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Sexual Precocity in a 16-Month-Old
, m: [% x4 J" C0 v1 e0 PBoy Induced by Indirect Topical
% ^" X1 R. u) y8 eExposure to Testosterone
' [( R2 a/ L: O; y2 I! E, m; FSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,29 t7 Q+ D p5 h4 _8 V% V* d f
and Kenneth R. Rettig, MD1
9 D6 Z5 Q$ L/ d- JClinical Pediatrics
1 {2 C* ]! ^9 C5 ?# o$ A% z; wVolume 46 Number 6
' M* m1 x& D3 @% `July 2007 540-5432 ~+ t, |! v. K0 [
© 2007 Sage Publications5 a7 a5 j; m: u- E
10.1177/00099228062966518 a- X. e$ [7 s* H' W8 z
http://clp.sagepub.com
( {* A3 l$ s; r% l/ y, C7 qhosted at
' Q" D: `3 S3 v" R1 q" K; V8 vhttp://online.sagepub.com
+ {) n# ]' f9 w5 {1 S6 xPrecocious puberty in boys, central or peripheral,
& S" J% z6 Z* v; W8 H2 ?/ V6 G) z+ bis a significant concern for physicians. Central
$ E- q4 K0 ^0 c5 dprecocious puberty (CPP), which is mediated, f" ]9 s h4 p( x+ H! Z
through the hypothalamic pituitary gonadal axis, has/ e' a4 R( [& L6 P
a higher incidence of organic central nervous system5 T4 C" }* h/ A- a/ l
lesions in boys.1,2 Virilization in boys, as manifested) z- s2 m6 H( b( R. _
by enlargement of the penis, development of pubic
- e% G2 j/ i7 Dhair, and facial acne without enlargement of testi-
! C/ O6 Z- H( Icles, suggests peripheral or pseudopuberty.1-3 We
# ]7 \' |$ L |. breport a 16-month-old boy who presented with the
$ `! e, W# U" [ benlargement of the phallus and pubic hair develop-+ p+ k* F9 Q/ [5 `
ment without testicular enlargement, which was due
- e9 j5 X/ O/ I( J2 Qto the unintentional exposure to androgen gel used by4 f" W' U& J3 f
the father. The family initially concealed this infor-. D& M' c3 w% @4 C* r2 l
mation, resulting in an extensive work-up for this
+ p3 J& m6 [9 V# Rchild. Given the widespread and easy availability of5 F9 W6 F2 n* `1 F& S6 a
testosterone gel and cream, we believe this is proba-
& G" x6 \+ Y0 ` \# Q2 H4 Xbly more common than the rare case report in the
9 X! h4 ~. Y% Hliterature.4. ]3 L8 x3 w& ]1 s3 ?% x, A( G) q
Patient Report
# l Q3 v, R' V9 p {A 16-month-old white child was referred to the7 q/ A* `3 V, ]( e5 _5 P3 z
endocrine clinic by his pediatrician with the concern
7 Q1 V8 ^' K1 @% m( }; [of early sexual development. His mother noticed% U1 U! _0 F+ m7 _0 x3 ?
light colored pubic hair development when he was7 _ i( l" l; a6 U
From the 1Division of Pediatric Endocrinology, 2University of
8 W1 Z, B; U' E3 T5 ASouth Alabama Medical Center, Mobile, Alabama.
' Y9 i \& e9 Z; W$ l" Y6 j" eAddress correspondence to: Samar K. Bhowmick, MD, FACE,
. B" [ T7 n% f( JProfessor of Pediatrics, University of South Alabama, College of( E' {8 d# j& R& j+ j* R- ~
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;& Z: z. K \$ L+ @/ [
e-mail: [email protected].
