- 註冊時間
- 2023-5-6
- 精華
- 在線時間
- 小時
- 米币
-
- 最後登錄
- 1970-1-1
累計簽到:5 天 連續簽到:1 天
|
發表於 2025-1-4 02:48:33
|
顯示全部樓層
Mohamed El Kholy , Rasha Tarif Hamza * , Mohamed Saleh and Heba Elsedfy
. y4 \5 c& N4 f- HPenile length and genital anomalies in Egyptian$ }7 {9 C$ M" f! X& S6 Y
male newborns: epidemiology and influence of
# a/ O3 `9 x% O: Bendocrine disruptors
/ `6 K e' |6 @2 ^Abstract: This is an attempt to establish the normal' W9 J6 I, K: n6 q
stretched penile length and prevalence of male geni-6 k. N( N5 m0 @1 F4 R, I; o( P
tal anomalies in full-term neonates and whether they9 @* t v+ ]- c: v: K" |
are influenced by prenatal parental exposure to endo-# `$ ~' O! ]4 p% j- S0 ^5 N4 `
crine-disrupting chemicals. A thousand newborns were& a" X0 _4 N5 j+ {3 E# H& P9 U9 w
included; their mothers were subjected to the following1 {- {# p0 @& X& f; Y ?
questionnaire: parents ’ age, residence, occupation, con-
0 M; f- M. U0 q: htact with insecticides and pesticides, antenatal exposure- @& f3 a3 F* c4 i
to cigarette smoke or drugs, family history of genital
# D* @* @9 a( Lanomalies, phytoestrogens intake and history of in vitro
0 ~ o% y) A7 Z+ F1 ^# O0 i* Hfertilization or infertility. Free testosterone was measured3 N. ^% ~8 n4 J0 G( W) i
in 150 neonates in the first day of life. Mean penile length
0 C7 U4 J" m' L1 k( R& ]0 ]was 3.4 ± 0.37 cm. A penile length < 2.5 cm was considered
3 ^9 V' {% R4 Mmicropenis. Prevalence of genital anomalies was 1.8 %& e' j, L* i1 O I, \
(hypospadias 83.33 % ). There was a higher rate of anoma-9 w: N- O! v/ n9 B3 ~
lies in those exposed to endocrine disruptors (EDs; 7.4 % ) `, Z( r/ \, r4 J" w
than in the non-exposed (1.2 % ; p < 0.0001; odds ratio 6,. l0 f( s+ H& G' l- T* N) m6 R$ t' f
95 % confidence interval 2 – 16). Mean penile length showed+ }! i, T* a2 w8 I
a linear relationship with free testosterone and was lower% i# Q8 ]- l+ k/ r, y2 C; ]
in neonates exposed to EDs.
7 S6 o: L4 F! O F& J! g3 z, TKeywords: endocrine disruptors; genital anomalies; male;
" ?$ i, f3 k5 @8 m) Mpenile length; testosterone.
* o8 W) H. b- c: P& H* C+ L*Corresponding author : Rasha Tarif Hamza, MD, Faculty of6 s0 J2 p" w' b+ `# e: \: m5 H8 J4 [
Medicine, Department of Pediatrics, Ain Shams University, 36! n! v8 o, F1 Y3 X8 Q+ b- x
Hisham Labib Street, off Makram Ebeid Street, Nasr City, Cairo3 r D; y" i% _8 q' ^
11371, Cairo, Egypt, Phone: + 20-2-22734727, Fax: + 20-2-26904430 ,
" ~# z! g" R0 Q9 n2 _ {E-mail: [email protected]2 h/ ~$ C) i& b3 H) V% h
Mohamed El Kholy, Mohamed Saleh and Heba Elsedfy: Faculty of5 @' w7 T. v# p2 F/ H" ?
Medicine , Department of Pediatrics, Ain Shams University, Cairo,3 r- C2 H' ~* S( k6 Q. E. \$ o
Egypt
+ w8 v& H' E7 V- M+ [0 A7 W% ^! t- MIntroduction# t% Y1 x- ?1 _- Z/ j. w: B8 C3 U
Determination of penile size is employed clinically in" F k2 F, {( B& x' a
the evaluation of children with abnormal genital devel-! r$ ]' G" a/ ~0 E
opment, such as, for example, micropenis, defined as a
4 H% T2 ?: {6 W; u+ Fpenis that is normal in terms of shape and function, but is
- f! a# I6 D) E( k' x3 l, ^more than 2.5 standard deviations (SD) smaller than mean" K; `1 c1 ?. l- N) k
size in terms of length (1) . However, these measurements
' [" v5 ~- q% r4 {; Zcan be subject to significant international variations, in, P; D! w ~ g
addition to being obtained with different methodologies
% q5 [" k2 P f0 V$ C* z1 J, }. _in some cases (2) .
7 ^- D6 H/ q# x3 FOver the past 20 years, the documented increase in! v( B' R$ g+ _ F& L7 O
disorders of male sexual differentiation, such as hypo- ]: D% o# o M" S# a7 C
spadias, cryptorchidism, and micropenis, has led to the
4 H2 Q# }6 v) r/ O% Z- Lsuspicion that environmental chemicals are detrimental
, \* y4 U9 ?2 k1 V9 G7 _to normal male genital development in utero (3) . The so-; U) r1 z- b6 i* {' w
called Sharpe-Skakkebaek hypothesis offered a possible& J$ c. g2 m6 Z- D
common cause and toxicological mechanism for abnor-- k7 B" z- W& X
malities in men and boys – that is, increased exposure to
% u2 N2 S$ X a: _' Zoestrogen in utero may interfere with the multiplication
& x' t$ \- k! o- s0 n, p2 z6 Iof fetal Sertoli cells, resulting in hormonally mediated
- E& o+ j f1 D3 d) M; t+ Rdevelopmental effects and, after puberty, reduced quality; Q/ h) _. Y7 n& |+ [
of semen (4) .
