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Sexual Precocity in a 16-Month-Old o$ _2 [# z) {
Boy Induced by Indirect Topical9 H% S8 x2 V+ \0 Q& b0 @8 D8 n
Exposure to Testosterone' w- m& F- z$ a8 G
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
- o: d9 z4 G5 g9 S8 Gand Kenneth R. Rettig, MD1
( ]$ y! {- T1 Q) \/ j$ o- F2 D, VClinical Pediatrics5 Y, w: `& e! v+ ]# M" t
Volume 46 Number 6
, ~& L+ h* P+ y" o8 r- eJuly 2007 540-543( T+ s$ o5 t J5 e
© 2007 Sage Publications
2 t1 I5 `$ s4 s* Y; f: w0 Q10.1177/0009922806296651
( B1 P: C& {( w# Q; _http://clp.sagepub.com* D9 L9 a4 e' K0 R
hosted at* g j! W% F' ?% _( O
http://online.sagepub.com9 @( w9 X6 E; k3 H* V: M& h2 z' h
Precocious puberty in boys, central or peripheral,/ W/ N! f0 D# A. L# S
is a significant concern for physicians. Central/ I7 E1 E/ ~( j! b
precocious puberty (CPP), which is mediated
0 R0 W! u1 b' u8 @& `# e/ U5 \through the hypothalamic pituitary gonadal axis, has
, ~5 R- C. g; ]& } C f: Ea higher incidence of organic central nervous system; }! y+ d7 @+ H( X+ }: I
lesions in boys.1,2 Virilization in boys, as manifested
$ p! R) d* S4 c2 b% A% mby enlargement of the penis, development of pubic% @4 X6 B6 H" `3 K+ g4 {
hair, and facial acne without enlargement of testi-
. c7 A6 {3 I* m4 w8 C( zcles, suggests peripheral or pseudopuberty.1-3 We
4 M" O) J$ Y- ?# U- l8 r% l$ Areport a 16-month-old boy who presented with the
+ S/ v4 L8 {9 m. L- z% a7 V, qenlargement of the phallus and pubic hair develop-9 ^7 B; V" n; [) b# H' b: |
ment without testicular enlargement, which was due+ G3 x+ {1 }, w; a" q: q
to the unintentional exposure to androgen gel used by
4 K, a0 K2 T0 W- Q5 e* Rthe father. The family initially concealed this infor-
) X, H: {, Z4 @# L0 N `& dmation, resulting in an extensive work-up for this9 A+ t; h. e2 |) K& y
child. Given the widespread and easy availability of
F* |+ u) r- ?5 }, stestosterone gel and cream, we believe this is proba-4 P9 [, A- a$ T& k5 I1 I- q
bly more common than the rare case report in the4 E2 l) u5 o3 j5 l' l# ~
literature.4
" r4 J8 T& v% ?5 b$ f& ?$ I* QPatient Report
% p9 P' V" z% L( e# Y- ~0 z3 QA 16-month-old white child was referred to the
4 a- Y- D# @" e* i% Z! b$ eendocrine clinic by his pediatrician with the concern
4 p, g/ Q1 p8 {' p9 L- w2 ?6 Z$ vof early sexual development. His mother noticed4 L: k7 M; T5 j: A* w; S
light colored pubic hair development when he was
. ~5 K5 |* Y3 x8 p* E9 r ~$ u7 PFrom the 1Division of Pediatric Endocrinology, 2University of
1 B' ~3 _0 H3 g/ @' j6 q) JSouth Alabama Medical Center, Mobile, Alabama." K; G- p1 C# N$ O) g6 m
Address correspondence to: Samar K. Bhowmick, MD, FACE,
7 r* k4 b8 _' f7 ^( d" pProfessor of Pediatrics, University of South Alabama, College of
6 H0 J0 g0 D1 j& YMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;3 p2 W5 h; b$ [
e-mail: [email protected].9 w; l" x8 {9 B1 Q6 D) |6 J
about 6 to 7 months old, which progressively became3 [3 l$ y C* X: W$ p8 @) ]
darker. She was also concerned about the enlarge-
) |, A' \) ^2 P7 N5 Q9 ^7 J$ bment of his penis and frequent erections. The child
- d. B. B, C) D* Qwas the product of a full-term normal delivery, with
2 ^" w. |+ W0 w. ka birth weight of 7 lb 14 oz, and birth length of
& @( n( F* r4 |, ~8 |+ u9 g1 W$ |20 inches. He was breast-fed throughout the first year% }7 X; b i; Q' S2 B2 |
of life and was still receiving breast milk along with; c" d5 c/ q8 X
solid food. He had no hospitalizations or surgery,# U X; m+ P+ v
and his psychosocial and psychomotor development; ^" ]6 P7 m- j7 P* K- i. s( X. {
