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Sexual Precocity in a 16-Month-Old# Q1 x" K. p6 ^' M
Boy Induced by Indirect Topical" A& j: l% N& ?* `4 Q: _
Exposure to Testosterone
A6 ?* m) L+ p. L$ ]5 E! WSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
! K1 i) q: T7 c, B+ H' i- u& dand Kenneth R. Rettig, MD1
|7 C' W9 N6 {) ] m% I, MClinical Pediatrics/ X6 c3 |% o3 m9 p0 }
Volume 46 Number 6
( W. `$ C4 T) B, AJuly 2007 540-543
5 x' D: }% d T© 2007 Sage Publications
! T5 ?. W9 B& A; X/ G10.1177/0009922806296651
' a9 b/ X+ f! e) i+ ?8 ahttp://clp.sagepub.com
( [, X N j$ E/ I$ Ehosted at% ^7 s, {7 t2 @; C
http://online.sagepub.com" b* K1 F# {4 j# w
Precocious puberty in boys, central or peripheral,
: |: }7 t; K& n4 ], N1 q3 cis a significant concern for physicians. Central' b( O, m, ? `$ q, B$ L! W+ Y
precocious puberty (CPP), which is mediated
3 x6 P, O" |. k& v2 S6 ~9 Pthrough the hypothalamic pituitary gonadal axis, has
; i0 r; J+ N& R" O+ `8 X4 G0 ea higher incidence of organic central nervous system
3 |8 {- y1 _& `& \- k$ a3 G) A3 Ylesions in boys.1,2 Virilization in boys, as manifested$ p- H' @, `8 o9 D6 u. I
by enlargement of the penis, development of pubic: I. g0 M3 M9 m, c+ \1 ~4 ^( w
hair, and facial acne without enlargement of testi-: c0 u( R$ e' p
cles, suggests peripheral or pseudopuberty.1-3 We6 N7 x1 j/ c$ W
report a 16-month-old boy who presented with the
1 j; M4 d5 X/ I5 nenlargement of the phallus and pubic hair develop-
* D5 {% ]6 q; M6 h9 V! mment without testicular enlargement, which was due
- [4 R3 A" i/ V) K$ wto the unintentional exposure to androgen gel used by5 ^6 i& Q f7 ?1 N5 v. |
the father. The family initially concealed this infor-
. l1 P: X, i4 r/ U: z/ rmation, resulting in an extensive work-up for this
% s* B. @# ~+ S! F r* D& B9 D4 Nchild. Given the widespread and easy availability of: e3 t; U8 @; R- R# s( k
testosterone gel and cream, we believe this is proba-
# V0 y# [ d$ ?: X! a, G& Z# xbly more common than the rare case report in the
$ \9 X9 z. L% y' M) H% F6 f, }literature.48 e( O& V" r+ K& v: x
Patient Report
3 A! {* g: Z$ p' eA 16-month-old white child was referred to the/ A% e8 P! J0 u+ _
endocrine clinic by his pediatrician with the concern$ o# L& E3 D- G+ J1 K; K/ R* O5 A; j* l# i
of early sexual development. His mother noticed) s8 N5 `+ R3 C
light colored pubic hair development when he was
/ k2 ?* n! q( `From the 1Division of Pediatric Endocrinology, 2University of
. ~" ^. _% L5 B3 c) a" `South Alabama Medical Center, Mobile, Alabama.# a1 [/ }8 o. ^5 t2 v! s
Address correspondence to: Samar K. Bhowmick, MD, FACE,
, X2 w2 a+ K# F% s; oProfessor of Pediatrics, University of South Alabama, College of
. N0 e. Q8 g1 O9 gMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
: f: q3 g8 o* f* Be-mail: [email protected].
