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Sexual Precocity in a 16-Month-Old
" ^# q( F/ E# x UBoy Induced by Indirect Topical
, @' s' W( g4 N; \Exposure to Testosterone% {" O ^8 E( x$ M
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
2 T4 _1 t6 ]0 i& ~+ F& qand Kenneth R. Rettig, MD1
0 m0 y, n2 X) F9 sClinical Pediatrics% e$ e' ^2 |& t& Q- Y; }/ j3 T( \
Volume 46 Number 6- z4 e& ~, B: T1 u/ Q
July 2007 540-5431 l9 J& p0 h g" x, ~# t
© 2007 Sage Publications( q2 L& r) }# O* Y
10.1177/0009922806296651
& D7 C6 o& g2 j. f% y$ h7 E$ Khttp://clp.sagepub.com+ Y1 j+ N$ D" p% f0 ~ e1 z
hosted at |3 q9 c& y! K. ?5 D9 @
http://online.sagepub.com# p; O4 C1 @! ?( p* k
Precocious puberty in boys, central or peripheral,
7 o1 l, [& j) h5 Y' T/ F' h0 Ris a significant concern for physicians. Central
0 I5 [6 i: N- yprecocious puberty (CPP), which is mediated
( q ]7 L/ q V+ O/ Lthrough the hypothalamic pituitary gonadal axis, has, d: \7 z" Z4 ]9 K9 d
a higher incidence of organic central nervous system
' Q+ k6 c Z( V$ f3 s0 clesions in boys.1,2 Virilization in boys, as manifested& l3 h Z+ w0 R, {' ^6 T
by enlargement of the penis, development of pubic
1 ~" i4 y/ E! A, r) Ahair, and facial acne without enlargement of testi-
. X- N0 P* m- y9 I4 v$ ecles, suggests peripheral or pseudopuberty.1-3 We
% Z) k$ G8 H: [7 Zreport a 16-month-old boy who presented with the
: u8 @! I( o* }7 a) A; @enlargement of the phallus and pubic hair develop-. S1 O/ ]- n8 U! U0 I% o
ment without testicular enlargement, which was due( }+ c7 O: D& r2 i) U( P) l
to the unintentional exposure to androgen gel used by
" D7 ^5 X" S& q' h1 Qthe father. The family initially concealed this infor-
% r3 j, f: @* O9 W3 v. tmation, resulting in an extensive work-up for this( ~1 |( v9 o! ~. V/ K
child. Given the widespread and easy availability of2 W: e& s3 T% `0 Z# {2 ?& J$ r
testosterone gel and cream, we believe this is proba-
0 W' [1 ^5 e8 M9 {! E! v/ jbly more common than the rare case report in the
! T$ s5 O: q' W9 b# ~- A- ^+ P" jliterature.4; o* q1 Z0 p4 i: v
Patient Report
( c% h' d5 I! \& w) n5 EA 16-month-old white child was referred to the
; \& x9 x) ~, Q# I; _$ V4 r' `endocrine clinic by his pediatrician with the concern. a% A0 T: o, `3 r+ J2 ~
of early sexual development. His mother noticed0 @/ P" O0 m% i0 s. G f
light colored pubic hair development when he was
' g- f+ Q6 u3 o, |9 m; zFrom the 1Division of Pediatric Endocrinology, 2University of) x; R4 _1 I) B1 b
South Alabama Medical Center, Mobile, Alabama.
; d1 \/ H. b; p4 j* ^Address correspondence to: Samar K. Bhowmick, MD, FACE,
& j" a+ `7 ^* D0 Y+ j) }Professor of Pediatrics, University of South Alabama, College of
+ e+ p% o9 ~( ?4 Y# L- }# UMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;# z1 c7 S5 R e' O
e-mail: [email protected].