; T: s9 Z, M, D) ?: j. D/ \It has been proposed that these disorders are part of
2 e: L3 i! F% { ya single common underlying entity known as the testicu-$ K3 O) F7 q1 M* C+ o& G
lar dysgenesis syndrome (TDS) (5) . TDS comprises various, `6 p0 g* M$ {+ k" F( G9 ~
aspects of impaired gonadal development and function,
8 h( d U6 b0 l" F' O" }. Mincluding abnormal spermatogenesis, cryptorchidism,
. |9 P4 I; K6 E; W, p, rhypospadias, and testicular cancer (6) .
, X v( A# Q) V! d( `; d- HThe etiological basis for this condition is complex
0 |2 _3 U8 N+ r4 Yand is thought to be due to a combination of both genetic. m' A' ^6 [1 F9 c) M' ~
and environmental factors that result in the disruption
6 ~5 C- ?6 S7 o9 u9 Zof normal gonadal development during fetal life. First,
v) e- W7 q. ^6 q* i; rit was proposed that environmental chemicals with oes-
8 P+ U1 o( X; A, w2 W" |trogen-like actions could have adverse effects on male; D4 v5 q2 l# O' J
gonadal development. This has since been expanded to! n2 Z! V: k' ?& {, `
include environmental chemicals with anti-androgen( C1 K' k1 K+ g; f
actions and it is now thought that an imbalance between
+ x R' {: c3 a+ P7 Z8 w* nandrogen and oestrogen activity is the key mechanism by
9 g, \5 a, }/ b6 nwhich exposure to endocrine disrupting chemicals (EDCs)' K& U0 F8 M; p, E4 D, L$ o, j. y
results in the development of TDS and male reproductive4 u2 K! v; D! S8 }! N+ B
tract abnormalities (5) .+ X+ z+ x1 F' w0 x
With the increasing use of environmental chemicals,
* ^4 z' }3 n# n+ n+ \* W# Kan attempt was made to establish the normal stretched
" w7 Y. q2 O, C0 ^penile length as well as the prevalence of male genital; D, O8 Y0 G) N! M$ U+ N7 H
anomalies in full-term neonates and whether there is an
7 `9 p/ W- s8 }& A6 w/ \+ binfluence of prenatal parental exposure to potential EDCs
' {: i- K4 a9 ~0 i( fon these parameters.2 [0 D7 n. J+ V& t3 w
Brought to you by | University of California - San Francisco
0 S2 ~/ a$ ^ \* W8 O( hAuthenticated2 b1 Z; C3 F4 J8 d/ @$ E4 z( O$ E9 L
Download Date | 2/18/15 4:26 AM
* \9 j8 f L w- g+ g/ f510 El Kholy et al.: Penile length and male genital anomalies! W6 U; q d- E6 j
Subjects and methods/ D |2 Z: ^& p1 `
Study population
' q4 G6 C2 M! q1 {* k/ S3 A; OThe study was conducted as a prospective cohort study at the Univer-1 n: d) p4 Z/ M+ ]; ~
sity Hospital of Ain Shams University, Cairo, Egypt. A sample of 1000' o$ w5 V2 s5 Z# u5 g
male full-term newborns was studied.* [; u4 G- R* X( P( E
Sampling technique
/ h: t* U- V% }: Q/ j- B8 mThree days per week were selected randomly out of 7 days. In each
) ]( n5 Q$ `" yday, all male full-term deliveries were selected during the time of fi eld
5 {6 d' L* F8 l' Kstudy (12 h) during the period from March 2007 to November 2007.
/ U8 J9 [( w. ZStatistical analysis
! n5 t8 e+ p) B( aThe computer program SPSS for Windows release 11.0 (SPSS Inc.,
' c' ], l( k9 B. aChicago, IL, USA) was used for data entry and analysis. All numeric& N. h6 m" x7 Z7 d- l
variables were expressed as mean ± SD. Comparison of diff erent vari-
) i) O5 e( Q, p' h4 Y% {ables between two groups was done using the Student ’ s t-test for0 @$ P1 i p9 ^6 N: }3 T
normally distributed variables. Comparisons of multiple groups were
' Z% f5 a+ F) Y( o( idone using analysis of variance and post hoc tests for normally dis-% |2 o R, f s! I0 c6 `
tributed variables. The χ 2 -test was used to compare the frequency of0 |( J. l* V7 d% I5 _3 @
qualitative variables among the diff erent groups; the Fisher exact test; u! t: r4 k- S# B4 d8 P. S% a
was performed in tables containing values < 5. The Pearson correla-. O& G& N6 g8 N E4 X) W0 C
