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Sexual Precocity in a 16-Month-Old) J5 f0 ?( V* f& M
Boy Induced by Indirect Topical1 E8 a) ] l0 H6 F8 S6 Q3 @
Exposure to Testosterone0 P$ _1 g& q, G0 _% K+ N: U6 G
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
' e. O* Z( R% [% w' R c5 X& ?, q/ hand Kenneth R. Rettig, MD1! d" N. w% S. C( X V0 o; _; S M# W5 @
Clinical Pediatrics
7 f- ?. D) K5 M$ y/ b4 HVolume 46 Number 6 @: } a5 w2 G4 o N: M. j. f* ?
July 2007 540-543& p7 o2 B, i% m% J2 n' d
© 2007 Sage Publications
6 x/ A5 d t O7 J/ f10.1177/0009922806296651, i6 g9 X) I1 J& h J4 U) D
http://clp.sagepub.com
' T: Y' B2 ~& n$ R; H1 Khosted at- N) I/ H' k l6 t; I; q, u
http://online.sagepub.com& ]/ [* K Z, ?! H
Precocious puberty in boys, central or peripheral,
) m2 q0 O' l% g0 }& Q1 d$ vis a significant concern for physicians. Central, U1 O- C' P- \2 c" F% `$ [( b* m0 Z
precocious puberty (CPP), which is mediated
" l0 R: z/ c; {# ?9 Tthrough the hypothalamic pituitary gonadal axis, has3 a: M3 w7 @7 R. l3 D* t
a higher incidence of organic central nervous system
5 g& `# A. ?) y: d) L0 S0 v( C/ nlesions in boys.1,2 Virilization in boys, as manifested
3 i3 b' M3 ]+ k8 r" Sby enlargement of the penis, development of pubic" X% S* C' _/ E% g" d1 l& @0 T
hair, and facial acne without enlargement of testi-
5 k' q1 Z1 j' m Mcles, suggests peripheral or pseudopuberty.1-3 We
: w9 i: \; W7 V! Q# s7 _report a 16-month-old boy who presented with the
" T7 @+ B8 a1 J; D" m! E% Henlargement of the phallus and pubic hair develop-
& P0 p( x8 {. ~0 pment without testicular enlargement, which was due4 G+ |; c8 q9 f$ R
to the unintentional exposure to androgen gel used by
" s8 O1 B5 m$ f% w3 o4 Ethe father. The family initially concealed this infor-! N6 x! W8 f$ G8 V
mation, resulting in an extensive work-up for this
7 ]& @3 Q- P/ y1 d1 Ochild. Given the widespread and easy availability of
$ P6 E6 R, o% ^8 @ Ctestosterone gel and cream, we believe this is proba-
, u% h* p' @4 Ybly more common than the rare case report in the
& T. k- J' K% ?5 V0 B5 Qliterature.4 Z9 ^! X3 q. j4 Y
Patient Report0 R L: t, b7 h* E' P& p) f$ |. _
A 16-month-old white child was referred to the
3 o2 ?( {/ e; i0 ^1 Qendocrine clinic by his pediatrician with the concern$ s1 ^* ^3 w. Z
of early sexual development. His mother noticed( V/ a+ p3 S! \# p* N; e
light colored pubic hair development when he was+ z5 Y1 i7 l# N ]* q
From the 1Division of Pediatric Endocrinology, 2University of
4 c6 Z3 q$ w. r* b9 }* t/ c7 N/ RSouth Alabama Medical Center, Mobile, Alabama.# d: P, G) A: y5 X t
Address correspondence to: Samar K. Bhowmick, MD, FACE,
4 X# l: ?* m7 rProfessor of Pediatrics, University of South Alabama, College of
9 J& w& y" P) Y- h: RMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;6 V. x9 @% j3 H) v8 M, W
e-mail: [email protected]., f/ g/ V9 V; K" }8 R8 K
about 6 to 7 months old, which progressively became
8 l5 @# m% e6 p9 I. q Fdarker. She was also concerned about the enlarge-
) \8 Q+ g+ G: n0 g2 s+ Wment of his penis and frequent erections. The child' d6 D3 Q. ~* y6 v" Q1 [
was the product of a full-term normal delivery, with
& A8 C& z; u5 K, v! @a birth weight of 7 lb 14 oz, and birth length of
& X8 G! I$ ^9 O* B6 l20 inches. He was breast-fed throughout the first year+ p: Z! S, k1 Q y% ~* o
of life and was still receiving breast milk along with% I. O! ^, S" X! S1 H
solid food. He had no hospitalizations or surgery,6 d. q0 F7 M0 R6 j6 N
and his psychosocial and psychomotor development
6 u# ]) {! O& ]4 v, t$ Jwas age appropriate., p" E/ N7 F4 i0 E: `
The family history was remarkable for the father,
4 y! Z4 @" e) E& l. @" Uwho was diagnosed with hypothyroidism at age 16," C# d7 S5 t( b& a
which was treated with thyroxine. The father’s( i g5 s* O# q0 i1 q3 }
height was 6 feet, and he went through a somewhat9 P( |) q n; d- [
early puberty and had stopped growing by age 14.