! g& a* B& v% F0 o ]* \1 ^; Xabout 6 to 7 months old, which progressively became4 r- k. _! v, f3 E: F
darker. She was also concerned about the enlarge-0 a" ~: H4 o- h* c1 |; r
ment of his penis and frequent erections. The child
" I4 e" ?) {$ N/ R6 [$ zwas the product of a full-term normal delivery, with( p* E% V# M2 @* `) m9 Z
a birth weight of 7 lb 14 oz, and birth length of- }, Y) ]8 F% \, |1 `
20 inches. He was breast-fed throughout the first year
* t1 A- D0 Y$ Uof life and was still receiving breast milk along with
" O G, |( q3 u4 T6 X" I, _" Xsolid food. He had no hospitalizations or surgery,2 d) y+ |! J: o6 N
and his psychosocial and psychomotor development
( ]2 t8 ]2 e% @, m8 [was age appropriate.* D5 }( M4 X8 k2 V5 ~
The family history was remarkable for the father,8 s8 k K1 E* N& j" M1 d
who was diagnosed with hypothyroidism at age 16,! A5 k+ F# a5 J3 R1 K+ R3 g# ^
which was treated with thyroxine. The father’s5 t& Z! ?. Z4 {6 c
height was 6 feet, and he went through a somewhat: j3 M" G5 u4 T h4 P! d; ?& d) u
early puberty and had stopped growing by age 14.
! w7 ?9 `0 `, H; @The father denied taking any other medication. The( t! f1 v3 v. K! A* _9 p+ W
child’s mother was in good health. Her menarche9 W) v! Z7 j( f j' l+ ?1 x
was at 11 years of age, and her height was at 5 feet
6 I9 N) D& e( t* b; \+ x, M5 inches. There was no other family history of pre-
2 U6 {3 W! ?( j. Y' Bcocious sexual development in the first-degree rela-0 V, d+ o* J0 s3 `. j% K
tives. There were no siblings.
: X: U" G C) oPhysical Examination" e% a' n4 h; h5 ]- g; |/ i( _
The physical examination revealed a very active,
" H% @; x2 ~; G2 n/ [playful, and healthy boy. The vital signs documented& _: F3 ]2 A c4 Z" [6 ~# k9 R
a blood pressure of 85/50 mm Hg, his length was
q0 _ u# m; n. I& o' }90 cm (>97th percentile), and his weight was 14.4 kg. {5 E+ F6 H& z! N Z$ _
(also >97th percentile). The observed yearly growth
: P- Y2 ~9 d ]. d. a3 R9 k( Pvelocity was 30 cm (12 inches). The examination of- I9 j9 Z' B) R) G, T4 _
the neck revealed no thyroid enlargement.7 e$ |" {2 ~/ |" X# H- w i' Q
The genitourinary examination was remarkable for; ?* H3 M2 q, q+ v% g' |
enlargement of the penis, with a stretched length of' U& E( \! O$ [2 p
8 cm and a width of 2 cm. The glans penis was very well! Z9 f! \" t0 O' c, _8 L9 b6 N- t( a
developed. The pubic hair was Tanner II, mostly around
r& c) t; ~4 b8 q4 w5 ]6 T540
7 K) h: a4 z' B) G" Oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from F0 E- K+ F/ d1 U' m; \/ p6 y
the base of the phallus and was dark and curled. The
" B" U1 B1 a& h r* N5 R! J- `testicular volume was prepubertal at 2 mL each.6 U) y" ^& j2 u3 W& q) M2 y, d
The skin was moist and smooth and somewhat
: C, T& z z; m2 K4 k" {, voily. No axillary hair was noted. There were no6 g& m1 {0 _- U& r3 p$ D$ n
abnormal skin pigmentations or café-au-lait spots./ m+ p, o. E) N' y) K+ W
Neurologic evaluation showed deep tendon reflex 2+1 w7 x) s7 I0 o" I ~9 W
bilateral and symmetrical. There was no suggestion) ^) P6 _2 g, N1 L5 p/ I, N
of papilledema. M! \; X. L# `9 ` ]5 {0 f
Laboratory Evaluation- a% o4 q8 \5 g3 B4 y
The bone age was consistent with 28 months by
6 _6 {% S B" g8 O) b* K$ c* `using the standard of Greulich and Pyle at a chrono-; d; j& \- C5 x: x0 V3 X
logic age of 16 months (advanced).5 Chromosomal