2 Y# [& p. \& \( d1 c0 t2 Babout 6 to 7 months old, which progressively became7 z. S4 _8 a# ?5 z
darker. She was also concerned about the enlarge-4 }6 r" j" |: V) e; s
ment of his penis and frequent erections. The child8 U7 J7 w5 ? H( s
was the product of a full-term normal delivery, with
) ]! b: r4 ?' ka birth weight of 7 lb 14 oz, and birth length of0 s/ _4 V, I" K+ u* T5 Z
20 inches. He was breast-fed throughout the first year
9 |! }- ]! a/ ? n- oof life and was still receiving breast milk along with
$ Y. s8 i. V7 C: f1 r2 Ssolid food. He had no hospitalizations or surgery,
: P3 U2 ^, D$ w7 K7 G4 eand his psychosocial and psychomotor development
0 R: J* n6 M3 L( ]- j8 nwas age appropriate.
* i7 K) T2 n4 O: D; IThe family history was remarkable for the father,' a% T1 i1 V" `3 w0 C
who was diagnosed with hypothyroidism at age 16,
& D4 h- |9 T6 I6 P3 {" Owhich was treated with thyroxine. The father’s
- p$ Z4 Y$ c' c- A1 s3 Aheight was 6 feet, and he went through a somewhat
/ m' u1 g+ [5 k ?" C) k' Bearly puberty and had stopped growing by age 14.
! J N7 h/ M+ kThe father denied taking any other medication. The6 e+ z/ d. N& x g8 l6 |
child’s mother was in good health. Her menarche; I6 l2 ]) l9 j$ {% x. g2 E
was at 11 years of age, and her height was at 5 feet
' T9 q5 H) Y) y. G. M1 G& H5 inches. There was no other family history of pre-# l4 q$ z1 j1 K- ~( F# T) ]; d
cocious sexual development in the first-degree rela-
3 b. D6 n6 Q" Q1 D. X' Gtives. There were no siblings.: P. x) T7 k! g( y& \8 y6 c
Physical Examination, u" K& v2 q9 B
The physical examination revealed a very active,
6 Y1 J' k) A. c9 Q, o ~playful, and healthy boy. The vital signs documented
- J5 e6 \3 |8 N# q1 q' Y0 ca blood pressure of 85/50 mm Hg, his length was
# B' R" w4 N0 Y. J90 cm (>97th percentile), and his weight was 14.4 kg
$ z: M7 J9 B) r" s(also >97th percentile). The observed yearly growth
, V" w2 z0 ^! W+ {9 D; ?velocity was 30 cm (12 inches). The examination of+ X: S; Z4 f2 b/ O7 a
the neck revealed no thyroid enlargement.
( ?) h+ ~7 r$ |/ `8 qThe genitourinary examination was remarkable for
$ _' _& O9 S8 Genlargement of the penis, with a stretched length of" H- P) t" E& Z" f0 W
8 cm and a width of 2 cm. The glans penis was very well5 @7 } Q4 A4 f& `1 v1 x: t& `9 \( G
developed. The pubic hair was Tanner II, mostly around0 e! x- ]7 F- \+ R$ l; ~
540' T7 l5 c: P/ M0 B$ m1 `" Z9 a; M; q! Z
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from2 |9 i0 x6 L! v1 o
the base of the phallus and was dark and curled. The: J8 n0 L) a9 X1 _2 f
testicular volume was prepubertal at 2 mL each.
2 _' J$ M- t: ]& }The skin was moist and smooth and somewhat! ]7 j, @# \ g) i- ?2 N
oily. No axillary hair was noted. There were no1 |# C" p! v0 d2 q
abnormal skin pigmentations or café-au-lait spots.3 Y; c$ [# N) _6 o$ T( ?8 p1 ?
Neurologic evaluation showed deep tendon reflex 2+
# u0 H) C! S& a- o' }bilateral and symmetrical. There was no suggestion
3 ^* \ J6 K0 \2 A0 C5 pof papilledema.0 ^% n. G# \1 ^7 l7 h
Laboratory Evaluation
3 B9 g) ^3 R" zThe bone age was consistent with 28 months by% C7 j* ?! v& ~+ d% ` j W3 J- t/ m( ^
using the standard of Greulich and Pyle at a chrono-6 G/ c, O( z. m6 K
logic age of 16 months (advanced).5 Chromosomal4 c5 y8 ^% j6 T: a, a: i
karyotype was 46XY. The thyroid function test
' Q; m- Y5 A J2 O8 t; r( d: ]showed a free T4 of 1.69 ng/dL, and thyroid stimu- d2 d9 C. f u2 u* X3 y
lating hormone level was 1.3 µIU/mL (both normal).
