZ volumes, than
men with scores below 10. Prostate volumes correlated inversely with
age-adjusted serum testosterone (T), dihydrotestosterone, sex hormone binding globulin, and sex hormone binding globulin-bound T
concentrations. These results demonstrate that before age 50 yr or
beforea prostate weight exceeds 30 g, prostate growth may be mainly
from enlargement of the PZ and after age 50, the TZ. In addition,
elevated T and dihydrotestosterone concentrations do not predispose
men to prostate enlargement or symptoms of benign prostatic hyperplasia. (J Clin Endocrinol Metab 82: 571–575, 1997)
B
ENIGN prostatic hyperplasia (BPH) is a common neoplasm of the prostate and causes considerable morbidity in aging men. BPH does not occur in androgen-deficient
men who fail to virilize (1). High 5␣-reductase activity of the
prostate converts testosterone to dihydrotestosterone (DHT),
which has higher affinity with the androgen receptor than
testosterone and is, therefore, the main androgen-influencing
prostate growth after puberty (1–5). Sex steroids secreted by
the testes contribute to the development of BPH by yet unresolved mechanisms.
The growth of the prostate rises from 1 g at birth to about
4 g before puberty and then to an average 20 g after virilization, after puberty, by age 20 yr (6 –9). BPH arises from the
periurethral glands [transition zone (TZ)], whereas prostate
cancer arises most commonly in the peripheral zones (PZ).
The TZ in young men comprises about 10% of the TV, and
by age 60 yr, the TZ averages 30% of the TV (7, 10 –13). Both
the PZ and TZ contribute to prostate enlargement except that,
in older men, the growth of the TZ exceeds that of the PZ. In
a recent report, we observed that, after the TV exceeded 50 g,
most of the growth was accounted for by the TZ. The cause
of the differential growth rate between the TZ and PZ is
unknown, but sex steroids and growth factors are thought to
contribute. During aging, several hormonal changes occur
that have been associated with development of BPH and
prostate cancer, including a rise in sex hormone binding
globulin (SHBG) and estrogen relative to testosterone (14 –
19). Except for autopsy data, little is known about the relative
rates of growth of the PZ and TZ after puberty and
virilization.
Accurate measurement of the TZ volume and TV of the
prostate has been made possible by transrectal ultrasound
(TRUS) and allows assessment of therapy and aging on relative changes of growth rates of zones of the prostate gland
(10, 11, 20 –25).
We previously have observed that familial (genetic and
environmental) factors substantially influence the variation
in plasma sex steroid concentrations in normal male twins
and in families at risk for prostate cancer (26 –31). We now
report on associations among ages, sex steroids, symptoms
of urethral obstruction, and the size of the PZ and TZ in
normal male twins ranging in age between 25 and 75 yr.
Materials and Methods
This study was done to assess the influence of age and hormonal
factors on prostate size and BPH in male twin-pairs between 25 and
75 yr old. More than 1500 potential participants have been identified
from data base registries, including a recent update of drivers license
information. This was obtained by coupling genealogy information
and birth and death records with drivers’ license data. We report data
on 214 twins of 360 twins that have been studied where both twins
of the pairs were evaluated and had no endocrine or health issues.
Received June 28, 1996. Revision received September 10, 1996. Accepted October 10, 1996.
Address all correspondence and requests for reprints to: A. Wayne
Meikle, M.D., University of Utah School of Medicine, 50 North Medical
Drive, Salt Lake City, Utah 84132.
* This work was supported in part by NIH Grants DK-45760, DK43344, and RR-00064.
571
572
JCE & M • 1997
Vol 82 • No 2
MEIKLE ET AL.
FIG. 1. Relationship between age (horizontal axis) and TV (A), TZ (B), PZ and
TZ/PZ (D) ratio of volumes (vertical
axis, respectively). The quadratic regression models with age are shown.
The r2 ⫽ 0.56 was for TV and age, 0.58
for TZ, 0.43 for PZ, and 0.65 for TZ/PZ
with P ⬍ 0.00001, respectively.
One-hundred-twenty-six twins were monozygotic (age, 55 ⫾ 12.5 yr,
mean ⫾ sd), range 30 –77 yr) and 88 dizygotic (age, 54.3 ⫾ 11.9 yr,
mean ⫾ sd), range, 27–72 yr). All men with prostate cancer or a history
of treatment for BPH were excluded from analysis. Informed consent
was obtained before entry into the study conducted on the Clinical
Research Center of the University of Utah. None of the subjects was
receiving medications known to affect sex steroid secretion. The
American Urologic Association (AUA) questionnaire was administered to each twin, and the symptom score was calculated (32).