& q- ~3 t7 B: Z8 Kkaryotype was 46XY. The thyroid function test
$ s! _& \% \, Tshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
, V. a8 n: d2 e4 e- a9 P8 E+ elating hormone level was 1.3 µIU/mL (both normal).+ i, ^ `# J& m( E: V- I/ v6 m
The concentrations of serum electrolytes, blood
$ N6 X5 [/ q8 ]/ Rurea nitrogen, creatinine, and calcium all were
1 m, F0 `; o5 C- L+ K5 a% Wwithin normal range for his age. The concentration' Y3 i* C2 Q& t2 C6 \
of serum 17-hydroxyprogesterone was 16 ng/dL( Q8 a/ l; `. O: u
(normal, 3 to 90 ng/dL), androstenedione was 20
2 O! i o G: L) W/ s/ F4 j( ]( l8 Png/dL (normal, 18 to 80 ng/dL), dehydroepiandros-7 q6 R+ c4 z& J+ U6 l1 o
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
' d- B$ a" l$ Wdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
9 g+ I2 C9 I7 F1 n4 F9 t, \( X49ng/dL), 11-desoxycortisol (specific compound S)' @7 D, ^7 o6 ~3 c. L
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
3 U6 C1 n" n7 ]tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total5 Z5 n8 ^7 T0 c$ f: Q9 Z3 f1 X! f8 |
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
. U# s4 D) {1 _- ?and β-human chorionic gonadotropin was less than+ ]8 ~( H2 l; C1 a' I4 u7 m
5 mIU/mL (normal <5 mIU/mL). Serum follicular- E. c6 b# J! M G
stimulating hormone and leuteinizing hormone
2 I7 _( }0 @: z4 X) Qconcentrations were less than 0.05 mIU/mL; h7 f8 s& m: r( O2 v4 q- @
(prepubertal).
8 W5 \+ ^! L& r8 {( _2 h- yThe parents were notified about the laboratory! D( W) @# N4 z( M) P- t0 B
results and were informed that all of the tests were* I" s4 Z/ `1 A) @
normal except the testosterone level was high. The
- I: J% r! J+ I5 Z. Q l9 N( G# Bfollow-up visit was arranged within a few weeks to
% j0 ^& s* `4 H* h3 m1 oobtain testicular and abdominal sonograms; how-) T1 U' a% v$ j+ X6 I8 F( ]
ever, the family did not return for 4 months.1 @% v+ T' Y$ T: Y* R% A+ U
Physical examination at this time revealed that the
, I) X3 S6 J$ p7 Fchild had grown 2.5 cm in 4 months and had gained6 q4 p3 U6 w% E4 A4 L i5 }$ L
2 kg of weight. Physical examination remained
6 `3 l1 S8 E/ K1 I3 e4 u% ]: [1 t0 h1 Aunchanged. Surprisingly, the pubic hair almost com-
" @* U7 f0 x! F! ] H O, Upletely disappeared except for a few vellous hairs at3 K3 u! `! U! p. j+ X
the base of the phallus. Testicular volume was still 2
) E6 X% ~6 j6 H, e4 u4 Z5 FmL, and the size of the penis remained unchanged./ _% S3 C( Y% K" R
The mother also said that the boy was no longer hav-
( i4 H: j* I* K9 z2 J5 ~ing frequent erections.: R Q0 Y( K, g' C5 s$ ?
Both parents were again questioned about use of. Q! v3 x; i. U9 Q5 i) x8 X
any ointment/creams that they may have applied to4 W. `- o R9 |, |* Q* \/ M
the child’s skin. This time the father admitted the
2 Y/ Y; X) g0 u+ CTopical Testosterone Exposure / Bhowmick et al 541) v3 E, t% {9 E, l; ]
use of testosterone gel twice daily that he was apply-
1 {$ I8 q' O% O( l) Y8 ting over his own shoulders, chest, and back area for
R' z; H; ?& Ya year. The father also revealed he was embarrassed
& h- g! s8 P- m6 \6 |to disclose that he was using a testosterone gel pre-/ F5 h& V- s9 M$ P$ v2 v1 M
scribed by his family physician for decreased libido
$ M! v2 Q4 i0 u% Nsecondary to depression.
' t: r8 ]) S% DThe child slept in the same bed with parents.
