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Sexual Precocity in a 16-Month-Old
+ s- n. K; s9 @. F2 r2 nBoy Induced by Indirect Topical
4 L+ e+ V N( F& @% rExposure to Testosterone0 o# M) R2 g8 H! Y, d( d
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
2 D- w9 `3 |3 r' G% _5 zand Kenneth R. Rettig, MD1. I5 I0 w( j* a$ r& n( |
Clinical Pediatrics
' T; I: S* f. v" V! P$ o JVolume 46 Number 62 C# P/ O3 L, c! v9 ]* l6 S
July 2007 540-5439 X" e( o% `0 ~. f
© 2007 Sage Publications! x- F5 w$ i' I
10.1177/0009922806296651# p& G9 }4 z5 v1 X5 T4 b
http://clp.sagepub.com
, k2 d; L% k) ~9 E" bhosted at1 ]5 I% P' \5 |- M8 z; G+ \
http://online.sagepub.com
! h, \( K8 g. V# u8 F/ n0 vPrecocious puberty in boys, central or peripheral,4 V* R+ k# F/ E! w5 U0 v: r
is a significant concern for physicians. Central
' h4 r' G) K, G& ~precocious puberty (CPP), which is mediated& ^% f! C, I& ~, [$ ^! q
through the hypothalamic pituitary gonadal axis, has+ Y, M$ k9 E* s! o7 O _1 C$ _
a higher incidence of organic central nervous system! J! R6 o9 J5 V1 \/ e
lesions in boys.1,2 Virilization in boys, as manifested1 d: [) ?( Q& g* y2 D: Q% P
by enlargement of the penis, development of pubic
6 c6 P* c; s% vhair, and facial acne without enlargement of testi-
7 |" K& N; x' i, L7 b2 tcles, suggests peripheral or pseudopuberty.1-3 We
; ]" @9 _# Q' X1 X ^, o) mreport a 16-month-old boy who presented with the9 T1 ^- n0 B/ ~! Z
enlargement of the phallus and pubic hair develop-5 R" `5 P# P; _; q% d
ment without testicular enlargement, which was due
% p d- ]! Q* f8 @! T& i* tto the unintentional exposure to androgen gel used by
; ~1 I/ I. m9 [ Ythe father. The family initially concealed this infor-
6 J! S! i( o& Q/ `9 f" Bmation, resulting in an extensive work-up for this8 I! V, u' Y' V- q
child. Given the widespread and easy availability of4 c! e: J5 |: B# \! v4 U
testosterone gel and cream, we believe this is proba-1 o+ _% ], b9 @' Z% `) O/ L6 `
bly more common than the rare case report in the
) C( [, Q4 K: O) u4 g0 X* [literature.4- |0 O; O7 Y% V( ^
Patient Report! x }( ?9 I4 O+ P3 C; T
A 16-month-old white child was referred to the E* J. |; A$ M! H# L: t+ a
endocrine clinic by his pediatrician with the concern9 l# N- N& T9 Q! a% i
of early sexual development. His mother noticed
+ Z( B, ?7 u: K8 [7 m2 Klight colored pubic hair development when he was
, ^: d4 L+ c/ X3 m! nFrom the 1Division of Pediatric Endocrinology, 2University of
* \7 u0 P1 y# ^3 k/ I& c$ p4 D( sSouth Alabama Medical Center, Mobile, Alabama.
M- y/ Z, i; mAddress correspondence to: Samar K. Bhowmick, MD, FACE,. r% i2 \+ [) I6 [ ?
