雪白纯净的美女老师，让体育生玩的全身都在舒爽 [30P]

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Mohamed El Kholy , Rasha Tarif Hamza * , Mohamed Saleh and Heba Elsedfy
Penile length and genital anomalies in Egyptian
male newborns: epidemiology and influence of
endocrine disruptors
Abstract: This is an attempt to establish the normal
stretched penile length and prevalence of male geni-
tal anomalies in full-term neonates and whether they
are influenced by prenatal parental exposure to endo-
crine-disrupting chemicals. A thousand newborns were
included; their mothers were subjected to the following
questionnaire: parents ’ age, residence, occupation, con-
tact with insecticides and pesticides, antenatal exposure
to cigarette smoke or drugs, family history of genital
anomalies, phytoestrogens intake and history of in vitro
fertilization or infertility. Free testosterone was measured
in 150 neonates in the first day of life. Mean penile length
was 3.4 ± 0.37 cm. A penile length < 2.5 cm was considered
micropenis. Prevalence of genital anomalies was 1.8 %
(hypospadias 83.33 % ). There was a higher rate of anoma-
lies in those exposed to endocrine disruptors (EDs; 7.4 % )
than in the non-exposed (1.2 % ; p < 0.0001; odds ratio 6,
95 % confidence interval 2 – 16). Mean penile length showed
a linear relationship with free testosterone and was lower
in neonates exposed to EDs.
Keywords: endocrine disruptors; genital anomalies; male;
penile length; testosterone.
*Corresponding author : Rasha Tarif Hamza, MD, Faculty of
Medicine, Department of Pediatrics, Ain Shams University, 36
Hisham Labib Street, off Makram Ebeid Street, Nasr City, Cairo
11371, Cairo, Egypt, Phone: + 20-2-22734727, Fax: + 20-2-26904430 ,
E-mail: rashatarif_2000@hotmail.com
Mohamed El Kholy, Mohamed Saleh and Heba Elsedfy: Faculty of
Medicine , Department of Pediatrics, Ain Shams University, Cairo,
Egypt
Introduction
Determination of penile size is employed clinically in
the evaluation of children with abnormal genital devel-
opment, such as, for example, micropenis, defined as a
penis that is normal in terms of shape and function, but is
more than 2.5 standard deviations (SD) smaller than mean
size in terms of length (1) . However, these measurements
can be subject to significant international variations, in
addition to being obtained with different methodologies
in some cases (2) .
Over the past 20 years, the documented increase in
disorders of male sexual differentiation, such as hypo-
spadias, cryptorchidism, and micropenis, has led to the
suspicion that environmental chemicals are detrimental
to normal male genital development in utero (3) . The so-
called Sharpe-Skakkebaek hypothesis offered a possible
common cause and toxicological mechanism for abnor-
malities in men and boys – that is, increased exposure to
oestrogen in utero may interfere with the multiplication
of fetal Sertoli cells, resulting in hormonally mediated
developmental effects and, after puberty, reduced quality
of semen (4) .
It has been proposed that these disorders are part of
a single common underlying entity known as the testicu-
lar dysgenesis syndrome (TDS) (5) . TDS comprises various
aspects of impaired gonadal development and function,
including abnormal spermatogenesis, cryptorchidism,
hypospadias, and testicular cancer (6) .
The etiological basis for this condition is complex
and is thought to be due to a combination of both genetic
and environmental factors that result in the disruption
of normal gonadal development during fetal life. First,
it was proposed that environmental chemicals with oes-
trogen-like actions could have adverse effects on male
gonadal development. This has since been expanded to
include environmental chemicals with anti-androgen
actions and it is now thought that an imbalance between
androgen and oestrogen activity is the key mechanism by
which exposure to endocrine disrupting chemicals (EDCs)
results in the development of TDS and male reproductive
tract abnormalities (5) .
With the increasing use of environmental chemicals,
an attempt was made to establish the normal stretched
penile length as well as the prevalence of male genital
anomalies in full-term neonates and whether there is an
influence of prenatal parental exposure to potential EDCs
on these parameters.
