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Sexual Precocity in a 16-Month-Old/ s* L# ~) N( X( {# I; n
Boy Induced by Indirect Topical- }. w& l9 G% e5 W; l
Exposure to Testosterone" b U+ R' z. e- p0 m3 ~. ~$ w
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
" W# t5 w2 S8 F) V9 R2 l! l! _and Kenneth R. Rettig, MD1
, e2 @3 u+ }; b2 a7 w8 A3 ^Clinical Pediatrics! ~, g- r" t q. [; E: ~$ [
Volume 46 Number 6
* c( l* b; [9 g2 m: GJuly 2007 540-5434 o8 K: f1 Y/ P$ R" Z
© 2007 Sage Publications
+ I1 |3 ^" W$ d, s, z10.1177/0009922806296651( o. |& g9 D, Q; j# Q
http://clp.sagepub.com5 g( M. P" D9 e+ i P+ G
hosted at
. |' L! A$ t+ ]http://online.sagepub.com& G4 x( O0 T7 K; o
Precocious puberty in boys, central or peripheral,
: l+ ^8 V% T2 S) O3 Ois a significant concern for physicians. Central8 o, R. \9 _; G' I$ Q8 V" F0 U
precocious puberty (CPP), which is mediated
7 Y. T3 g! L: h& L. ythrough the hypothalamic pituitary gonadal axis, has
, d! T6 L6 Z( b' xa higher incidence of organic central nervous system
* R. R# c+ o- Y4 k blesions in boys.1,2 Virilization in boys, as manifested1 {6 l$ a. F( C1 q
by enlargement of the penis, development of pubic
- f% L8 I# j _! S- mhair, and facial acne without enlargement of testi-
r5 N. K, N% U& L+ K- R s. Ccles, suggests peripheral or pseudopuberty.1-3 We
2 v# Z' e% `" ~9 Freport a 16-month-old boy who presented with the
3 Z# o& t9 j4 fenlargement of the phallus and pubic hair develop-4 p, R7 G# O( {) z
ment without testicular enlargement, which was due
$ ^7 e/ e( r4 v2 p( S/ Fto the unintentional exposure to androgen gel used by9 M. N. D- S7 P0 f5 u9 ]8 Z
the father. The family initially concealed this infor-: X6 p, A& _9 b$ e* D
mation, resulting in an extensive work-up for this
: m( Q/ S% `* A9 \3 Z$ Qchild. Given the widespread and easy availability of4 v5 c7 \$ \# {4 K3 j- r8 O$ j
testosterone gel and cream, we believe this is proba-
* V: p2 R7 P7 R* P9 Lbly more common than the rare case report in the) n( b5 f) O" h
literature.4/ m6 b& X# t* R& I* {& A. [
Patient Report
- N/ _! c( k7 q' z# kA 16-month-old white child was referred to the
+ o# B8 U3 d8 i) E! ?: fendocrine clinic by his pediatrician with the concern
- f. b. X7 u2 y/ X5 D3 Gof early sexual development. His mother noticed9 ?5 v) S$ a8 N% x; m* H% P8 y
light colored pubic hair development when he was* O) F# r/ r) U; n& \
From the 1Division of Pediatric Endocrinology, 2University of5 ~9 l& s, m, q; P% E6 A% K
South Alabama Medical Center, Mobile, Alabama.
. I, T, r; D# u- y) |/ p8 t% zAddress correspondence to: Samar K. Bhowmick, MD, FACE,# F' a; L8 H# R: a
Professor of Pediatrics, University of South Alabama, College of
; z( k* l3 Q/ Z2 L3 s. G4 T7 b- UMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
+ k5 T# V2 ]& n3 J1 De-mail: [email protected].
1 Z0 [* j6 k- z( ]) |2 [6 X8 Mabout 6 to 7 months old, which progressively became1 I' C6 U) H, \/ t- [7 J9 i7 Q: g
darker. She was also concerned about the enlarge-
' v9 d! p% Q2 H# k2 ^2 Yment of his penis and frequent erections. The child
! i/ {3 Y; g# awas the product of a full-term normal delivery, with
5 Q# t) y" a9 t3 t, O% xa birth weight of 7 lb 14 oz, and birth length of
; M; K; v5 W# E$ y20 inches. He was breast-fed throughout the first year! A, P Y$ y5 @2 O; `
of life and was still receiving breast milk along with
4 S3 ?6 H( p6 r* R1 e/ Bsolid food. He had no hospitalizations or surgery,5 S8 f0 j6 Z; P: E+ L
and his psychosocial and psychomotor development: b$ a# t0 n5 H; |" s9 W
was age appropriate.