. D1 c. d/ m3 v% T; GThe concentrations of serum electrolytes, blood
0 d! ]- ?6 p6 D( |; H7 R! ]) m" Zurea nitrogen, creatinine, and calcium all were" }9 V& a, \, M9 K+ p
within normal range for his age. The concentration8 l2 G( ?" s' B0 H
of serum 17-hydroxyprogesterone was 16 ng/dL; w( z" L2 z1 s% q( [" z" J) A7 a" `
(normal, 3 to 90 ng/dL), androstenedione was 20
& j# _( e4 [! F4 C `5 h: C# ?ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros- `4 n/ \8 {) B7 \
terone was 38 ng/dL (normal, 50 to 760 ng/dL),6 b3 `5 H! B* K
desoxycorticosterone was 4.3 ng/dL (normal, 7 to9 u P' y! n8 D k) N8 H; ?
49ng/dL), 11-desoxycortisol (specific compound S)
; j, A* r0 u) i% g% Wwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
4 n( m" [' n1 Itisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total7 ?, b& O3 [3 g! t* \
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),/ p7 n J% G% T) N/ }, k$ D) ]. y
and β-human chorionic gonadotropin was less than0 i( D( b# \. p+ m4 v! s
5 mIU/mL (normal <5 mIU/mL). Serum follicular
2 j2 n6 W$ _0 I" p hstimulating hormone and leuteinizing hormone
: M; f9 B: E. V9 xconcentrations were less than 0.05 mIU/mL- G1 C- b4 ]" e/ y7 z6 G/ v, m
(prepubertal).0 F( h6 g4 k* K1 T! {( p
The parents were notified about the laboratory
9 c0 f( f, b+ e4 \2 eresults and were informed that all of the tests were
1 x8 y6 L# ?& I2 U( H# mnormal except the testosterone level was high. The7 R5 q4 C% N* e; r( T" W
follow-up visit was arranged within a few weeks to# _! }' c% [: D; Y- }0 [
obtain testicular and abdominal sonograms; how-
* g: C0 @( E! g) ^) m* eever, the family did not return for 4 months.
2 f. o) U( N: x! g4 CPhysical examination at this time revealed that the
x) g. o" M2 Q7 b$ d, ychild had grown 2.5 cm in 4 months and had gained
# x+ a' M9 ?, B; J2 n2 kg of weight. Physical examination remained* J0 D! u' F) M+ j$ Q* P+ Z- V
unchanged. Surprisingly, the pubic hair almost com-
x& W( ]; I. ?3 l; Cpletely disappeared except for a few vellous hairs at7 q/ h! I7 J& C. N, u5 p' u
the base of the phallus. Testicular volume was still 26 T' `; d# y" \4 t1 [) H" k5 _! s5 d
mL, and the size of the penis remained unchanged.
9 X* l6 c4 W* X$ k/ ?0 H O/ f# i5 IThe mother also said that the boy was no longer hav-
, K5 A; O5 ~/ M8 _. R! [ing frequent erections.4 h7 B9 L N/ x# ?4 `- y8 S
Both parents were again questioned about use of8 I& `3 [+ _9 D" @ \3 B! G* R
any ointment/creams that they may have applied to
1 C. P7 v, R# q: Ithe child’s skin. This time the father admitted the6 v6 q" V7 p' X5 o( x
Topical Testosterone Exposure / Bhowmick et al 541( G8 S5 v8 ^ P# ]
use of testosterone gel twice daily that he was apply-/ H0 t8 x2 W' P6 g. R A& ?* ?% W3 M
ing over his own shoulders, chest, and back area for: ]; a0 Q: ~- j4 p8 e
a year. The father also revealed he was embarrassed
' o z$ P- r, c' W) Y/ S: r1 Xto disclose that he was using a testosterone gel pre-
/ O# ?. H6 v' D8 |scribed by his family physician for decreased libido7 x5 K+ F* M: t' o2 W. O" d ]4 ?
secondary to depression.- c; A T3 ^" c; `) i
The child slept in the same bed with parents.
1 ~7 ?2 w2 X$ i# Y/ {7 e, F( \The father would hug the baby and hold him on his
$ R, ~3 ]% E& e5 X' Vchest for a considerable period of time, causing sig-3 o3 ?! D- ^1 W' i5 ]
nificant bare skin contact between baby and father.
