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is a significant concern for physicians. Central- t, K2 u k$ F
precocious puberty (CPP), which is mediated* @3 C: G* }; y# D. k3 N) L8 ?
through the hypothalamic pituitary gonadal axis, has
) b2 F% r* |: X" D E# v2 wa higher incidence of organic central nervous system
Z$ v9 n4 B2 h elesions in boys.1,2 Virilization in boys, as manifested
4 b- \9 k; _( {7 Z7 j( H0 M* rby enlargement of the penis, development of pubic/ n! m" Z# h; Y$ }
hair, and facial acne without enlargement of testi-
4 J& ]( P, v6 l9 [cles, suggests peripheral or pseudopuberty.1-3 We
8 l! y+ b# y% ?- V6 c+ w* @report a 16-month-old boy who presented with the
( B+ D2 i1 A- j3 W* H Q5 F( t: fenlargement of the phallus and pubic hair develop-
, k3 _' ?. o) A- f7 r7 c2 o( qment without testicular enlargement, which was due) k! Y/ w; V9 F0 V' ^
to the unintentional exposure to androgen gel used by! E- V% c" B( { M( b
the father. The family initially concealed this infor-0 j% c; j Z0 ]8 e& q: s0 Q3 C
mation, resulting in an extensive work-up for this! @2 u) z& M3 g8 \9 l
child. Given the widespread and easy availability of* C, _6 g' W4 y, d
testosterone gel and cream, we believe this is proba-
' Y1 a/ P- K+ P' A2 X) xbly more common than the rare case report in the
" W7 M: F& }, L* ]& K% I* Tliterature.4
2 s3 k5 e; a2 ^/ _- pPatient Report
9 s+ d+ S, f0 b# xA 16-month-old white child was referred to the* f! J' K2 n( `' [3 E; q8 z
endocrine clinic by his pediatrician with the concern" _# D# g5 d$ `3 I+ j a0 B* W
of early sexual development. His mother noticed
' [( F9 m+ T) @$ \ }light colored pubic hair development when he was: m0 e: i, q- |+ Q: K: z' O
From the 1Division of Pediatric Endocrinology, 2University of" S& D% R/ Z- O7 q$ F8 \: G3 I
South Alabama Medical Center, Mobile, Alabama.) C. p# w2 z) Q1 l0 W
Address correspondence to: Samar K. Bhowmick, MD, FACE,2 F0 k( A4 T/ ~0 \& a0 C
Professor of Pediatrics, University of South Alabama, College of& ]: L2 z" R8 J5 f, [6 V9 ~
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;5 X, v6 t; v @1 E* p
e-mail: [email protected]., i$ y1 }& Y& j
about 6 to 7 months old, which progressively became3 u+ ]) m' a! j7 @, s
darker. She was also concerned about the enlarge-* `7 [& ]: F8 P' n
ment of his penis and frequent erections. The child! ^( L* w% K+ z! }, w5 ~
was the product of a full-term normal delivery, with
8 _! g9 T7 U$ c# @a birth weight of 7 lb 14 oz, and birth length of3 Y0 G& n, D; y& K# l( `% O8 D
20 inches. He was breast-fed throughout the first year
7 ^. k4 Y. U: @2 C. J, `of life and was still receiving breast milk along with
4 f6 I/ z" x7 isolid food. He had no hospitalizations or surgery,9 ~6 q) }( i0 @+ }3 ?# X0 A1 }# S
and his psychosocial and psychomotor development
0 W$ u% z) R0 P+ K+ \% p, Ywas age appropriate.) X* F4 ]2 h- |4 x
The family history was remarkable for the father,
( V" w, b( a+ W4 n E7 E) uwho was diagnosed with hypothyroidism at age 16,
& B1 z3 n% r3 J* Q, \ [which was treated with thyroxine. The father’s
- p3 G! N* j6 z) R) Sheight was 6 feet, and he went through a somewhat6 A1 [% h1 j7 j0 z& x1 A# C
early puberty and had stopped growing by age 14.
