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is a significant concern for physicians. Central8 P/ J# y. [- Z+ z% j( u* C2 j3 m. S
precocious puberty (CPP), which is mediated
" U* w o+ A9 m1 U* l) l2 Ythrough the hypothalamic pituitary gonadal axis, has' U8 Q; V! U) P. ?5 o# i
a higher incidence of organic central nervous system
( t: L0 B4 j2 ^: [; [- `6 D! E9 hlesions in boys.1,2 Virilization in boys, as manifested3 c# D3 ~2 {% F8 V% p' l
by enlargement of the penis, development of pubic
# Z) y9 y; l, z8 A4 mhair, and facial acne without enlargement of testi-+ i8 \& q5 N {. `3 d
cles, suggests peripheral or pseudopuberty.1-3 We3 ~+ `3 X% U1 y3 N* V
report a 16-month-old boy who presented with the
" w# w) Y0 |5 ] r4 renlargement of the phallus and pubic hair develop-9 i3 W! n0 Q& r' ?
ment without testicular enlargement, which was due% d$ G D- ?: b8 j% J
to the unintentional exposure to androgen gel used by
* r6 Z3 T0 `/ W: }the father. The family initially concealed this infor-
, x, p! v8 c2 r- I: V% _mation, resulting in an extensive work-up for this
# q$ u' s! l2 q& \2 x8 Y4 o5 D gchild. Given the widespread and easy availability of+ B( v/ S" U* Q& A- m
testosterone gel and cream, we believe this is proba-
" D$ \; b0 T2 E. E. Xbly more common than the rare case report in the
6 C1 T! W/ w2 h! M$ k4 rliterature.4* k+ W* X9 f! U+ T4 C
Patient Report9 O8 I K# p$ [; ]: v
A 16-month-old white child was referred to the+ b( X; X" W! p! R
endocrine clinic by his pediatrician with the concern
5 n$ z& U; G" Y4 r& q6 D _of early sexual development. His mother noticed
c; z# @( T. T7 I, Clight colored pubic hair development when he was
( j: y( Y8 \* N, U4 d6 x) mFrom the 1Division of Pediatric Endocrinology, 2University of* g9 B8 \6 P3 i
South Alabama Medical Center, Mobile, Alabama.
% @' f& t& J% L% vAddress correspondence to: Samar K. Bhowmick, MD, FACE,& }. o9 v0 H; a; `
Professor of Pediatrics, University of South Alabama, College of/ Q$ \# ]1 Q0 R$ j
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
3 |0 x7 z% B d( y( ?e-mail: [email protected]." k4 S( A4 F" x! ^2 g
about 6 to 7 months old, which progressively became$ G/ \$ @ M7 s h0 { B
darker. She was also concerned about the enlarge-+ c" _7 E0 o% m/ Z3 n" P1 f U
ment of his penis and frequent erections. The child
. W4 J* ]/ ^: S+ w- x, K4 {was the product of a full-term normal delivery, with
% ^# B) L3 x- Y* G. ~7 d' la birth weight of 7 lb 14 oz, and birth length of
9 u0 D$ @7 r* a3 a! y20 inches. He was breast-fed throughout the first year% M- D( C- C0 {: g/ W8 X, j |
of life and was still receiving breast milk along with! ]4 Q; {9 f( A
solid food. He had no hospitalizations or surgery,
# ]* u; D$ R) u, Land his psychosocial and psychomotor development
: d7 j! k" o4 G3 F6 [- Fwas age appropriate.3 D+ h1 X W: Q& Y" S6 `% k3 x
The family history was remarkable for the father,
* f9 i' |( C4 P6 i& |7 o1 [5 Wwho was diagnosed with hypothyroidism at age 16,
- F: |! _) j; m0 d% H2 d- P* ~which was treated with thyroxine. The father’s
. p* x# q& j }6 dheight was 6 feet, and he went through a somewhat6 A2 ?. @' V4 j s
early puberty and had stopped growing by age 14.
+ ^4 L- \" n* C' eThe father denied taking any other medication. The
: W1 I8 `$ n& \5 V7 |4 U, Jchild’s mother was in good health. Her menarche
- i# @; n- }# \+ r$ \/ Hwas at 11 years of age, and her height was at 5 feet" C' g+ {; U# V: Y6 ?