* i+ S) n& Q. K# T2 JThe father also admitted that after the phone call," i; t4 q7 _/ @: A9 J' Z
when he learned the testosterone level in the baby \- h' U$ @0 ~8 W" u
was high, he then read the product information
! S* I" z- a( C q9 [! `packet and concluded that it was most likely the rea-
" W. ^& H* G4 J! C1 k- O6 Uson for the child’s virilization. At that time, they7 Z6 f0 J/ f0 `* q$ T7 G7 ], Z
decided to put the baby in a separate bed, and the- P% a4 f3 a7 `7 [
father was not hugging him with bare skin and had
" S5 j: Z+ D' A! R6 _been using protective clothing. A repeat testosterone
7 R5 H$ }$ f0 J/ Y/ {' itest was ordered, but the family did not go to the# b6 O$ r+ M d
laboratory to obtain the test.
! X; q" Z0 ~6 H& T: P! rDiscussion
6 @. T9 e& |, ^1 [" S) APrecocious puberty in boys is defined as secondary
/ F/ R! Q) m0 p9 m o* ~$ E3 ~sexual development before 9 years of age.1,4
: M: W" _+ [1 {% [Precocious puberty is termed as central (true) when3 I: J; @6 d' Y5 I; [# C1 ]3 l% N5 C' ^
it is caused by the premature activation of hypo-6 o6 [; w) b- S1 d, d7 \, |8 v/ S
thalamic pituitary gonadal axis. CPP is more com-
5 t7 W9 t7 b9 _) vmon in girls than in boys.1,3 Most boys with CPP( F, b5 b; ^' {2 F9 |4 ?/ e- ]
may have a central nervous system lesion that is
7 Y3 w1 h- S& w$ j1 M4 Xresponsible for the early activation of the hypothal-) a" z9 c' ^+ f: y" O+ T
amic pituitary gonadal axis.1-3 Thus, greater empha-
; M* @/ j* O1 J5 j2 e# o& Nsis has been given to neuroradiologic imaging in! o% R2 _* d3 x/ Q% Z- g
boys with precocious puberty. In addition to viril-
! V: n1 z% a2 uization, the clinical hallmark of CPP is the symmet-
; Q6 o4 a+ ^ ?6 mrical testicular growth secondary to stimulation by' h% T: R+ _7 i) Y
gonadotropins.1,31 Q* q' b% d+ L
Gonadotropin-independent peripheral preco- z5 u" L4 B% Q, ]' N
cious puberty in boys also results from inappropriate
+ K* e6 I! h9 m5 O- I! r a+ dandrogenic stimulation from either endogenous or
! Z9 ?, v: G+ Z! r2 _7 \exogenous sources, nonpituitary gonadotropin stim- S. z/ ^* K- R0 m/ a
ulation, and rare activating mutations.3 Virilizing
2 p# k' l' _; ?congenital adrenal hyperplasia producing excessive
, [. i. t: n, B1 e8 qadrenal androgens is a common cause of precocious
! X8 C* U+ W5 A8 opuberty in boys.3,4
; S. }7 G+ l1 R. k7 n# vThe most common form of congenital adrenal! L f4 d4 K1 O8 y% d
hyperplasia is the 21-hydroxylase enzyme deficiency.8 R% F; |2 z$ G6 q5 R! K
The 11-β hydroxylase deficiency may also result in% F$ Z( a# A V$ K
excessive adrenal androgen production, and rarely,. u) g, t" v7 b. p0 ^
an adrenal tumor may also cause adrenal androgen
/ F$ P* x- M8 r, d0 g5 g# ]excess.1,3
$ l* q& Z/ l: k5 H7 V* o' fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
& g% B' k& K4 g" B' W3 S542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
8 Z3 `- d2 p; aA unique entity of male-limited gonadotropin-( B8 ^( e% {1 T2 s8 s/ u5 @% L! `% o
independent precocious puberty, which is also known% \! L- \2 \! w! {# k
as testotoxicosis, may cause precocious puberty at a! c, \3 h! q( ^% u- _/ k
very young age. The physical findings in these boys
B$ d" T' N; F' u" Z3 i5 Gwith this disorder are full pubertal development," _; t; C/ ~* p+ v: P9 q
including bilateral testicular growth, similar to boys
