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Sexual Precocity in a 16-Month-Old
6 U& }) F6 ~# UBoy Induced by Indirect Topical/ F0 a) K, a8 _( A" s# F* N0 q
Exposure to Testosterone6 {/ E$ P, p1 d
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2/ m0 a% \, a! {& i: T K8 o& G
and Kenneth R. Rettig, MD1
9 `; ^/ }! O) {* E& U3 SClinical Pediatrics
; W7 l/ T( J, x7 G( gVolume 46 Number 67 Z: ~, I" O4 t$ `) L- W) k, K
July 2007 540-543# j* K7 R( D, O" h
© 2007 Sage Publications
5 h8 M# r4 b+ \; `10.1177/0009922806296651
$ j7 ^" w$ M( u6 k0 H/ v) ?9 ^http://clp.sagepub.com
x# F/ l. Z$ S1 p; N5 i, Shosted at6 [4 w" A: I" b& n$ L
http://online.sagepub.com
- d: l8 v) l. O8 |5 C$ Y1 L7 vPrecocious puberty in boys, central or peripheral,
$ L# k) Q8 X* R. @7 l. k" H% g4 Ois a significant concern for physicians. Central1 L5 ~- H1 _, r* B, ?' p2 \) E3 n) r
precocious puberty (CPP), which is mediated
+ r- h" ?! y2 O' e; t" `through the hypothalamic pituitary gonadal axis, has
0 f ]+ }) }. b( W8 o. ba higher incidence of organic central nervous system% |' C2 L4 j0 z) u; k! m$ O
lesions in boys.1,2 Virilization in boys, as manifested$ V! D4 M* w5 \; h1 V1 O
by enlargement of the penis, development of pubic
3 A" w, _& Y( X* ~hair, and facial acne without enlargement of testi-
k0 C+ L+ `9 z( g7 Icles, suggests peripheral or pseudopuberty.1-3 We
% X- [) L' h; _! L( C+ jreport a 16-month-old boy who presented with the2 n' ]! n j0 F
enlargement of the phallus and pubic hair develop-0 f6 c/ q+ q$ ]
ment without testicular enlargement, which was due
' U; A! @) I! q* c8 ]to the unintentional exposure to androgen gel used by8 ]- l- R( H$ u7 e0 l. z9 Z
the father. The family initially concealed this infor-
( _+ V) N9 x8 Umation, resulting in an extensive work-up for this
9 R* L C( j8 lchild. Given the widespread and easy availability of
0 g8 t& N6 x5 c! D8 [+ g8 xtestosterone gel and cream, we believe this is proba-2 M6 z {# B% b$ F2 v% s
bly more common than the rare case report in the
* r) F. D8 _& z9 y0 x L/ D; k& @literature.48 X; B' y$ D+ W; H9 D
Patient Report! v y* d& ?2 H4 E/ i. e9 T
A 16-month-old white child was referred to the5 E8 U: ~8 ?" e$ z8 @+ [9 z
endocrine clinic by his pediatrician with the concern, |4 T$ S8 }- e: s" ~4 M
of early sexual development. His mother noticed
4 ~, j* ^% h C% a) Mlight colored pubic hair development when he was
% R" \$ n" f, w5 Q; S) p9 \6 | nFrom the 1Division of Pediatric Endocrinology, 2University of. @ s; ?( k% |/ a" ^9 f
South Alabama Medical Center, Mobile, Alabama.
8 S: _& H3 j/ I( \3 f' k8 ?% _4 YAddress correspondence to: Samar K. Bhowmick, MD, FACE,/ i" c- \* B% H& g/ N7 B$ Q
Professor of Pediatrics, University of South Alabama, College of2 D# ^+ |& C% d6 p4 B7 \6 \" \
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;9 \2 x4 ?9 C. P9 ^* p3 ?
e-mail: [email protected].