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510 El Kholy et al.: Penile length and male genital anomalies
Subjects and methods
Study population
The study was conducted as a prospective cohort study at the Univer-
sity Hospital of Ain Shams University, Cairo, Egypt. A sample of 1000
male full-term newborns was studied.
Sampling technique
Three days per week were selected randomly out of 7 days. In each
day, all male full-term deliveries were selected during the time of fi eld
study (12 h) during the period from March 2007 to November 2007.
Statistical analysis
The computer program SPSS for Windows release 11.0 (SPSS Inc.,
Chicago, IL, USA) was used for data entry and analysis. All numeric
variables were expressed as mean ± SD. Comparison of diff erent vari-
ables between two groups was done using the Student ’ s t-test for
normally distributed variables. Comparisons of multiple groups were
done using analysis of variance and post hoc tests for normally dis-
tributed variables. The χ 2 -test was used to compare the frequency of
qualitative variables among the diff erent groups; the Fisher exact test
was performed in tables containing values < 5. The Pearson correla-
tion test was used for correlating various variables. For all tests, a
probability (p) < 0.05 was considered signifi cant (10) .
Results
Data collected
A researcher completed a structured questionnaire during inter-
views with the mothers. The questionnaire gathered information
on the following: age of parents; residence; occupation of the
parents; contact with insecticides and pesticides and their type and
frequency of contact; maternal exposure to cigarette smoke during
pregnancy; maternal drug history during gestation; family history
of hypospadias, cryptorchidism, or other congenital anomalies; in-
take of foods containing phytoestrogens, e.g., soy beans, olive oil,
garlic, hummus, sesame seed, and their frequency; and, also, his-
tory of in vitro fertilization or infertility (type of infertility and drugs
given).
Environmental exposure to chemicals was evaluated for its po-
tential of causing endocrine disruption. Chemicals were classifi ed
into two groups on the basis of scientifi c evidence for their having
endocrine-disrupting properties: group I: evidence of endocrine dis-
ruption high and medium exposure concern; group II: no evidence of
endocrine disruption and low exposure concern (7) .
Descriptive data
The mean age of newborns ’ fathers was 36 ± 6 years (range
20 – 50 years) and that of mothers was 26 ± 5 years (range
19 – 42 years). Exposure to EDs started long before preg-
nancy and continued throughout pregnancy. Regard-
ing therapeutic history during pregnancy, 99 mothers
(9.9 % ) received progestins, 14 (1.4 % ) received insulin,
6 (0.6 % ) received heparin, 4 (0.04 % ) received long-
acting penicillin, 3 (0.3 % ) received aspirin, 2 (0.2 % )
received B2 agonist, and 1 (0.1 % ) received thyroxin,
while the rest did not receive any medications during
pregnancy except for the known multivitamins and
calcium supplementations. In addition, family history
of newborns born small for gestational age was positive
in 21 cases (2.1 % ).
Examination
In addition to the full examination by the paediatric staff , each boy
was examined for anomalies of the external genitalia during the
fi rst 24 h of life by one specially trained researcher. Examination
of the genital system included measurement of stretched penile
length (8) and examination of external genitalia for congenital
anomalies such as cryptorchidism (9) and hypospadias. Hypospa-
dias was graded as not glanular, coronal, penile, penoscrotal, scro-
tal, or perineal according to the anatomical position. Cases of iso-
lated malformed foreskin without hypospadias were not included
as cases.
Penile length
Laboratory investigations
Free testosterone level was measured in 150 randomly chosen neo-
nates from the studied sample in the fi rst day of life (enzyme im-
munoassay test supplied by Diagnostics Biochem Canada, Inc.,
Dorchester, Ontario, Canada).
Mean penile length was 3.41 ± 0.37 cm (range 2.4 – 4.6 cm).
A penile length < 2.5 cm was considered micropenis ( < the
mean by 2.5 SD). Two cases (0.2 % ) were considered to
have micropenis. Mean penile length was lower (p = 0.041)
in neonates exposed to EDs (n = 81, 3.1 cm) compared to the
non-exposed group (n = 919, 3.4 cm; Figure 1 ).