Professor of Pediatrics, University of South Alabama, College of3 H9 x' G! y* k5 \, f4 t7 |% ~
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;9 T) i. d( Z6 Z/ b) W- f* T
e-mail: [email protected].* K: {! k/ Z7 b
about 6 to 7 months old, which progressively became
1 \4 C; Q T% jdarker. She was also concerned about the enlarge-8 F! s) ?) w8 x$ O Y7 A, l# ]) n# j
ment of his penis and frequent erections. The child) l0 L3 b# q2 r' k: f0 M' h. W, i! w
was the product of a full-term normal delivery, with, \% G% O* x5 w8 y( q" H: P. O
a birth weight of 7 lb 14 oz, and birth length of
9 ?* Y1 F. b0 a. `0 c. q& D20 inches. He was breast-fed throughout the first year
) d* |+ C* T- C/ v3 U( iof life and was still receiving breast milk along with0 x' h X3 j1 k
solid food. He had no hospitalizations or surgery,
3 W7 A/ j9 i* X0 N4 }6 Y& S% Zand his psychosocial and psychomotor development
. c$ E9 n4 R X/ D8 C7 b, r4 ]7 zwas age appropriate.. W5 p; a* W. f% U6 G
The family history was remarkable for the father,
, u, n4 E; N$ Mwho was diagnosed with hypothyroidism at age 16,
0 t6 m8 K( `4 n, Owhich was treated with thyroxine. The father’s
/ G) p6 b% K/ ?height was 6 feet, and he went through a somewhat
' N' H2 Q+ r* a; C! gearly puberty and had stopped growing by age 14.
- X" L3 S! O l+ rThe father denied taking any other medication. The
6 ]2 b" s# ^) t+ T& ichild’s mother was in good health. Her menarche0 }7 O0 p0 X/ B, r4 J# j- @% i ^; Y
was at 11 years of age, and her height was at 5 feet3 B) _1 p; u6 P7 |3 x4 x2 R
5 inches. There was no other family history of pre-
+ I5 W, |& C/ p7 w! ]: @9 }& wcocious sexual development in the first-degree rela-2 [% M! Y7 n" h4 ?: ~0 b3 k
tives. There were no siblings.
7 H6 N" Q/ W1 |5 N2 \ ]Physical Examination
- v) g4 ~4 K- V, D/ m( \The physical examination revealed a very active,
% H7 w2 E$ `7 ?4 Aplayful, and healthy boy. The vital signs documented
" d' x# r: A: ja blood pressure of 85/50 mm Hg, his length was k. N& B0 Y. c" z0 U$ ~8 F
90 cm (>97th percentile), and his weight was 14.4 kg# S' R" C0 v6 C6 J l4 u
(also >97th percentile). The observed yearly growth
- W! [, u! t6 W2 @0 _, Y0 ~velocity was 30 cm (12 inches). The examination of
9 z+ d) R5 C J& n6 q/ h1 t( h, p5 Vthe neck revealed no thyroid enlargement.
5 ^: M, g, D- O2 K; y$ ^The genitourinary examination was remarkable for+ H) h4 K" h) P7 Z
enlargement of the penis, with a stretched length of8 ?3 ]9 r7 f( A( o: J+ {$ i
8 cm and a width of 2 cm. The glans penis was very well% @5 h: {. I8 ^2 K8 q# {9 t7 ?
developed. The pubic hair was Tanner II, mostly around
4 ~! ?! m' s4 i# C' Y& N& ^) Y0 A% O! w5405 |2 O+ M& I' f4 X& A6 w' B
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from% d+ ]: ?7 X1 w* }8 g5 h
the base of the phallus and was dark and curled. The
: u& b# E$ Y) w9 Q* K$ ]8 ~( ?testicular volume was prepubertal at 2 mL each.
# m$ n$ v* {5 A* IThe skin was moist and smooth and somewhat3 ~. |$ t. B& e; C
oily. No axillary hair was noted. There were no( Y/ V+ Q: p3 d& t# s, X
abnormal skin pigmentations or café-au-lait spots.
4 s0 N* |8 I$ k9 r3 m. |; VNeurologic evaluation showed deep tendon reflex 2+
, S: R) P _2 M3 r6 o- p# |0 d* Obilateral and symmetrical. There was no suggestion8 y& |! \& U: e4 v* Y, H$ F) \+ O
of papilledema.