was age appropriate./ f: `4 P; U6 R! Q" Q
The family history was remarkable for the father,% L) ?) i* X( d) y+ J3 B
who was diagnosed with hypothyroidism at age 16,
6 K7 P9 F9 j! v, L, lwhich was treated with thyroxine. The father’s: ?& q6 E! i! ~0 E4 B
height was 6 feet, and he went through a somewhat
# u; O [& w& eearly puberty and had stopped growing by age 14.
, v; T7 y3 q. ~7 ~( j% `% [1 KThe father denied taking any other medication. The
( i* B2 o6 e! Z0 mchild’s mother was in good health. Her menarche
* Y- s% P+ Y% c/ L. F" G0 V+ @was at 11 years of age, and her height was at 5 feet) ?/ B% u( j$ s" ?9 I0 Y
5 inches. There was no other family history of pre-6 |3 C0 x: x. N- o k
cocious sexual development in the first-degree rela-
" a# X/ u# X) P& J- L7 Mtives. There were no siblings.
7 ~* i& i5 y% w/ b, l) J- VPhysical Examination1 ~/ m$ g- v" a
The physical examination revealed a very active, k0 X& `: E; g o8 w4 t
playful, and healthy boy. The vital signs documented- N! S' B* n+ n/ H5 B
a blood pressure of 85/50 mm Hg, his length was, Y a6 @' }2 w9 N' J0 {" D
90 cm (>97th percentile), and his weight was 14.4 kg
/ B! R1 S0 x: G) g% T) R(also >97th percentile). The observed yearly growth
) n/ U, k* L$ o& jvelocity was 30 cm (12 inches). The examination of
# P& X9 U. L5 f$ c/ o& W% c& _the neck revealed no thyroid enlargement.. s( W) t, R' [9 q' U: |" y! r
The genitourinary examination was remarkable for
; O6 W, V2 l/ B2 I4 e$ penlargement of the penis, with a stretched length of
3 ~, h- a0 O+ k, W( c! \' b8 cm and a width of 2 cm. The glans penis was very well" U6 a/ m/ K5 ?* Y _) D6 C% ^
developed. The pubic hair was Tanner II, mostly around
3 w& p! K+ n0 i$ \. @' ]540
) s4 e+ W7 E- p- b+ l4 O% {0 N2 A X, Uat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 [0 H3 [9 b' X+ \& s, A9 A2 M
the base of the phallus and was dark and curled. The% i3 N9 m5 g# T! ~) c
testicular volume was prepubertal at 2 mL each.
6 U' u6 o4 T' M/ P; g7 pThe skin was moist and smooth and somewhat
% E* b7 U: F3 j/ _8 Z2 uoily. No axillary hair was noted. There were no! @/ \9 w! ^$ `0 P2 b4 j) M8 O: o
abnormal skin pigmentations or café-au-lait spots.
- ~" j7 k, X4 ?# m6 j3 H1 ^: ^" eNeurologic evaluation showed deep tendon reflex 2+8 ?6 |8 O+ d; Q8 M! g9 A0 V
bilateral and symmetrical. There was no suggestion& }0 L v2 J8 T
of papilledema.