There was a linear relationship between penile length
and the length of the newborn with a regression coef-
ficient of 0.05 (95 % CI 0.04 – 0.06; p < 0.0001), i.e., there
was an increase of 0.05 cm for each unit increase in length
(cm). Similarly, there was a linear relationship between
penile length and the weight of the newborn with a regres-
sion coefficient of 0.14 (95 % CI 0.09 – 0.18; p < 0.0001), i.e.,
there was an increase of 0.14 cm for each unit increase in
weight (kg).
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El Kholy et al.: Penile length and male genital anomalies 511
3.45
3.40
3.35
3.30
3.25
3.20
3.15
3.10
3.05
3.00
2.95
2.90
Mean
penile
length
an odds ratio of 6 (95 % CI 2 – 16), i.e., the exposed persons
were six times more likely to develop anomalies than
those not exposed (Table 1 ).
Genital anomalies were detected in the offspring
of those exposed to chlorinated hydrocarbons (9.52 % ),
phthalate esters (8.70 % ), and heavy metals (6.25 % ). In
contrast, none of the newborns exposed to phenols had
genital anomalies (Table 2 ).
Exposed
Non exposed
Penile lengths according to exposure to endocrine
Figure 1 disruptors.
Serum free testosterone levels
Exposure to cigarette smoke and progestins
during the first trimester
None of the mothers in the study was an active smoker;
350 were only exposed through passive smoking. There
was no difference between rates of anomalies among
those exposed to cigarette smoke when compared to those
not exposed (1.1 % vs. 2.2 % ). Similarly, there was no differ-
ence between the rates of anomalies among those exposed
to progestins during the first trimester when compared to
the non-exposed ones (2 % vs. 1.8 % ).
In the first day of life, serum free testosterone levels
ranged between 7.2 and 151 pg/mL (mean 61.9 ± 38.4 pg/mL;
median 60 pg/mL). There was a linear relationship
between penile length and testosterone level of the
newborn with a regression coefficient of 0.002 (95 % CI
0.0004 – 0.003; p = 0.01), i.e., there was an increase of 0.2 cm
in penile length per 100 pg/mL increase in testosterone
level. Moreover, serum testosterone level was significantly
lower in newborns exposed to EDs (49.50 ± 22.3 pg/mL)
than in the non-exposed group (72.20 ± 31.20 pg/mL;
p < 0.01).
Table 1 Frequency of genital anomalies according to type of
exposure to endocrine disruptors.
Exposure to endocrine
disruptors
Prevalence of genital anomalies
Anomalies Total
Negative Positive
Negative exposure 908 11 919
98.8 % 1.2 % 100.0 %
Positive exposure 75 6 81
92.6 % 7.4 % 100.0 %
Total 983 17 1000
98.3 % 1.7 % 100.0 %
χ 2 = 25.05, p < 0.0001.
Over the study period, the birth prevalence of genital
anomalies was 1.8 % , i.e., 18/1000 live birth. Hypospadias
accounted for 83.33 % of the cases. Fourteen had glanu-
lar hypospadias and one had coronal hypospadias. One
had penile torsion and another had penile chordee. Right-
sided cryptorchidism was present in one newborn.
Exposure to EDCs
Among the whole sample, 81 newborns (8.10 % ) were
exposed to EDs. The duration of exposure varied from
2 to 32 years with a frequency of exposure ranging from
weekly to 2 – 3 months per year.
There was a significantly higher rate of anomalies
among those who were exposed to EDs when compared
to non-exposed newborns (7.4 % vs. 1.2 % ; p < 0.0001), with
Table 2 Type of endocrine disruptor and percentage of anomalies in
the group of neonates exposed to endocrine disruptors (n = 81).