* }/ R1 G3 S' j B+ B5 ~3 S- Z( g, oThe father denied taking any other medication. The
D1 R5 _" g6 Nchild’s mother was in good health. Her menarche: p2 h* \3 S1 ?8 S
was at 11 years of age, and her height was at 5 feet) X. _# K3 f' ]6 d4 K l( g% x
5 inches. There was no other family history of pre-
% j& D. |% q! p5 U6 x+ Jcocious sexual development in the first-degree rela-. h* ~$ l. j r; ^+ j* H3 c
tives. There were no siblings.' y" @) K+ m- \9 j
Physical Examination, |; |/ k. {8 c P
The physical examination revealed a very active,
' w, k& h- K l$ P# Y2 \. v8 Rplayful, and healthy boy. The vital signs documented
$ m, i4 `* r- O, A- U. Aa blood pressure of 85/50 mm Hg, his length was
, h# N4 p5 Z2 t9 k. u" l4 N90 cm (>97th percentile), and his weight was 14.4 kg+ M: p' R, Q* D# Z4 ^- {
(also >97th percentile). The observed yearly growth
, \0 ~0 ]: I: E" H0 q* X# Svelocity was 30 cm (12 inches). The examination of5 J& j$ w# x3 k9 `
the neck revealed no thyroid enlargement.8 M8 v" `4 m- l7 p; C
The genitourinary examination was remarkable for
) n' E- A2 Q# d" t5 T' Cenlargement of the penis, with a stretched length of
$ o; o8 q- w, h4 w8 cm and a width of 2 cm. The glans penis was very well
# j9 M( V5 I9 w; N$ v: tdeveloped. The pubic hair was Tanner II, mostly around$ Z4 w7 K+ M9 l5 u+ x: u
5405 {7 [ ?5 a6 V7 R
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
% d' a$ k2 i$ w! e9 ?; Y0 Dthe base of the phallus and was dark and curled. The4 h' [+ T/ q5 S% M4 {' G% R
testicular volume was prepubertal at 2 mL each.
3 }' J' V. p' }, D: pThe skin was moist and smooth and somewhat
) m9 p* }& K* Foily. No axillary hair was noted. There were no U) L1 w! m/ T% \; o: E
abnormal skin pigmentations or café-au-lait spots.
; }, w0 ~" t. {9 zNeurologic evaluation showed deep tendon reflex 2+( M5 a9 R" N! i5 n: U
bilateral and symmetrical. There was no suggestion
9 v8 j9 z9 n4 ?$ _: n. X- Sof papilledema.
4 c2 A r: q( w6 O: DLaboratory Evaluation) y2 [4 ]# ]' X, s: K
The bone age was consistent with 28 months by: ?* R7 ]" z% T* |+ s
using the standard of Greulich and Pyle at a chrono-1 v w! M& p6 {6 i. h
logic age of 16 months (advanced).5 Chromosomal
) B7 [; j# P3 K1 e" u, ukaryotype was 46XY. The thyroid function test8 U; Q/ x8 r1 q8 \+ d+ q7 [! h
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
+ X1 Z* ^( `) z/ Mlating hormone level was 1.3 µIU/mL (both normal).