5 inches. There was no other family history of pre-
2 t5 ] G/ H# `7 e' @cocious sexual development in the first-degree rela-6 \# e8 H& E, H: `* ]7 Y) q; l
tives. There were no siblings." j% k g$ r$ J* @. Q) B
Physical Examination+ \* r$ [4 e/ D' q
The physical examination revealed a very active,- [; K& D9 x3 q7 z0 @
playful, and healthy boy. The vital signs documented1 S2 S) L6 A- B" [, G2 T! r# }
a blood pressure of 85/50 mm Hg, his length was
. x A% r) P, N90 cm (>97th percentile), and his weight was 14.4 kg/ q, [; ?* T2 ?4 l0 z9 w2 Q/ h! Z! Y
(also >97th percentile). The observed yearly growth
; S, g) ?2 N. w% Wvelocity was 30 cm (12 inches). The examination of# B7 O f. |6 k. M' F5 y
the neck revealed no thyroid enlargement.. m" @- p9 l9 h7 v1 e
The genitourinary examination was remarkable for
0 d- r: q- {7 K4 l. j. g4 {4 Aenlargement of the penis, with a stretched length of* l# X8 y3 r$ s0 K% t( a9 t
8 cm and a width of 2 cm. The glans penis was very well9 g. t! D' b* \/ f
developed. The pubic hair was Tanner II, mostly around
* b m9 U; T7 G' b" h5 @540
; N$ l8 V% l8 s' ?0 k e; v& Cat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 j$ {2 d7 [) R2 Ithe base of the phallus and was dark and curled. The
2 Y, u; C" Q' E/ }, q6 Z9 Xtesticular volume was prepubertal at 2 mL each.
% H1 V. U. O* |; k+ UThe skin was moist and smooth and somewhat
- p: V% E9 v, K2 ]oily. No axillary hair was noted. There were no
9 c' A9 ]$ C3 eabnormal skin pigmentations or café-au-lait spots.
6 g k" B" n1 G% y/ }Neurologic evaluation showed deep tendon reflex 2+( j3 m4 Y4 d! y! s% g
bilateral and symmetrical. There was no suggestion& D/ d8 ~) U7 x2 @
of papilledema.
% U1 q$ ]# b$ ~' R( \Laboratory Evaluation
- {2 L# R2 W- [( N3 ZThe bone age was consistent with 28 months by
3 f6 l$ R& L0 ?0 V6 K- H& Zusing the standard of Greulich and Pyle at a chrono-9 Q) Z" s. W! w5 X$ I
logic age of 16 months (advanced).5 Chromosomal2 g# Z( y" J0 D' d4 @
karyotype was 46XY. The thyroid function test
- a6 I$ b. g7 g# k. Ushowed a free T4 of 1.69 ng/dL, and thyroid stimu-
$ q' d/ k* v; ^! [( llating hormone level was 1.3 µIU/mL (both normal).0 j5 b/ j" Z% \" S5 `. {; n
The concentrations of serum electrolytes, blood
* T. `3 M ]* X O* Yurea nitrogen, creatinine, and calcium all were. A( E& i2 B1 b2 k. K. p
within normal range for his age. The concentration9 c+ n, K! g7 z' z
of serum 17-hydroxyprogesterone was 16 ng/dL% a. p& x- [; I8 c, c
(normal, 3 to 90 ng/dL), androstenedione was 204 i1 o3 q' G) I" r( U7 N
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-" ^" ]/ s( t$ O4 m
terone was 38 ng/dL (normal, 50 to 760 ng/dL),0 a t' X: j/ Y# P" t
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
; |0 q4 f3 ]. j: M; N49ng/dL), 11-desoxycortisol (specific compound S)4 R2 K( D( P" n
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
5 Z# F% X }, d3 B) Wtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
# Y+ r' H& S5 U* _9 s! ]6 i5 ntestosterone was 60 ng/dL (normal <3 to 10 ng/dL),7 l# \! e( B9 I5 P$ w- w: x: H8 L( N
and β-human chorionic gonadotropin was less than2 d$ c$ [1 y! U `& x7 e- n$ n
5 mIU/mL (normal <5 mIU/mL). Serum follicular* A0 P9 V/ E; L
stimulating hormone and leuteinizing hormone
6 y$ `% b$ d9 nconcentrations were less than 0.05 mIU/mL
$ O3 E) E w& G(prepubertal).5 L3 M' }# _7 M* D$ c' T
The parents were notified about the laboratory
) X6 n! }+ U8 P- @; d5 vresults and were informed that all of the tests were
/ i% F, Q) s0 J; Mnormal except the testosterone level was high. The
# B; i! b, J& v% V1 y; O9 Ifollow-up visit was arranged within a few weeks to2 s% \* \8 \. w5 s- N
obtain testicular and abdominal sonograms; how-9 W4 c2 c6 l/ \- W
ever, the family did not return for 4 months.