tion test was used for correlating various variables. For all tests, a
8 N) Z& H5 l/ Vprobability (p) < 0.05 was considered signifi cant (10) .
6 y. F( U, Q* J% b+ @% DResults4 K" V8 Q# P q: E
Data collected
! y6 @ j* m+ o3 [/ PA researcher completed a structured questionnaire during inter-2 i: U, b" C' C; ]8 V) D9 @- ?' ^
views with the mothers. The questionnaire gathered information
7 I- {( J$ K3 A% u" H( ?- Ron the following: age of parents; residence; occupation of the
: S7 M6 v5 z+ H9 @parents; contact with insecticides and pesticides and their type and
8 ]4 e E2 f. [" c1 Ffrequency of contact; maternal exposure to cigarette smoke during
+ q8 c+ ]# o8 I6 Z1 t0 T6 x; rpregnancy; maternal drug history during gestation; family history# x: z2 n0 a* ]* c% o
of hypospadias, cryptorchidism, or other congenital anomalies; in-# M5 r3 w% x' D# Z9 X. P
take of foods containing phytoestrogens, e.g., soy beans, olive oil,
. T" B$ d% f' |garlic, hummus, sesame seed, and their frequency; and, also, his-
7 k8 P3 D4 K/ h5 \0 {tory of in vitro fertilization or infertility (type of infertility and drugs
5 h0 H" k: f m+ N3 t. Sgiven).
) q/ o" b: r4 C4 V: O; `1 f% L9 SEnvironmental exposure to chemicals was evaluated for its po-
6 Y f$ { J2 ttential of causing endocrine disruption. Chemicals were classifi ed
1 X1 x- w$ S2 K, e3 \into two groups on the basis of scientifi c evidence for their having
. E9 |0 {9 e/ [endocrine-disrupting properties: group I: evidence of endocrine dis-
" Z) v) R' e2 P8 R( _ruption high and medium exposure concern; group II: no evidence of C! ~( [! q: d* p
endocrine disruption and low exposure concern (7) .0 I* {3 y0 W2 a' q6 i- }# [2 H/ L, S
Descriptive data
4 l/ F8 |8 ]3 ~- zThe mean age of newborns ’ fathers was 36 ± 6 years (range
0 B7 p$ {9 |0 `) N3 \: Q20 – 50 years) and that of mothers was 26 ± 5 years (range7 h, \* C. {+ v9 ?% ? r$ \0 V
19 – 42 years). Exposure to EDs started long before preg-
6 h K! w- t5 ]( L$ dnancy and continued throughout pregnancy. Regard-
" W- l# w1 A6 R, Ging therapeutic history during pregnancy, 99 mothers
/ I2 z! t% _, T) u2 \(9.9 % ) received progestins, 14 (1.4 % ) received insulin,! z$ h: d' G3 A8 F
6 (0.6 % ) received heparin, 4 (0.04 % ) received long-' {9 N8 f' A/ w9 B5 Q
acting penicillin, 3 (0.3 % ) received aspirin, 2 (0.2 % )# j) A' S$ L7 v- m' C$ K* f
received B2 agonist, and 1 (0.1 % ) received thyroxin,
1 B- ]7 w: K) j/ A3 N i, R3 ]3 pwhile the rest did not receive any medications during
( L/ B; @ M3 L3 |, [& ^pregnancy except for the known multivitamins and
/ T7 w& ^4 I' o1 Z# J9 e: F& Ecalcium supplementations. In addition, family history
& p+ ^: h# t- [( }of newborns born small for gestational age was positive6 p! e5 M8 K3 e+ u
in 21 cases (2.1 % ).1 E) Q6 K6 g% I% n1 p- }- _1 Y& t2 Q
Examination
1 U I2 G. g _In addition to the full examination by the paediatric staff , each boy$ A1 [( V1 x, o6 H. U) M
was examined for anomalies of the external genitalia during the
! H! A, C- Q+ Dfi rst 24 h of life by one specially trained researcher. Examination
4 i- v& `3 ^1 k) t1 m% F6 x/ }! eof the genital system included measurement of stretched penile
& F8 k% d# U$ H9 k' C- q( Plength (8) and examination of external genitalia for congenital
# ?4 z% \3 q2 q3 I8 zanomalies such as cryptorchidism (9) and hypospadias. Hypospa-7 G+ M& z& Y, ~4 g' A! K' ?
dias was graded as not glanular, coronal, penile, penoscrotal, scro-7 M6 i6 i6 u, N! Y p: x" ^
tal, or perineal according to the anatomical position. Cases of iso-
. [+ U A% ^& j9 K* _: z7 U q( mlated malformed foreskin without hypospadias were not included
6 D8 `! s- Q. J8 a, L1 Sas cases.! s* P3 G s0 H- Q/ b. h
Penile length8 S8 G7 J0 Z/ S. B
Laboratory investigations* Q/ Z$ u% r: H% F
Free testosterone level was measured in 150 randomly chosen neo-
! H" N4 t8 Q9 w. I- qnates from the studied sample in the fi rst day of life (enzyme im-# \% j4 ?3 |! P
munoassay test supplied by Diagnostics Biochem Canada, Inc.,
4 q" c' k, U$ ?& \0 I: h# [& z1 GDorchester, Ontario, Canada).
/ U/ @1 ?+ d/ d% t9 bMean penile length was 3.41 ± 0.37 cm (range 2.4 – 4.6 cm).% _6 _$ x0 ~# G
A penile length < 2.5 cm was considered micropenis ( < the% `, d: L6 X0 J# `2 f1 i8 b
mean by 2.5 SD). Two cases (0.2 % ) were considered to; c; _" \7 r @7 u' b, r6 i
have micropenis. Mean penile length was lower (p = 0.041)
4 S G% P4 t Q6 Oin neonates exposed to EDs (n = 81, 3.1 cm) compared to the
6 d1 R \' e4 {* enon-exposed group (n = 919, 3.4 cm; Figure 1 ).