$ h1 c2 k& I& _, L4 c+ F5 bLaboratory Evaluation0 m0 C5 O/ d! q% {& ]
The bone age was consistent with 28 months by& I2 U+ d1 f% t
using the standard of Greulich and Pyle at a chrono-. O- x$ B4 m. w' w ~
logic age of 16 months (advanced).5 Chromosomal
% Q ~! j( ]" y+ @" Wkaryotype was 46XY. The thyroid function test, }$ G. |, ~) V; ]
showed a free T4 of 1.69 ng/dL, and thyroid stimu-( a) L2 a0 |( n% K6 O5 L
lating hormone level was 1.3 µIU/mL (both normal).3 g1 x& x/ H1 ~ {9 p0 ~! d; r9 U
The concentrations of serum electrolytes, blood
2 q' ^! i4 \* b5 S; H4 kurea nitrogen, creatinine, and calcium all were a# G5 w \) i* ^. ], B
within normal range for his age. The concentration
) x! g X2 \0 x8 dof serum 17-hydroxyprogesterone was 16 ng/dL
( R* R9 r! T6 G/ @- ]& u4 o(normal, 3 to 90 ng/dL), androstenedione was 20! I9 Q: X+ T2 O
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-/ g! H5 w6 A. K- V% `/ f
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
) }$ s0 ?, Q% Rdesoxycorticosterone was 4.3 ng/dL (normal, 7 to" ^4 @3 S# w! B6 g, P
49ng/dL), 11-desoxycortisol (specific compound S)1 [& M# \' v! l6 T3 D
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-( J2 }: `7 Y; R2 }: I9 B0 ^
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
9 |, T) X2 f8 {0 h' u6 b8 Q9 ptestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
. N( ?5 A1 I, \and β-human chorionic gonadotropin was less than+ K- A! Z* c- b; e3 T
5 mIU/mL (normal <5 mIU/mL). Serum follicular. l6 t; C" s3 w5 F$ l
stimulating hormone and leuteinizing hormone
' O3 s. Z3 o8 i9 \( c' g* _concentrations were less than 0.05 mIU/mL' z# N9 \8 z+ C# Q/ L% Q
(prepubertal).0 N; j% y3 C# n ^' d7 |
The parents were notified about the laboratory
0 y: z- y# @6 ?! Y! qresults and were informed that all of the tests were: y' z( q9 D4 Z
normal except the testosterone level was high. The( h" A R6 m1 O6 O
follow-up visit was arranged within a few weeks to
! d4 t. u# I; Robtain testicular and abdominal sonograms; how-
$ d! Y5 z9 E+ c4 eever, the family did not return for 4 months.
1 X( m q0 V3 kPhysical examination at this time revealed that the
' {+ f; t b% p) r0 ]1 }8 Schild had grown 2.5 cm in 4 months and had gained
" S) J9 V J: {. u7 E2 kg of weight. Physical examination remained! d& E. n2 `( K2 b1 R7 W" x
unchanged. Surprisingly, the pubic hair almost com-
( _5 ~% Q- ~+ Y1 Y2 G( vpletely disappeared except for a few vellous hairs at
; X1 P+ q+ x8 ?0 H! |the base of the phallus. Testicular volume was still 2$ P. W: Q+ M" F" i* ~
mL, and the size of the penis remained unchanged.
, P* N$ d$ X" S; jThe mother also said that the boy was no longer hav-" z' u) @: l: D4 p* P
ing frequent erections." a/ T7 Q3 i5 N, a! Y% f4 z! A1 V
Both parents were again questioned about use of
" Y n1 q+ ~- U+ Q6 {$ B9 Cany ointment/creams that they may have applied to
5 ^. W4 F6 K. j% `, uthe child’s skin. This time the father admitted the
" n8 g1 l* |/ r4 r' a V& p" yTopical Testosterone Exposure / Bhowmick et al 5417 v1 G" K: K8 z$ |9 s) c# K
use of testosterone gel twice daily that he was apply-& ^) [% T9 W( d1 r* G; E! \
ing over his own shoulders, chest, and back area for* w. D: M0 D) y8 Q: G; B) L4 `) p. Q
a year. The father also revealed he was embarrassed
. \+ _8 Z, M8 zto disclose that he was using a testosterone gel pre-" M6 Y6 g/ A- P9 Z* N u
scribed by his family physician for decreased libido' a& }# }& j3 h& U* w
secondary to depression.
: I$ ]* G/ A- CThe child slept in the same bed with parents.
Z$ y. H; G5 _3 u2 XThe father would hug the baby and hold him on his X7 [' @1 ~- `' ]2 S
chest for a considerable period of time, causing sig-: X' @ b+ e9 f5 `$ u6 F6 X
nificant bare skin contact between baby and father.