% ?; D6 C1 j' E8 K" Oabout 6 to 7 months old, which progressively became5 m' u" @# z1 ~: R# E7 V
darker. She was also concerned about the enlarge-
, T; }9 n( a5 jment of his penis and frequent erections. The child( n$ ^" N5 b. i [
was the product of a full-term normal delivery, with* b2 r! M2 X6 t$ i# X8 r
a birth weight of 7 lb 14 oz, and birth length of
& b5 F5 a, U) q# w( k20 inches. He was breast-fed throughout the first year0 [/ ?/ B( L v0 I% t. O
of life and was still receiving breast milk along with* Y8 v) o" K5 \0 d
solid food. He had no hospitalizations or surgery,
/ z: g9 W$ u9 I& wand his psychosocial and psychomotor development! m+ m; A7 R/ |* ]% i, h
was age appropriate.
t) l+ }; p! ~/ k0 G" ]The family history was remarkable for the father,
! v/ N, T' E! O$ {( twho was diagnosed with hypothyroidism at age 16,1 p! a) o; o s% V% J
which was treated with thyroxine. The father’s
; S: x+ D5 i! D! d9 Q3 H, Z/ ^height was 6 feet, and he went through a somewhat
3 V5 Q, x- Z2 @. w/ S! q0 I- bearly puberty and had stopped growing by age 14.
7 i+ w k( d d( I; o9 z2 R! y" m* aThe father denied taking any other medication. The
4 Y3 F" d2 Z/ R1 R' u t! |5 _+ j; ichild’s mother was in good health. Her menarche
% D, e, H: Y" Wwas at 11 years of age, and her height was at 5 feet' S( b6 P' g9 H2 j; P4 `$ U4 _% d
5 inches. There was no other family history of pre-
u$ [1 L$ \# u$ b( E$ J0 Wcocious sexual development in the first-degree rela-
# G) F5 M9 J5 D& _ Q9 N5 P# s& _. [4 Etives. There were no siblings.5 c% ?. c, Q5 F
Physical Examination! d+ Q2 l6 K3 j/ d7 j
The physical examination revealed a very active,
5 b* |- {) d% v6 o0 \playful, and healthy boy. The vital signs documented* j, X; o( _& v3 X: r
a blood pressure of 85/50 mm Hg, his length was
$ w+ f3 K& [2 A0 k+ X) M! a90 cm (>97th percentile), and his weight was 14.4 kg
! c7 }/ ~& V* w9 ?' g- ?$ c(also >97th percentile). The observed yearly growth
; A9 Q+ ^+ \7 Ovelocity was 30 cm (12 inches). The examination of" W7 C+ m! _# w
the neck revealed no thyroid enlargement.3 p* Y+ g+ {: b" Q
The genitourinary examination was remarkable for8 e& L; b% S! |+ r4 m1 e' U+ I( j
enlargement of the penis, with a stretched length of
1 G9 `* w$ E# ]/ o' e; o+ Q8 cm and a width of 2 cm. The glans penis was very well$ Z5 v$ |0 V- c
developed. The pubic hair was Tanner II, mostly around
- m+ e7 X2 b4 x I540' A6 q s I7 T7 m( K4 H
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
2 M. Q( b+ t6 _# x- t; dthe base of the phallus and was dark and curled. The' n# v! I) r: P, m, m
testicular volume was prepubertal at 2 mL each.
( @: ~/ x1 N2 `8 o: P; t5 v& VThe skin was moist and smooth and somewhat- f; ~5 v9 H5 d, g- W
oily. No axillary hair was noted. There were no2 f \/ F9 F, w. f# Z: _
abnormal skin pigmentations or café-au-lait spots.
' l6 ?) r! [4 y aNeurologic evaluation showed deep tendon reflex 2+
$ r1 l( F* {- S8 H* lbilateral and symmetrical. There was no suggestion
& r3 [- c* Q1 G/ Q# _9 cof papilledema.
3 ?' i& S4 X: p; q8 f! @Laboratory Evaluation: l2 M& i+ Y9 i2 r( I) E0 N9 V r
The bone age was consistent with 28 months by
( i$ g/ @3 K0 Z4 k) @using the standard of Greulich and Pyle at a chrono-
! W$ ~: L V9 r' wlogic age of 16 months (advanced).5 Chromosomal
' ] Y: A( [: _( P ckaryotype was 46XY. The thyroid function test( J. \$ W* Z. m* t6 ^5 t
showed a free T4 of 1.69 ng/dL, and thyroid stimu-: f8 s# d( w3 q7 ~& f
lating hormone level was 1.3 µIU/mL (both normal).