# `/ ^: U2 L5 Z3 Y+ wThe father denied taking any other medication. The
2 D3 U- s9 _! b% E" j! ^6 `+ ? B2 Hchild’s mother was in good health. Her menarche
$ ]- P0 h; y, ?- b. _was at 11 years of age, and her height was at 5 feet4 Q$ ^( C3 I! B& u: n
5 inches. There was no other family history of pre-1 ] D: a( B6 ?% i7 F- D9 S
cocious sexual development in the first-degree rela-+ H( L% u ?& k! w# `
tives. There were no siblings.
: j- f0 ^$ a7 g& r( m, f- G* n pPhysical Examination
! Z8 C0 d+ @" J( ]/ b8 C+ GThe physical examination revealed a very active,( `0 n9 ]4 P! {4 Y
playful, and healthy boy. The vital signs documented, w& Y( l9 G" O4 o: E0 w
a blood pressure of 85/50 mm Hg, his length was; L7 l( Q) n4 @, C, U
90 cm (>97th percentile), and his weight was 14.4 kg7 r. T0 k* o5 V2 n
(also >97th percentile). The observed yearly growth
: m1 o3 |' B3 H( Z% ~$ g* hvelocity was 30 cm (12 inches). The examination of; }) V4 J) L9 Q
the neck revealed no thyroid enlargement.
* R9 R( z6 a+ cThe genitourinary examination was remarkable for1 K& Q% k7 p( K/ Y
enlargement of the penis, with a stretched length of( J8 q _! z: |( [2 k
8 cm and a width of 2 cm. The glans penis was very well8 v5 O, c& g2 I+ }/ o
developed. The pubic hair was Tanner II, mostly around
8 h' Q4 }, x0 ]8 w H( e5403 }" h- n o S9 }4 x0 ]3 W
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from3 X; T+ y* i, b/ s, `4 d
the base of the phallus and was dark and curled. The
) |1 f7 A6 J% X Y$ h- Vtesticular volume was prepubertal at 2 mL each.
+ j2 z% ~% L; _; CThe skin was moist and smooth and somewhat
7 s1 Y7 p8 |# goily. No axillary hair was noted. There were no+ G H. r. T/ Q, P. `5 J5 |3 @
abnormal skin pigmentations or café-au-lait spots.- |( _& c; m M
Neurologic evaluation showed deep tendon reflex 2+
$ S& U7 _% q. ~" l$ O, Dbilateral and symmetrical. There was no suggestion
; I$ E+ d: U$ d1 n9 o( X* e! ]6 Dof papilledema.
" z; D, D9 y6 ~8 s% o* _+ l2 sLaboratory Evaluation
8 [7 C( S3 {7 q: a2 A) E- j/ u" VThe bone age was consistent with 28 months by
4 @* k/ O8 x& S4 L2 H( U& h% n9 V! Z2 Ousing the standard of Greulich and Pyle at a chrono-
$ t; x G- e/ @# N& o9 S3 W5 n% Rlogic age of 16 months (advanced).5 Chromosomal3 S$ i$ j! T" U4 y9 B i
karyotype was 46XY. The thyroid function test
+ ]( k' x7 |/ Z4 k1 h8 {! ?/ i( ishowed a free T4 of 1.69 ng/dL, and thyroid stimu-8 B4 {; n+ }. `' m
lating hormone level was 1.3 µIU/mL (both normal).