4 W4 X3 I) `( Y, T9 PThere was a linear relationship between penile length
% V: V% X: c8 X: Y& i* Yand the length of the newborn with a regression coef-$ g, a7 M2 x: \- B+ }
ficient of 0.05 (95 % CI 0.04 – 0.06; p < 0.0001), i.e., there2 o4 p' l. F3 G3 t0 v8 |
was an increase of 0.05 cm for each unit increase in length
9 A5 [" K8 x" X% T" ^(cm). Similarly, there was a linear relationship between: r: X' Z5 t! h# R
penile length and the weight of the newborn with a regres-
( X5 K! j) m! k4 I! J7 b ]% E# Csion coefficient of 0.14 (95 % CI 0.09 – 0.18; p < 0.0001), i.e.,
. {3 Z X( W3 D* g4 v7 @8 q* W( ]there was an increase of 0.14 cm for each unit increase in$ t9 A8 a+ W3 F8 ~4 S# t
weight (kg).
8 ?* Z& Q; g( t' F X: `Brought to you by | University of California - San Francisco/ ^# j; S( o8 L0 m6 K3 M
Authenticated) T; G9 K) A) V- P! p* w& e6 y8 j6 S
Download Date | 2/18/15 4:26 AM
- G% `6 O1 w5 `7 {- c( DEl Kholy et al.: Penile length and male genital anomalies 511
1 k( C/ b- q" y1 p3 E% O. p3.45
' ?9 y6 X: B Y7 d- t' ~/ ^3.40+ M, w/ m3 N6 t! h6 b% [/ h
3.35' l1 G$ O4 F* }* D
3.30
6 z/ V) c1 B; W! I$ ?3.253 v/ X; g" b1 s- N
3.20! m5 M T/ X" ^/ q# s
3.15
7 N Y& j+ k ]3.104 I# h$ S& W: F1 {3 V' B; D
3.05+ d# t* F Y6 v& X, @8 d) z$ J0 O1 z
3.00
; ]9 ~: I/ ?" ~8 G4 v2.95" T5 Z# b# W) j8 x
2.90
3 J3 D2 m. y7 y( {Mean% _: u* t! a, J8 l% z
penile! m6 U$ Q! v* s& B3 D: q& f
length* X5 r9 i$ Y& H Z( q1 H3 C& I9 a0 d
an odds ratio of 6 (95 % CI 2 – 16), i.e., the exposed persons
9 ^( C0 [3 \1 W6 y/ _. l' Rwere six times more likely to develop anomalies than
7 M9 B; M; J/ `2 Q" Sthose not exposed (Table 1 ).) j' f0 V6 c4 _5 [; a
Genital anomalies were detected in the offspring" `* l( k" Z# E$ a
of those exposed to chlorinated hydrocarbons (9.52 % ),
* a) y9 y7 b% f7 kphthalate esters (8.70 % ), and heavy metals (6.25 % ). In
* N9 q& J( }- I5 fcontrast, none of the newborns exposed to phenols had
1 \* M9 I$ Q e# t) b9 qgenital anomalies (Table 2 ).
* Y9 j3 }" ?, G. f5 |- HExposed% D/ ~# g0 @& O- W; u9 m+ r
Non exposed6 B+ M" T, \ K4 p
Penile lengths according to exposure to endocrine& R* Y) E, S- C1 k
Figure 1 disruptors.
2 B, \. c/ H4 ]$ q2 m2 \8 pSerum free testosterone levels
7 I- y7 O7 L% W/ C4 x1 ?Exposure to cigarette smoke and progestins
9 ~8 D" r+ o8 {( jduring the first trimester* Y* V; G) ~2 e2 u8 Z6 |6 o
None of the mothers in the study was an active smoker;. a3 |' v0 j7 i8 M
350 were only exposed through passive smoking. There
' t, u# R% p b! y/ j, a) ~6 Bwas no difference between rates of anomalies among
r: o9 f" [. l) {6 V8 _those exposed to cigarette smoke when compared to those. C% t4 e3 T* }) B
not exposed (1.1 % vs. 2.2 % ). Similarly, there was no differ-
0 g9 D7 @$ i: k2 d* U8 h. \: l, Bence between the rates of anomalies among those exposed# e' ?' H7 x1 k2 `- g, L( {9 P
to progestins during the first trimester when compared to; Q3 F: z5 C! `9 w7 B$ o& p
the non-exposed ones (2 % vs. 1.8 % ).
2 u9 G9 \( K; ^7 QIn the first day of life, serum free testosterone levels) H+ `) w3 w% u& ^5 D0 {
ranged between 7.2 and 151 pg/mL (mean 61.9 ± 38.4 pg/mL;
3 ^+ {$ e! z- t9 U1 m" `6 S4 }/ Nmedian 60 pg/mL). There was a linear relationship$ F! N' H+ U4 L; Y4 U4 G% N! z
between penile length and testosterone level of the
; o6 b: t4 E$ h0 O) Pnewborn with a regression coefficient of 0.002 (95 % CI
+ w- x3 l1 F% }( N$ u1 \0.0004 – 0.003; p = 0.01), i.e., there was an increase of 0.2 cm6 s1 P: y2 j$ h
in penile length per 100 pg/mL increase in testosterone
5 e! v ~! j. m. f; [$ i @level. Moreover, serum testosterone level was significantly" a: ?( f/ N5 b* p
lower in newborns exposed to EDs (49.50 ± 22.3 pg/mL)
3 ^4 j; C z" p6 x3 }) vthan in the non-exposed group (72.20 ± 31.20 pg/mL;
' a/ Y7 Z: O% Z( o1 u, ^/ o$ d Pp < 0.01).