Anomalies Total
Negative Positive
Chlorinated hydrocarbons (farmers) 19 2 21
90.48 % 9.52 % 100.0 %
Heavy metals (iron smiths, welders) 30 2 32
93.75 % 6.25 % 100.0 %
Phthalate esters (house painters) 21 2 23
91.30 % 8.70 % 100.0 %
Phenols (car mechanics) 5 0 5
100.0 % 0 % 100.0 %
Total 75 6 81
92.60 % 7.40 % 100.0 %
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512 El Kholy et al.: Penile length and male genital anomalies
Discussion
Previously reported penile lengths varied from 2.86 to 3.75 cm
(11 – 16) and depended on ethnicity. In Saudi Arabia (13) ,
mean newborn penile length was 3.55 ± 0.57 cm, slightly
higher than our mean value. However, the cut-off lower
limit ( – 2.5 SD) was calculated to be 2.13 cm (vs. 2.5 cm in
our cohort). This emphasizes the importance of establish-
ing the normal values for each country because the normal
range could vary markedly. In a multiethnic community,
a mean length of – 2.5 SD was used for the definition of
micropenis and was 2.6, 2.5, and 2.3 cm for Caucasian,
East-Indian, and Chinese babies, respectively (p < 0.05).
This is close to the widely accepted recommendation that
a penile length of 2.4 – 2.5 cm be considered as the lowest
limit for the definition of micropenis (8) . The recognition
of micropenis is important, because it might be the only
obvious manifestation of pituitary or hypothalamic hor-
monal deficiencies (17) .
The timing for measurement of testosterone in new-
borns is highly variable but, generally, during the first 2
weeks of life (18) . In our study, serum testosterone level
was measured in all newborns on day 1 in order to fix a
time for sample withdrawal in all newborns and, also, to
make sure that all samples were withdrawn before mothers
were discharged from the maternity hospital. We found a
linear relationship between penile length and testosterone
levels of newborns. Mean penile length was lower in neo-
nates exposed to EDs compared to the non-exposed group,
which could be related to the lower testosterone levels in
the exposed group. The etiology of testicular dysgenesis
syndrome (TDS) is suspected to be related to genetic and/or
environmental factors, including EDs. Few human studies
have found associations/correlations between EDs, includ-
ing phthalates, and the different TDS components (18) .
Some reports have suggested an increase in hypo-
spadias rates during the period 1960 – 1990 in European
and US registries (19 – 23) . There are large geographical
differences in reported hypospadias rates, ranging from
2.0 to 39.7/10,000 live births (23 – 25) . Several explanations
have been proposed for the increasing trends and geo-
graphical differences. As male sexual differentiation is
critically dependent on normal androgen concentrations,
increased exposure to environmental factors affecting
androgen homeostasis during fetal life (e.g., EDs with
estrogenic or anti-androgenic properties) may cause
hypospadias (3, 4) .
In Western Australia, the average prevalence of hypo-
spadias in male infants was 67.7 per 10,000 male births.
When applying the EUROCAT definition (24), the average
prevalence of hypospadias during 1980 – 2000 was 21.8 per
10,000 births and the average annual prevalence increased
significantly over the study period by 2.2 % per year. The
prevalence of hypospadias in this study was much higher
at 150 per 10,000; by excluding glanular hypospadias, the
prevalence fell sharply to 10 per 10,000 (26) .
We found a higher rate of anomalies among newborns
exposed to EDs when compared to non-exposed newborns
(7.4 % vs. 1.2 % ); this raises the issue that environmental
pollution might play a role in causing these anomalies.
Within the last decade, several epidemiologic studies
have suggested environmental factors as a possible cause
for the observed increased incidence of abnormalities in
male reproductive health (27) . Parental environmental/
occupational exposure to EDs before/during pregnancy
indicates that fetal contamination may be a risk factor for
the development of male external genital malformation
(27 – 29) .
Received October 25, 2012; accepted January 27, 2013; previously
published online March 18, 2013
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El Kholy et al.: Penile length and male genital anomalies 513
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kaifka · 發表於 2025-1-4 03:05:44

RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND
GONADOTROPIN
RICHARD C. KLUGO* AND JOSEPH C. CERNY
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan
ABSTRACT
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average
increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
occurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
growth. The response appears to be greater in younger children, which is consistent with previ-
ously published studies of age-related 5 reductase activity.