% L8 G' N0 b; m( |! O' {2 s& ^The concentrations of serum electrolytes, blood2 H5 v3 G6 D% { @- _& u
urea nitrogen, creatinine, and calcium all were
* r9 a( ?4 P5 `, Ywithin normal range for his age. The concentration" O* l( _# m9 x
of serum 17-hydroxyprogesterone was 16 ng/dL
c( c3 Z9 ]2 v) g0 @, n(normal, 3 to 90 ng/dL), androstenedione was 20. e" q+ r6 W- ^/ x2 E1 \
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
. j4 r5 f/ t9 q* iterone was 38 ng/dL (normal, 50 to 760 ng/dL),& {9 ~3 _! q) L! r7 i! s
desoxycorticosterone was 4.3 ng/dL (normal, 7 to/ {+ v3 Q: F3 {0 v
49ng/dL), 11-desoxycortisol (specific compound S)% ^2 Q' l5 o# `! ]1 m% V! j9 l
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-7 d U, B8 I+ P( A4 z
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
$ e3 }( c8 M, V9 L, g- T( E4 f6 V6 Btestosterone was 60 ng/dL (normal <3 to 10 ng/dL),- W5 s1 C/ D1 c. ]
and β-human chorionic gonadotropin was less than
4 |7 \, d' {8 ~+ P. C! Y2 K7 C! ]4 w5 mIU/mL (normal <5 mIU/mL). Serum follicular
+ p* w, e1 h) F) jstimulating hormone and leuteinizing hormone
( F* q) a, ^5 Z; Z T+ H& aconcentrations were less than 0.05 mIU/mL
8 E- n6 B+ X% P: N. _& Z, Q(prepubertal).7 ~' s% J- O, G$ U8 ~9 e
The parents were notified about the laboratory" m' w& P# } u H* y; \
results and were informed that all of the tests were0 M7 [9 m. C3 b1 R
normal except the testosterone level was high. The
/ }1 D7 j4 F3 `follow-up visit was arranged within a few weeks to4 K4 Z+ }- \# P# V- l
obtain testicular and abdominal sonograms; how-
/ e9 V: f B q. v" w7 Aever, the family did not return for 4 months.
6 U+ P2 k9 d, D; ^: L1 ^/ SPhysical examination at this time revealed that the1 Q* X/ G) T0 n9 M# f! g
child had grown 2.5 cm in 4 months and had gained
i6 r# F; m: I2 kg of weight. Physical examination remained( e: C: b P* c0 N4 D; q- M) u
unchanged. Surprisingly, the pubic hair almost com-- C& ^( h* }3 Q9 `' o# _+ x! V
pletely disappeared except for a few vellous hairs at& e4 T% O4 n7 ?1 G D/ [6 Q
the base of the phallus. Testicular volume was still 2) F1 ?) S, K# _# i* Y: u* a
mL, and the size of the penis remained unchanged.
2 ?; w- |2 V4 M" I cThe mother also said that the boy was no longer hav-7 _* ?, D2 N1 @" z- j8 @: j
ing frequent erections.8 z& M! g! M: M% H. O1 g2 C
Both parents were again questioned about use of) L6 n% y- D; A; @
any ointment/creams that they may have applied to
! j; i4 J4 b) p4 [& Z! Q& D3 qthe child’s skin. This time the father admitted the
& S* I* ]/ T6 O9 t& l) \( d3 h, @3 yTopical Testosterone Exposure / Bhowmick et al 541* X! x9 d' K) r
use of testosterone gel twice daily that he was apply-, k" `, n: L+ M6 {
ing over his own shoulders, chest, and back area for' Y# ?7 ~1 k$ T9 q; d9 o5 u) o5 B$ ? P
a year. The father also revealed he was embarrassed
3 m0 G( }0 K( ^: kto disclose that he was using a testosterone gel pre-1 N) Z3 F7 p& E2 s2 H$ v/ x