( `7 m3 T) \* a' r, }4 VTable 1 Frequency of genital anomalies according to type of
2 k w% W. O* ]2 Rexposure to endocrine disruptors.
4 u9 _& d: T) A m8 J" Q) s4 NExposure to endocrine5 U- u5 V& U f8 i, X! u! V! c8 _
disruptors
# k! Y1 P% q, VPrevalence of genital anomalies3 j! V2 ^" N; u" ~) G2 }/ T; ^6 n
Anomalies Total! W* |/ z( R1 v
Negative Positive5 {1 t; s0 A2 R- t# Q0 C& E
Negative exposure 908 11 919
: }7 q5 c0 T, ^: t: D98.8 % 1.2 % 100.0 %* A" g) l$ h. `4 ~
Positive exposure 75 6 81
. K* { _1 }+ a/ p8 R0 \' _92.6 % 7.4 % 100.0 %
; r) [3 y8 x) A! `Total 983 17 10001 x7 n# ~2 s; }7 {0 l$ J' `
98.3 % 1.7 % 100.0 %
* n3 G; V% F9 _& r& A: {& Mχ 2 = 25.05, p < 0.0001.
2 ^( n/ F }5 n# V ^$ \9 YOver the study period, the birth prevalence of genital
7 x% K0 `& B) [. E2 v( Lanomalies was 1.8 % , i.e., 18/1000 live birth. Hypospadias4 ]2 h' v# U3 B* S* \/ X4 I
accounted for 83.33 % of the cases. Fourteen had glanu-
! W% x1 E p4 Z; v+ ?lar hypospadias and one had coronal hypospadias. One. [3 e+ D/ f1 {
had penile torsion and another had penile chordee. Right-" p: i2 o5 `! ]% e( _% Q
sided cryptorchidism was present in one newborn.4 I7 i# u/ ^5 w
Exposure to EDCs
, \- @5 J- `" w0 A0 i I }! kAmong the whole sample, 81 newborns (8.10 % ) were
. g2 T+ p4 l5 K$ oexposed to EDs. The duration of exposure varied from
5 I, x8 \; ?% r% y- ^" H; J2 to 32 years with a frequency of exposure ranging from
; _$ x2 a9 @& w* G8 aweekly to 2 – 3 months per year.- N/ s$ r& P& ], @% o
There was a significantly higher rate of anomalies4 p2 c( ?5 ^4 [# }6 Z
among those who were exposed to EDs when compared
7 R& ?9 R$ k3 m0 C8 B* E; @( e. jto non-exposed newborns (7.4 % vs. 1.2 % ; p < 0.0001), with2 F1 V$ G5 t: ~! S' y$ Q0 a6 T
Table 2 Type of endocrine disruptor and percentage of anomalies in0 J" {* A4 L( { `
the group of neonates exposed to endocrine disruptors (n = 81).
8 m. @. q5 {8 ], ^ q: nAnomalies Total
, _. h$ [/ \" k8 X6 e' p; pNegative Positive/ q% J2 m/ Y; E; D) A; k
Chlorinated hydrocarbons (farmers) 19 2 21
2 |% [/ }- r/ a90.48 % 9.52 % 100.0 %
4 m$ V0 E2 ?" m6 u$ aHeavy metals (iron smiths, welders) 30 2 320 ~% ]9 o4 W% L! b% c, f
93.75 % 6.25 % 100.0 %
& H! I3 e( r5 ` D5 uPhthalate esters (house painters) 21 2 23
2 t) Q- ]" h4 e% z- \7 C# R' i91.30 % 8.70 % 100.0 %0 P8 Y" t( x/ }8 F/ K
Phenols (car mechanics) 5 0 5% V3 m+ _8 w& |% M# D& k) W3 q
100.0 % 0 % 100.0 %3 c+ ]& k/ h: I7 c8 |! k; c) g
Total 75 6 81) e0 I) s2 ] M+ m
92.60 % 7.40 % 100.0 %- N4 t: @- B% M+ R
Brought to you by | University of California - San Francisco4 X6 t" t; X9 B/ t8 A+ W
Authenticated
6 c: f9 P0 r" _+ O) M' Q2 CDownload Date | 2/18/15 4:26 AM- B$ y& b0 K( u9 S0 q
512 El Kholy et al.: Penile length and male genital anomalies6 ]# A. ~7 R k
Discussion K! }! {. f: T! F ^
Previously reported penile lengths varied from 2.86 to 3.75 cm" i" \6 D% n0 Z. _( C _0 I5 D5 K
(11 – 16) and depended on ethnicity. In Saudi Arabia (13) ,
5 m# _4 t0 i3 |% {0 cmean newborn penile length was 3.55 ± 0.57 cm, slightly6 L% I# ]: }7 b& ]/ C5 B. {
higher than our mean value. However, the cut-off lower' a. V5 C8 R. b3 U% C L% q5 T
limit ( – 2.5 SD) was calculated to be 2.13 cm (vs. 2.5 cm in
: G; |& z. p2 e' x+ {9 b4 Q! your cohort). This emphasizes the importance of establish-
$ w0 E1 m: {0 f B0 H5 D0 i, {ing the normal values for each country because the normal
1 @5 W# Q6 |4 E8 N9 D" N grange could vary markedly. In a multiethnic community,0 k, w/ c- e8 R$ Z# C
a mean length of – 2.5 SD was used for the definition of
/ G( [! R6 f- F- gmicropenis and was 2.6, 2.5, and 2.3 cm for Caucasian,& q. ` j6 i/ \; {+ k7 ~
East-Indian, and Chinese babies, respectively (p < 0.05).