8 I$ u- ]( W) j+ U8 YPhysical examination at this time revealed that the
- f4 S& F1 s# }9 r. B8 } schild had grown 2.5 cm in 4 months and had gained5 D7 a$ A2 I5 e2 ]8 h5 u1 L
2 kg of weight. Physical examination remained
) P" N/ n' e# S8 _" W- Kunchanged. Surprisingly, the pubic hair almost com-
4 u& @; S- G. g0 }/ Zpletely disappeared except for a few vellous hairs at3 ]) G* N2 p) @* i) U6 }. I5 @# T
the base of the phallus. Testicular volume was still 2
. \3 N* X. T* M' _% U* \mL, and the size of the penis remained unchanged.
* _8 P s! y' W/ b' ^; H! M+ g6 jThe mother also said that the boy was no longer hav-! e R! K2 x" q: h. W& H2 P
ing frequent erections.0 d& H9 I* B' D% H2 \/ e' s% b
Both parents were again questioned about use of
0 m0 x7 ~# D9 ]8 z4 X9 bany ointment/creams that they may have applied to
7 p+ x& Y4 f) ], F" u) Fthe child’s skin. This time the father admitted the
4 Q2 N* e9 C) W) |4 g* VTopical Testosterone Exposure / Bhowmick et al 541
& e* N3 H5 R: b; {9 l4 Iuse of testosterone gel twice daily that he was apply-. Q( @3 y6 P) F1 e! u9 n& `- G
ing over his own shoulders, chest, and back area for
) p) X6 _8 T+ [6 d, { Ca year. The father also revealed he was embarrassed
2 @# z) e" E1 Z0 Z+ a0 q0 Qto disclose that he was using a testosterone gel pre-7 v6 S/ r9 Q( }5 W) j( t0 V) [
scribed by his family physician for decreased libido
: l( |, \! A9 ? Z5 x# O1 ^) Isecondary to depression.* Z6 T* p# E( w: w( h( C. z
The child slept in the same bed with parents." ~" F; W7 C1 i7 h0 Q
The father would hug the baby and hold him on his% w* C* n' k3 B; s
chest for a considerable period of time, causing sig-
. b M# G# }" D8 x! j$ `/ Pnificant bare skin contact between baby and father.) `5 K L" K: x) ?( U
The father also admitted that after the phone call,
5 A$ R5 e X% l4 e4 E" pwhen he learned the testosterone level in the baby4 f- m. I4 b6 R% T3 y
was high, he then read the product information0 I. N* \, U; h3 Q9 d( o4 d \
packet and concluded that it was most likely the rea-7 d9 e# V3 L) f& c- p O8 Z
son for the child’s virilization. At that time, they
3 x6 y" B$ l, x, u& E* x* ]2 vdecided to put the baby in a separate bed, and the# ^' n' p' j" i) O& Z
father was not hugging him with bare skin and had
0 b! ]# t4 M. W" obeen using protective clothing. A repeat testosterone/ t4 @* ^& W; Y6 j4 I2 W+ c2 D
test was ordered, but the family did not go to the
4 f9 L- F8 Y9 D# [laboratory to obtain the test. V2 x+ ~: f' V w
Discussion
/ D) C9 j4 n8 fPrecocious puberty in boys is defined as secondary$ a" b4 E+ y$ v5 `) A% F
sexual development before 9 years of age.1,4; f/ e. w, h; r
Precocious puberty is termed as central (true) when! b* w/ O0 ^: V. @' w' |
it is caused by the premature activation of hypo-8 G9 M' a1 D2 v
thalamic pituitary gonadal axis. CPP is more com-
7 A; P: v6 F8 @. Rmon in girls than in boys.1,3 Most boys with CPP4 ~) I3 e9 N& n% Z
may have a central nervous system lesion that is
6 Q) R8 Y) m9 G$ I& B3 s1 H+ ]3 Mresponsible for the early activation of the hypothal-
/ k, @! v/ U' O; V3 B) i- G4 l) Jamic pituitary gonadal axis.1-3 Thus, greater empha-5 M( q6 e5 j0 z8 `! v
sis has been given to neuroradiologic imaging in# f3 ?! |9 _5 u: C