; |+ C& L. S, \The concentrations of serum electrolytes, blood7 K# w6 P7 Q# m3 M6 E l' [
urea nitrogen, creatinine, and calcium all were6 _6 @9 T% _5 x" E9 c
within normal range for his age. The concentration6 W5 D$ ^/ t/ P9 A7 u" _* |3 {4 ^
of serum 17-hydroxyprogesterone was 16 ng/dL2 M) s" L: F! {" y( T9 T
(normal, 3 to 90 ng/dL), androstenedione was 20( \8 t$ B; r! ~2 u' n
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
4 E1 P( z+ q9 l$ d; ?terone was 38 ng/dL (normal, 50 to 760 ng/dL),. ^# T+ s: e* d* Z
desoxycorticosterone was 4.3 ng/dL (normal, 7 to3 O+ `2 |" A! `2 U: c5 `
49ng/dL), 11-desoxycortisol (specific compound S)
# C7 G/ i5 R1 L. Swas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! @8 M) p5 Q9 k$ e5 Gtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
" @- V0 s. n$ H. r+ L0 Qtestosterone was 60 ng/dL (normal <3 to 10 ng/dL)," Q7 V+ d% R$ x
and β-human chorionic gonadotropin was less than6 a5 R: ~3 X: ~1 r
5 mIU/mL (normal <5 mIU/mL). Serum follicular
4 i1 f" S- C! v! estimulating hormone and leuteinizing hormone
/ ^7 O0 o8 S9 ?5 o7 p! Mconcentrations were less than 0.05 mIU/mL
- _' P$ _! x! X4 |# Z1 J# x5 G6 x+ H7 d(prepubertal).5 A' ~' X: S4 @4 D2 x# W
The parents were notified about the laboratory Q- @/ n4 n5 s' P- v
results and were informed that all of the tests were; K8 u+ @/ [( d- @
normal except the testosterone level was high. The% M3 _# F2 d a( P
follow-up visit was arranged within a few weeks to: z# ^( d3 e/ [6 K# s
obtain testicular and abdominal sonograms; how-5 W, D2 u+ d# y! E8 u8 p) R% Q: ?
ever, the family did not return for 4 months." @0 F" g7 C P
Physical examination at this time revealed that the
" G }6 Y4 S) X4 c; ^5 z' X+ pchild had grown 2.5 cm in 4 months and had gained- ?& C5 u% O: e! P6 k- \& u D
2 kg of weight. Physical examination remained
/ [5 }" Q! Q0 D! R5 D) X& b2 cunchanged. Surprisingly, the pubic hair almost com-
4 D3 R" V2 J N( v; u" fpletely disappeared except for a few vellous hairs at
; D, f8 K! r6 [, U# lthe base of the phallus. Testicular volume was still 2. W$ N% Z3 \/ l" m# v( s) ]
mL, and the size of the penis remained unchanged.& H+ j2 Y/ g7 S6 }! @. ^
The mother also said that the boy was no longer hav-
& k7 \. s3 z5 X+ V3 King frequent erections.; m* D' G/ A/ \& J9 \3 s
Both parents were again questioned about use of9 u( l! i/ H& @ C" i3 g$ }
any ointment/creams that they may have applied to* M8 x, O; J( p/ p+ y
the child’s skin. This time the father admitted the8 b# Y4 _ D6 s; I
Topical Testosterone Exposure / Bhowmick et al 541
# T, B. N$ _/ A% G% x9 Iuse of testosterone gel twice daily that he was apply- F! H+ n P& k# X$ j" p
ing over his own shoulders, chest, and back area for
4 U1 K; ~& M( |, y) O/ d8 a" ua year. The father also revealed he was embarrassed
+ B/ ^6 D) p1 `% lto disclose that he was using a testosterone gel pre-
% e8 I, v/ y- R9 mscribed by his family physician for decreased libido
. N+ M F9 @( y( k9 k4 y, `; Gsecondary to depression.' R* `3 r$ G! c$ O, L0 O
The child slept in the same bed with parents. a# \1 o. i! J' V# P) S9 k
The father would hug the baby and hold him on his: t8 @. P* Q6 p+ U% |8 ~
chest for a considerable period of time, causing sig-. ~5 Z, g& f& @( s% ~( F
nificant bare skin contact between baby and father.