) G Y& s# C# RThis is close to the widely accepted recommendation that
/ W0 j" ^% b h( I8 ea penile length of 2.4 – 2.5 cm be considered as the lowest" o W' O2 o% V! x
limit for the definition of micropenis (8) . The recognition
' [4 n# F$ ^( jof micropenis is important, because it might be the only: v2 k% m* a) m# i+ \0 u0 o% O
obvious manifestation of pituitary or hypothalamic hor-
+ G; |, t: q1 _1 Z- }1 _monal deficiencies (17) .* x4 ~ v3 e5 J1 F
The timing for measurement of testosterone in new-
# `3 D! `( o( Y" Xborns is highly variable but, generally, during the first 2 h0 B* A% K6 X! ?. g
weeks of life (18) . In our study, serum testosterone level( j6 X" K0 N8 \7 k7 G
was measured in all newborns on day 1 in order to fix a4 A9 }3 B; T1 G: x# z, E
time for sample withdrawal in all newborns and, also, to
8 v* k$ n2 U: W3 H# ^8 Gmake sure that all samples were withdrawn before mothers6 S( B& \1 E" W3 q9 Y5 W# L
were discharged from the maternity hospital. We found a
# x. @+ S, q. M( H% \& Ilinear relationship between penile length and testosterone2 N, {8 H. i4 |% P2 L& p5 u
levels of newborns. Mean penile length was lower in neo-8 D" Z8 `2 ]/ T- W1 U) ?
nates exposed to EDs compared to the non-exposed group,( ~- W3 N3 g( A; k. X' [, c% i& n
which could be related to the lower testosterone levels in
7 K1 x) \- S4 k4 fthe exposed group. The etiology of testicular dysgenesis
8 [: s! k+ A5 f3 @syndrome (TDS) is suspected to be related to genetic and/or* G" ?4 J% v' L, a3 @' \
environmental factors, including EDs. Few human studies
" K9 S! E7 Q, |/ }' H m4 q( }. Khave found associations/correlations between EDs, includ-
C4 f5 }& Q' X6 N9 _ing phthalates, and the different TDS components (18) .& i5 a* x- ~8 V# d' B( E8 Y2 w
Some reports have suggested an increase in hypo-. G3 s# T* I: z, k5 \* z
spadias rates during the period 1960 – 1990 in European6 \ g. x" O$ t2 ~+ t
and US registries (19 – 23) . There are large geographical
$ W: y- e; h* Pdifferences in reported hypospadias rates, ranging from8 F8 g; b1 }& B) _7 h/ Z* D
2.0 to 39.7/10,000 live births (23 – 25) . Several explanations
5 @/ t+ g* f) Yhave been proposed for the increasing trends and geo-
- U9 n/ {6 x2 |0 @graphical differences. As male sexual differentiation is9 \+ ~! [4 A$ o9 g' e3 j+ b. K
critically dependent on normal androgen concentrations,
3 X5 a; i) k. F1 g; Iincreased exposure to environmental factors affecting
+ _* d9 I7 S+ @androgen homeostasis during fetal life (e.g., EDs with
" Q* _ q% ]" S# K* qestrogenic or anti-androgenic properties) may cause
( F% O' n4 w2 U. v+ Z/ _! t( phypospadias (3, 4) .
$ j, Q, C6 @; q3 O$ v/ i- {In Western Australia, the average prevalence of hypo-% Z% V5 k) r5 ^" R6 c
spadias in male infants was 67.7 per 10,000 male births.
, |6 y* L' @; r, P1 \! o' F& [When applying the EUROCAT definition (24), the average
% {7 G0 h1 S5 p5 Z& V0 V. Y7 wprevalence of hypospadias during 1980 – 2000 was 21.8 per
! ?# M+ u" s3 N m10,000 births and the average annual prevalence increased. b6 x9 h( P n5 k0 J
significantly over the study period by 2.2 % per year. The5 d8 \( d4 K0 w$ p
prevalence of hypospadias in this study was much higher; Y& R4 Z! @& x( t: W. ?% e
at 150 per 10,000; by excluding glanular hypospadias, the7 n. f5 N( l7 Y. M4 b8 v; J7 X
prevalence fell sharply to 10 per 10,000 (26) .