Between 0800 and 1030 h, three blood samples for hormone concentrations were obtained in tubes by venipuncture at intervals of 15 to 20
min. An equal volume of each sample was pooled and stored at ⫺20 C
until assayed.
The concentrations of testosterone, DHT, estradiol, estrone, SHBG,
free testosterone, bioavailable testosterone, androstanediol glucuronide,
LH, FSH, and prostate specific antigen were measured by assays reported previously (28, 29, 31). Intra- and interassay coefficients of variation were less than 12 % (33).
Bioelectrical impedance was used to measure body fat, lean body mass,
and body water (34, 35). The ratio of lean body mass to body fat was
calculated. A digital rectal examination was done before TRUS imaging,
using a Bruel and Kjaer 1 instrument fitting with a 7-mHz transducer (B&K
Medical Systems, North Billerica, MA). The TV (assuming 1cc ⫽ 1 g) and
the volume of the TZ were calculated by ␲/6 ⫻ width (maximal transverse
dimension), length (maximal anterior and posterior dimension), and height
(maximal sagittal proximal to distal dimension) (33). The TZ is significantly
hypoechoic relative to PZ echodensities. This permits accurate visualization
of zonal boundaries for the purposes of measurements used in volume
calculations. The PZ volume (central zone is included in PZ calculation) was
calculated by subtracting the TZ from the TV. The coefficient of variation
is 5 % for TV and 11 % for TZ.
Statistical analyses
Data were obtained from a study of male twins. In the current
analysis, correlations between twin pairs were accounted for by
weighting twin pairs where both twins had data available. The effect
of age on the growth of zones of the prostate was evaluated by filling
linear models with quadratic (age, age**2) terms for age. The relationship between prostate zones and TV also was investigated. Linear
models and ANOVA were used to determine whether sex hormone
concentrations influenced the variation in prostate size. Models included quadratic terms for age and were fit for all age groups and for
men more than 50 yr old.
Results
Age effects on TV
Figure 1, A–D shows an increase in TV, TZ and PZ volumes, and TZ/PZ with age. These figures show a quadratic
AGE, HORMONES, AND PROSTATE ZONES
573
relationship with age for the TV, TZ and PZ volume, and the
ratio of TZ/PZ, but the TZ shows a steeper increase compared with the TV and PZ volume. Age significantly correlated with the TV (r ⫽ 0.56, P ⬍ 0.00001), TZ (r ⫽ 0.58, P ⬍
0.00001), PZ (r ⫽ 0.43, P ⬍ 0.0001), the ratio of the TZ/TV (r ⫽
0.65, P ⬍ 0.00001), and TZ/PZ (r ⫽ 0.57, P ⬍ 0.00001). These
results confirm our previous observations that age influences
the TZ volume (26). These results suggest that, after age 50,
both the PZ and TZ increase in volume, but the rise of the TZ
is more rapid than the PZ volume.
Relationships of the volume of prostate zones
Both the TZ and PZ volumes and the ratio of TZ/PZ (Fig.
2, A–C) correlated highly (r ⫽ 0.87, 0.90, and 0.52, respectively; P ⬍ 0.00001; n ⫽ 214) with the total volume. The TZ
and PZ volumes also correlated significantly with each other
(r ⫽ 0.51, P ⬍ 0.00001, n ⫽ 214). In contrast to the increase
of TZ volume related to TV, the rise of PZ volume became
attenuated as the TV exceeded 30 g. TV up to 30 g were
predominated by the PZ volume relative to the TZ; TV above
30 g accounted for the further enlargement of the TZ. They
also confirm the high correlation between the TV and the TZ
(r ⫽ 0.87, P ⬍ 0.00001) and TV and PZ (r ⫽ 0.90, P ⬍ 0.00001),
suggesting that both the PZ and TZ contribute to the prostate
enlargement associated with aging.
Prostate volumes and hormonal relationships
Linear models were used to evaluate the relationship between sex hormones and TV and zones (TV, PZ, PZ). Any
effect of age was accounted for through the inclusion of
quadratic terms in the model. Table 1 gives statistical values
for different effects of the sex hormone on prostate size.