scribed by his family physician for decreased libido
! ]4 @0 y6 H" Nsecondary to depression. o/ G8 s j; Q) @- O: C- _, w( s
The child slept in the same bed with parents.& L2 l! l- c. g$ e. t( v) S
The father would hug the baby and hold him on his
0 O- b/ i# h% e# p) u! L0 S2 _# Hchest for a considerable period of time, causing sig-
7 S: S% V( A* x4 k ~7 G7 Nnificant bare skin contact between baby and father.
1 s2 B- m' s/ G. u1 |5 e9 GThe father also admitted that after the phone call,
% E# e4 D, _# I7 Q% M/ a7 o3 ]when he learned the testosterone level in the baby! f3 w/ [) T; j8 Z$ ~# i
was high, he then read the product information
" K+ ] [1 D7 xpacket and concluded that it was most likely the rea-, S8 L' H7 K' d+ @' c, f7 }2 a
son for the child’s virilization. At that time, they1 I5 b9 W0 j. w* A% N6 [
decided to put the baby in a separate bed, and the
# B4 t) e( L: g, G5 qfather was not hugging him with bare skin and had* u0 @8 w. W0 T
been using protective clothing. A repeat testosterone
# k( |( }+ |3 E# O: ?test was ordered, but the family did not go to the
! M% T0 }& d: o3 L9 o' K* Jlaboratory to obtain the test." o' j; L" I1 l& H' M# k
Discussion
; A: E2 x3 E" f$ b u7 s8 i4 ?Precocious puberty in boys is defined as secondary
9 N2 }. ^9 T# u* X; xsexual development before 9 years of age.1,4; z' P, S+ I, t0 g7 I w: _
Precocious puberty is termed as central (true) when
% l8 \) k: W9 y Pit is caused by the premature activation of hypo-
) b H, K: r0 [3 \; Rthalamic pituitary gonadal axis. CPP is more com-$ t6 z- N/ P1 p. j1 c, |2 |
mon in girls than in boys.1,3 Most boys with CPP S0 }: G% y( D' v- b
may have a central nervous system lesion that is
3 a) ?3 ^ r3 G0 j. xresponsible for the early activation of the hypothal-& t2 b- V* j6 P
amic pituitary gonadal axis.1-3 Thus, greater empha-! a; r# j/ O8 p
sis has been given to neuroradiologic imaging in
! Z4 O; z9 U% u' G) {boys with precocious puberty. In addition to viril-
( C4 b2 H$ q5 _3 k6 _ization, the clinical hallmark of CPP is the symmet-
% c4 a+ L4 C3 W0 drical testicular growth secondary to stimulation by
& r4 Q0 b- A" Xgonadotropins.1,3/ A4 g, Q' n# S" {* X# _
Gonadotropin-independent peripheral preco-. ]# L, L/ l* w* d4 V5 S
cious puberty in boys also results from inappropriate
% J2 V3 v+ k3 d# E) V' }androgenic stimulation from either endogenous or" T, d0 N/ T% V1 K) g
exogenous sources, nonpituitary gonadotropin stim-
" d% j$ [6 b! nulation, and rare activating mutations.3 Virilizing
) x- k* m5 Q5 @: E: L5 s/ g5 J( jcongenital adrenal hyperplasia producing excessive7 R/ r) M7 }1 A3 L: m0 R
adrenal androgens is a common cause of precocious
0 [! [. C; x& V( P, j0 spuberty in boys.3,4
+ f% I& f) I9 ~5 G: BThe most common form of congenital adrenal) m K+ P6 a! D# U- M# a6 Y1 C
hyperplasia is the 21-hydroxylase enzyme deficiency.