# A6 Q4 B0 K( @/ r, z9 Kabout 6 to 7 months old, which progressively became7 ]" r3 n( R' _4 z- y& J
darker. She was also concerned about the enlarge-
- `* Y- p0 Y& P0 @ment of his penis and frequent erections. The child
5 T u% j/ ^! q4 g; Gwas the product of a full-term normal delivery, with1 _* [. X8 @" v/ A* R
a birth weight of 7 lb 14 oz, and birth length of
) t6 i& ~; F* y _3 v2 |5 d' e7 M8 R20 inches. He was breast-fed throughout the first year* U4 a2 B' @ d8 w- p
of life and was still receiving breast milk along with
) f) E3 i& M& z U! q0 g Csolid food. He had no hospitalizations or surgery,
# o% O# i1 e+ I- S6 [. cand his psychosocial and psychomotor development/ v2 M: W- e; |* ?7 X$ F- u" ]
was age appropriate.- \0 e3 r G0 U; P& D7 z
The family history was remarkable for the father,( F8 N/ O( N0 k6 @+ g5 z0 [& N
who was diagnosed with hypothyroidism at age 16,
# g$ m5 m9 B+ w1 @6 F) fwhich was treated with thyroxine. The father’s
1 I; I( o$ d% Y1 }height was 6 feet, and he went through a somewhat# ?+ u1 s* k1 S8 t
early puberty and had stopped growing by age 14., J' U8 n6 G' o7 Y" R% E0 f- ~ Z* W
The father denied taking any other medication. The; E: [& o3 k! m- W$ c m( l
child’s mother was in good health. Her menarche4 s3 a/ j$ V) W
was at 11 years of age, and her height was at 5 feet2 Y1 o1 q M/ Q* d
5 inches. There was no other family history of pre-& n# _" J1 v% v4 d* \) X y
cocious sexual development in the first-degree rela-
* g. z# K" [0 j8 r4 `7 ^1 E1 M$ F" `9 Utives. There were no siblings.
# Q7 {4 F1 z" nPhysical Examination
: i/ U3 n- F& u! P% mThe physical examination revealed a very active,1 j9 e; Y6 n0 R& l; i* V
playful, and healthy boy. The vital signs documented4 s8 Y4 I4 o5 m+ q' L4 X
a blood pressure of 85/50 mm Hg, his length was3 }6 i- c# l; X/ p8 U% S1 e+ T( d
90 cm (>97th percentile), and his weight was 14.4 kg: w9 E- j) j2 i3 b' ^2 b C9 d
(also >97th percentile). The observed yearly growth
% a2 X% H( X6 B( `velocity was 30 cm (12 inches). The examination of
0 D8 U% H( L1 G& R* ^the neck revealed no thyroid enlargement.& n5 z# r6 g7 {! ~! K
The genitourinary examination was remarkable for, `+ v1 K( g; Z, e# M6 M5 s7 Q
enlargement of the penis, with a stretched length of- q/ ~$ J/ [+ F3 m7 @* o
8 cm and a width of 2 cm. The glans penis was very well$ |% F1 b7 L$ [& d, @
developed. The pubic hair was Tanner II, mostly around
& Y% e7 B* u7 w. Q# B# |; {540/ U; E6 l$ a; b* X6 G7 J2 ~% v
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
* s: _* _6 u& o& fthe base of the phallus and was dark and curled. The7 J) ~5 F" a) ?: O
testicular volume was prepubertal at 2 mL each.) W- m& A1 G. {
The skin was moist and smooth and somewhat
) u& N* T4 q" ^- X- M. ?oily. No axillary hair was noted. There were no
. ^" G% D# b2 U6 O7 ]abnormal skin pigmentations or café-au-lait spots.
) U0 \; [+ Y% |2 N2 z0 _/ QNeurologic evaluation showed deep tendon reflex 2+, v. `6 c* v" V+ ?
bilateral and symmetrical. There was no suggestion
/ P- [9 P) V$ W$ K B; O6 v4 u5 O6 jof papilledema.
( U/ i8 ^+ `4 h' x( `% f0 i' qLaboratory Evaluation2 d2 I9 }8 V6 a
The bone age was consistent with 28 months by
$ p" G m4 Y4 I. W' J+ N; ousing the standard of Greulich and Pyle at a chrono-
& u( ^3 }1 o, [logic age of 16 months (advanced).5 Chromosomal
7 d. Y+ _$ B2 V/ Ekaryotype was 46XY. The thyroid function test
$ L+ |& D9 v% d s8 [. [) Mshowed a free T4 of 1.69 ng/dL, and thyroid stimu-, P+ L$ w4 j1 [$ `2 h
lating hormone level was 1.3 µIU/mL (both normal).