boys with precocious puberty. In addition to viril-
5 a' g& N+ |2 H. Y& V* Iization, the clinical hallmark of CPP is the symmet-% O8 u0 i( d: ~- E6 b/ v# G
rical testicular growth secondary to stimulation by- N- u! s6 W" F5 Q4 {8 d
gonadotropins.1,3 x6 p" O" p+ r5 Q' n( h
Gonadotropin-independent peripheral preco-4 h8 M; m! O3 ]* F$ h) j% [
cious puberty in boys also results from inappropriate
, }% |3 k& y3 P) \1 ?- s; s+ Bandrogenic stimulation from either endogenous or. u7 ]4 u; N, h! Z
exogenous sources, nonpituitary gonadotropin stim-+ o- z" Q4 y# s: W9 r: h2 e
ulation, and rare activating mutations.3 Virilizing
8 i( W% I1 x. C3 N0 G* @congenital adrenal hyperplasia producing excessive
, Y% d( K W1 V" D) Padrenal androgens is a common cause of precocious
6 ?: [# U8 v9 L- Y- Opuberty in boys.3,4) n5 G: e1 Z9 B% ?8 A
The most common form of congenital adrenal& O2 D9 a: z$ w1 K9 R0 u* U
hyperplasia is the 21-hydroxylase enzyme deficiency.8 J. X& p6 a9 }8 J# t2 D4 B1 t
The 11-β hydroxylase deficiency may also result in
. `' }# T: j; qexcessive adrenal androgen production, and rarely,
: X0 l) ~& g: L# d( D- W9 K2 i4 dan adrenal tumor may also cause adrenal androgen' J0 n R1 k8 z" \5 A
excess.1,3
* P2 P2 i# x' D- T oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from. n% T( N0 G, T2 H2 S9 o
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007& P* s# l# J# Q i3 U
A unique entity of male-limited gonadotropin-) n+ z! p: l) x
independent precocious puberty, which is also known
6 B8 r' P5 ]# N4 E: W2 G3 ^6 oas testotoxicosis, may cause precocious puberty at a/ `! E3 I4 C6 w6 u" h+ y
very young age. The physical findings in these boys4 B( v- ]% l. c0 D3 h% [% F
with this disorder are full pubertal development,' a7 G! d4 K% n4 x0 a
including bilateral testicular growth, similar to boys
: I1 C# d T5 k! Mwith CPP. The gonadotropin levels in this disorder4 j. ^2 ^$ N$ F% U' M( t$ d# |) e( U
are suppressed to prepubertal levels and do not show
% K" T! Y& A4 \6 ^' e' o ?pubertal response of gonadotropin after gonadotropin-' E8 p w2 q# g
releasing hormone stimulation. This is a sex-linked( S6 `7 B- o0 x) N/ t$ |
autosomal dominant disorder that affects only
. ]7 _' f3 V& [" I) g4 Umales; therefore, other male members of the family% {, O( ?" T+ [0 ^! _% l( ~
may have similar precocious puberty.3
; h1 T( `! J/ p3 O( wIn our patient, physical examination was incon-" U! t$ e. K7 t: I" k& V' ?) T
sistent with true precocious puberty since his testi-
/ Y( P: }8 G9 ecles were prepubertal in size. However, testotoxicosis
' m$ H+ ]" o+ i w! n5 P+ uwas in the differential diagnosis because his father
" n, p) r0 K* y( f) n E. w' ~started puberty somewhat early, and occasionally,
. e+ n! {7 p0 O+ k) J0 o( _4 g4 ctesticular enlargement is not that evident in the
( q4 Y; W/ a1 c* C3 U# {beginning of this process.1 In the absence of a neg-9 I/ G' f- z, o- I; p
ative initial history of androgen exposure, our! u0 T# J; e- g a6 }4 a+ J. p) C4 b
biggest concern was virilizing adrenal hyperplasia,9 E2 j. |3 M: @
either 21-hydroxylase deficiency or 11-β hydroxylase5 _( O! L4 D' R. [6 H0 h( F, a
deficiency. Those diagnoses were excluded by find-* K! I1 d0 C1 P0 D4 g
ing the normal level of adrenal steroids.