- k( S" n2 T; F8 r5 R4 @/ |Laboratory Evaluation( ]0 P# w- t9 A
The bone age was consistent with 28 months by
; J" N7 J y& C0 Pusing the standard of Greulich and Pyle at a chrono-
/ u' s; r# E% Q! Blogic age of 16 months (advanced).5 Chromosomal
6 T1 i$ G$ T9 B+ O( \2 r" j$ pkaryotype was 46XY. The thyroid function test- w! e k; Y* |7 P1 S( L; m
showed a free T4 of 1.69 ng/dL, and thyroid stimu-2 T: U+ G2 q: s+ _
lating hormone level was 1.3 µIU/mL (both normal).2 T5 I- v1 D/ Y
The concentrations of serum electrolytes, blood
. c3 w4 G1 J9 |. a# O7 e# l" Uurea nitrogen, creatinine, and calcium all were
$ Y! h8 |) l0 C! R7 z5 _within normal range for his age. The concentration
% W1 x" Y* m8 V/ Z+ tof serum 17-hydroxyprogesterone was 16 ng/dL
" Z$ a( S2 o1 ]2 x L2 n(normal, 3 to 90 ng/dL), androstenedione was 20( _. V# G4 O) e' S
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
: E% r0 l+ x1 u- i, zterone was 38 ng/dL (normal, 50 to 760 ng/dL),
) F1 o+ u& S; @% j; ^ T7 W6 s% z0 o1 C. udesoxycorticosterone was 4.3 ng/dL (normal, 7 to/ O# _2 X9 i0 ?+ X0 M$ w
49ng/dL), 11-desoxycortisol (specific compound S)( n4 [" |0 M T* c3 {
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
9 N* S, }& Y3 { b" M& Dtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total1 D" Y% h1 _* q5 R
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),! J# ^: J; X: z' S" B- g2 s) w/ W, H
and β-human chorionic gonadotropin was less than
4 _. i" f. b$ J# Y! W5 mIU/mL (normal <5 mIU/mL). Serum follicular$ N0 Q, |3 w, k1 f0 [1 q% Z# b
stimulating hormone and leuteinizing hormone* y) ^! z3 }) R$ C9 i
concentrations were less than 0.05 mIU/mL
% @6 w/ d6 u9 z3 v(prepubertal).) X& t) M, A/ H2 S- B; O0 z
The parents were notified about the laboratory
! K5 ?. [! Z9 Aresults and were informed that all of the tests were
% j7 X7 s2 b/ G4 G+ n0 Mnormal except the testosterone level was high. The/ l( P5 z' A! U" |
follow-up visit was arranged within a few weeks to8 p$ b+ F. |* v! t, e2 \
obtain testicular and abdominal sonograms; how-$ @7 I' z; i. v' \' `4 y
ever, the family did not return for 4 months.- m- {, S& q) `0 D, \8 u7 l, O- b) h
Physical examination at this time revealed that the8 b( T# u+ y3 h* t9 I1 x: l
child had grown 2.5 cm in 4 months and had gained1 S. Z8 S4 J/ F* h$ q q
2 kg of weight. Physical examination remained
# x3 T. p- Q, o# funchanged. Surprisingly, the pubic hair almost com-$ H' U. {0 m" t6 w
pletely disappeared except for a few vellous hairs at w6 S) l3 Z0 W! r# w
the base of the phallus. Testicular volume was still 2
6 H/ ?& A7 _: J* W+ c+ EmL, and the size of the penis remained unchanged.% g# O8 L* P6 L# O
The mother also said that the boy was no longer hav-) w% K$ `0 I O
ing frequent erections.
* Y9 i0 w0 n8 s/ u' j- D: _Both parents were again questioned about use of
2 X/ h6 s* i( ~# n' s5 ?: Pany ointment/creams that they may have applied to, d# i5 j2 i1 n5 V$ `* S9 ^
the child’s skin. This time the father admitted the' B: K0 F- v ^- H6 p
Topical Testosterone Exposure / Bhowmick et al 541
' @. }; Q4 G3 a# s$ buse of testosterone gel twice daily that he was apply-4 C( T6 ?) l: [6 r2 x+ x, b. @
ing over his own shoulders, chest, and back area for$ ^7 u e; t" c3 Z
a year. The father also revealed he was embarrassed+ }' S; m7 ]$ K( X3 M5 I
to disclose that he was using a testosterone gel pre-: B. s7 V( e7 L4 U: U3 p& O
scribed by his family physician for decreased libido
8 ~; }$ I! z; _/ h! K* Msecondary to depression.