8 K0 _+ E$ M0 V/ a/ A B% wThe 11-β hydroxylase deficiency may also result in) e2 H# _3 H% m
excessive adrenal androgen production, and rarely,7 }4 f1 y( r7 p2 d' N7 m9 X
an adrenal tumor may also cause adrenal androgen
. m6 [7 F# a2 Iexcess.1,3
) b1 e0 u; d" Y3 S9 R& I1 _at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 z) F/ p, @9 b542 Clinical Pediatrics / Vol. 46, No. 6, July 2007 ^; a$ @+ l2 i+ v) A+ K
A unique entity of male-limited gonadotropin-$ J8 s6 o0 W) a! O
independent precocious puberty, which is also known: H$ {6 o( h% |( _) q" f" t
as testotoxicosis, may cause precocious puberty at a! P( E, H$ `4 m' h+ D- U
very young age. The physical findings in these boys
) m3 f5 O* u8 L: y' u9 x/ hwith this disorder are full pubertal development,1 s* h7 A; e& h# H0 `7 g/ `6 f
including bilateral testicular growth, similar to boys& Q# ]1 h3 P, q! ]
with CPP. The gonadotropin levels in this disorder
! k9 r9 g8 d9 f4 l1 i: @are suppressed to prepubertal levels and do not show. z3 a- g) b; r
pubertal response of gonadotropin after gonadotropin-, s. `" R* V4 b/ ^3 v
releasing hormone stimulation. This is a sex-linked
# I) I% S% O; e% R, \/ j2 Kautosomal dominant disorder that affects only7 i% ^ C4 n& _- L% }, P C; S
males; therefore, other male members of the family
; w0 w' H. ]! E' v9 W/ umay have similar precocious puberty.3
3 F5 V V# J% `& OIn our patient, physical examination was incon-3 r# e& ]# q! A. x4 @# }
sistent with true precocious puberty since his testi-( E3 I# B6 O% V
cles were prepubertal in size. However, testotoxicosis
1 ~1 g4 s( m) s( y! iwas in the differential diagnosis because his father
. p% C' t4 s ystarted puberty somewhat early, and occasionally,
& f* X- m' k# {+ z# jtesticular enlargement is not that evident in the" K- m0 y/ Q0 L& N; ] D& `7 @6 I6 T
beginning of this process.1 In the absence of a neg-
7 c: e9 b$ @! d8 Uative initial history of androgen exposure, our
0 y7 O, T: f4 G% k: f$ N0 Rbiggest concern was virilizing adrenal hyperplasia,
. i k# R: Z3 heither 21-hydroxylase deficiency or 11-β hydroxylase
/ s2 Y+ z$ o4 A( adeficiency. Those diagnoses were excluded by find-' [! a- z' u% u, m
ing the normal level of adrenal steroids.) n0 F" e. u; Z6 l, m ~; s
The diagnosis of exogenous androgens was strongly2 d- k* M* `& z7 |
suspected in a follow-up visit after 4 months because. c# L, Y s7 m/ C* ]; r- @+ k5 J
the physical examination revealed the complete disap-9 R# [$ F: A) N
pearance of pubic hair, normal growth velocity, and
3 h t1 h) P/ t) b- Hdecreased erections. The father admitted using a testos-% E' c& ]% A7 f8 e) k6 U* q8 n
terone gel, which he concealed at first visit. He was
. d/ c4 n, n- _; b( P( n, }& z5 n+ tusing it rather frequently, twice a day. The Physicians’3 r4 t, P( b+ r' ~4 a# z
Desk Reference, or package insert of this product, gel or( ^4 o3 e4 i7 `0 |5 @
cream, cautions about dermal testosterone transfer to2 s1 y. n; \$ X6 x3 }. `+ k8 |
unprotected females through direct skin exposure.# w" `8 r; s: X8 D, I! }
Serum testosterone level was found to be 2 times the' i# w$ }/ N* b" t0 f) N
baseline value in those females who were exposed to: ?$ S. y5 q; |+ K( z% A2 L4 r) k