! j# Q c3 s/ t9 h& L* f$ e( V# \' B( [The concentrations of serum electrolytes, blood
2 A! p7 n" u2 D8 Z2 G) V7 V' Rurea nitrogen, creatinine, and calcium all were7 \6 K# S4 t; Q4 I# W
within normal range for his age. The concentration: t3 s% k( p/ L& q- t" X0 ~) s: ?
of serum 17-hydroxyprogesterone was 16 ng/dL
4 `1 V" O" p5 ?) X# D* U9 h+ q(normal, 3 to 90 ng/dL), androstenedione was 20$ ]: Z1 c. s2 H' I- A7 Y! ]* h' u, C
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
) Y1 ]+ j4 G# ]& v+ I v4 s1 O6 J1 F" iterone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ q v* Q' p4 X/ u3 B) rdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
2 v& b! {1 D2 e7 N- u6 @49ng/dL), 11-desoxycortisol (specific compound S)" g \. @& P* y( X- m% x
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-$ a' X. o/ P {( ^; V
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total$ q& i4 }5 W! Q6 T' H% R9 ~
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
8 y6 L, ], C( u) g2 y1 mand β-human chorionic gonadotropin was less than
! M, ]% z% j5 ~$ i( \5 mIU/mL (normal <5 mIU/mL). Serum follicular
/ Z, l# [1 E) X& G; U8 mstimulating hormone and leuteinizing hormone
6 p# o1 n( J+ ?0 J# pconcentrations were less than 0.05 mIU/mL
5 g7 V9 E3 X4 x. L! l7 z/ k(prepubertal).8 A7 y) r/ v: u4 n9 w
The parents were notified about the laboratory
, s6 A9 `9 R5 G, ^4 |8 Kresults and were informed that all of the tests were
K7 G) G( j! k& nnormal except the testosterone level was high. The" b- p$ S3 _+ ?& S0 \. x. S
follow-up visit was arranged within a few weeks to. w. h3 l5 M' D
obtain testicular and abdominal sonograms; how- L3 f8 @ S. ?" ]& |
ever, the family did not return for 4 months., H, Q7 U( _5 z* H$ Z
Physical examination at this time revealed that the
/ {- n+ O3 f+ T8 Ychild had grown 2.5 cm in 4 months and had gained
6 q8 ~: c9 y- q8 K6 o$ H+ K2 kg of weight. Physical examination remained
* p- k/ L/ j' ^$ |2 d/ r) f' Junchanged. Surprisingly, the pubic hair almost com-; ?8 c' J, r& X: y% Y/ f
pletely disappeared except for a few vellous hairs at" o$ C; q; x% v* _
the base of the phallus. Testicular volume was still 2' m1 K) P# c& M' E3 b( U
mL, and the size of the penis remained unchanged.
% M9 g9 a8 k3 ^The mother also said that the boy was no longer hav-+ G& k1 D l; j+ A6 h! L& i
ing frequent erections.
8 ^% N& a+ A( V0 R& `. MBoth parents were again questioned about use of4 m; j# g, b9 A1 G
any ointment/creams that they may have applied to% n. @3 W* l% t
the child’s skin. This time the father admitted the
' ?/ t: f) t8 V" |# B1 ]Topical Testosterone Exposure / Bhowmick et al 541
2 k4 {' c9 w: r6 o. Juse of testosterone gel twice daily that he was apply-
; M4 [; `1 q. ding over his own shoulders, chest, and back area for
2 {5 i2 {& y5 I( `# c. w# e, T. @a year. The father also revealed he was embarrassed# V: x. F9 L2 T- K* B8 K# u9 B
to disclose that he was using a testosterone gel pre-
' i% d" _8 |) Y2 L) A, N/ Vscribed by his family physician for decreased libido8 q, M Y5 Q! N% U
secondary to depression.
4 ^+ d% M" Z3 B- T3 ?( b, FThe child slept in the same bed with parents.
7 A5 |% E% }2 w) f- ^, rThe father would hug the baby and hold him on his
4 s1 |, x) c' Tchest for a considerable period of time, causing sig-# R! J: a( m* Z( _* L- F
nificant bare skin contact between baby and father.