9 }9 c% H% j7 iThe diagnosis of exogenous androgens was strongly
0 L& ?( e( S1 K4 s" Rsuspected in a follow-up visit after 4 months because
! i6 {7 I3 n% ?the physical examination revealed the complete disap-" [6 e7 p. U2 r5 G& ^& |: z B0 @& {
pearance of pubic hair, normal growth velocity, and, \1 r* F9 X- J- S6 W
decreased erections. The father admitted using a testos-
0 f# m3 ~8 F! r [terone gel, which he concealed at first visit. He was; R ~6 W# Q- L
using it rather frequently, twice a day. The Physicians’
. J% g/ ^0 w* @$ q7 M4 dDesk Reference, or package insert of this product, gel or8 l4 S+ s3 Y* J, E2 _2 u1 b
cream, cautions about dermal testosterone transfer to
, n9 I+ b2 Z0 A7 q8 q9 V, Z8 a% `unprotected females through direct skin exposure.
; F! Z/ E8 B6 }" F4 T/ }& BSerum testosterone level was found to be 2 times the6 X* r* D1 r/ S2 M
baseline value in those females who were exposed to! y$ h/ L3 q4 w3 l2 c8 v1 r
even 15 minutes of direct skin contact with their male0 D. O% z" Z9 ^% i$ l
partners.6 However, when a shirt covered the applica-: j( J2 s& s; T& G9 a
tion site, this testosterone transfer was prevented.
* k R" \# R j+ p/ [9 bOur patient’s testosterone level was 60 ng/mL,
& Q" ~! G) `7 S! `9 k e% g% f2 qwhich was clearly high. Some studies suggest that, t" q. v+ ?6 P
dermal conversion of testosterone to dihydrotestos-5 `; [& f: C U+ i& l: C
terone, which is a more potent metabolite, is more+ B5 |8 s# J' h3 {# s
active in young children exposed to testosterone. s3 n6 L$ \& T/ O3 `# a6 y0 L
exogenously7; however, we did not measure a dihy-, [" k' x7 M/ H% W; {/ N
drotestosterone level in our patient. In addition to# D+ [ u( j: h
virilization, exposure to exogenous testosterone in: J( u2 u0 s$ o. M/ b
children results in an increase in growth velocity and3 Y6 b- e; s& K( c, d3 L
advanced bone age, as seen in our patient. @, A; `# l3 v7 I8 _$ ~& b
The long-term effect of androgen exposure during
) S- ^# l+ M" }2 @/ L2 Eearly childhood on pubertal development and final
* e/ `" b( V- `# ^ ^/ C0 Badult height are not fully known and always remain
* a5 w& v/ D# R1 c1 x& H5 |a concern. Children treated with short-term testos-0 X! }: t: C( o% z1 d' N5 ]
terone injection or topical androgen may exhibit some
" [4 j) ~- [. Sacceleration of the skeletal maturation; however, after/ E5 p3 T. w+ M% |& L
cessation of treatment, the rate of bone maturation" x1 \" X% i5 j2 V
decelerates and gradually returns to normal.8,9
7 I' ]2 Q- W# c2 X8 WThere are conflicting reports and controversy& a' Q3 `7 D* Q* ^7 R
over the effect of early androgen exposure on adult2 J& i. o1 B' A! F2 t; w
penile length.10,11 Some reports suggest subnormal8 r1 b0 z3 K& O/ Z- N+ ?) o( c
adult penile length, apparently because of downreg-
% h: i$ h9 @4 b$ z! A+ f' zulation of androgen receptor number.10,12 However,1 ?5 \. V1 }- E( D; C# P
Sutherland et al13 did not find a correlation between
6 G* ?% \9 N; `childhood testosterone exposure and reduced adult
3 u0 e8 c, ~- }/ ipenile length in clinical studies.