9 m: a& a8 u. B+ K. ^The concentrations of serum electrolytes, blood0 U# H$ O" v, @3 E
urea nitrogen, creatinine, and calcium all were
1 E) J/ @- P+ T& S% F; r+ ]/ ywithin normal range for his age. The concentration
. a+ y' C- M: E4 iof serum 17-hydroxyprogesterone was 16 ng/dL
0 a. Y6 z7 B( z6 a+ b(normal, 3 to 90 ng/dL), androstenedione was 20
# Z) Q+ z9 u+ T! F0 x# ^ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
6 @8 K! {( a3 [terone was 38 ng/dL (normal, 50 to 760 ng/dL),2 p1 l8 e1 A# K4 h( [
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
7 {. u7 N t7 Q5 V49ng/dL), 11-desoxycortisol (specific compound S) j4 b, O, b$ k8 \6 D1 u
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
/ ? |2 ^9 q. Q; g2 ptisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total# J3 S' k- G0 ?, k# z- |
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
+ \$ j6 x9 D$ @# K/ | K& c# R2 W A) U# D/ dand β-human chorionic gonadotropin was less than
+ Z$ u4 ]6 M4 a1 y- H5 mIU/mL (normal <5 mIU/mL). Serum follicular1 V% J# G* |' I
stimulating hormone and leuteinizing hormone
9 W; a& j9 ]/ L# u1 m! X5 x. }6 ]concentrations were less than 0.05 mIU/mL; x6 ^3 s9 J/ }8 _
(prepubertal).
' Y) I7 Z4 D$ ` | ?, cThe parents were notified about the laboratory
7 M9 ], R5 P7 j1 \1 b- L* yresults and were informed that all of the tests were
, a/ d h2 y3 N1 U+ o9 w6 C: |normal except the testosterone level was high. The; d" j0 M l# }- ?3 f0 W! o' c
follow-up visit was arranged within a few weeks to
" W6 Z- v* W4 v) ?2 J' gobtain testicular and abdominal sonograms; how-* r+ [' o5 Q0 Z. [ y `' X
ever, the family did not return for 4 months.
8 T Y5 f' A6 F( lPhysical examination at this time revealed that the
: Z r' ~, d; Rchild had grown 2.5 cm in 4 months and had gained
9 C9 y! N8 c) x) v2 kg of weight. Physical examination remained7 r, Y- R9 o! ~( X) U7 Y" n
unchanged. Surprisingly, the pubic hair almost com-$ C8 ~# S2 q+ f1 X3 L8 r' q c
pletely disappeared except for a few vellous hairs at
! \2 ^+ v% k' B1 G( R: o/ N2 q( othe base of the phallus. Testicular volume was still 2# z3 j1 Y7 X/ O" ^
mL, and the size of the penis remained unchanged.
$ U, X" n1 N R+ C9 U4 W6 V3 lThe mother also said that the boy was no longer hav-
- g/ w7 Y% Q$ ving frequent erections.0 E9 ]& W* S: s8 z/ x% a$ z; ~" j( O
Both parents were again questioned about use of) b9 l8 C/ K9 k% g+ H4 j
any ointment/creams that they may have applied to
! }$ ?: n; @9 p1 n- l2 Jthe child’s skin. This time the father admitted the& ~' G: Q5 w6 O; Z& m2 x) R3 F
Topical Testosterone Exposure / Bhowmick et al 541" q) D- z* _( ]$ B6 x) l2 ~, P" i0 s
use of testosterone gel twice daily that he was apply-# g, [& d" E6 B* u, j. U. x' _