Study individuals were split into the upper and lower quartiles of the entire group and of those 50 yr old or less (Table
1). For TV and PZ volume, serum testosterone (T) was significantly lower (P ⬍ 0.05 and 0.02, respectively) in men over
50 yr old with larger prostate volumes than those with
smaller prostates, and for TZ volumes, DHT was significantly lower (P ⫽ 0.002) in the older men with larger TZ
volumes. For all three prostate volume measurements,
SHBG-bound T (TV, P ⫽ 0.03; PZ, P ⫽ 0.03) was significantly
lower in those with larger TV and PZ volume, and marginally significant for TZ volumes (P ⫽ 0.07). These results might
suggest that a relative androgen deficiency independent of
aging contributes to growth of the gland because the data
were corrected for aging influences. Any age effect on prostate volume was removed from the variable by quadratic
transformation before statistical comparison.
As shown in Table 2, the AUA symptom score was higher
in the twins with larger TZ volumes (upper quartile) compared with those with smaller volumes. To evaluate this
relationship further, those with a symptom score more than
10 (suggesting BPH) were compared with those with a score
less than 10. The TV and TZ volume were significantly
greater in men with higher scores compared with those with
lower scores (P ⬍ 0.001), but no significant relationship between the score and PZ volume was observed (Table 2).
These results suggest that symptoms of BPH are produced,
FIG. 2. Relationship of TV (horizontal axis) with volumes of TZ (A),
PZ (B) and TZ/PZ ratio of volumes (vertical axis, respectively). The
best fitting quadratic regression models are shown. The r2 ⫽ 0.87 for
TZ and TV, 0.9 for PZ, 0.52 for TZ/PZ with P ⬍ 0.00001, respectively.
in part, by enlargement of TZ and total prostate, but not
enlargement of the PZ.
Table 3 summarizes the relationships of volumes of the
prostate and hormonal values adjusted for age. This confirms
574
JCE & M • 1997
Vol 82 • No 2
MEIKLE ET AL.
TABLE 1. Comparison of prostate volumes in the upper and lower quartiles for all men and greater than 50 yr old
TV
⬎50 yr
Lower quart. mean ⫾
T, nmol/L
SHBG-T, nmol/L
Lean/fat
TZ
SHBG-T, nmol/L
DHT, nmol/L
PZ
T, nmol/L
T/SHBG
SHBG-T, nmol/L
Lean/fat
All
Upper quart. mean ⫾
SE
SE
P value
Lower quart. mean ⫾
SE
Upper quart. mean ⫾
SE
P value
17.5 ⫾ 1.0
8.4 ⫾ 0.53
4.39 ⫾ 0.34
15.0 ⫾ 0.9
7.2 ⫾ 0.77
3.5 ⫾ 0.2
.05
NS
⬍.02
17.7 ⫾ 1.4
7.9 ⫾ 0.65
4.0 ⫾ 0.41
14.7 ⫾ 0.98
6.0 ⫾ 0.37
3.5 ⫾ 0.34
⬍.05
⬍.03
NS
7.82 ⫾ 0.46
1.6 ⫾ 0.13
7.35 ⫾ 0.55
1.25 ⫾ 0.1
NS
.01
7.9 ⫾ 0.69
1.66 ⫾ 0.14
6.0 ⫾ 0.35
1.08 ⫾ 0.08
.07
.0002
17.0 ⫾ 1.0
0.34 ⫾ 0.03
⫺8.2 ⫾ 0.59
4.24 ⫾ 0.31
15.8 ⫾ 0.97
0.27 ⫾ 0.02
7.37 ⫾ 0.75
3.62 ⫾ 0.18
0.08
.05
NS
0.02
17.9 ⫾ 1.5
0.28 ⫾ 0.02
7.6 ⫾ 0.65
3.76 ⫾ 0.32
14.22 ⫾ 1.0
0.22 ⫾ 0.06
5.9 ⫾ 0.36
3.55 ⫾ 0.33
.02
.07
.03
NS
SHBG-T, bound to SHBG; NS, not significant.
TABLE 2. Comparison of prostate volume in men with AUA
symptom scores less than and greater than 10
Sx Score ⬍10
ⱖ10
P value
TV, g 24.5 ⫾ 0.085
TZ, g 6.6 ⫾ 0.04
PZ, g 17.9 ⫾ 0.05
32.1 ⫾ 2.6
12.7 ⫾ 1.5
19.9 ⫾ 1.6
⬍0.001
⬍0.001
⬍0.2
Sx score AUA, symptoms score.