: P" m2 M6 s5 _Nonetheless, we do not believe our patient is
. |! C& A/ O/ f, I% `going to experience any of the untoward effects from
6 R/ l" n( i4 F: z! E. a9 A, Wtestosterone exposure as mentioned earlier because
4 U$ {' _# s N% n3 @( I4 \1 uthe exposure was not for a prolonged period of time.2 t% E' C9 U! y4 N
Although the bone age was advanced at the time of
6 K9 }1 X, R9 s4 Bdiagnosis, the child had a normal growth velocity at
. S2 J7 ^% w8 J& [3 rthe follow-up visit. It is hoped that his final adult
) E# m& P$ N0 k1 L0 S$ dheight will not be affected.- a: c1 |0 Q, k
Although rarely reported, the widespread avail-" S- q' ^1 H/ ^% ^
ability of androgen products in our society may
. ~ |+ H( T" r5 Q: a2 n; V/ Zindeed cause more virilization in male or female
, f, R* w, y- O# H/ N! Dchildren than one would realize. Exposure to andro-1 x) [: c: _$ C4 d
gen products must be considered and specific ques-- t$ J, L: T5 x+ b' c/ j' n8 x
tioning about the use of a testosterone product or& b7 g! X/ S4 p- d! X5 k+ R
gel should be asked of the family members during, ~0 N1 e. s$ I5 d; r9 I: s
the evaluation of any children who present with vir-
1 f. s. @$ }' R) w& S5 milization or peripheral precocious puberty. The diag-$ P& B0 l" m8 k+ Z' k2 {' T
nosis can be established by just a few tests and by
2 c1 \: q; ?* O) G, l" Xappropriate history. The inability to obtain such a1 g5 N+ f1 y4 m3 Y9 v8 F' k
history, or failure to ask the specific questions, may
8 P; b/ k+ n: }* J3 `" |3 t0 b* `8 presult in extensive, unnecessary, and expensive' _, v% r: q+ B0 ]
investigation. The primary care physician should be
) U, ~5 t# E$ vaware of this fact, because most of these children% v; k) Y- D, L$ `5 m
may initially present in their practice. The Physicians’: u& o# Z' S# U4 r/ w. y. A( T
Desk Reference and package insert should also put a5 F! _% f* L- W1 d$ y0 b
warning about the virilizing effect on a male or
: N3 @9 P6 u, h: @% Lfemale child who might come in contact with some-1 u7 w% H- w: k& }
one using any of these products.& G$ V- m( z ?+ b
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1. Styne DM. The testes: disorder of sexual differentiation' H+ J: r8 ^" {/ J# d5 G( b
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Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;# b" _* @: ^' r9 m! [: [
2002: 565-628.2 R" v# ^; y$ S1 s, a! E
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious4 I: D+ ^* C' F) z9 n
puberty in children with tumours of the suprasellar pineal
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7 e R* k1 @& \ C0 hDekker Inc; 2003:211-238.
+ H& U1 I# A; y& z6 s! a5 }4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual* ^# x" ^- s0 M- E8 e, O- N' I
development in a two-year-old boy induced by topical2 t( r3 Q2 p9 B3 a6 p
exposure to testosterone. Pediatrics. 1999;104:e23.% k6 q3 D+ B- c% k3 i; g& Q
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' i% Q/ ^, r3 ~8 Q! uStanford, CA: Stanford University Press; 1959.; H8 B+ w8 S3 R: s ?1 D3 `
6. Physicians’ Desk Reference. Androgel 1% testosterone,3 [+ t7 \# D! d! v
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) D5 p/ F% K( u5 G" Y! l' L& s9 iEconomics Company, Inc; 2004:3239-3241.
/ R; r6 r1 }" U. p7. Klugo RC, Cerny JC. Response of micropenis to topical
& W3 v- }" u7 h5 w% c# ptestosterone and gonadotropin. J Urol. 1978;119:
) P, q& O/ j0 w667-668.
7 j R( v4 r& m8. Guthrie RD, Smith DW, Graham CB. Testosterone
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