! P8 [ S4 _: RThe family history was remarkable for the father,( [0 N. X$ {# l" O
who was diagnosed with hypothyroidism at age 16,
. B8 N+ M7 x1 J6 e* i e2 Jwhich was treated with thyroxine. The father’s) W3 d1 Q1 } [8 U* x
height was 6 feet, and he went through a somewhat5 |" }0 d+ e. [5 J5 V
early puberty and had stopped growing by age 14.
/ A9 `$ Q% ^- E9 B" Y/ ?) LThe father denied taking any other medication. The
3 O2 C" Z' _( n1 Zchild’s mother was in good health. Her menarche
, K# Q" V u1 [# ?! Y" r% h; pwas at 11 years of age, and her height was at 5 feet
6 D6 t' V7 j& {: d9 G6 m5 inches. There was no other family history of pre-
6 d) O7 C. t" _0 v0 f: J9 E$ @' ococious sexual development in the first-degree rela-: h+ Z$ e- [9 g
tives. There were no siblings.3 w' n# ^" ]3 a* o
Physical Examination0 c8 ?2 S Z2 r) p
The physical examination revealed a very active,* T& Z* G& a R1 L: {* t
playful, and healthy boy. The vital signs documented
/ Q8 k" r j: ba blood pressure of 85/50 mm Hg, his length was2 `; ]3 E }' k% a! R6 A
90 cm (>97th percentile), and his weight was 14.4 kg' x: p8 a- C3 L5 w% ~
(also >97th percentile). The observed yearly growth
% ?, C/ E- ?3 I8 ?( |% @, Uvelocity was 30 cm (12 inches). The examination of# p% P; N; t1 n! r( T! T) w$ V
the neck revealed no thyroid enlargement.
* |9 T' c- q/ W1 ^. N0 v- bThe genitourinary examination was remarkable for
2 [+ [# O& W1 O* {enlargement of the penis, with a stretched length of
/ _( J9 c; |% Z0 i' W6 q8 cm and a width of 2 cm. The glans penis was very well$ l s2 `: _' k9 L( k
developed. The pubic hair was Tanner II, mostly around
# E8 R4 x8 e2 P% @) F# ^+ [; K540 _) z% c) ] T9 R
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from& Z0 O4 q0 s8 ^) {5 c; t$ ]0 u+ R- l+ t
the base of the phallus and was dark and curled. The
) I) E/ P- \% i8 S; x7 ntesticular volume was prepubertal at 2 mL each.
5 F5 j- B# B |+ u6 xThe skin was moist and smooth and somewhat
7 {8 L- ?& |/ y' ioily. No axillary hair was noted. There were no
/ C- _3 G. s6 ], Q' P1 V4 N0 d4 Zabnormal skin pigmentations or café-au-lait spots.& P1 I* }0 G A T
Neurologic evaluation showed deep tendon reflex 2+
? v3 A( j1 {' b5 Obilateral and symmetrical. There was no suggestion. c# m" f/ ?, y8 Q0 ~. j9 b4 i
of papilledema.
# r& M Y: E M: e% C& lLaboratory Evaluation; @) o7 f8 u0 Z) F" R1 [
The bone age was consistent with 28 months by1 B/ ?/ x; C$ j# l7 D
using the standard of Greulich and Pyle at a chrono-5 c. p7 S; k+ M8 H
logic age of 16 months (advanced).5 Chromosomal
( L2 n% e3 s/ vkaryotype was 46XY. The thyroid function test
1 E# n( [0 y- H# D; ]1 ~* }9 Ashowed a free T4 of 1.69 ng/dL, and thyroid stimu-
. Z% V# Q3 ]' e8 ?! i2 Qlating hormone level was 1.3 µIU/mL (both normal).