even 15 minutes of direct skin contact with their male
0 S" K( Q1 u1 V: F! Y2 Hpartners.6 However, when a shirt covered the applica-
3 L6 g0 {% R( I1 ytion site, this testosterone transfer was prevented.
4 c- B- n6 z2 M4 m) _+ dOur patient’s testosterone level was 60 ng/mL,; g6 U& Q- E+ @, z b) G$ o
which was clearly high. Some studies suggest that& j) X7 C+ _" { e( w
dermal conversion of testosterone to dihydrotestos-
, n+ z5 X/ ?, o- V# m; Cterone, which is a more potent metabolite, is more. i8 Z, V( L- b7 d/ j
active in young children exposed to testosterone7 N) ]; ?: D8 P) D1 J" K
exogenously7; however, we did not measure a dihy-
3 f' Z, H$ Q5 B, V5 ddrotestosterone level in our patient. In addition to0 y# J q/ A3 O) H6 D6 ~
virilization, exposure to exogenous testosterone in
* a5 k4 K7 z! C/ Wchildren results in an increase in growth velocity and6 W/ z! A7 T7 {1 u
advanced bone age, as seen in our patient.% X+ Y* U* m8 M
The long-term effect of androgen exposure during
8 O* F6 K. E% i' j2 qearly childhood on pubertal development and final
8 q: v/ w+ _* D. G: [adult height are not fully known and always remain
/ ]. Q. z" v, @a concern. Children treated with short-term testos-/ R4 F9 P# K k* A* p* U% @ e& Q; N
terone injection or topical androgen may exhibit some9 }% {$ J6 L+ H2 h/ @
acceleration of the skeletal maturation; however, after! m, t- g3 R% L( k. k
cessation of treatment, the rate of bone maturation
/ ?( V2 ^1 o' i$ odecelerates and gradually returns to normal.8,9
A2 K& E6 @! M- Z& lThere are conflicting reports and controversy
6 u+ k* [8 M0 X6 Gover the effect of early androgen exposure on adult8 q1 N t1 o5 w1 w- x
penile length.10,11 Some reports suggest subnormal
. B+ x2 F [+ C8 {$ iadult penile length, apparently because of downreg-
- I- U* m' j/ \( uulation of androgen receptor number.10,12 However,
& c7 x. [2 `# j3 }Sutherland et al13 did not find a correlation between1 k% ]: K- V& m0 G$ Y7 G9 e1 n
childhood testosterone exposure and reduced adult3 x! P& h' D( s9 E8 N
penile length in clinical studies.
6 p3 D) E+ G1 ], t1 fNonetheless, we do not believe our patient is
) \ Q! w$ v1 D a1 H+ R: Igoing to experience any of the untoward effects from0 q- B- _0 V: w- R9 t7 ~
testosterone exposure as mentioned earlier because
/ H( K' k$ f6 @1 @" L$ t9 Y# Mthe exposure was not for a prolonged period of time.1 R5 [( l8 l5 _) A [4 K
Although the bone age was advanced at the time of) ~7 n9 g, w% a/ a L3 ]7 o
diagnosis, the child had a normal growth velocity at5 v5 Z6 |. r W2 T9 F! z) x* n; E
the follow-up visit. It is hoped that his final adult
+ I Y' K% ]% A5 kheight will not be affected.% {0 W Z3 `' E" A6 d
Although rarely reported, the widespread avail-
/ P2 p2 j7 p+ h, `ability of androgen products in our society may- g6 \2 g$ m' @, j
indeed cause more virilization in male or female, c" X8 G q( c0 ?! \
children than one would realize. Exposure to andro-
' u* T0 x6 a4 }" R2 k: i ~gen products must be considered and specific ques-% y; `7 }6 Y; b
tioning about the use of a testosterone product or' B0 b& o8 Y+ k [$ @* g! B* L
gel should be asked of the family members during
9 j, c1 k3 \- z4 t q5 Kthe evaluation of any children who present with vir-
: M: W- M) e4 o0 dilization or peripheral precocious puberty. The diag-3 s# A$ s2 l" @8 p Z
nosis can be established by just a few tests and by9 p0 h8 ?+ c" Q: {1 Q
appropriate history. The inability to obtain such a
4 l4 r' b! w" Rhistory, or failure to ask the specific questions, may; h: B v: }! Y3 z; n
result in extensive, unnecessary, and expensive
_+ X, H' `! x+ u5 l5 _investigation. The primary care physician should be) Y& j) `' M: L% ~! D$ R# _
aware of this fact, because most of these children
4 J% f0 q- ^1 [8 {+ G imay initially present in their practice. The Physicians’) e( z/ c a3 o
Desk Reference and package insert should also put a8 c+ b) a. R" S' k; }5 m) L# }
warning about the virilizing effect on a male or
8 A+ V6 s4 g: |5 H" ]/ o) Bfemale child who might come in contact with some-/ Z6 n$ g/ P% C+ t8 Z
one using any of these products./ f" i& b+ |) o
References
9 |, |4 c5 w9 W& Q1. Styne DM. The testes: disorder of sexual differentiation& I& H4 M t5 B& w
and puberty in the male. In: Sperling MA, ed. Pediatric& q8 l9 `/ W! N$ O8 h$ o
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;9 _, }! B& j9 W, G& H* n ^0 N6 b
2002: 565-628.