f9 c* D- ?4 T, vwith CPP. The gonadotropin levels in this disorder
; T& n: t& f/ u6 r5 R: W' V3 Xare suppressed to prepubertal levels and do not show
% K, _+ O1 J% |4 x5 epubertal response of gonadotropin after gonadotropin-
! f% ]0 {. H* x' X h4 |releasing hormone stimulation. This is a sex-linked
$ o4 Y7 `, t3 U3 Y* Wautosomal dominant disorder that affects only) M5 M4 R( t: f. ]0 ~6 ]3 }
males; therefore, other male members of the family
# h! x$ @9 W4 rmay have similar precocious puberty.3
, a$ \1 j+ A5 \6 l3 @7 S7 gIn our patient, physical examination was incon-
8 W9 ~, n/ s4 s: Osistent with true precocious puberty since his testi-4 E% Z o+ F! f# V) H% I
cles were prepubertal in size. However, testotoxicosis# d# W* t4 S3 D1 [
was in the differential diagnosis because his father; u/ O( B+ R/ }2 @% Y% w6 W2 X
started puberty somewhat early, and occasionally,
: k3 Z) W+ @6 E" a, z; a1 j& G2 y, ktesticular enlargement is not that evident in the
7 k c2 Q5 @( t- g& n6 M2 abeginning of this process.1 In the absence of a neg-& s3 @+ b ~% J7 Z B& G2 h3 V5 |
ative initial history of androgen exposure, our# T, q7 c- s, l% u! [% |
biggest concern was virilizing adrenal hyperplasia,
' k1 O2 l( J1 J( K, _: C" [either 21-hydroxylase deficiency or 11-β hydroxylase2 |7 W* {! y. r- ?6 v
deficiency. Those diagnoses were excluded by find-
; X3 \% e& v7 [% q }ing the normal level of adrenal steroids.
9 t" A- U6 O2 @% x( ?The diagnosis of exogenous androgens was strongly+ b- J; d# `! ?% \! C
suspected in a follow-up visit after 4 months because
) y( W, F& d; W) hthe physical examination revealed the complete disap-
& b9 |# S; N- }' o! d) t1 W& qpearance of pubic hair, normal growth velocity, and3 a, m5 {) [$ C9 t1 Y7 C
decreased erections. The father admitted using a testos-7 ^& }5 e( U0 D' b* s6 G$ R
terone gel, which he concealed at first visit. He was a' z0 P. \( |; g2 v1 ]
using it rather frequently, twice a day. The Physicians’3 t1 R* H/ Q& \, ?' Z# v
Desk Reference, or package insert of this product, gel or
% d- e' {) C* A. u8 T) u( \cream, cautions about dermal testosterone transfer to
1 }/ N8 w8 a Z1 d6 M1 Z+ Munprotected females through direct skin exposure.* g" o( e D$ B! @& @) @( f8 F
Serum testosterone level was found to be 2 times the
0 d0 P" \: [* p; V0 i# Gbaseline value in those females who were exposed to
8 H9 L9 _; W6 Feven 15 minutes of direct skin contact with their male# ^( M/ O+ Y( I( q6 H; J/ r
partners.6 However, when a shirt covered the applica-1 t4 i9 K! | j0 y9 j1 I! [& T
tion site, this testosterone transfer was prevented.
$ O8 f& b! N! y% @Our patient’s testosterone level was 60 ng/mL,- y. M+ I0 d! m8 B0 i- f) y
which was clearly high. Some studies suggest that T. x, b2 a) g3 _% ]) _( F" G
dermal conversion of testosterone to dihydrotestos-
1 p* A5 x e* H& \terone, which is a more potent metabolite, is more# R6 d1 H3 ^: O, Y- [
active in young children exposed to testosterone" D7 n& v+ ^+ z$ M0 u3 Q* N* K
exogenously7; however, we did not measure a dihy-0 {. R, T% l" n1 V0 T
drotestosterone level in our patient. In addition to; F. [5 z$ S& p" c5 g
virilization, exposure to exogenous testosterone in, s1 R3 x, j! P: d% z0 k) o
children results in an increase in growth velocity and7 y/ N; F$ Y. P* D
advanced bone age, as seen in our patient.