! {' g( ^6 }# f' L! C6 A4 i! _The concentrations of serum electrolytes, blood
( H/ a) }$ H: Y5 W1 {urea nitrogen, creatinine, and calcium all were# F) E& n4 z& I; p0 ?0 E
within normal range for his age. The concentration
3 a7 B, m0 E/ T* dof serum 17-hydroxyprogesterone was 16 ng/dL
9 D/ S1 S+ F- x4 Z* H2 ^/ C(normal, 3 to 90 ng/dL), androstenedione was 20
9 k9 n* \# A5 C' v# Q& Wng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-9 ]4 R5 J1 H* C0 |( v8 K8 K
terone was 38 ng/dL (normal, 50 to 760 ng/dL),/ `3 w- G+ [' @" F6 l2 N
desoxycorticosterone was 4.3 ng/dL (normal, 7 to s# H2 ~8 C# f8 `
49ng/dL), 11-desoxycortisol (specific compound S)+ b5 w) H4 l8 Z* }; Z, M
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
; b* X7 ?- o) @& J' jtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
* r9 n! N+ A* D, _; p U1 }7 \2 [testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
1 w/ y' q$ G- ? E" jand β-human chorionic gonadotropin was less than
% F8 [$ @: ]+ q( m6 d+ g$ f, t5 mIU/mL (normal <5 mIU/mL). Serum follicular3 m) C# @( S! }" { n% n
stimulating hormone and leuteinizing hormone4 q: |. ^. ]6 A1 G6 o. {" x+ W2 k
concentrations were less than 0.05 mIU/mL1 K1 j* C1 C, X+ N8 N# J
(prepubertal).3 B; J- b1 O! `0 \* U
The parents were notified about the laboratory" o: D6 b6 f S! M+ B* f* y) X8 W- k
results and were informed that all of the tests were9 H: b$ h- V$ ~: H! M
normal except the testosterone level was high. The+ w8 T4 N: \1 F. T
follow-up visit was arranged within a few weeks to
. d2 y1 X# S+ z+ d' F- \6 Robtain testicular and abdominal sonograms; how-$ R! h" m7 n! ?. s
ever, the family did not return for 4 months.
$ V; m) T; _7 `' r5 o; S& FPhysical examination at this time revealed that the# y3 k0 B( p! q! I/ G0 r5 M
child had grown 2.5 cm in 4 months and had gained
2 u( L6 G) W% v( q2 ^7 D2 kg of weight. Physical examination remained2 }- K! j6 O9 ?) ^' r( f
unchanged. Surprisingly, the pubic hair almost com-$ i* q* J' R" S. _! _4 e6 Q
pletely disappeared except for a few vellous hairs at- T* X" Z' F0 g) p5 s
the base of the phallus. Testicular volume was still 2
+ X' c. f$ n% P" v# J, i% [4 W/ ?mL, and the size of the penis remained unchanged.
6 A' u- P( b5 C X+ x) B: tThe mother also said that the boy was no longer hav-
9 x0 |' g4 L7 V) S3 Xing frequent erections.
( M% z% f, E" D5 ZBoth parents were again questioned about use of: W* M) B% e' B- p/ V7 C) U$ [
any ointment/creams that they may have applied to
& i2 V/ H, m- w l# Q; F' v7 x' ethe child’s skin. This time the father admitted the
7 R2 A4 a: c. t% z( ^Topical Testosterone Exposure / Bhowmick et al 5416 G' w% }" V4 _" E
use of testosterone gel twice daily that he was apply-
, i# l. [4 J5 M* o7 fing over his own shoulders, chest, and back area for2 D; ^& N- N+ K, }+ ?4 b" L
a year. The father also revealed he was embarrassed
( q {6 u; U- J- n, v/ K' I) gto disclose that he was using a testosterone gel pre-4 H' G( v$ I( H" o# ~* `1 l
scribed by his family physician for decreased libido
5 K" w4 {1 L0 @; E8 N! wsecondary to depression.
" N; g2 v& v( M! f9 MThe child slept in the same bed with parents.