+ {5 z4 A6 u* X! U6 m% n2 MWe found a higher rate of anomalies among newborns' {( I! e" k6 P6 F. @
exposed to EDs when compared to non-exposed newborns
3 Z2 U% |8 z/ G(7.4 % vs. 1.2 % ); this raises the issue that environmental
; b% S& Z' ]1 Y3 @. r% [+ C' [; hpollution might play a role in causing these anomalies.0 |0 F; U" W8 ^- r" ]6 O+ U
Within the last decade, several epidemiologic studies {* e% a! p3 E, `6 m) j
have suggested environmental factors as a possible cause# W, t& A; D) p
for the observed increased incidence of abnormalities in
# t& L3 F' _$ v$ N9 `male reproductive health (27) . Parental environmental/
( }* r" q0 A6 U: A, w8 J$ Soccupational exposure to EDs before/during pregnancy! @1 i1 N! D, L( o* z* [3 ?, h) b
indicates that fetal contamination may be a risk factor for3 y( J* W) G) m9 m. s
the development of male external genital malformation9 Z" G7 ?- F9 I0 ^0 i
(27 – 29) .
- Z+ V2 A1 K; W R% x9 oReceived October 25, 2012; accepted January 27, 2013; previously5 Y4 A% v: p% y+ q0 M7 l
published online March 18, 2013
+ [ `/ f, t% T5 D2 t# f! g$ BReferences) J, T7 X5 d/ Z, f
1. Aaronson IA. Micropenis: medical and surgical implications. J& E9 {1 @: G- E
Urol 1994;152:4 – 14.9 b' ]: G* J: f1 I
2. Gabrich PN, Vasconcelos JS, Dami ã o R, Silva EA. Penile anthro-; U! n6 P) \3 d
pometry in Brazilian children and adolescents. J Pediatr (Rio J)! j0 O( V; o( X: r' v$ {. L
2007;83:441 – 6.3 S, }; W2 \' a/ E
3. Sultan C, Balaguer P, Terouanne B, Georget V, Paris F, et al.( {7 B- Z0 r5 V& \% l+ }7 f
Environmental xenoestrogens, antiandrogens and disorders of( W# O+ k, G* J
male sexual differentiation. Mol Cell Endocrinol 2001;10:178:
% O. G* B, z3 M0 H6 w99 – 105.
: x# {: W" Z: m# u# E9 J4. Sharpe RM, Skakkeb æ k NE. Are oestrogens involved in falling% \7 X5 f, h: S$ s& }
sperm counts and disorders of the male reproductive tract ?+ Q5 h1 a' ]8 y' _9 P7 u1 a
Lancet 1993;341:1392 – 5.
. V! S8 i+ |$ N( m5. Acerini CL, Hughes IA. Endocrine disrupting chemicals: a new
4 D. {5 l. v6 z- wand emerging public health problem ? Arch Dis Child 2006;91:0 u$ c- r" j% Z) P, b
633 – 41.
7 Q) x2 g' y3 b9 G) P2 j6. Joensen UN, J ø rgensen N, Rajpert-De Meyts E, Skakkebaek NE.
t( c! O* X- E. J0 ^; c1 UTesticular dysgenesis syndrome and Leydig cell function. Basic; ^; }+ b* g9 B5 p) O
Clin Pharmacol Toxicol 2008;102:155 – 61. r/ M1 X* i" N5 u
7. IEH. Chemicals purported to be endocrine disruptors: a
1 s# c; c$ O* Ocompilation of published lists. (Web Report W20), Leicester,/ m+ k) l% a7 z! s( v. r
UK: MRC Institute for Environmental Health, 2005. Accessed on
3 Y6 [* t. E/ b. b' r0 L U' WMarch 2005. Available at http://www.le.ac.uk/ieh/.
1 S5 u+ ^' `$ U9 E# c8. Cheng PK, Chanoine JP. Should the definition of micropenis vary/ |7 c5 f; Q; q. r! B
according to ethnicity ? Horm Res 2001;55:278 – 81.
+ J4 ?" [ p: {* oBrought to you by | University of California - San Francisco
5 p" D* B3 t% d8 VAuthenticated
, \4 v D% o/ Y! I1 v& o# lDownload Date | 2/18/15 4:26 AM
) ^3 g" j9 \* D2 R# C9 NEl Kholy et al.: Penile length and male genital anomalies 513/ d- O4 l% e$ g& ?4 K w
21. K ä ll é n B, Bertollini R, Castilla E, Czeizel A, Knudsen LB, et al.) g8 W4 f# e$ x- V
A joint international study on the epidemiology of hypospadias.) C1 b( l( `& n. G# O( R
Acta Paediatr Scand 1986;324(Suppl):1 – 52.- P/ K* }! _$ g( l0 C" @
22. Paulozzi LJ, Erickson JD, Jackson RJ. Hypospadias trends in two! @+ [7 @3 y! d% e, ` E
US surveillance systems. Pediatrics 1997;100:831 – 4.6 H$ ]7 Q4 w) ]" L6 v2 i
penile length in newborn and infants. BJU Int 1999;84 : 1093 – 4.0 a0 j( y! b+ i- W0 ]8 b$ @6 Q- M& o
J Pediatr Endocrinol Metab 2000;13 : 55 – 62.
1 d2 n/ m( I7 p4 G9 oVasudevan G, Manivarmane B, Bhat BV, Bhatia BD, Kumar S.! T0 m+ e' i4 D' |3 T1 i$ @
Genital standards for south Indian male newborns. Indian J3 {8 D* D7 L: {
9. Scorer CG. The incidence of incomplete descent of the testicle at3 T! @0 G5 y/ J* c# m3 Y" c
birth. Arch Dis Child 1956;31:198 – 202.