+ q1 t0 K: F0 H4 Q( X# a0 F) h. A" N$ Q4 NThe child slept in the same bed with parents.2 Z9 j" J+ L: C
The father would hug the baby and hold him on his
% h* T- g, q7 Y' }+ ochest for a considerable period of time, causing sig-
! v3 z2 z i: qnificant bare skin contact between baby and father.. e3 f1 L. y8 N4 P" |8 h
The father also admitted that after the phone call,0 c' l* y7 y+ i2 f S9 b$ f8 e
when he learned the testosterone level in the baby
! ^& y' X* y# R0 Rwas high, he then read the product information
/ n' S& b" ^: Z$ J& fpacket and concluded that it was most likely the rea-3 o9 f' V0 G) G% ]. C. L- Y
son for the child’s virilization. At that time, they
% d8 N. l7 k; H& Mdecided to put the baby in a separate bed, and the2 N( P' U( @& Q5 ]
father was not hugging him with bare skin and had
B5 E1 q7 o$ `" e5 V0 @7 Fbeen using protective clothing. A repeat testosterone+ s N+ B: d+ j0 ?: }, C9 p5 ?$ B
test was ordered, but the family did not go to the
2 r. q! C$ K" p elaboratory to obtain the test.
; n, Z4 \# b5 p6 mDiscussion: v- M8 R+ _3 Q/ j- I
Precocious puberty in boys is defined as secondary
+ q; Z" \% y. K- N) gsexual development before 9 years of age.1,49 G. ?5 R' b6 U+ p; ^ |9 [- ^
Precocious puberty is termed as central (true) when J/ H6 j( S n9 E6 R
it is caused by the premature activation of hypo-1 j3 E/ v/ z7 k& |
thalamic pituitary gonadal axis. CPP is more com-
7 ]2 J+ x R6 Z& Q8 ymon in girls than in boys.1,3 Most boys with CPP
, b0 v" |. u; }) S, o7 Q- Hmay have a central nervous system lesion that is
4 M; I& L! {/ H1 \responsible for the early activation of the hypothal-
4 g/ t0 ?+ O$ y, g! k4 O \amic pituitary gonadal axis.1-3 Thus, greater empha-
( b" k# |$ _" y0 I1 x1 C3 gsis has been given to neuroradiologic imaging in
% U/ ~% R& |; F" C0 V! a2 D8 Nboys with precocious puberty. In addition to viril-% H& l6 v9 e! d, c) O3 o