ing over his own shoulders, chest, and back area for
1 R4 H$ l- }( Q2 J5 h% ~a year. The father also revealed he was embarrassed% I' B9 t l4 S3 ?
to disclose that he was using a testosterone gel pre-
5 H- N) {; ^, |9 U. x/ T5 oscribed by his family physician for decreased libido
& G" q! D9 \5 i9 A d: Q3 [secondary to depression.# H( s0 J# ?8 S1 L) n' v
The child slept in the same bed with parents. R- E* B+ d/ T# v3 N( X2 U
The father would hug the baby and hold him on his8 R- A E- W$ r, E/ a: A
chest for a considerable period of time, causing sig-1 t3 O' u, A$ G9 E' @4 S7 N
nificant bare skin contact between baby and father.0 a6 h" x B4 A5 O, ~2 i7 s1 Q
The father also admitted that after the phone call,( H( |: k# O2 J- x3 |
when he learned the testosterone level in the baby! |" L3 ]2 C, N p
was high, he then read the product information
6 ~) b* y+ M/ g& m. Cpacket and concluded that it was most likely the rea-
, M5 ] X% g$ g; wson for the child’s virilization. At that time, they" T+ R& P7 A2 W) k# N! b' W
decided to put the baby in a separate bed, and the
/ X8 M% E$ t4 Z% j, qfather was not hugging him with bare skin and had
@ w- }- N8 k% ]% u" fbeen using protective clothing. A repeat testosterone
# u/ F- i" J7 W1 C/ Xtest was ordered, but the family did not go to the, j) n9 k& D0 G0 Q5 H. s$ g' t
laboratory to obtain the test.
2 Q2 m! _, J* kDiscussion
8 K0 o" \( x$ ^( P" PPrecocious puberty in boys is defined as secondary
+ {1 u ^! s1 Wsexual development before 9 years of age.1,43 p2 D9 _- E+ M" W7 x
Precocious puberty is termed as central (true) when* O O. a% R) c. q. t9 i) ]6 h. s" ^6 K
it is caused by the premature activation of hypo-8 B5 K- @" S. N; b
thalamic pituitary gonadal axis. CPP is more com-
* R5 [( g7 y, e& S( R' hmon in girls than in boys.1,3 Most boys with CPP4 D0 W- |3 \ x% u
may have a central nervous system lesion that is
, O8 m' p& ~$ q ^2 Jresponsible for the early activation of the hypothal-- b5 Q+ A0 G5 ]4 E" ^" x
amic pituitary gonadal axis.1-3 Thus, greater empha-
& g+ c( h) b7 x4 K T% {sis has been given to neuroradiologic imaging in6 Y% K8 [; A/ k$ ]
boys with precocious puberty. In addition to viril-
( Y+ o. e) Q' Bization, the clinical hallmark of CPP is the symmet-$ w9 y" m0 A; \7 C
rical testicular growth secondary to stimulation by" U( y" i* L. z
gonadotropins.1,3; |6 V% S) G: y9 _8 k5 b7 D
Gonadotropin-independent peripheral preco-* M2 [0 ^8 P% m9 P' S( V
cious puberty in boys also results from inappropriate
3 m7 i$ f( T2 Bandrogenic stimulation from either endogenous or
; Y, G9 J6 H7 {8 W6 U4 uexogenous sources, nonpituitary gonadotropin stim-
/ j4 t/ F1 V- e Z Y; c& E- lulation, and rare activating mutations.3 Virilizing
4 c( S: F. @- |% N0 I5 o I+ _+ ~congenital adrenal hyperplasia producing excessive
& Q& T' P8 ~3 V: yadrenal androgens is a common cause of precocious1 G) r3 {$ n( N8 u
puberty in boys.3,46 Z3 R0 l, z$ N4 y. }% o9 L( Y# a
The most common form of congenital adrenal
' }8 Q# F: g" Y. I% k4 Shyperplasia is the 21-hydroxylase enzyme deficiency.* _! F8 _' R3 P0 M1 a+ }
The 11-β hydroxylase deficiency may also result in; h' H/ y' v/ p" V
excessive adrenal androgen production, and rarely,9 n2 D, L5 ]1 R
an adrenal tumor may also cause adrenal androgen; V) o0 x9 a$ y A
excess.1,3
9 Z9 w' L" u0 [! Y0 q! j9 u' v$ g% |% Fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from2 t: R0 ?$ Q. e% I R$ Z3 k
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
0 p( z. F) k1 ~1 Z" @* v# OA unique entity of male-limited gonadotropin-3 T7 U; @1 p+ a, x9 w m
independent precocious puberty, which is also known
. a6 \1 D% _! K9 U& Qas testotoxicosis, may cause precocious puberty at a
U' o5 j5 d' ]! Tvery young age. The physical findings in these boys9 ^( \' c. o& u$ K) B$ B
with this disorder are full pubertal development,. B' g. s; t! u' p9 @9 ]* N& T
including bilateral testicular growth, similar to boys3 m E x$ T5 M, u& w" T
with CPP. The gonadotropin levels in this disorder4 f% E& V$ L% J7 _" _8 H0 J
are suppressed to prepubertal levels and do not show6 `0 Z$ }2 a$ E4 |( f1 g' o7 F3 r
pubertal response of gonadotropin after gonadotropin-( l3 ^: y! M H x5 p