TABLE 3. Relationship between prostate volumes and hormone
concentrations adjusted for age
T
Free T
DHT
DHEAS
FSH
LH
Estrone
Estradiol
SHBG
AG
DHT/T
Estradiol/T
T/SHBG
SHBG-bound T
TV
TZ
PZ
0.05 (⫺)
0.40
0.622
0.34
0.21
0.11
0.09
0.36
⬍0.01 (⫺)
0.51
0.89
0.92
0.09
0.24
0.17
0.38
0.01 (⫺)
0.76
0.38
0.03 (⫹)
0.14
0.48
0.62
0.27
0.04 (⫺)
0.63
0.23
0.32
0.08
0.71
0.18
0.08
0.04 (⫹)
0.18
0.09
0.56
⬍0.01 (⫺)
0.84
0.16
0.79
0.05 (⫹)
⬍0.01 (⫺)
DHEAS ⫽ dehydroepiandrosterone; AG ⫽ androstanediol glucuronide. P-values for TV with SHBG, TZ with DHT and LH, PZ with
SHBG and SHBG-bound T required a quadratic model for an adequate fit. All other models include a linear term for the hormone level.
For significant P-values (p ⬍ 0.05), an indication of the relationship
between the prostate volume and hormone level is given. (⫹), prostate
volume increases as hormone level increases. (⫺), prostate volume
decreases as the hormone level increases.
the inverse relationship between T and SHBG and TV, DHT
and DHT/T and TZ, and SHBG and SHBG-bound T and PZ.
A positive relationship was observed for LH and TZ and FSH
and T/SHBG and PZ. These findings do not suggest that
higher serum sex steroid concentrations are associated with
prostate enlargement.
Discussion
TRUS has made it possible to quantitate the volume of
zones of the prostate and to evaluate the influences of age and
therapy on them. This study shows that as men age, the
relative size of zones of the prostate has variable influences
on TV. Both the TZ and PZ volumes correlate with age and
with TV of the gland, but they show a variable relationship
with size of the gland at various ages. PZ enlargement and,
to a lesser extent, the TZ contribute to moderate enlargement
of the prostate between 25 and 50 yr old, and beyond age 50,
the growth of the TZ predominates over the PZ.
These results are consistent with the well-recognized clinical correlation that symptomatic BPH is variable among men
after age 40 yr. The current results corroborate our previous
report that TZ volume, as measured by TRUS, increases in
men between 50 and 80 yr old. In contrast to previous findings where neither the PZ nor TV increased significantly with
age in men between 45 and 80 yr, both PZ and TZ correlated
significantly with age in men 25–75 yr old. Thus, in the
current study, the adult relationships between size of zones
of the prostate and age can be assessed more completely
because of the broader age range.
The findings of the association concerning relationships
between age and enlargement of the TZ and TV are consistent with published reports on autopsy and TRUS studies of
prostate size (10, 11, 24, 25, 36). Although autopsy studies did
not selectively compare the TZ volume with the total or PZ
volume, they have established that total prostate size increases, but not in all men, particularly after age 50 yr (6 – 8,
25). In men with and without BPH, Greene et al. (11) performed TRUS and observed an increase in the size of the TZ
with age, but they did not study the relationship among the
zone volumes of the prostate. Partin et al. (14) reported that
the volume of prostate tissue removed by transurethral resection for treatment of symptomatic BPH correlated significantly with age. In a cross-sectional study, Jakobsen et al. (12)
found the TZ and PZ volumes measured by TRUS began
increasing after age 25 yr, but the PZ growth rate was less
than for the TZ. Those studies are consistent with the current
study finding that PZ volume largely contributes to TV before age 50 yr and TZ after age 50. Long-term serial studies
would be required to assess this possibility.
The growth of the prostate up to 30 g is explained by the
enlargement of both the PZ and TZ, with the PZ predominating over the TZ. As the gland increases above 30 g, the rate
of growth of the TZ tends to exceed the PZ. Although age had
a profound influence on prostate volume, the relationship of
TV and age to TZ and PZ were even higher, indicating the
strong influence of both zones of the prostate on TV. The ratio
of TZ/PZ showed weaker relationships with TV than the
AGE, HORMONES, AND PROSTATE ZONES
volumes of the TZ and PZ, suggesting the differential rates
of growth of these zones in contributing to TV.