- O4 [5 k5 Y: S, Q% w& ZThe father also admitted that after the phone call,& X* q: N" k. H; A
when he learned the testosterone level in the baby4 h8 D b4 G2 |% ~/ g
was high, he then read the product information
: `" N, |, r" q! t2 a3 I& [- j0 b ]( d9 Zpacket and concluded that it was most likely the rea-2 H. y. ?$ M+ _4 C1 n) Q
son for the child’s virilization. At that time, they
9 D$ l$ O0 E, V2 Pdecided to put the baby in a separate bed, and the
' [7 ]! R. s" _# ifather was not hugging him with bare skin and had: R( n4 s: u5 r, a6 i8 T1 u
been using protective clothing. A repeat testosterone. A+ T% p4 |& f/ m% x$ R
test was ordered, but the family did not go to the
$ h3 T; z' d% F7 e3 q9 u/ `laboratory to obtain the test.
3 ^$ n8 T: y2 t9 NDiscussion- T" P( S- c4 F2 n) D+ j
Precocious puberty in boys is defined as secondary2 W* S" J8 l- E5 M" H
sexual development before 9 years of age.1,4
5 P6 s- F2 H& C1 XPrecocious puberty is termed as central (true) when8 t. j$ e$ D7 ?8 a$ \
it is caused by the premature activation of hypo-
: d3 `8 u8 w3 o8 E' l" v+ a3 Athalamic pituitary gonadal axis. CPP is more com-" w1 i4 P5 w$ j7 @9 q
mon in girls than in boys.1,3 Most boys with CPP$ U2 y+ D% i- A7 ^
may have a central nervous system lesion that is9 W' J! N4 T1 W7 n% y
responsible for the early activation of the hypothal-% _3 c8 K1 H9 I! {- Z' b8 j0 u
amic pituitary gonadal axis.1-3 Thus, greater empha-1 |7 N& A0 R( M2 C" u8 O% ~
sis has been given to neuroradiologic imaging in! i& }& O( y% c" Z5 k, k# Z0 w% r! w
boys with precocious puberty. In addition to viril-1 [! t0 i* i, ~5 }) k. d
ization, the clinical hallmark of CPP is the symmet-
, j5 Q% U" p2 K& ^% B- yrical testicular growth secondary to stimulation by
h6 g& t) Q* ~$ cgonadotropins.1,32 L$ Y; X# W2 u
Gonadotropin-independent peripheral preco-# U# h4 m7 a- Z. ~& d
cious puberty in boys also results from inappropriate C) \9 M# h0 y; B; g3 ?! g
androgenic stimulation from either endogenous or
, }: w5 a. `. g3 h: I5 xexogenous sources, nonpituitary gonadotropin stim-
! {. }6 V0 p6 h$ v- C/ Zulation, and rare activating mutations.3 Virilizing4 i6 y0 p, v9 B: ]! L- K
congenital adrenal hyperplasia producing excessive
% D& W: I3 L0 g. m5 N/ y$ gadrenal androgens is a common cause of precocious
0 m. d9 S6 O T; }- Qpuberty in boys.3,4- _/ c+ H, h7 t/ p
The most common form of congenital adrenal( |/ o+ E7 H+ H, r' e% u
hyperplasia is the 21-hydroxylase enzyme deficiency.$ X5 u7 ?, G/ E
The 11-β hydroxylase deficiency may also result in/ t5 g& X( o. C
excessive adrenal androgen production, and rarely,% P# w( m v1 U4 Q+ ]% q6 t
an adrenal tumor may also cause adrenal androgen
# d" v3 N0 s# w. L. N0 R/ T+ x% _excess.1,3
6 T% M3 K( c o& S t2 Y2 ?at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from4 u- p$ }* K. H; k5 T
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
0 n4 R8 P/ \3 v2 c5 N. b, KA unique entity of male-limited gonadotropin-