releasing hormone stimulation. This is a sex-linked1 M- q7 B( [- F! t" t+ U4 i) X. O
autosomal dominant disorder that affects only
* B7 d$ X* i5 kmales; therefore, other male members of the family( l: E$ J' E2 i7 B# Z
may have similar precocious puberty.36 \! K9 D, q$ {& _: Q
In our patient, physical examination was incon-
0 ^# E; W* B6 K7 Y+ U/ l$ Jsistent with true precocious puberty since his testi-
2 T+ V8 {0 S J, I Fcles were prepubertal in size. However, testotoxicosis3 C' [6 j; {( h5 B
was in the differential diagnosis because his father
$ i {( _& _$ _9 Gstarted puberty somewhat early, and occasionally,
* w7 X, a9 v1 y) p* g/ Ktesticular enlargement is not that evident in the+ p* f1 r3 O: Y
beginning of this process.1 In the absence of a neg-1 {9 E7 J1 h, N. w6 a
ative initial history of androgen exposure, our
5 N) K; x" r+ G- Lbiggest concern was virilizing adrenal hyperplasia,* [. c+ m/ i4 P- a- t: B( z5 [ Y5 F
either 21-hydroxylase deficiency or 11-β hydroxylase' V$ }. p# r# Y. ]+ G* v
deficiency. Those diagnoses were excluded by find-9 ?/ @5 U1 n- O% H/ @8 _$ ~
ing the normal level of adrenal steroids.
: U7 J7 n& u. _3 ?3 _8 nThe diagnosis of exogenous androgens was strongly( x8 n1 f( V' f' T+ u
suspected in a follow-up visit after 4 months because
+ h7 F' {7 A0 b! [3 d/ }the physical examination revealed the complete disap-. _2 ^. u2 q6 j. k7 {4 w
pearance of pubic hair, normal growth velocity, and/ q# K( a- J: v
decreased erections. The father admitted using a testos-
5 D$ m1 t C1 K& h$ {1 jterone gel, which he concealed at first visit. He was$ q' x1 h$ f" t6 E4 o- m3 l
using it rather frequently, twice a day. The Physicians’# |# t. K& F+ A3 q8 g+ r
Desk Reference, or package insert of this product, gel or
6 m6 T( z& C( _9 ?% n1 Fcream, cautions about dermal testosterone transfer to
4 ]& f4 l5 b, g% B! ^6 Lunprotected females through direct skin exposure." N U: @; D" A2 L* g
Serum testosterone level was found to be 2 times the; e6 ]' r9 f0 q4 o: `* A9 e6 `
baseline value in those females who were exposed to t' S# v4 w) a4 n+ \
even 15 minutes of direct skin contact with their male+ _5 |5 K+ C+ I* n& Z7 u
partners.6 However, when a shirt covered the applica-% h2 ~4 R9 K4 ^+ g8 G
tion site, this testosterone transfer was prevented.' G( L7 X8 n; o1 {, P( |
Our patient’s testosterone level was 60 ng/mL,+ y; g! S7 [8 U U
which was clearly high. Some studies suggest that1 V2 x( O6 S! ^ ]$ I% u) ~
dermal conversion of testosterone to dihydrotestos-: x( s$ O; ]8 I! i/ A) r5 Q
terone, which is a more potent metabolite, is more
8 o& q0 N8 L. Vactive in young children exposed to testosterone
1 c* Z& A; C3 N4 Rexogenously7; however, we did not measure a dihy-0 T+ A4 s4 q7 {8 \9 t
drotestosterone level in our patient. In addition to
+ W# M% f8 N1 vvirilization, exposure to exogenous testosterone in
; U/ U U! }1 R. p! G q+ z) i7 b2 qchildren results in an increase in growth velocity and4 ~' \. Z0 ~# F5 y6 [, h5 u7 R
advanced bone age, as seen in our patient.4 T f8 M$ \! v6 T$ Z3 P# I
The long-term effect of androgen exposure during
) z" {0 H( R1 C' {8 qearly childhood on pubertal development and final7 e0 S5 W3 o8 k4 [3 H' O) K
adult height are not fully known and always remain
S1 Z" o8 d- ~a concern. Children treated with short-term testos-
: M# U0 m" P, |- E9 Y& sterone injection or topical androgen may exhibit some+ H% v( J. ` r4 S) g5 E, O2 G8 k
acceleration of the skeletal maturation; however, after9 J; G9 Q1 M# z2 K1 T
cessation of treatment, the rate of bone maturation L- `4 \* c) J; c0 n
decelerates and gradually returns to normal.8,9
" W' C( e. S& t9 a4 tThere are conflicting reports and controversy
6 f* E, K, f: ]- E9 rover the effect of early androgen exposure on adult# j- }& ?" a( z+ N: j
penile length.10,11 Some reports suggest subnormal
5 R5 r! ?. p) @8 g3 N3 h3 Q; `- _adult penile length, apparently because of downreg-
9 z; c1 N( X+ h. p5 f: z) Pulation of androgen receptor number.10,12 However,9 u' d) @9 i- x& g2 Y: d5 f
Sutherland et al13 did not find a correlation between
; p" Q% `4 q/ ~$ O6 {childhood testosterone exposure and reduced adult+ P3 R! B G7 t+ a9 p, U9 v6 C
penile length in clinical studies.