1 O* q2 R/ ^0 q8 n! j ?7 |* hThe father would hug the baby and hold him on his( b2 |! J- k$ S
chest for a considerable period of time, causing sig-( y- m% ?2 |! Z+ D, n) Z7 P8 n; _
nificant bare skin contact between baby and father.) |3 p* S5 {4 m" g
The father also admitted that after the phone call,
# p$ a1 D$ F# u cwhen he learned the testosterone level in the baby; c7 M$ w* ]( K1 o1 j: v$ C
was high, he then read the product information
- ]' C6 l X$ E# ]: C+ Z6 V: h7 Hpacket and concluded that it was most likely the rea-* k2 w6 [: I" \# Q5 a8 j
son for the child’s virilization. At that time, they& s# E! V% O' _$ q7 V6 B% |# \: F
decided to put the baby in a separate bed, and the" R5 P9 T! H4 p' h% v) ]
father was not hugging him with bare skin and had% a3 L6 ^$ s4 i2 v& S
been using protective clothing. A repeat testosterone8 H9 o; R3 Z" {9 h9 L/ ?
test was ordered, but the family did not go to the
; q8 n7 ?4 E. L* h V# dlaboratory to obtain the test.
0 p0 N* F4 w$ a) N& VDiscussion
3 c# M; S" i& l/ x5 ~Precocious puberty in boys is defined as secondary. V% A0 a$ z& ]0 V0 B( y6 r
sexual development before 9 years of age.1,4- j8 V' ~: L7 S; o1 ^: {" b2 X
Precocious puberty is termed as central (true) when% ~% m( G" Y ^
it is caused by the premature activation of hypo-1 j+ \2 M" P1 |; J% Q
thalamic pituitary gonadal axis. CPP is more com-
$ W/ D/ r3 V( {" r0 `mon in girls than in boys.1,3 Most boys with CPP
+ d i( ~, b3 r& w+ tmay have a central nervous system lesion that is/ R2 C0 x0 M$ p9 F8 T5 J
responsible for the early activation of the hypothal-' Y3 l! c# @1 f
amic pituitary gonadal axis.1-3 Thus, greater empha-
5 M; g9 P! j- d5 i8 Y8 V+ _$ K# Tsis has been given to neuroradiologic imaging in
/ f" n2 n* e) X% u* n, R6 B4 Uboys with precocious puberty. In addition to viril-
' {- T. m7 S) G: {9 ?/ g' v5 Jization, the clinical hallmark of CPP is the symmet-1 k; v7 x- b b7 F/ R5 `* o
rical testicular growth secondary to stimulation by" \9 H: @! i3 U
gonadotropins.1,3" B- x# d3 g% p" Z% z
Gonadotropin-independent peripheral preco-6 y; d+ b/ J- v* n L
cious puberty in boys also results from inappropriate
5 b+ y6 f( v5 @, F- ?' dandrogenic stimulation from either endogenous or
! H' J/ s! a* q3 C, rexogenous sources, nonpituitary gonadotropin stim-0 h% K4 b0 A( a
ulation, and rare activating mutations.3 Virilizing
" R( A% b' A( Xcongenital adrenal hyperplasia producing excessive! s9 d/ l+ G) W! m) t0 P( Z. n/ ]
adrenal androgens is a common cause of precocious
' }+ P0 w6 E8 b. ~# x7 q9 Spuberty in boys.3,43 ?8 D. Q5 c" \3 O
The most common form of congenital adrenal
1 f: `. `. M5 s: bhyperplasia is the 21-hydroxylase enzyme deficiency.