4 O4 s6 W/ l. h, j5 k. K/ g- Bindependent precocious puberty, which is also known5 U0 I h6 z# f" _3 E) t, l7 }
as testotoxicosis, may cause precocious puberty at a
8 Q& g6 K, M+ Tvery young age. The physical findings in these boys7 ` x0 Y1 ^% a/ i" c
with this disorder are full pubertal development,
2 i+ X& {. m7 e$ X& i, [including bilateral testicular growth, similar to boys/ k: X; |6 W" z* @' q2 m
with CPP. The gonadotropin levels in this disorder
. [ O7 l/ E$ J4 I" k- B* lare suppressed to prepubertal levels and do not show
6 T; C4 r* v* y4 o1 hpubertal response of gonadotropin after gonadotropin-' a$ M% }! G$ @4 U
releasing hormone stimulation. This is a sex-linked5 ?* g4 B# i: x7 O, O' R# E
autosomal dominant disorder that affects only2 { g8 g h; C% R
males; therefore, other male members of the family5 R9 n9 p& q) o; u
may have similar precocious puberty.3 U6 V% `. J3 a0 z* Y7 r
In our patient, physical examination was incon-0 y7 h7 y1 l8 v9 h' M2 F8 F, }
sistent with true precocious puberty since his testi-0 j$ w) }+ Z) V" R- {* \
cles were prepubertal in size. However, testotoxicosis
/ o/ |1 L7 _) k% h. Q9 D# `8 Z4 B( Swas in the differential diagnosis because his father& m" m, A; L- A' S8 X9 a5 U
started puberty somewhat early, and occasionally,( l( [2 v# b' J" y) g3 F) t
testicular enlargement is not that evident in the9 r& B0 G3 _/ m" z7 ]
beginning of this process.1 In the absence of a neg-
* f# J: |5 r) R8 ?2 {5 j9 Sative initial history of androgen exposure, our
/ N! I4 D- v* i" R/ e' ^biggest concern was virilizing adrenal hyperplasia,/ l5 {% Q6 h! W
either 21-hydroxylase deficiency or 11-β hydroxylase
( W3 H+ K6 x4 g, e: O: F) A1 V6 ddeficiency. Those diagnoses were excluded by find-
9 s# U: y& b) n4 x% aing the normal level of adrenal steroids.
/ L v6 K( A% v, z H% L4 fThe diagnosis of exogenous androgens was strongly! A+ K0 ~. x2 q! U) A
suspected in a follow-up visit after 4 months because
. w1 Y/ |. _$ p9 Cthe physical examination revealed the complete disap-
; A3 u8 m' u# [& _: @: O# q# q& q8 Kpearance of pubic hair, normal growth velocity, and
( m! [; V; f+ `3 L( S0 pdecreased erections. The father admitted using a testos-; B. w A/ _0 E
terone gel, which he concealed at first visit. He was5 b% }" [+ T+ _; [7 Y
using it rather frequently, twice a day. The Physicians’1 ^/ k. c: F/ E$ Y/ {! P, K
Desk Reference, or package insert of this product, gel or& l X, F5 \3 u5 W- V# I
cream, cautions about dermal testosterone transfer to/ j9 k' T$ ~: X; N
unprotected females through direct skin exposure.
" A2 Q; e% U+ q& WSerum testosterone level was found to be 2 times the/ s, k& R3 ~- J/ U! u- M! ~. Y0 c
baseline value in those females who were exposed to0 p, b# R U" Q d* Z" i$ P2 l V
even 15 minutes of direct skin contact with their male8 n6 @9 m5 W. b. W
partners.6 However, when a shirt covered the applica-! @3 k! U7 ~5 N) I4 y- i; a8 X7 ^
tion site, this testosterone transfer was prevented.