! m; S- Q! G! }10. Daniel WW. Biostatistics: a foundation for analysis in the health
5 A3 _9 ^! Q, Dsciences, 6th ed. New York: John Wiley and Sons, Inc., 1995.
2 }! P* r5 }1 L E% P11. Flatau E, Josefsberg Z, Reisner SH, Bialik O, Iaron Z. Letter:
; C4 E$ E& S6 Y; ^7 ~penile size in the newborn infants. J Pediatr 1975;87:663 – 4.; ^1 M8 C5 y4 F, s3 E. f! t5 Z
12. Ozbey H, Temiz A, Salman T. A simple method for measuring+ A4 w& Q5 F5 f, r4 j5 A2 v& B
13. Al-Herbish AS. Standard penile size for normal full term
2 l! a: T! v7 L/ E" D7 Xnewborns in the Saudi population. Saudi Med J 2002;23:314 – 6.* c" h( p1 ]: v7 r) B0 x# d
14. Lian WB, Lee WR, Ho LY. Penile length of newborns in Singapore.
- B+ N$ y4 M6 A" I15. Pediatr 1995;62:593 – 6.
3 K, p+ k8 a9 R9 l4 F' o" y( E16. Boas M, Boisen KA, Virtanen HE, Kaleva M, Suomi AM, et al.
4 O6 M' U' ^5 U9 a E4 @3 }% [+ u% ~2 _% |Postnatal penile length and growth rate correlate to serum
: }* Y M5 D1 e2 U/ ytestosterone levels: a longitudinal study of 1962 normal boys.
, u, _; M. G7 B2 {' J4 x s7 y5 u' oEur J Endocrinol 2006;154:125 – 9.6 l u7 G) D; l1 J2 C+ i( ?
17. Camurdan AD, Oz MO, Ilhan MN, Camurdan OM, Sahin F,0 o$ q, C6 X i! ?& B
et al. Current stretched penile length: cross-sectional study6 O* b. m/ v( B$ R
of 1040 healthy Turkish children aged 0 to 5 years. Urology
3 O$ m3 A3 Z: E3 F( a6 `2007;70:572 – 5.
0 K [" ]! ~% b4 ?) G6 H; w18. Bay K, Asklund C, Skakkebaek NE, Andersson AM. Testicular* q% ]" y: f' G
dysgenesis syndrome: possible role of endocrine disruptors.
# n6 H# M2 t, d+ _' X" YBest Pract Res Clin Endocrinol Metab 2006;20:77 – 90.
, x* j6 U- Y2 u! j19. Czeizel A. Increasing trends in congenital malformations of male4 |6 }2 z! B7 r+ A% A# d9 ?" R& ^
external genitalia. Lancet 1985;i:462 – 3.% h% w2 U& Q# W
20. Matlai P, Beral V. Trends in congenital malformations of external0 ]6 T' s7 e0 W) W) k1 j( A7 p
genitalia. Lancet 1985;i:108.
6 ]; ^6 s. M% A& d23. Paulozzi LJ. International trends in rates of hypospadias. J4 m. ?* ?; N( G
and cryptorchidism. Environ Health Perspect 1999;107:2 f2 {6 I5 Y9 A) n0 n2 C/ d$ [7 g
297 – 302.
( B: U- D+ b# c T A9 U" s- G24. EUROCAT Working Group. EUROCAT report 7. 15 years of
, @; Y8 k5 H% f' w8 `surveillance of congenital anomalies in Europe 1980 – 1994.
" m# R \4 f0 m6 [! P( |Brussels, Belgium: Scientific Institute of Public Health-Louis w# B! `9 d8 h/ l
Pasteur, 1997.. m$ h( U7 E$ @
25. Toppari J, Kaleva M, Virtanen HE. Trends in the incidence
, v/ n+ T6 m" lof cryptorchidism and hypospadias, and methodological
& I% ]# {7 V6 Slimitations of registry-based data. Hum Reprod Update
0 p z# O5 C* O* W2001;7:282 – 6.
! k7 E( x* u; j26. Nassar N, Bower C, Barker A. Increasing prevalence of
5 Q: R6 E, o5 {6 D2 \5 T2 yhypospadias in Western Australia, 1980 – 2000. Arch Dis Child
9 g& n8 i2 _# f$ r2007;92:580 – 4.
0 n6 d2 i7 V9 \27. Wang MH, Baskin LS. Endocrine disruptors, genital
5 W- m6 F% J% bdevelopment, and hypospadias. J Androl 2008;29:499 – 505.: C( u3 W1 H8 J3 {+ L6 o1 a2 ?( d
28. Morales-Su á rez-Varela MM, Toft GV, Jensen MS, Ramlau-Hansen( n5 N, u+ @7 z1 K, _
C, Linda Kaerlev L, et al. Parental occupational exposure to
9 r( m$ O' D. s" gendocrine disrupting chemicals and male genital malfor-6 b( F* R2 r( @+ r _0 H! ?
mations: a study in the Danish National Birth Cohort Study.8 _! V& o' D. H( E/ }% [ m
Environ Health 2011;10:3.2 s8 X4 o, S/ B( F( c
29. Gaspari L, Sampaio DR, Paris F, Audran F, Orsini M, et al. High
* A9 w; _- `% z3 h7 p# W* Eprevalence of micropenis in 2710 male newborns from an6 N! e. O1 V8 G/ P/ L
intensive-use pesticide area of Northeastern Brazil. Int J Androl6 L; c8 R8 r- l! k6 p1 q: D5 G
2012;35:253 – 64. |
|