The relationship between prostate volume and symptomatic BPH are inconsistent. However, studies of prostate volume and symptoms of BPH have not been related to volumes
of zones of the prostate. We found that men with higher AUA
symptom scores (32), which are consistent with symptomatic
BPH, have greater TZ volume and TV than men without
symptomatic BPH. The PZ volumes did not show a relationship with the symptom score. These findings are consistent with the postulate that the growth of the TZ, as men
age, results in urinary obstructive symptoms.
Hormonal profiles of men with larger prostate volumes do
not suggest that androgen excess causes BPH or prostate
enlargement before or after age 50. We observed that men
with larger prostates have lower serum T and DHT concentrations. A new finding in the current study is that men with
lower T, DHT, and SHBG-bound T had larger prostate volumes. Rosner et al. (37) reported that cAMP formation in BPH
tissue, in response to the SHBG-estradiol receptor, was inhibited by T and DHT. Our findings do not support the
hypothesis that elevated T or DHT cause excessive prostate
growth in aging men, but they may support the postulate that
the activity of the SHBG-estradiol receptor increases in men
with larger prostates because they have lower concentrations
of T or DHT to inhibit the SHBG-estradiol receptor. Further,
our observation and those reported elsewhere do not suggest
that androgens are unimportant in prostate enlargement of
aging men.
References
1. Moore RA. 1944 Benign hypertrophy and carcinoma of the prostate. Occurrence and experimental production in animals. Surgery. 16:152–167.
2. Walsh PC. 1984 Human benign prostatic hyperplasia: etiological considerations. Prog Clin Biol Res. 145:1–25.
3. Walsh PC, Harrod MJ, Goldstein JL, et al. 1974 Familial incomplete male
pseudohermaphroditism, type 2, decreased dihydrotestosterone formation in
pseudovaginal perineoscrotal hypospadias. N Engl J Med. 291:944 –949.
4. Ehrlichman RJ, Isaacs JT, Coffey DS. 1981 Differences in the effects of estradiol on dihydrotestosterone induced prostatic growth of the castrate dog
and rat. Invest Urol. 18:466 – 470.
5. Imperato-Mcginley J, Peterson RE, Gantier T, et al. 1982 Hormonal evaluation
of a large kindred with complete androgen insensitivity: evidence of a secondary 5 ␣-reductase deficiency. J Clin Endocrinol Metab. 54:931–941.
6. McNeal JE. 1984 Anatomy of the prostate and morphogenesis of BPH. Prog
Clin Biol Res. 145:27–53.
7. Berry SJ, Coffey DS, Walsh PC, Ewing LL. 1984 Development of benign
prostatic hyperplasia with age. J Urol. 132:474 – 479.
8. Grover M. 1923 Statistical study of the etiology of benign hypertrophy of the
prostate gland. Johns Hopkins Hospital Report. 21:231–295.
9. Isaacs JT. 1984 Common characteristics of human and canine benign prostatic
hyperplasia. In: Kimball FA, Buhl AE, Carter DB, eds. New approaches to the
study of benign prostatic hyperplasia. New York: Alan R. Liss, Inc.; 217–234.
10. Jensen KM, Jorgensen JB, Morgensen P. 1986 Some clinical aspects of uroflowmetry in elderly males. A population survey. Scand J Urol Nephrol.
20:93–99.
11. Greene DR, Egawa S, Hellerstein DK, Scardino PT. 1990 Sonographic mea-
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
575
surements of transition zone of prostate in men with and without benign
prostatic hyperplasia. Urology. 36:293–299.
Jakobsen H, Torp-Pedersen S, Juul N. 1988 Ultrasonic evaluation of agerelated human prostatic growth and development of benign prostatic hyperplasia. Scand J Urol Nephrol. (suppl) 107:26 –31.
Guess HA. 1992 Benign prostatic hyperplasia: antecedents and natural history.
Epidemiol Rev. 14:131–153.
Partin AW, Oesterling JE, Epstein JI, et al. 1991 Influence of age and endocrine
factors on the volume of benign prostatic hyperplasia. Urology. 145:405– 409.