* i& t' X- O1 r3 D, s+ A; @3 YOur patient’s testosterone level was 60 ng/mL,
( e/ v1 X* H2 J' S5 _( p) D+ Wwhich was clearly high. Some studies suggest that
7 P5 M; u0 v% e# r/ ]/ `( xdermal conversion of testosterone to dihydrotestos-. I9 ]9 A$ H. d
terone, which is a more potent metabolite, is more
m' B, r# Z4 y8 A, r/ F; y5 Factive in young children exposed to testosterone: L. u# d" i3 r$ G+ { Q' l
exogenously7; however, we did not measure a dihy-
! ]# `9 {% h) b" ^# B% ldrotestosterone level in our patient. In addition to
, [) d# r) r$ v$ m9 `; w: _virilization, exposure to exogenous testosterone in
( k! b* z: a5 `* ?8 t- i& hchildren results in an increase in growth velocity and
" D8 O. n9 Y& hadvanced bone age, as seen in our patient.5 Q" Y" @3 C1 M, I9 s8 ?& Q
The long-term effect of androgen exposure during
9 \; ~* F, @5 H6 w5 v0 mearly childhood on pubertal development and final
8 v* \6 d* h0 H3 s; M, b8 g9 n) Nadult height are not fully known and always remain
7 k5 k$ x4 h3 e4 T+ Ra concern. Children treated with short-term testos-! a' i+ v7 k* W0 \3 V5 i
terone injection or topical androgen may exhibit some' m; r6 _3 T% [
acceleration of the skeletal maturation; however, after/ v6 L( o$ J2 V, R
cessation of treatment, the rate of bone maturation
4 [8 i* W; T0 Udecelerates and gradually returns to normal.8,9
* l. W8 n7 u: Z9 S3 G; d# R' rThere are conflicting reports and controversy2 J, P& p2 b( @
over the effect of early androgen exposure on adult
( [' P7 @! n% k; s4 Dpenile length.10,11 Some reports suggest subnormal
2 [ }- R" Y) h' r$ ?+ ~& L. W4 w# hadult penile length, apparently because of downreg-, K$ H' _" }6 J" F! v0 X4 G
ulation of androgen receptor number.10,12 However,
) R6 w- ]; X7 l) \2 sSutherland et al13 did not find a correlation between
3 f1 j* [/ `7 r: Xchildhood testosterone exposure and reduced adult
( Z9 a8 W' S, H8 Y3 m) N' qpenile length in clinical studies.5 u# \+ ^9 X1 d' g. i5 `
Nonetheless, we do not believe our patient is# @) @+ z7 ~" Z" v
going to experience any of the untoward effects from
/ ?4 {5 m' M& S5 _: ]& Dtestosterone exposure as mentioned earlier because
3 ^0 k; @7 n( v$ G' Ethe exposure was not for a prolonged period of time.
: `+ K1 z6 U# H: eAlthough the bone age was advanced at the time of; U! c: E. F- u
diagnosis, the child had a normal growth velocity at/ `$ n' f) y C
the follow-up visit. It is hoped that his final adult
' h h# w0 h- _! S4 q! Kheight will not be affected. Q7 Q) y4 v6 P7 |
Although rarely reported, the widespread avail-
$ m. t, ?: | m Z0 q/ Qability of androgen products in our society may
* F0 N5 U6 M/ e m) J. w0 R& Iindeed cause more virilization in male or female9 E: |1 M. |) r/ d/ z3 T* Y
children than one would realize. Exposure to andro-8 Y% z& J5 X! c$ W
gen products must be considered and specific ques-1 d3 m; D& b7 _- x8 E
tioning about the use of a testosterone product or1 a. _+ n) V5 g, |6 o7 R* s
gel should be asked of the family members during. O8 S8 q' a: \, H0 `( [
the evaluation of any children who present with vir-( U5 |6 W' ]/ H3 ^9 h9 J
ilization or peripheral precocious puberty. The diag-
$ a+ C5 d$ m/ Q; r' G/ J hnosis can be established by just a few tests and by# u' R- v( W7 q
appropriate history. The inability to obtain such a# w( R3 |0 ^/ Q$ H5 ]. d* R
history, or failure to ask the specific questions, may0 V4 h# }5 E. z% s* N0 T
result in extensive, unnecessary, and expensive% e0 m' y4 R9 t8 G. N8 I
investigation. The primary care physician should be
% k/ r. x5 E- m: [; @8 A) [( Haware of this fact, because most of these children
2 Q: R2 C* H0 @3 @0 U# x$ B* hmay initially present in their practice. The Physicians’& T& D6 j+ F" n1 T/ |
Desk Reference and package insert should also put a
' Y. B, y* H N8 _" X% |* W+ ]warning about the virilizing effect on a male or
1 X6 f6 N. q2 m: Zfemale child who might come in contact with some-5 n6 R+ q1 t$ w2 p+ s, p9 Y$ s$ |
one using any of these products.7 y$ K8 R d" q$ O
References) d5 m7 y! x+ U2 [
1. Styne DM. The testes: disorder of sexual differentiation$ \! P' u5 |0 G- ~- z8 H: x8 u
and puberty in the male. In: Sperling MA, ed. Pediatric
9 I1 X' d1 e8 k+ c6 FEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;4 E# i" i3 Z( @) P0 G
2002: 565-628.) O6 H" e9 {" q0 @' Q* ^
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious3 n1 L; |7 N3 {: \/ o3 L9 t
puberty in children with tumours of the suprasellar pineal |
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