ization, the clinical hallmark of CPP is the symmet-# X; c6 }3 v" g0 \* q7 _0 S
rical testicular growth secondary to stimulation by
; c6 y/ K+ \" D* ^& Rgonadotropins.1,3" C A& p. o5 F4 ]; ^% i. O
Gonadotropin-independent peripheral preco-
J, W% s* y; L Dcious puberty in boys also results from inappropriate
0 D% A: d6 v: I+ U% ?androgenic stimulation from either endogenous or3 C r! ^. W& Q# {9 S
exogenous sources, nonpituitary gonadotropin stim-
6 E- E* Q- w9 J; e4 n% gulation, and rare activating mutations.3 Virilizing
' ^8 |% W* t5 F" I- _) fcongenital adrenal hyperplasia producing excessive
* N1 n$ W0 }! z' ]" V) _adrenal androgens is a common cause of precocious
0 {, n# Z% O$ D0 \puberty in boys.3,4
# ]8 J' M% S* q: e E* c( C9 NThe most common form of congenital adrenal
0 S8 u* V; s1 f; `hyperplasia is the 21-hydroxylase enzyme deficiency.
/ m3 t" b4 g/ TThe 11-β hydroxylase deficiency may also result in* c1 S* R; Q+ i" [
excessive adrenal androgen production, and rarely,
2 B8 j- `1 k) ~+ Z x- n- S' b dan adrenal tumor may also cause adrenal androgen) I+ P* h; I; I, ?: o g4 K# m6 Z
excess.1,3( F4 H+ i+ w+ i
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from- e. u: H2 p+ l3 y, N$ p; _& w# {( C
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
' k# L: n- r" Z; B8 V% xA unique entity of male-limited gonadotropin-
* O |, r7 R! T U7 Rindependent precocious puberty, which is also known3 n3 t1 |/ O0 ?9 K
as testotoxicosis, may cause precocious puberty at a
8 E) B) X" C5 f" p1 ~2 jvery young age. The physical findings in these boys! D% H9 i8 w* q7 P8 s
with this disorder are full pubertal development,0 r; W% C9 z7 f& k7 D- Y) r% W
including bilateral testicular growth, similar to boys5 T" m% J- X' E
with CPP. The gonadotropin levels in this disorder
$ Z- [& u% _9 Q X% s0 y$ fare suppressed to prepubertal levels and do not show
' O% f P# _- xpubertal response of gonadotropin after gonadotropin-
7 w: z! F, B/ G1 G6 a2 B/ d& O! z1 jreleasing hormone stimulation. This is a sex-linked& C. ^: K2 O! E F
autosomal dominant disorder that affects only3 }# @2 `$ T/ L9 z+ k
males; therefore, other male members of the family
* A" ]# }1 h4 s/ U& c& |- d2 n# Ymay have similar precocious puberty.3
6 E+ G' s$ R( A; ^( ]In our patient, physical examination was incon-5 r9 i1 A0 F. a2 ?$ Y
sistent with true precocious puberty since his testi-+ o, z- \! l+ Y+ L$ ?8 f2 M
cles were prepubertal in size. However, testotoxicosis' o" l9 V* E! z$ @
was in the differential diagnosis because his father1 q% Y1 i6 {7 t" L; `
started puberty somewhat early, and occasionally,
$ i& v. T" _7 C8 @# gtesticular enlargement is not that evident in the
( o5 M2 u: f) a) J0 v3 S& j% jbeginning of this process.1 In the absence of a neg-
! Z% ~# Z0 g. x3 K- ~ative initial history of androgen exposure, our
& S; _" I5 O# E& j% ]3 s! ?biggest concern was virilizing adrenal hyperplasia,! a0 i7 I: S Z- g; D9 f% x
either 21-hydroxylase deficiency or 11-β hydroxylase( n4 c6 x$ m0 B$ Z" M/ P5 v
deficiency. Those diagnoses were excluded by find-: s p5 Q% ^9 P2 y
ing the normal level of adrenal steroids.
1 y5 @) o+ V f' C# }3 w; K8 [The diagnosis of exogenous androgens was strongly5 }: m E7 x: W
suspected in a follow-up visit after 4 months because5 [: P+ a2 k' Q; O
the physical examination revealed the complete disap-
~9 J" l8 D- e. v% M0 [% apearance of pubic hair, normal growth velocity, and% t, K& ]8 T/ f" c7 C6 j
decreased erections. The father admitted using a testos-
8 d3 e9 d4 a4 Z+ Q/ m! w# dterone gel, which he concealed at first visit. He was
# U- ^0 `/ y4 ^( q0 z* {0 ausing it rather frequently, twice a day. The Physicians’
0 r& l! @+ T/ y; }Desk Reference, or package insert of this product, gel or
6 W! \! I( U" `: A, A7 J5 O- ~- fcream, cautions about dermal testosterone transfer to
* t N j. |/ Y1 j( Punprotected females through direct skin exposure.- j6 N# y: z: [
Serum testosterone level was found to be 2 times the
: U5 e& Q; x! q# g% ?! i# g' }5 jbaseline value in those females who were exposed to/ T# x$ L* G3 i9 t7 S6 }
even 15 minutes of direct skin contact with their male+ I" I/ Y5 }% h8 J: d; n
partners.6 However, when a shirt covered the applica-
% N8 b/ l9 S; ~. P1 u/ wtion site, this testosterone transfer was prevented.