! I2 T1 P- G4 C/ }The father would hug the baby and hold him on his9 Y9 Y1 z+ g4 x R& i
chest for a considerable period of time, causing sig-6 y( d8 U# l! j
nificant bare skin contact between baby and father.) Y) c! w0 v' S
The father also admitted that after the phone call,% P. `% R0 r; B2 `+ A) k) C
when he learned the testosterone level in the baby
$ G* w# Q1 p) W, Q( } V P) owas high, he then read the product information) b: O4 e9 ~5 y3 S4 G$ q2 \
packet and concluded that it was most likely the rea-$ ~8 I5 a, m5 d; e: i2 {4 u6 P! ]1 Y
son for the child’s virilization. At that time, they* U3 d! v. I, [" K: i) B
decided to put the baby in a separate bed, and the* Z4 |3 \+ _+ X
father was not hugging him with bare skin and had2 C/ N2 s8 B" R. f6 i+ O
been using protective clothing. A repeat testosterone6 {: S$ N# M1 f, N
test was ordered, but the family did not go to the
7 X& z/ y. Y! h6 O* blaboratory to obtain the test.: |( [8 m: P9 f
Discussion
# E4 Q L/ M6 ?Precocious puberty in boys is defined as secondary
" w# F- h! W6 G @sexual development before 9 years of age.1,4
- l+ n9 \- x( w; N Q5 n* mPrecocious puberty is termed as central (true) when
+ G" K1 [! F# S6 _it is caused by the premature activation of hypo-
' V3 k0 O% J9 d. q+ q" ithalamic pituitary gonadal axis. CPP is more com-
& Y! c V- w6 X: e7 Umon in girls than in boys.1,3 Most boys with CPP5 t9 o) l N; v
may have a central nervous system lesion that is, b4 A$ G* |7 i" Y# f* ~% I
responsible for the early activation of the hypothal-
% x6 F+ j( V; A6 `2 d; x' Jamic pituitary gonadal axis.1-3 Thus, greater empha-
) i7 U8 y( b" f# dsis has been given to neuroradiologic imaging in7 B2 J. A$ ]* d! [4 V- b) }1 B- o. Z
boys with precocious puberty. In addition to viril-$ ]/ h, i j& z+ M% B9 A
ization, the clinical hallmark of CPP is the symmet-
9 Z9 U* `0 B9 G6 grical testicular growth secondary to stimulation by! h' O7 U) g( k& O( t. z1 Y9 T
gonadotropins.1,38 j9 z; i2 Q# {. T# B/ v' F* M
Gonadotropin-independent peripheral preco-
+ D& i* D. v2 {" u$ j9 ycious puberty in boys also results from inappropriate
$ z, U3 }6 d$ |" R9 kandrogenic stimulation from either endogenous or
5 T6 _. k1 S2 s( ^) |; Rexogenous sources, nonpituitary gonadotropin stim-
0 q5 e# E' X2 c. gulation, and rare activating mutations.3 Virilizing9 _: k" N% [/ T" ?3 M
congenital adrenal hyperplasia producing excessive
& ]1 ?* z0 Y6 c4 O C* Ladrenal androgens is a common cause of precocious
3 W- g2 |/ t- c, r+ t1 o/ {2 G5 mpuberty in boys.3,4
! }0 E" k, Y; s# N+ R/ kThe most common form of congenital adrenal/ j0 h- \7 O: `& _$ Y
hyperplasia is the 21-hydroxylase enzyme deficiency.* a9 X% x/ [% N4 r
The 11-β hydroxylase deficiency may also result in
' T1 g7 Y4 b; k! O7 j5 U2 Bexcessive adrenal androgen production, and rarely,( q1 Q* t- G. r3 n
an adrenal tumor may also cause adrenal androgen; Q9 \' L8 u) W3 h' T
excess.1,3% ~; M2 e. }0 h1 E* |% `
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from$ F/ e. H; V, q q: @
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