H% g T2 L& N3 ?0 B, eNonetheless, we do not believe our patient is( r0 j! O3 B; H/ g
going to experience any of the untoward effects from
; r, K. T; H8 M6 J3 ?testosterone exposure as mentioned earlier because
8 y. w3 G+ c) u9 {: Vthe exposure was not for a prolonged period of time.1 |- ?/ q+ ]. B8 T$ n K. ^( m7 m& k$ M
Although the bone age was advanced at the time of
# S, X" y- q0 U$ rdiagnosis, the child had a normal growth velocity at) T! H4 ?/ X* S( ]8 x
the follow-up visit. It is hoped that his final adult2 t- t0 l' q0 n' p" ]! Q
height will not be affected.; }2 `5 f+ N. B Z8 x) x y
Although rarely reported, the widespread avail-/ |, ^! J# p' _; a$ @& k
ability of androgen products in our society may
b8 F/ A$ V8 i; Hindeed cause more virilization in male or female
( O3 g p% s" P4 K$ ~5 s9 F0 Achildren than one would realize. Exposure to andro-) e4 T( T8 k3 b k* z5 x; _
gen products must be considered and specific ques-7 d. Q4 A) e2 K& i: y4 q
tioning about the use of a testosterone product or* \# n' p) ?. T
gel should be asked of the family members during
2 U( |3 U' J+ Cthe evaluation of any children who present with vir-% e: g' @) R* z4 ?+ H( {+ F/ a
ilization or peripheral precocious puberty. The diag-+ o$ _5 @* w8 S* I0 K4 A
nosis can be established by just a few tests and by
3 F2 r, k% x% {% I! ~8 r) eappropriate history. The inability to obtain such a
( O* q6 f* m9 l0 u' V( y0 Thistory, or failure to ask the specific questions, may, q$ n) R! o% M$ y
result in extensive, unnecessary, and expensive; x/ Y, Z+ W6 E F, w7 r
investigation. The primary care physician should be/ v; r( M! { H6 Y
aware of this fact, because most of these children
8 _+ l$ Z# I" @( V7 }* ymay initially present in their practice. The Physicians’" G* C0 Y5 ~0 @% m# g6 M- M
Desk Reference and package insert should also put a- }4 h3 S& s" H3 i
warning about the virilizing effect on a male or; ?6 C6 t/ G' {8 d+ X2 h V ~% z( P
female child who might come in contact with some-8 A) u: \5 ~' u& q* |4 X( x
one using any of these products.8 k& E& [) _6 T
References
! k8 \* j6 H4 Z7 b& d) S! M8 ?1. Styne DM. The testes: disorder of sexual differentiation
5 i4 w, Y* T, Q! X8 R% Hand puberty in the male. In: Sperling MA, ed. Pediatric
" ]% j) d' k. E, T% Y9 {' c& t& F! h, mEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
3 L( _, q. g) I- B7 z0 l/ J2002: 565-628./ V2 D0 q* w j, {( _% b/ A
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
! R5 v% ?8 e5 t+ i0 y/ }5 dpuberty in children with tumours of the suprasellar pineal |
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