- T% P) j; C% W* zThe father also admitted that after the phone call,
" w; o. _# k) X4 `: Y4 L- Twhen he learned the testosterone level in the baby0 U5 _0 H+ F; ^( {
was high, he then read the product information
" S5 ~6 L/ C5 O% \( ipacket and concluded that it was most likely the rea-, E( m7 ]7 q& J4 @+ l9 W+ V
son for the child’s virilization. At that time, they1 M7 X7 H, V. F( A) I. h
decided to put the baby in a separate bed, and the! H7 i+ j e1 F/ N8 w8 y
father was not hugging him with bare skin and had
4 e4 K, n8 _( \; J( ^7 j, Tbeen using protective clothing. A repeat testosterone
& _$ J2 D( z7 c. s* i& mtest was ordered, but the family did not go to the1 U# w7 ^/ R1 c3 @5 A
laboratory to obtain the test., ]$ {0 z5 I* u6 @
Discussion3 H6 `. F6 S( R( C* E- N! w' }
Precocious puberty in boys is defined as secondary
- y. c+ R' G: B' ~6 _5 ysexual development before 9 years of age.1,4- @+ G9 Y( J! ?- R- Y
Precocious puberty is termed as central (true) when
! j! Y4 N' t0 T7 Z/ Pit is caused by the premature activation of hypo-8 t( S7 X$ j/ q+ }; R! ~( t
thalamic pituitary gonadal axis. CPP is more com-# m9 p* l$ Z3 J( `) q
mon in girls than in boys.1,3 Most boys with CPP6 ]' S# A" p" \% s$ S. q
may have a central nervous system lesion that is- q4 H% R7 g* Q$ d
responsible for the early activation of the hypothal-6 |; \" W f, w2 N0 J" g$ ]" F+ o
amic pituitary gonadal axis.1-3 Thus, greater empha-
6 Y3 C6 Q5 M, t: |) h5 k tsis has been given to neuroradiologic imaging in1 s1 a) i# j( w4 d/ v" i& |
boys with precocious puberty. In addition to viril-5 y8 t+ w" l1 i/ }2 E
ization, the clinical hallmark of CPP is the symmet-
0 Y+ N8 ^! ~' c, S% mrical testicular growth secondary to stimulation by
7 b; \4 l8 ?- T1 u: @8 K8 q6 [7 ugonadotropins.1,35 T* Q9 }; y) J
Gonadotropin-independent peripheral preco-- U) G. P; w7 d9 O; U- D
cious puberty in boys also results from inappropriate U8 Z: m2 e D# A6 w
androgenic stimulation from either endogenous or& k7 q& Z' @* `/ b B) J- i' A
exogenous sources, nonpituitary gonadotropin stim-+ a+ x+ e* W, ~
ulation, and rare activating mutations.3 Virilizing
- Y! D" H- N! Y. m7 v6 ccongenital adrenal hyperplasia producing excessive
1 n0 M4 [$ v8 m/ @/ H/ B% ]# U. j# o$ y O# ~adrenal androgens is a common cause of precocious
2 g" K5 W$ o* Q9 t. xpuberty in boys.3,4: f- `/ |& P1 a( |
The most common form of congenital adrenal) c7 e' C7 X- S! U! @; O& }* h
hyperplasia is the 21-hydroxylase enzyme deficiency.