' Y% H- f: R& j( cOur patient’s testosterone level was 60 ng/mL,- A* u' T* X1 f; Z
which was clearly high. Some studies suggest that
6 X9 l8 l; D) X( k0 _dermal conversion of testosterone to dihydrotestos-1 O" \0 Z/ p I/ n/ l, e: u
terone, which is a more potent metabolite, is more" R. J4 {9 y# F8 [2 @: U1 z
active in young children exposed to testosterone: f$ X* c# V2 G1 o4 J# B
exogenously7; however, we did not measure a dihy-+ ^1 n6 v: n5 [$ Y% K
drotestosterone level in our patient. In addition to
/ ]4 m- r G+ A3 H+ ?4 K! nvirilization, exposure to exogenous testosterone in
/ y3 J3 t9 @2 u/ [children results in an increase in growth velocity and
# X! q; R& Y- x4 r, y' c2 T kadvanced bone age, as seen in our patient.5 J F* v$ S9 x' q: E9 Z
The long-term effect of androgen exposure during8 c5 a( n7 O f b5 o) J& B
early childhood on pubertal development and final/ T% g9 U0 l5 G0 F3 O# q
adult height are not fully known and always remain5 r9 V" z, m0 h* a9 _
a concern. Children treated with short-term testos-
3 h6 i" H+ z+ T- e$ Y; `terone injection or topical androgen may exhibit some
9 [* d z6 K' D Z G- v! zacceleration of the skeletal maturation; however, after' r5 Y- A9 q) d
cessation of treatment, the rate of bone maturation
" l: P/ ^: k- w: W! E" r/ Mdecelerates and gradually returns to normal.8,9! o' f3 P$ n) f. Z- C
There are conflicting reports and controversy6 {+ a/ J8 ~- @9 |1 l+ W; a
over the effect of early androgen exposure on adult
3 \- i* ]$ w" \" t, z2 s- }* k& Ipenile length.10,11 Some reports suggest subnormal
6 z1 k" i; D- q# wadult penile length, apparently because of downreg-
3 o, G& R$ Z( n' G( W, j+ mulation of androgen receptor number.10,12 However,+ {6 x* Z1 ]9 ~6 @, E
Sutherland et al13 did not find a correlation between
. m, J, F/ U' D& r* c6 [$ Echildhood testosterone exposure and reduced adult, C# p$ D& l& {5 r# r+ k4 |+ O
penile length in clinical studies.2 h. `# ?% E) b
Nonetheless, we do not believe our patient is
* ]0 y- R% u. N) Lgoing to experience any of the untoward effects from; ~: @) a5 `0 Z9 N$ W
testosterone exposure as mentioned earlier because: T+ y b+ P& C0 ]1 ~. R4 S6 m! Z
the exposure was not for a prolonged period of time.- U! _. J2 _) {
Although the bone age was advanced at the time of' ^- l8 ^0 U; a$ P' {) S2 |5 U
diagnosis, the child had a normal growth velocity at
: z3 R5 I5 ]/ c* p9 Qthe follow-up visit. It is hoped that his final adult
* [1 C {5 Q2 i/ B( Pheight will not be affected.! Q- r" T, [- }- a. d7 ^* C* {
Although rarely reported, the widespread avail-3 i7 ^. R- ^) y$ h
ability of androgen products in our society may, L& w" V) f! ~, J$ S
indeed cause more virilization in male or female) v. D/ y. O9 t- w- ]1 @
children than one would realize. Exposure to andro-
. U$ G' G" x; ]0 N8 Y! T( ugen products must be considered and specific ques-
0 u. y/ x @5 y& G: [3 k) [ A0 Utioning about the use of a testosterone product or
$ U0 n6 }9 G( y) V( o4 Y* ugel should be asked of the family members during7 r/ U- l$ K4 }
the evaluation of any children who present with vir-
( J' t2 H$ T0 A, vilization or peripheral precocious puberty. The diag-% F! B! R: V. @- d, @
nosis can be established by just a few tests and by
' N, `" W- r1 Z% oappropriate history. The inability to obtain such a
8 J4 s4 N7 v! f; V8 z( chistory, or failure to ask the specific questions, may
- a- k0 y) S4 o3 u3 o9 Yresult in extensive, unnecessary, and expensive5 J; c! b6 q6 _; c- [* H. B
investigation. The primary care physician should be& P; Y: v/ l3 S6 b z- t& N+ J
aware of this fact, because most of these children6 m, {( |1 D. g+ _% ~" ` B
may initially present in their practice. The Physicians’% r& P% P! a0 [2 C4 K" d7 T0 w2 J
Desk Reference and package insert should also put a
6 l0 D2 y# E$ T$ Rwarning about the virilizing effect on a male or) H1 L3 x F+ p" t; \' R" }
female child who might come in contact with some-* }) D' @- s7 y q- x9 G1 V
one using any of these products.3 S! r% e, Z6 `5 ^6 M4 p
References
8 E3 c3 T- q: J6 v7 E1. Styne DM. The testes: disorder of sexual differentiation3 L+ U4 X/ |$ i' R7 C
and puberty in the male. In: Sperling MA, ed. Pediatric) E( q9 j3 N0 ~0 V8 V) e* U
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
% C8 d W, e v$ k& Z5 C/ f2002: 565-628.
9 l$ B! ?) n3 A' Z; M# f2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious0 \& |6 }; u5 F$ f& o. t2 S
puberty in children with tumours of the suprasellar pineal |
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