' c, b) Z# p! x2 N2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
# w+ b( H/ n- H; \puberty in children with tumours of the suprasellar pineal- w2 C. ^( t* t
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from' q/ P! m# {" }5 M
Topical Testosterone Exposure / Bhowmick et al 543
4 T+ `* x3 Q1 F5 Wareas: organic central precocious puberty. Acta Paediatr.
, I2 b5 K# v; e5 n2001;90:751-756.- I' o F: N4 A5 c( g
3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
. N" e+ ^* |7 a7 y* p& CPediatric Endocrinology. 4th ed. New York, NY: Marcel
# L3 l/ j% |: Z# u, K; O( vDekker Inc; 2003:211-238.0 P/ y1 f8 Z9 \! k2 n0 b( o
4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual
. g+ n0 j* t+ W% jdevelopment in a two-year-old boy induced by topical
9 n- @* C' ?; h" jexposure to testosterone. Pediatrics. 1999;104:e23." U: C. P/ T& a
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of
% ]# s2 i6 \7 \- t8 N% s" NSkeletal Development of the Hand and Wrist. 2nd ed.
$ i1 X! F- g# A5 P# q) q& U2 }, `; }Stanford, CA: Stanford University Press; 1959.* U% v8 W& R5 ]
6. Physicians’ Desk Reference. Androgel 1% testosterone,
- R( S: T# Q' t7 ?1 b( gUnimed Pharmaceutical Inc. Montvale, NJ: Medical, }" q3 ^) O0 S- a7 O# k
Economics Company, Inc; 2004:3239-3241.# l/ x) n) K0 Q" _! c: v- o
7. Klugo RC, Cerny JC. Response of micropenis to topical
4 f) l/ E3 f/ ?testosterone and gonadotropin. J Urol. 1978;119:# Z& s1 U. S* o n
667-668.
0 }# L2 F; l1 P m" _; c3 w. L8. Guthrie RD, Smith DW, Graham CB. Testosterone
D5 m6 K& U- l/ xtreatment for micropenis during early childhood. J Pediatr.( m; Y4 A# |5 B5 m9 S
1973;83:247-252." J% e9 B5 m+ C! G4 T
9. Jacobs SC, Kaplan GW, Gittes RF. Topical testosterone6 Q5 K. x* ^8 f& ~
therapy for penile growth. Urol. 1975;6:708-710.
( m, P+ J; p7 O! t9 R/ p/ P; r. E8 c10. Husmann DA, Cain MP. Microphallus: eventual phallic
2 M) }/ M, v- M0 s$ ^size is dependent on the timing of androgen administra-. U ?, @6 H! l3 P
tion. J Urol. 1994;152:734-739.
5 `' O% H m5 |- R8 T2 |" ]: G2 h11. McMahon DR, Kramer SA, Husmann DA. Micropenis:
* l9 z& o) j j9 Odoes early treatment with testosterone do more harm0 u4 V4 n6 d6 ]" G
than good? J Urol. 1995;154:825-829.
, x+ h8 \, v! \- @' b3 T6 f+ @. t12. Takane KK, George FW, Wilson JD. Androgen receptor
" l4 u" a' j3 Mof rat penis is down-regulated by androgen. Am J Physiol.- ]% ?- q. H& F) o) z3 e
1990;258:E46-E50.! J8 v* l9 H# P/ R& [" n
13. Sutherland RS, Kogan BA, Baskin LS, et al. The effect
$ p- C- O/ j* K" B8 q. pof prepubertal androgen exposure on adult penile
& X0 y) t9 m& Q( d6 llength. J Urol. 1996;156:783-787. |
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