, V( t2 t# x$ z8 z5 e, CThe father also admitted that after the phone call,0 B7 [; v9 ]( E" P. T; C
when he learned the testosterone level in the baby2 W4 X z" ~# s, f( m
was high, he then read the product information
% ]% [4 R m; q1 h0 C U2 Mpacket and concluded that it was most likely the rea-
9 ^& ?1 R# `) B( n' N% ?$ Lson for the child’s virilization. At that time, they
/ ?3 R6 |# W9 Tdecided to put the baby in a separate bed, and the
0 ~8 ?2 i! ~3 i* S5 R5 W& `father was not hugging him with bare skin and had
" d% w; b Q% u7 b" C" [" K* Pbeen using protective clothing. A repeat testosterone
* X a) D7 W5 b P' s% ~ Ytest was ordered, but the family did not go to the
/ s7 \* L8 V2 a, Rlaboratory to obtain the test.+ @1 K* M& R- m8 j
Discussion4 b5 h( S4 y/ i; m+ [; L. q
Precocious puberty in boys is defined as secondary+ U d8 `2 q8 `5 k( p$ W( q0 m
sexual development before 9 years of age.1,4. }. t. o' |0 Y) A7 `: J: b
Precocious puberty is termed as central (true) when1 o- ], b* V6 [- [" Q
it is caused by the premature activation of hypo-& P/ x8 @8 C1 A& T
thalamic pituitary gonadal axis. CPP is more com-. e Q B7 j3 |" u. ]8 D
mon in girls than in boys.1,3 Most boys with CPP
. a( ^$ N4 p( _# xmay have a central nervous system lesion that is) y: O; |* A! P3 ]
responsible for the early activation of the hypothal-! K) y* d3 c, X4 L2 A: e, I/ V; k" W# O
amic pituitary gonadal axis.1-3 Thus, greater empha-& v8 a- _3 ^8 V9 k0 Q9 n4 M
sis has been given to neuroradiologic imaging in
5 Q/ w0 M2 w$ F5 L. b! m, _- cboys with precocious puberty. In addition to viril-
' n1 l5 ~& g7 e" i9 Kization, the clinical hallmark of CPP is the symmet-
& E& c/ i# C9 Y. @4 n8 x( drical testicular growth secondary to stimulation by, F8 @* S- Z/ M( |/ S) _% p
gonadotropins.1,32 z+ {3 N3 F% ?1 r( n% g6 S
Gonadotropin-independent peripheral preco-
7 {4 r" a" P4 K& P9 `( \) P* J; |* qcious puberty in boys also results from inappropriate
8 Q3 G. N- P E$ e7 |androgenic stimulation from either endogenous or* [7 c. v4 n _6 G! S5 X" M
exogenous sources, nonpituitary gonadotropin stim-
0 M) W% b/ _* h8 N/ L: Iulation, and rare activating mutations.3 Virilizing \: W6 o D0 ?. {& d5 z' A
congenital adrenal hyperplasia producing excessive
2 D8 U6 R; o ?7 V8 I9 madrenal androgens is a common cause of precocious
4 N& J& H5 x* @/ v7 |puberty in boys.3,40 D0 e. z1 x/ n, `9 r/ Z/ S+ f
The most common form of congenital adrenal- Z; x k O, t: ]7 Y; i
hyperplasia is the 21-hydroxylase enzyme deficiency.