" I# Z: b, v* H: r% PThe 11-β hydroxylase deficiency may also result in
( A# A5 Q% U8 v' \- Dexcessive adrenal androgen production, and rarely,
! A [: B( Z6 z/ ~! \% l" F( Han adrenal tumor may also cause adrenal androgen
4 K! q; [9 D; |# s1 Sexcess.1,3
, k: w# M9 `5 [, Gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from1 Q2 }: U& V7 T# _: F4 P
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
. ?) p, H$ U" y$ K% p- XA unique entity of male-limited gonadotropin-
`2 L; d p$ o( U8 Q Aindependent precocious puberty, which is also known
- s5 u: Y2 Z- J5 G# A+ i5 E/ `) ~' Uas testotoxicosis, may cause precocious puberty at a5 C( X/ {2 O6 w1 L2 ?6 {
very young age. The physical findings in these boys7 U- ]5 z. O6 S# A) ]8 k+ f8 ~
with this disorder are full pubertal development,
/ e; _+ E# z: Z* [, {1 V$ Tincluding bilateral testicular growth, similar to boys
! `6 E' { @ d j1 v8 Lwith CPP. The gonadotropin levels in this disorder
/ _" G" d) ]8 ~/ e2 Ware suppressed to prepubertal levels and do not show
" g+ }. @; o! `. @pubertal response of gonadotropin after gonadotropin-: ?' l4 m- B, Q9 R* H) c) Z# ^
releasing hormone stimulation. This is a sex-linked
( ~/ G$ L* K' yautosomal dominant disorder that affects only; |( O" Q+ B* ], x" @5 v* I1 [& D
males; therefore, other male members of the family e, H8 T! h7 L* {: E
may have similar precocious puberty.3# w8 M* _5 \$ I6 D$ g9 P
In our patient, physical examination was incon-
/ h1 d8 m$ o' a' s' A. ]sistent with true precocious puberty since his testi-
7 R- ~8 D$ g2 F& a( zcles were prepubertal in size. However, testotoxicosis( O" G7 O% _" f; b! C: U, }/ T/ J
was in the differential diagnosis because his father
8 i5 O6 T. [: ]7 ?( {9 I7 Fstarted puberty somewhat early, and occasionally,' \9 x8 W( Y$ | p, m
testicular enlargement is not that evident in the
# w e; A1 N9 q1 D# c1 pbeginning of this process.1 In the absence of a neg-0 W- m. f4 c0 ?
ative initial history of androgen exposure, our
7 A, D6 G; `# A# ?0 D( mbiggest concern was virilizing adrenal hyperplasia," H" t9 C, n9 J* H- W1 e
either 21-hydroxylase deficiency or 11-β hydroxylase
1 w; ^+ c9 u6 n$ [: Ddeficiency. Those diagnoses were excluded by find-' u3 c# Z4 X' | \0 e! p4 Q
ing the normal level of adrenal steroids.; Y$ Q7 C! I; n- x0 W0 t
The diagnosis of exogenous androgens was strongly$ A5 k& F" J& X8 H# p
suspected in a follow-up visit after 4 months because
- P; C9 k* O3 A' sthe physical examination revealed the complete disap-
* U8 |; O. | Y* Tpearance of pubic hair, normal growth velocity, and
# i4 a6 t% v0 {& {) ]$ f: z2 g: q9 S+ |decreased erections. The father admitted using a testos-! R- t2 V: M; d+ X) n1 t
terone gel, which he concealed at first visit. He was
- l: t* b( a0 S( I* {1 ousing it rather frequently, twice a day. The Physicians’
8 t0 E: l1 E a7 u: LDesk Reference, or package insert of this product, gel or
; g8 l) p# S9 _3 f0 h3 o) q& Gcream, cautions about dermal testosterone transfer to; Z. F, z' a% T C) Y/ v9 w
unprotected females through direct skin exposure.
: R! t( h) y5 s1 Z \/ WSerum testosterone level was found to be 2 times the4 A7 i+ R1 r; V6 C, l
baseline value in those females who were exposed to
% h8 Q* y2 r3 Q: n( m( L) `$ c5 e1 Reven 15 minutes of direct skin contact with their male
: e: M6 f& ~1 C, o9 j }& m1 Xpartners.6 However, when a shirt covered the applica-. e$ Z$ F0 M4 v s9 ]8 j4 M
tion site, this testosterone transfer was prevented.
; i% A8 ~! p6 J8 ]) t) AOur patient’s testosterone level was 60 ng/mL,
+ U4 r" K% u- }' a( y, a* }which was clearly high. Some studies suggest that
( }* V; P8 V9 N. D( q! L2 `4 M0 G. u9 vdermal conversion of testosterone to dihydrotestos-
$ i! V8 j: D4 Hterone, which is a more potent metabolite, is more
8 m: _4 J" V6 e" y3 ]active in young children exposed to testosterone
! ]" D/ Y. T/ ]% s! Uexogenously7; however, we did not measure a dihy-) c6 K$ q5 g/ X# X
drotestosterone level in our patient. In addition to: Y. |, V9 d/ e$ C0 g$ r
virilization, exposure to exogenous testosterone in; K9 e0 k* c& M7 s
children results in an increase in growth velocity and$ j( S6 y4 g8 l6 N: G4 ~& g1 ?+ u
advanced bone age, as seen in our patient.