7 H3 |& I c; ]# bA unique entity of male-limited gonadotropin-1 R0 ]( J/ K2 g! t9 x
independent precocious puberty, which is also known
0 e9 @: }/ j" C+ C3 D4 Has testotoxicosis, may cause precocious puberty at a
% X9 C! r% u3 @% _2 Ivery young age. The physical findings in these boys6 k% w" ~. `# ~6 G7 J) U
with this disorder are full pubertal development,2 m# d& Y, U4 I( F2 q# D
including bilateral testicular growth, similar to boys) J( d- M% ]$ g, o" W
with CPP. The gonadotropin levels in this disorder
( |# t# K+ O* ~5 ware suppressed to prepubertal levels and do not show
/ z1 `1 F% y! D2 I' x. Bpubertal response of gonadotropin after gonadotropin-
* H8 Y- v! R& N: ]' i# X) @9 jreleasing hormone stimulation. This is a sex-linked5 |6 R) X2 s, @" g
autosomal dominant disorder that affects only' U/ C3 [+ G; \4 |) C. v7 |; p
males; therefore, other male members of the family+ m: `2 x$ s- ^4 b& c6 o) P8 W
may have similar precocious puberty.3
3 f V! A3 x+ [+ z9 K3 |7 PIn our patient, physical examination was incon-
0 M4 R% ]1 W6 c& i$ Ysistent with true precocious puberty since his testi-& L. u, S m& g5 E2 z5 Q
cles were prepubertal in size. However, testotoxicosis# |( V; V4 V+ K3 c. ^' T& ?: B
was in the differential diagnosis because his father# p& A+ j/ R5 i3 g( H5 c
started puberty somewhat early, and occasionally,: v! N* e+ H, q( F
testicular enlargement is not that evident in the
$ y) ?$ w+ M6 Z4 j3 Y% n. fbeginning of this process.1 In the absence of a neg-
( E- t m& `% c c7 Y& h) jative initial history of androgen exposure, our
% |& v) ?* t) w% O. P7 I N9 xbiggest concern was virilizing adrenal hyperplasia,
: t+ C6 h. ]# q, R0 g6 Yeither 21-hydroxylase deficiency or 11-β hydroxylase
' Z% ^) b5 p1 I: sdeficiency. Those diagnoses were excluded by find-
7 f K: J; C) k0 E6 k$ m. z5 V% a- ting the normal level of adrenal steroids.( Z7 C4 l. u, x' c3 F
The diagnosis of exogenous androgens was strongly
X, Q- M8 N. D6 w$ t% h W6 k/ \9 j( E! Ssuspected in a follow-up visit after 4 months because. A/ _0 M" m: \0 q: r5 H s$ ^
the physical examination revealed the complete disap-
8 m, o" T$ ]- Y! n/ E! f6 [; C5 hpearance of pubic hair, normal growth velocity, and
9 n8 p( L; a& E9 |) A: I5 Idecreased erections. The father admitted using a testos-
8 J) e. r5 Y( H. oterone gel, which he concealed at first visit. He was
0 [/ Q7 U, f; `1 m" p vusing it rather frequently, twice a day. The Physicians’$ d0 v* r' ]+ p+ K4 c8 M; o
Desk Reference, or package insert of this product, gel or
6 o( L5 U8 h. a! J0 o' C, @cream, cautions about dermal testosterone transfer to8 N; ^1 n- `# r9 q/ E" h
unprotected females through direct skin exposure.
7 u; Q, G2 X! z3 A# |Serum testosterone level was found to be 2 times the6 P+ z1 ~) i. y8 U$ _ v5 ~
baseline value in those females who were exposed to
. r* z6 B4 T N$ yeven 15 minutes of direct skin contact with their male
" E# D* o& r( J0 ]) R/ Lpartners.6 However, when a shirt covered the applica-
- E* O+ ?9 ]( Q6 W: s rtion site, this testosterone transfer was prevented.