3 B4 U. B3 |' ^6 ^- P6 o8 O; DThe 11-β hydroxylase deficiency may also result in
. v7 c3 m7 z/ b9 S; t9 |excessive adrenal androgen production, and rarely,# Y z, c1 ^+ |9 \) W) G
an adrenal tumor may also cause adrenal androgen7 U* d: W5 A( B3 `
excess.1,3 T$ H' ^' c; V8 w7 k" I
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 V; N; W2 l1 k, z3 E" P/ }542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
5 D5 v5 h$ N, `# UA unique entity of male-limited gonadotropin-4 X$ e9 F2 ?- T) a6 j) v
independent precocious puberty, which is also known
$ e# f1 t' O6 m/ Las testotoxicosis, may cause precocious puberty at a
- s4 g; _% `) X- \4 j8 zvery young age. The physical findings in these boys, g2 I# u! M+ S7 m. i f; r
with this disorder are full pubertal development,9 t' C) C( D8 f9 `5 D" `7 B* p# Z
including bilateral testicular growth, similar to boys9 w, V4 E1 [4 F/ q. ^& w6 C4 I* X
with CPP. The gonadotropin levels in this disorder' B8 F" ^8 y4 \" b! j
are suppressed to prepubertal levels and do not show
% P. {! S; A ?% y# ypubertal response of gonadotropin after gonadotropin-
# g- q: q0 e6 O! K( `releasing hormone stimulation. This is a sex-linked) o7 S! F0 n* R$ E
autosomal dominant disorder that affects only, g' Z: v2 B! `
males; therefore, other male members of the family
( \. J4 z5 O& L$ n" Umay have similar precocious puberty.3$ Q" B8 B. w, b9 U; s
In our patient, physical examination was incon-
4 U- S' z l% C" g& B5 xsistent with true precocious puberty since his testi-
) I1 U- e% Z. kcles were prepubertal in size. However, testotoxicosis0 M; a# _' d3 `$ s
was in the differential diagnosis because his father
0 K0 K" Y2 B4 v; o1 D, w8 T/ Sstarted puberty somewhat early, and occasionally,
# ?- J* R/ n" H% b2 o0 Ztesticular enlargement is not that evident in the
1 r) k& @& J4 g4 `6 W: e: Ibeginning of this process.1 In the absence of a neg-& L. ?9 G6 t, G+ V, Z5 _5 K3 d! K
ative initial history of androgen exposure, our
2 V3 M& W; ]& I nbiggest concern was virilizing adrenal hyperplasia,
) _: c4 J( X& U; x g- leither 21-hydroxylase deficiency or 11-β hydroxylase1 V7 D0 Q4 D" D/ @
deficiency. Those diagnoses were excluded by find-
! ?8 [$ f- v3 W# r4 Hing the normal level of adrenal steroids., |, U1 {. }% V% Y I* k+ a( f
The diagnosis of exogenous androgens was strongly d0 A% O z0 U* d* c1 v% x( O
suspected in a follow-up visit after 4 months because
1 R$ _8 r2 H/ j5 K; N$ x, Pthe physical examination revealed the complete disap-
( a" Z& X8 L! tpearance of pubic hair, normal growth velocity, and2 y0 b2 q7 T& E4 K/ m, n/ m3 l
decreased erections. The father admitted using a testos-
6 q. M. H' S- [/ V0 y0 |terone gel, which he concealed at first visit. He was
. ~' W# ?, e. `8 w% ?3 ^( n& ~using it rather frequently, twice a day. The Physicians’$ f* `# P1 T% }$ \; V
Desk Reference, or package insert of this product, gel or% x+ u+ ]% H3 z- r: Q
cream, cautions about dermal testosterone transfer to
5 J+ G: k) s" A' V1 runprotected females through direct skin exposure.! W, ^) X5 Y0 D( N( E& X8 s
Serum testosterone level was found to be 2 times the
! j; m7 Z. l0 i6 K' ubaseline value in those females who were exposed to
# n; r+ E2 Q/ Geven 15 minutes of direct skin contact with their male
7 s7 K3 l3 [2 lpartners.6 However, when a shirt covered the applica-
5 q- x. e' |! Y; Rtion site, this testosterone transfer was prevented.
1 _ \# H* m4 h: F3 ^# YOur patient’s testosterone level was 60 ng/mL,
1 _8 d7 {4 j& g; i1 Hwhich was clearly high. Some studies suggest that* l2 h! p$ S9 ~. U2 M
dermal conversion of testosterone to dihydrotestos-
& x- H" R$ E9 c1 Aterone, which is a more potent metabolite, is more
5 m7 N) ]4 m- p; e2 j s eactive in young children exposed to testosterone
' H+ l* T7 l& P* N; J' _exogenously7; however, we did not measure a dihy-
! n0 o6 g6 k2 w3 h# tdrotestosterone level in our patient. In addition to
- o& g1 ?! W0 F5 N; Vvirilization, exposure to exogenous testosterone in! d: v6 ]% v% E6 g
children results in an increase in growth velocity and8 k9 |( O5 s1 B* ?
advanced bone age, as seen in our patient.