Children with microphallus regardless of its etiology will
require augmentation or consideration for alteration of exter-
nal genitalia. In many instances urethroplasty for hypo-
spadias is easier with previous stimulation of phallic growth.
The use of testosterone administered parenterally or topically
has produced effective phallic growth. 1- 3 The mechanism of
response has been considered as local or systemic. With this
in mind we studied 5 children with microphallus for response
to gonadotropin and to topical testosterone independently.
MATERIALS AND METHODS
Five 46 XY male subjects between 3 and 17 years old were
evaluated for serum testosterone levels and hypothalamic
function. Of these 5 boys 2 were considered to have Kallmann's
syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
lamic deficiency. After evaluation of response to luteinizing
hormone-releasing hormone these patients were treated with
1,000 units of gonadotropin weekly for 3 weeks. Six weeks
after completion of gonadotropin therapy 10 per cent topical
testosterone was applied to the phallus twice daily for 3 weeks.
Serum testosterone, luteinizing hormone and follicle-stimulat-
ing hormone were monitored before, during and after comple-
tion of each phase of therapy. Penile stretch length was
obtained by measuring from the symphysis pubis to the tip of
the glans. Penile circumferential (girth) measurements were
obtained using an orthopedic digital measuring device (see
figure).
RESULTS
Serum testosterone increased moderately to levels between
50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-
terone levels with topical testosterone remained near pre-
treatment levels (35 ng./dl.) or were elevated to similar levels
developed after gonadotropin therapy (96 ng./dl.). Higher
serum levels were noted in older patients (12 and 17 years old),
while lower levels persisted in younger patients (4, 8, and 10
years old) (see table). Despite absence of profound alterations
of serum testosterone the topical therapy provided a greater
Accepted for publication July 1, 1977. ·
Read at annual meeting of American Urological Association,
Chicago, Illinois, April 24-28, 1977.
* Requests for reprints: Division of Urology, Henry Ford Hospital,
2799 W. Grand Blvd., Detroit, Michigan 48202.
improvement in phallic growth compared to gonadotropin.
Average phallic growth with gonadotropin was 14.3 per cent
increase in length and 5.0 per cent increase of girth. Topical
testosterone produced a 60.0 per cent increase of phallic length
and 52.9 per cent increase of girth (circumference). The
response to topical testosterone was greatest in children be-
tween 4 and 8 years old, with a gradual decrease to age 17
years (see table).
DISCUSSION
Topical testosterone has been used effectively by other
clinicians but its mode of action remains controversial. Im-
mergut and associates reported an excellent growth response
to topical testosterone with low levels of serum testosterone,
suggesting a local effect.1 Others have obtained growth re-
sponse with high. levels of serum testosterone after topical
administration, suggesting a systemic response. 3 The use of
gonadotropin to obtain levels of serum testosterone compara-
ble to levels obtained with topical testosterone would seem to
provide a means to compare the relative effectiveness of
topical testosterone to systemic testosterone effect. It cer-
tainly has been established that gonadotropin as well as par-
enteral testosterone administration will produce genital
growth. Our report shows that the growth of the phallus was
significantly greater with topical applications than with go-
nadotropin, particularly in children less than 10 years old.
The levels of serum testosterone remained similar or lower
than with gonadotropin during therapy, suggesting that topi-
cal application produces genital growth by its local effect as
well as its systemic effect.
Review of our patients and their growth response related to
age shows a greater growth response at an earlier age. This is
consistent with the findings of Wilson and Walker, who
reported an increased conversion of testosterone to dihydrotes-
tosterone in the foreskin of neonates and infants.4 This activ-
ity gradually decreases with age until puberty when it ap-
proaches the same level of activity as peripheral skin. It may
well be that absorption of testosterone is less when applied at
an earlier age as suggested by lower serum levels in children
less than 10 years old. This fact may be explained by the
greater ability of phallic skin to convert testosterone to dihy-
drotestosterone at this age. Conversely, serum levels in older
patients were higher, possibly because of decreased local
667
668 KLUGO AND CERNY
Pt. Age
(yrs.)