8 O" C. f! L( U$ E7 e' I- V; hThe 11-β hydroxylase deficiency may also result in1 X) e% M) h; I/ c6 f: \; W
excessive adrenal androgen production, and rarely," h% }% T: A/ x1 X% H
an adrenal tumor may also cause adrenal androgen% \; C1 O6 E* G7 G2 A3 a
excess.1,3; m% ]% \: L* f0 w, ^0 K
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from: U7 v4 x% Y4 b1 \* @5 g
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007 G/ g8 p3 ?6 U' x5 j- I7 {
A unique entity of male-limited gonadotropin-
8 E8 |( w+ ^' [" ~! o1 jindependent precocious puberty, which is also known' Q. g# J* |( ]6 E
as testotoxicosis, may cause precocious puberty at a
$ F/ a+ f( T7 H! F2 [very young age. The physical findings in these boys
' g. f' x" f# T+ kwith this disorder are full pubertal development,: I/ t9 H4 a- S& o& G
including bilateral testicular growth, similar to boys1 ~" z# e/ c) t9 k# E& k- t* N3 E
with CPP. The gonadotropin levels in this disorder
# B) j, |$ j- ?! Pare suppressed to prepubertal levels and do not show- F- o w, Y* g+ G- Y: e! u7 G
pubertal response of gonadotropin after gonadotropin-9 A4 {8 u% a* _& V, O' j
releasing hormone stimulation. This is a sex-linked
d. ]: }3 b- U+ j! d, I2 uautosomal dominant disorder that affects only7 j% j' o$ ^* R8 I, `$ \
males; therefore, other male members of the family! D: t% O# }9 C ^1 c
may have similar precocious puberty.3
# c# h; D# a1 Q# P+ V2 CIn our patient, physical examination was incon-* p% j& c; u* ~% @
sistent with true precocious puberty since his testi-
2 J) g% U$ l# E. M2 @cles were prepubertal in size. However, testotoxicosis
% _2 M" r7 |7 F2 e3 g; jwas in the differential diagnosis because his father
2 D- u4 o! |% j% }+ b' D, Bstarted puberty somewhat early, and occasionally,7 {* A- }! I/ `* r# B$ P
testicular enlargement is not that evident in the2 A/ |& C# I% X! H; p. c
beginning of this process.1 In the absence of a neg-
5 {) [$ T6 z& c6 qative initial history of androgen exposure, our
% f+ F$ U& M( O8 i" Z2 ~, U% u( }biggest concern was virilizing adrenal hyperplasia,# o& x1 X/ c% ^8 Y7 N9 H# w
either 21-hydroxylase deficiency or 11-β hydroxylase
n$ t& t" v3 X: @deficiency. Those diagnoses were excluded by find-
1 I6 K: W. Q) j; fing the normal level of adrenal steroids.
% G; ^: l1 ~& N* eThe diagnosis of exogenous androgens was strongly
$ H+ S" d" C6 j; A3 u/ `+ isuspected in a follow-up visit after 4 months because, Q% p! ~; l M ^9 v( B
the physical examination revealed the complete disap-
9 t, j/ o% P9 Q$ k+ ~# spearance of pubic hair, normal growth velocity, and/ C( k# `* `/ Q( F! b m
decreased erections. The father admitted using a testos-- z' f7 K a5 p
terone gel, which he concealed at first visit. He was; K/ h3 W; w& W+ o2 @# ~
using it rather frequently, twice a day. The Physicians’
, N" |& N+ N# p/ L0 [Desk Reference, or package insert of this product, gel or
" P5 Q }. N, r" Kcream, cautions about dermal testosterone transfer to
; ?% r; R3 X$ _8 Z. ], aunprotected females through direct skin exposure.
1 M ^6 r5 p7 ?: b4 GSerum testosterone level was found to be 2 times the
# Y) D2 \: W$ m+ f a" o( L6 K6 ybaseline value in those females who were exposed to' \9 u+ j. l$ ]' r5 M( a
even 15 minutes of direct skin contact with their male
; j& d* I0 j# @9 r2 M* o4 ?+ cpartners.6 However, when a shirt covered the applica-
$ `6 Q9 m# {4 S- d" @6 ytion site, this testosterone transfer was prevented.) z9 g+ J+ t+ _1 |
Our patient’s testosterone level was 60 ng/mL,
7 x! }4 c& l+ m' v" Nwhich was clearly high. Some studies suggest that
& U! q9 o" o6 R& F9 X. qdermal conversion of testosterone to dihydrotestos-! g! t, ~ g+ h" j4 \2 Y2 M9 k
terone, which is a more potent metabolite, is more
" F* {% s) O1 f8 J, Yactive in young children exposed to testosterone4 u( G# W- w( I
exogenously7; however, we did not measure a dihy-
0 Y1 u5 F; z6 I) n- U3 ~7 r( \drotestosterone level in our patient. In addition to
9 m9 J4 }# c+ [" M& L* {! V$ Hvirilization, exposure to exogenous testosterone in; Q! j/ P$ k% b7 o
children results in an increase in growth velocity and" n4 f0 o/ {6 H6 }
advanced bone age, as seen in our patient.& h! S' o0 V9 X) I
The long-term effect of androgen exposure during
2 k, f+ c5 _6 [$ bearly childhood on pubertal development and final
. B: Q2 N' I4 D: y3 Ladult height are not fully known and always remain7 D: s9 T/ q T$ d) f/ F
a concern. Children treated with short-term testos-5 x9 Q6 y5 T" u) {
terone injection or topical androgen may exhibit some
, f8 N1 q; g; F: o0 U( e. [2 Z. Kacceleration of the skeletal maturation; however, after
# s( N: b! ~5 ^/ y* F rcessation of treatment, the rate of bone maturation
* X1 c3 L; L3 Udecelerates and gradually returns to normal.8,9 ^. _/ r" K' l3 k: c7 s
There are conflicting reports and controversy( r6 ^3 Y4 _( K5 P2 E6 q
over the effect of early androgen exposure on adult/ f- d- y$ U8 H6 O4 |- y1 L
penile length.10,11 Some reports suggest subnormal5 g: k. Q. v3 M3 e
adult penile length, apparently because of downreg-3 M' R4 c: P; V
ulation of androgen receptor number.10,12 However,
; g% `; W5 g; R |: [Sutherland et al13 did not find a correlation between7 k5 D% K2 z2 |: P
childhood testosterone exposure and reduced adult
8 a( F; ^8 ]5 L. Ipenile length in clinical studies.