7 P$ M, ^, ~% d2 n" PThe long-term effect of androgen exposure during
- p. m% q$ P7 A# @1 H" wearly childhood on pubertal development and final
$ W' y j. j2 K$ radult height are not fully known and always remain9 o) U% o o7 [/ L$ _' |7 G
a concern. Children treated with short-term testos-
$ p& B0 W0 O+ F5 O% l' o: _terone injection or topical androgen may exhibit some3 e: q$ ~( a* m. u; A5 M# L% K. H
acceleration of the skeletal maturation; however, after3 J% C# P _0 Q+ X, `2 M# F
cessation of treatment, the rate of bone maturation7 L0 j+ X1 D) B/ i8 k0 x
decelerates and gradually returns to normal.8,9/ w" \& n/ j8 V8 m5 T! e
There are conflicting reports and controversy& g, L# Q( J$ _5 i# ?
over the effect of early androgen exposure on adult
& M% \) R1 d) x9 A* ?& A+ Jpenile length.10,11 Some reports suggest subnormal: a* t1 W" R* P: E4 m
adult penile length, apparently because of downreg-4 B) o0 A$ K2 d. P: T# L
ulation of androgen receptor number.10,12 However,
( a- e, K8 Z0 z+ m- @; i8 r% tSutherland et al13 did not find a correlation between
: F( Z& d7 U2 r: P( i! T6 w# Achildhood testosterone exposure and reduced adult
8 C1 @ e) b2 ]) U0 epenile length in clinical studies.0 [* `9 f8 I2 T
Nonetheless, we do not believe our patient is- y- @2 `8 G, u3 R
going to experience any of the untoward effects from5 u. M0 _, s7 T
testosterone exposure as mentioned earlier because" G, [( q6 i# F/ f
the exposure was not for a prolonged period of time.! ^2 i4 U+ a9 W+ o
Although the bone age was advanced at the time of
$ q2 n" G* G* W* Ydiagnosis, the child had a normal growth velocity at" [2 P# a7 V; L, r2 b1 }/ R7 G
the follow-up visit. It is hoped that his final adult
8 ]. j6 ~3 H: B7 C- q7 p+ Sheight will not be affected. g+ {* Z6 W0 R
Although rarely reported, the widespread avail-
6 @9 ^- s! P" X$ b& W# f' Xability of androgen products in our society may* p9 f/ p: e& `1 |" ^- _
indeed cause more virilization in male or female
& _- K( {- Z0 O( {1 qchildren than one would realize. Exposure to andro-
% N! S" S) ?( Q! Z- \8 hgen products must be considered and specific ques-8 @" A# t# L9 l$ [5 _
tioning about the use of a testosterone product or
" }% [4 l3 X% [7 Mgel should be asked of the family members during" H7 E0 ]3 e' K5 x! g8 q
the evaluation of any children who present with vir-- r2 u" U0 G! h( J- Y/ E3 K" q
ilization or peripheral precocious puberty. The diag-* Z( E; a+ U4 E9 Y H( v6 B
nosis can be established by just a few tests and by2 H; w- @: L( V$ R0 Y
appropriate history. The inability to obtain such a" E; g M' S8 H2 b. I* o$ V' K
history, or failure to ask the specific questions, may
/ }4 T8 B1 Y: O; |& R! ?6 \result in extensive, unnecessary, and expensive
3 G) G8 A6 k7 a" n5 j) I Dinvestigation. The primary care physician should be$ p' L" |/ ~, S O* y l' j+ F; z. r
aware of this fact, because most of these children
& f7 t' A+ s. P- Kmay initially present in their practice. The Physicians’
, T7 d$ C8 W$ k3 Z" J. z" ADesk Reference and package insert should also put a$ l7 U2 g; X6 C, [/ |* b
warning about the virilizing effect on a male or7 A( X0 j7 Z) O3 x9 f! g
female child who might come in contact with some-% L4 _+ A: x- C: B( W1 l" T3 O2 x3 d
one using any of these products.
2 r; c+ @$ }" u8 @References1 s" ?* R/ b' L4 H/ Q5 [
1. Styne DM. The testes: disorder of sexual differentiation8 I8 \# t: S6 }3 l6 y
and puberty in the male. In: Sperling MA, ed. Pediatric
) o! x& [! n, NEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
- L% u( z2 [7 ~0 D; `% y2002: 565-628.+ g3 g! X# `) G; ?+ e2 J
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious' b- u! e' d1 v+ P- [
puberty in children with tumours of the suprasellar pineal |
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