' {) m0 t1 c5 [8 p: V* R( s6 nOur patient’s testosterone level was 60 ng/mL,% t6 F0 v# Y5 ?& W/ a
which was clearly high. Some studies suggest that: ^" Z, O3 I* g" n, y2 \/ W
dermal conversion of testosterone to dihydrotestos-) h! s- K& C8 ~7 o
terone, which is a more potent metabolite, is more
: v9 z- a3 Y6 V1 f a9 pactive in young children exposed to testosterone
% G6 X8 S$ q$ W _: Q& z" w2 _/ ?' y4 T; _exogenously7; however, we did not measure a dihy-; O: D* m# i$ i2 y, x; \1 c
drotestosterone level in our patient. In addition to
; w& {9 Z8 o2 {- xvirilization, exposure to exogenous testosterone in6 O/ I; N& x7 Z
children results in an increase in growth velocity and8 H% c( P% O: ~6 c* j7 l! f
advanced bone age, as seen in our patient.) |, Z/ D& ?+ f' ^" L7 C
The long-term effect of androgen exposure during
5 ?. f' Z& r" X' P& qearly childhood on pubertal development and final5 k f6 H9 k8 o) i' P. q
adult height are not fully known and always remain
0 P# c! b3 B# [a concern. Children treated with short-term testos-
& f( M3 i% h/ Q' w7 H9 @0 q& M/ T8 u- wterone injection or topical androgen may exhibit some
5 B; W/ F% z0 H) N1 f1 jacceleration of the skeletal maturation; however, after
' f! J1 y* i" J( T7 @4 q5 \ E- bcessation of treatment, the rate of bone maturation
$ {7 p/ `8 n" r7 edecelerates and gradually returns to normal.8,9* `8 S8 Z3 A- ~( Q: _
There are conflicting reports and controversy$ r% y: H X8 n/ t5 [) ^
over the effect of early androgen exposure on adult
2 I2 T+ |, \- |5 @ e# O8 `3 ipenile length.10,11 Some reports suggest subnormal) L& L4 S9 D1 r5 b8 U
adult penile length, apparently because of downreg-
F5 J- V8 j! ?7 m% T! q: i2 m0 b Uulation of androgen receptor number.10,12 However,3 h' ?. x9 @2 V( a" J
Sutherland et al13 did not find a correlation between
3 |! M: [ n% n* F+ y$ Bchildhood testosterone exposure and reduced adult% q" B) f# K/ @- b9 q
penile length in clinical studies.0 m/ G6 O2 C) K4 v1 j' S, s9 v
Nonetheless, we do not believe our patient is9 G& x0 e; c! j5 B2 v) U
going to experience any of the untoward effects from) @8 E) ?, i" Q" O/ r
testosterone exposure as mentioned earlier because8 P1 X4 D& {# S8 {/ @7 |$ _) B! S3 B
the exposure was not for a prolonged period of time.
+ Q. w2 P% G$ tAlthough the bone age was advanced at the time of& `/ n0 ]9 o, |; Z: l* C
diagnosis, the child had a normal growth velocity at9 D! a8 k* Y' K. g
the follow-up visit. It is hoped that his final adult3 | L, l1 l& m* W$ ?
height will not be affected.
' L" }' r- X, `! U" E& uAlthough rarely reported, the widespread avail-9 p) {- v/ v4 r+ }# o H# @3 y, Y
ability of androgen products in our society may1 K7 D. a! h, U& E, D4 P9 r
indeed cause more virilization in male or female
* L- W: y& j6 V' Y, I+ [) k2 q3 Hchildren than one would realize. Exposure to andro-
6 t% C5 Y/ X, I. hgen products must be considered and specific ques-$ w5 [0 s# D: F7 ~' M$ r
tioning about the use of a testosterone product or
; H. A8 \/ R* L/ Z( S, ~gel should be asked of the family members during
5 ]# S- n, {/ n6 j4 ]; athe evaluation of any children who present with vir-* h) N c- Y% t5 g
ilization or peripheral precocious puberty. The diag-; ^- T! ~! O( }' h8 O
nosis can be established by just a few tests and by/ H7 ^* P# W, u& V6 J. t9 a
appropriate history. The inability to obtain such a
) H) }; ]! T/ c4 E) Xhistory, or failure to ask the specific questions, may- D8 P/ Q& H+ j, \
result in extensive, unnecessary, and expensive* s9 k, z- V5 f6 `4 ~6 i
investigation. The primary care physician should be
9 c( L9 _ [# E$ {. eaware of this fact, because most of these children* s9 W; ~4 ?* b2 e
may initially present in their practice. The Physicians’% p6 X+ x! L3 }3 x
Desk Reference and package insert should also put a! q7 H% o p) p5 @$ d$ p& ]
warning about the virilizing effect on a male or
0 B: t0 l. Y5 \! R2 f! Pfemale child who might come in contact with some-" i4 D$ ^0 K# A$ d, @6 R/ {
one using any of these products.
. b0 Z7 \" x: A7 CReferences4 A# N K @8 C/ X3 X% l9 b
1. Styne DM. The testes: disorder of sexual differentiation2 o7 J1 V! P2 }1 a
and puberty in the male. In: Sperling MA, ed. Pediatric( ~4 G% \7 z+ M' M2 K n
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;- ] n( K' w u5 z2 p8 I" l
2002: 565-628.
7 K6 |8 a8 n! l! e# b, h2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
. f4 Y: a" Y0 C6 @- upuberty in children with tumours of the suprasellar pineal |
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