# w+ Q% ~2 L+ C! e' |The long-term effect of androgen exposure during3 c. w0 g( N; i- g) f4 l# V
early childhood on pubertal development and final# r! `; C. L( w W/ b
adult height are not fully known and always remain! }5 I5 j$ U K6 r3 p8 A* H
a concern. Children treated with short-term testos-
: W6 L O! @* }+ b" Dterone injection or topical androgen may exhibit some
. Z. K8 H8 h) j% ]' r4 Yacceleration of the skeletal maturation; however, after
$ i; _2 }: @5 C- gcessation of treatment, the rate of bone maturation
9 t' m3 J4 N* T1 Z+ _/ |' ]$ B8 bdecelerates and gradually returns to normal.8,9- t% l9 ]$ m6 j" }3 L( e
There are conflicting reports and controversy8 U) t1 k. D$ W4 b- ]
over the effect of early androgen exposure on adult5 K6 w( M6 Z; ]
penile length.10,11 Some reports suggest subnormal( @; o( L# G) M) t
adult penile length, apparently because of downreg-
+ ~" F' k+ Q6 U2 dulation of androgen receptor number.10,12 However,
2 A+ {! a q5 `8 J) _2 \% nSutherland et al13 did not find a correlation between ~. o0 A* G2 W" k0 X+ _* k
childhood testosterone exposure and reduced adult
) [5 L _# `* ]3 G; Mpenile length in clinical studies.
3 t# ~. w/ ~) U9 O) o& xNonetheless, we do not believe our patient is: P# b- [% X) }4 X- b
going to experience any of the untoward effects from: Q0 h2 n. h/ Z, x
testosterone exposure as mentioned earlier because0 c$ _8 F( d+ ~, v
the exposure was not for a prolonged period of time.
8 b. {8 p' R$ Z& p+ I, WAlthough the bone age was advanced at the time of
: Q% ^- r& V2 Gdiagnosis, the child had a normal growth velocity at; X; R% w% E/ V' J+ z8 _( Y
the follow-up visit. It is hoped that his final adult
. W `: }) O* ^$ c) fheight will not be affected.7 K/ `! C' [1 W K$ h
Although rarely reported, the widespread avail-* L2 w: _7 C+ o) @
ability of androgen products in our society may4 J1 D D' |- H2 ?9 Y
indeed cause more virilization in male or female, h2 s% M Y3 C
children than one would realize. Exposure to andro-3 s2 X. R/ n# f3 v! m
gen products must be considered and specific ques-* g/ ^3 n* H# h$ O4 a5 f3 `
tioning about the use of a testosterone product or% g0 j5 F* n9 I, W
gel should be asked of the family members during
7 D4 B; T3 B* N) dthe evaluation of any children who present with vir-
: O% t& ~: p9 z3 ^ilization or peripheral precocious puberty. The diag-, }; E5 E L5 A
nosis can be established by just a few tests and by3 G: k( l) v3 L; E
appropriate history. The inability to obtain such a7 G& R, }8 B1 v- W' S/ C
history, or failure to ask the specific questions, may; _$ L5 z, N8 }# P4 E) d" ]2 K
result in extensive, unnecessary, and expensive6 W+ @1 A m: q7 G
investigation. The primary care physician should be
% \/ m* H; p# I* e) m' b5 `aware of this fact, because most of these children
+ p4 Y4 @$ V$ B# l; Tmay initially present in their practice. The Physicians’7 e+ l' A5 B% t. V! L$ q
Desk Reference and package insert should also put a6 s0 X; J9 H3 i# x U
warning about the virilizing effect on a male or( O" {( f( Z2 v8 k
female child who might come in contact with some-/ _, j3 j6 X$ a) q, g
one using any of these products.6 e% ^1 y% s! }) `& i- j i) Q r
References
' V/ p( E/ e: x) c+ ^5 Z, i1. Styne DM. The testes: disorder of sexual differentiation
; a. f8 n; \$ u! N% }3 aand puberty in the male. In: Sperling MA, ed. Pediatric
. ]; ?& d4 Z: K" O4 W4 i( EEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
( X* {4 @& p; t+ r7 G; v2002: 565-628., ?7 ~ Q: J; O- N+ w8 R6 O
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious$ t6 l5 @( X, {7 d/ P
puberty in children with tumours of the suprasellar pineal |
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