* s2 [( v9 X1 x4 v& q7 eThe long-term effect of androgen exposure during' M, n. a8 A, C, ~1 E2 J
early childhood on pubertal development and final
! H. q& R! W/ q* uadult height are not fully known and always remain
/ s% Y) p3 j( ?0 ~, p: q2 C9 Ba concern. Children treated with short-term testos-, j y; Z$ {$ |3 ^) R& b
terone injection or topical androgen may exhibit some
4 O' B, ?4 R: K4 Q; ~6 F9 nacceleration of the skeletal maturation; however, after/ i. `; F0 x8 h
cessation of treatment, the rate of bone maturation
2 Q/ g- G- F O9 u. ~$ G; j7 C$ b6 Tdecelerates and gradually returns to normal.8,9
; X7 n9 @3 `" C# d6 I5 VThere are conflicting reports and controversy
' w* A9 X9 Y( H+ T, U5 Tover the effect of early androgen exposure on adult- j8 [4 i, p# [2 Z8 f
penile length.10,11 Some reports suggest subnormal
% r: a' E% L2 [ U; n& C$ xadult penile length, apparently because of downreg-
9 F* c" w* O2 bulation of androgen receptor number.10,12 However,
3 T+ ?7 |$ f% Y$ K: O, f$ c' DSutherland et al13 did not find a correlation between7 A" C5 a3 C3 z1 L
childhood testosterone exposure and reduced adult! C$ L+ X" d2 R5 F1 T& A; X2 Y
penile length in clinical studies.- G; c! F: [ r9 o
Nonetheless, we do not believe our patient is
# h0 p! q- i/ f, f& ~& rgoing to experience any of the untoward effects from9 N/ ^5 Z; U6 r2 S* O
testosterone exposure as mentioned earlier because
$ O- C' W1 w" B) x' d, tthe exposure was not for a prolonged period of time.
! Q. y, z- H# } LAlthough the bone age was advanced at the time of' v$ u5 t: `& o' p, Q" X& s Z9 T" W
diagnosis, the child had a normal growth velocity at% ]# l$ S: k5 M4 p% h
the follow-up visit. It is hoped that his final adult- s2 z& w1 q" l) R
height will not be affected.
8 ]3 ~- [8 a4 ]# hAlthough rarely reported, the widespread avail-/ I8 x4 E. J2 |% |, Q1 O/ V' W' x
ability of androgen products in our society may2 n: p- R1 \* J* }; W: |" C8 W0 T
indeed cause more virilization in male or female8 U& w2 Z3 w& t! M& d5 n# V
children than one would realize. Exposure to andro-
8 n& D% l* j% m) Egen products must be considered and specific ques-7 T) R. w$ X! f
tioning about the use of a testosterone product or
, b. ^+ r H) A8 d( V, m3 vgel should be asked of the family members during
7 a4 T. m- M( z0 p3 fthe evaluation of any children who present with vir-) {) v$ R0 |9 I) E% U$ a
ilization or peripheral precocious puberty. The diag-
" z0 K6 L0 Z1 x% fnosis can be established by just a few tests and by# H1 i0 A- `& e) [6 E
appropriate history. The inability to obtain such a
9 _ l( w% g( t8 \8 qhistory, or failure to ask the specific questions, may
# ~% [/ ]" L% L, ^& g% Y1 }; wresult in extensive, unnecessary, and expensive0 a/ [& J# r1 j& A C7 g$ a2 w' V
investigation. The primary care physician should be' U8 ^. u# {6 e7 t( I
aware of this fact, because most of these children$ S& @+ J& x# d9 c+ S# s
may initially present in their practice. The Physicians’
& X* T- B& M) [/ S3 L' lDesk Reference and package insert should also put a
2 C2 ]! c; ]5 `- `warning about the virilizing effect on a male or5 i& W8 ] J" ^4 z' Q9 B
female child who might come in contact with some-* H) u9 l6 ?% t2 h' C
one using any of these products.
# B+ \$ E/ p; |3 w8 LReferences
3 E" |% |; ?$ n5 Y" ?* Y; z1 v x1. Styne DM. The testes: disorder of sexual differentiation+ X4 E' W3 ~$ D
and puberty in the male. In: Sperling MA, ed. Pediatric" D. L3 p+ z& l( j5 {
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;* M5 u- X6 d' @& c- Z
2002: 565-628.
; w$ ~" Z% g8 |0 U. |4 V9 h2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious) w+ A' v- G( W+ S- ?/ k4 m
puberty in children with tumours of the suprasellar pineal |
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