6 l" o6 ^/ p9 F& @: |: iNonetheless, we do not believe our patient is
% C% U" b% x$ p C2 [6 ygoing to experience any of the untoward effects from3 k0 K: ?7 W) n" V/ v: z
testosterone exposure as mentioned earlier because. a$ k! g6 M+ Y* p9 Y$ O
the exposure was not for a prolonged period of time.
3 E, p; K6 g6 ] h: ?0 Y3 |0 o/ YAlthough the bone age was advanced at the time of5 h5 z7 A! b% ]9 j$ o
diagnosis, the child had a normal growth velocity at
# E, U7 u( a( y: W. L( o7 N* f" l. s: Hthe follow-up visit. It is hoped that his final adult, p7 ]! i% w+ p* @& o9 o/ U+ Z
height will not be affected.# b6 q7 H/ g! t* P5 e+ v% q
Although rarely reported, the widespread avail-
' ?& V0 d, _: F+ r+ ]. e: `7 Hability of androgen products in our society may
5 s3 J) g+ ]1 G5 Oindeed cause more virilization in male or female
, v7 N3 h- Y) O4 u" mchildren than one would realize. Exposure to andro-
5 c2 j3 I7 J! m! l! Y0 N- cgen products must be considered and specific ques-
) L; E c3 R0 J$ N/ M0 xtioning about the use of a testosterone product or
* T+ r4 U3 p5 l! s ~6 b/ `gel should be asked of the family members during
6 a1 y# T& n s" Othe evaluation of any children who present with vir-, d3 I2 a$ ^. n6 E& \5 v. B
ilization or peripheral precocious puberty. The diag-4 i, P% ]3 a& y; U" U+ Y/ v
nosis can be established by just a few tests and by
) w9 |% }: O2 T+ Yappropriate history. The inability to obtain such a( _* ` K. |; ~: E# t/ k, _
history, or failure to ask the specific questions, may
/ H6 Z4 a: V# R# J; ^) Nresult in extensive, unnecessary, and expensive
% `$ j+ ?. _7 A- v! D( l' W2 Rinvestigation. The primary care physician should be
# @. B7 l) V, `2 Maware of this fact, because most of these children9 P$ K$ o E# h( S* O' K& f
may initially present in their practice. The Physicians’6 q* v! @3 k9 p3 l0 j
Desk Reference and package insert should also put a
5 \% @. X0 B1 ]: U! ~7 Q) ~2 kwarning about the virilizing effect on a male or: u ^) v7 E0 u8 v
female child who might come in contact with some-
' o" B0 B5 Q2 L- hone using any of these products.4 j `% u7 I7 w6 _. W- g
References
; O9 j+ V0 K- X. S R1. Styne DM. The testes: disorder of sexual differentiation
" V4 q9 I0 ]% S+ d9 T1 wand puberty in the male. In: Sperling MA, ed. Pediatric
: i* {8 m4 b0 K7 Z. b$ dEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
8 X! L6 t$ M/ R' F2002: 565-628.& c& d! k+ S* v
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
- G2 b* v' M( h& p3 Npuberty in children with tumours of the suprasellar pineal |
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