Deslypere JP, Vermeulen A. 1984 Leydig cell function in normal men: effect
of age, life-style, residence, diet, and activity. J Clin Endocrinol Metab.
59:955–961.
Vermeulen A, Verdonck L, Van Der Straeten M, Orie N. 1969 Capacity of the
testosterone-binding globulin in human plasma and influence of specific binding of testosterone on its metabolic clearance rate. J Clin Endocrinol Metab.
29:1470 –1480.
Vermeulen A, Rubens R, Verdonck L. 1972 Testosterone secretion and metabolism in male senescence. J Clin Endocrinol Metab. 34:730 –735.
Mirovics JC, Dunlop M, Rennie GC. 1976 Changes in the pituitary-testicular
system with age. Clin Endocrinol (Oxf). 5:349 –372.
Baker HW, Burger DM, de Kretser DM, et al. 1976 Changes in the pituitarytesticular system with age. Clin Endocrinol (Oxf). 5:349 –372.
Rubin RT, Gouin PR, Lubin A, et al. 1975 Nocturnal increase of plasma
testosterone in men: relation to gonadotropins and prolactin. J Clin Endocrinol
Metab. 40:1027–1033.
Ohe H, Watanabe H. 1988 Kinetic analysis of prostatic volume in treating
prostatic cancer and its predictability for prognosis. Cancer. 62:2325–2329.
Peters CA, Walsh PC. 1987 The effect of nafarelin acetate, a luteinizinghormone-releasing hormone agent agonist, on benign prostatic hyperplasia.
N Engl J Med. 317:599 – 604.
Gabrilove JL, Levine AC, Kirschenbaum A, Droller M. 1989 Effect of longacting gonadotropin-releasing hormone analog (leuprolide) therapy on prostatic size and symptoms in 15 men with benign prostatic hypertrophy. J Clin
Endocrinol Metab. 69:629 – 632.
Tempany CMC, Partin AW, Zerhouni SJ, et al. 1993 The influence of finasteride on the volume of the peripheral and periurethral zones of the prostate
in men with benign prostatic hyperplasia. Prostate. 22:39 – 42.
Bostwick DG, Cooner WH, Denis L, et al. 1992 The association of benign
prostatic hyperplasia and cancer of the prostate. Cancer. [Suppl]70:291–301.
Meikle AW, Stephenson RA, McWhorter WP, et al. 1995 Effects of age, sex
steroids, and family relationships on volumes of prostate zones in men with
and without prostate cancer. Prostate. 26:253–259.
Woolf CM. 1960 An investigation of the familial aspects of carcinoma of the
prostate. Cancer. 13:739 –744.
Meikle AW, Stanish WM. 1982 Familial prostatic cancer risk and low testosterone. J Clin Endocrinol Metab. 54:1104 –1108.
Meikle AW, Stanish WM, Taylor N, et al. 1982 Familial effects on plasma
sex-steroid content in man: testosterone, estradiol and sex hormone-bindingglobulin. Metabolism. 31:6 –9.
Meikle AW, Smith JA, Stringham JD. 1987 Production, clearance, and metabolism of testosterone in men with prostate cancer. Prostate. 10:25–31.
Meikle AW, Bishop DT, Stringham JD, West DW. 1986 Quantitating genetic
and nongenetic factors that determine plasma sex-steroid variation in normal
male twins. Metabolism. 35:1090 –1095.
Grayhack JT. 1992 Benign prostatic hyperplasia: the scope of the problem.
Cancer. 70:275–279.
McWhorter WP, Hernandez AD, Meikle AW, et al. 1992 A screening study
of prostate cancer in high risk families. J Urol. 148:826 – 828.
Lukaski HC, Johnson PE, Bolonchuk WW, et al. 1985 Assessment of fat free
mass using bio-electrical impedance measurements of the human body. Am J
Clin Nutr. 41:810 – 817.
Segal KR, Gutin B, Presta E, et al. 1985 Estimation of human body composition
by electrical impedance methods; a comparative study. J Appl Physiol.
58:1565–1571.
Watanabe H. 1986 Natural history of benign prostatic hypertrophy. Ultrasound Med Biol. 12:567–571.
Nakhla AM, Ding VDH, Khan MS, et al. 1995 5 [Alpha]-Androsta-3␣,17␤-diol
is a hormone: stimulation of cAMP accumulation in human and dog prostate.
J Clin Endocrinol Metab. 80:2259 –2262.