Serum Testosterone Phallus (cm.) Change Length
(ng./dl.) Girth x Length (%)
4
8
10
12
17
Gonadotropin
71.6 2.0 X 3 16.6
50.4 4.0 X 5.0 20.0
22.0 4.5 X 4.0 25.0
84.6 4.0 X 4.5 11.1
85.9 4.5 X 5.5 9.0
Av. 14.3
4
8
10
12
17
Topical testosterone
34.6 4.5 X 6.5 85
38.8 6.0 X 8.5 70
40.0 6.0 X 6.5 62.5
93.6 6.0 X 7.0 55.5
95.0 6.5 X 7.0 27.2
Av. 60.0
available testosterone. Again, emphasis should be placed on
early therapy when lower levels of testosterone appear to
provide the best responses. The earlier therapy is instituted
the more likely there will be an excellent response with low
serum levels. Response occurs throughout adolescence as
noted in nomograms of phallic growth. 7 The actual response
to a given serum level of testosterone is much greater at birth
and gradually decreases as boys reach puberty. This is most
likely related to the conversion of testosterone to dihydrotes-
tosterone and correlates well with the studies of testosterone
conversion in foreskin at various ages.
The question arises regarding early treatment as to whether
one might sacrifice ultimate potential growth as with acceler-
ated bone growth. The situation appears quite the reverse
with phallic response. If the early growth period is not used
when 5a reductase activity is greatest then potential growth
may be lost. We have not observed any regression of growth
attained with topical or gonadotropin therapy. It may well
be that some patients will show little or no response to any
form of therapy. This would suggest a defect in the ability to
convert testosterone to dihydrotestosterone and indicate that
phallic and peripheral skin, and subcutaneous tissue should
be compared for 5a reductase activity.
A, loop enlarges to measure penile girth in millimeters. B,
example of penile girth computed easily and accurately.
conversion of testosterone to dihydrotestosterone. It is in this
older group that others have noted high levels of serum
testosterone with topical application. It would also appear
that phallic response during puberty is related directly to the
serum testosterone level. There also is other evidence of local
response to testosterone with hair growth and with spermato-
genesis. 5• 6
Administration of larger doses of gonadotropin or systemic
testosterone, as well as topical applications that produce
higher levels of serum testosterone (150 to 900 ng./dl.), will
also produce phallic growth but risks accelerated skeletal
maturation even after stopping treatment. It would appear
that this may be avoided by topical applications of testosterone
and monitoring of serum testosterone. Even with this control
the duration of our therapy did not exceed 3 weeks at any
time. It is apparent that the prepuberal male subject may
suffer accelerated bone growth with testosterone levels near
200 ng./dl. When skeletal maturation is complete the level of
serum testosterone can be maintained in the 700 to 1,300 ng./
dl. range to stimulate phallic growth and secondary sexual
changes. Therefore, after skeletal maturation parenteral tes-
tosterone may be used to advantage. Before skeletal matura-
tion care must be taken to avoid maintaining levels of serum
testosterone more than 100 ng./dl. Low-dose gonadotropin
depends upon intrinsic testicular activity and may require
prolonged administration for any response.
Alternately, topical testosterone does not depend upon tes-
ticular function and may provide a more constant level of
REFERENCES
1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
R.: The local application of testosterone cream to the prepub-
ertal phallus. J. Urol., 105: 905, 1971.
2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
treatment for micropenis during early childhood. J. Pediat.,
83: 247, 1973.
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
one therapy for penile growth. Urology, 6: 708, 1975.
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
skin slices of man. J. Clin. Invest., 48: 371, 1969.
5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth
by topical application of androgens. J.A.M.A., 191: 521, 1965.
6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
androgenic effect of interstitial cell tumor of the testis. J.
Urol., 104: 774, 1970.
7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-
tion in the male genitalia from birth to maturity. J. Urol., 48:

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