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Sexual Precocity in a 16-Month-Old
1 u$ }: ? P: a5 y; H MBoy Induced by Indirect Topical- E1 y, p8 N) t0 h
Exposure to Testosterone( q' Y( Q2 w3 h: r! R3 s
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,26 e& [7 z7 d$ J l% i9 K
and Kenneth R. Rettig, MD1
/ E1 t' H8 b9 B2 F7 L) W" iClinical Pediatrics9 ?$ V0 ]- c" R6 I; `
Volume 46 Number 6
5 T0 S8 |4 J' A2 AJuly 2007 540-5433 h6 U& u/ F# m# o
© 2007 Sage Publications% y8 F" p Q4 C
10.1177/0009922806296651
! c! h& V' Z0 T l7 ^# g9 Chttp://clp.sagepub.com- `! N! i3 ~! d' X
hosted at
- ]. n8 C% Z; qhttp://online.sagepub.com
0 ~ l+ p: ?. h; FPrecocious puberty in boys, central or peripheral,
4 Y3 c& m+ T+ U# Kis a significant concern for physicians. Central
/ M8 q7 ~3 ^% \5 zprecocious puberty (CPP), which is mediated
, e) N6 G6 h2 g/ b+ Tthrough the hypothalamic pituitary gonadal axis, has
+ u6 |! ~ t% [0 Ia higher incidence of organic central nervous system
G0 z* I" `1 {' A4 z( tlesions in boys.1,2 Virilization in boys, as manifested
$ M; l- C5 Y) [) g% Y, e( {! R( Cby enlargement of the penis, development of pubic
3 R# d- ]- L$ K* T( c* qhair, and facial acne without enlargement of testi-
8 w2 o, B. a. fcles, suggests peripheral or pseudopuberty.1-3 We
9 Y w* q& L, A% Nreport a 16-month-old boy who presented with the
7 }$ J8 @8 A9 ^0 M" K% N8 oenlargement of the phallus and pubic hair develop-
2 S5 a+ p# D# ~# @ment without testicular enlargement, which was due: i; X! ^) ~4 U: Z0 u1 k
to the unintentional exposure to androgen gel used by2 S, Q% ^* W L( |1 l( P
the father. The family initially concealed this infor-. O, `$ y% d8 b% N
mation, resulting in an extensive work-up for this2 E8 {' k" x( s4 k& s& q2 X' t
child. Given the widespread and easy availability of5 s+ d8 O) b/ A( e2 S: q1 H6 t
testosterone gel and cream, we believe this is proba-
, E4 ]/ b5 q+ S; w4 _9 o' ibly more common than the rare case report in the
) u0 d' G! v7 x6 lliterature.4
* b Z! B* b: j/ X2 D; @Patient Report
3 R( Y4 c7 }" fA 16-month-old white child was referred to the+ T! ^ N+ Q& {1 \; a) O
endocrine clinic by his pediatrician with the concern
+ v$ L; b0 Z) d& | \0 @7 gof early sexual development. His mother noticed; ~8 P6 k2 g5 L5 O
light colored pubic hair development when he was3 `6 v) V3 l1 C: p# [( X
From the 1Division of Pediatric Endocrinology, 2University of
% M$ D! Z3 z5 ^South Alabama Medical Center, Mobile, Alabama.
1 l, Q3 _0 g/ v2 }, A! _Address correspondence to: Samar K. Bhowmick, MD, FACE,
6 G9 i. v/ v* t8 {4 r7 Z/ e# KProfessor of Pediatrics, University of South Alabama, College of9 l% J: y$ J2 b9 I# I
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
+ W0 _ L' s6 C4 r: W4 @1 j/ ge-mail: [email protected].
# ^# Y" I# b8 M- xabout 6 to 7 months old, which progressively became
" Q# h$ W Q, l- }5 c$ I8 {darker. She was also concerned about the enlarge-( u+ l9 }/ O2 y* O
ment of his penis and frequent erections. The child
6 [( I' @+ T0 B5 o8 a7 Vwas the product of a full-term normal delivery, with! `, t4 V, C6 k b5 j b" h* o* _( T
a birth weight of 7 lb 14 oz, and birth length of
1 T6 f$ }4 D& {( j( L1 @20 inches. He was breast-fed throughout the first year5 \3 p4 ^9 x6 i4 K8 j- u- @% L i
of life and was still receiving breast milk along with
+ v. x7 ~: _) Dsolid food. He had no hospitalizations or surgery,4 @9 J8 V" d2 ^" }7 T
and his psychosocial and psychomotor development3 ~) E7 p. _! Y0 F4 b3 W
was age appropriate.. |1 B8 Y1 J2 Z% A6 Y: [
The family history was remarkable for the father,
( r! C6 x' ?$ f( F4 Twho was diagnosed with hypothyroidism at age 16,
; P; t$ r2 t8 b1 T d2 z( ^which was treated with thyroxine. The father’s
; b& F0 B( P' a% P4 Theight was 6 feet, and he went through a somewhat
* v7 ^4 T( G2 nearly puberty and had stopped growing by age 14.
9 x1 m: b8 C9 J. A9 oThe father denied taking any other medication. The8 y6 ~7 }# g R% ]6 \1 M- l
child’s mother was in good health. Her menarche
7 s3 j( C$ S" ~$ bwas at 11 years of age, and her height was at 5 feet7 Z3 d. U+ G/ `3 w9 `! [2 @
5 inches. There was no other family history of pre-, @0 p' t* c5 ]
cocious sexual development in the first-degree rela-3 \- U1 @7 S1 }- y
tives. There were no siblings.0 q# d) Z& W! d7 Y, x# H. S
Physical Examination
9 L6 Q: U: O8 s; E& E mThe physical examination revealed a very active,
: k( ?! Q5 p6 S; [4 lplayful, and healthy boy. The vital signs documented5 o) n7 g% ?4 p! Y
a blood pressure of 85/50 mm Hg, his length was$ h7 L$ `" u9 k3 B
90 cm (>97th percentile), and his weight was 14.4 kg
% c( Y5 s8 n. x; h; b0 V g) m(also >97th percentile). The observed yearly growth0 s3 X2 [3 J/ G9 S+ [/ E
velocity was 30 cm (12 inches). The examination of$ t' T K" W# _# N/ G" y
the neck revealed no thyroid enlargement.
: ]( U3 h2 a4 X H. F0 q' OThe genitourinary examination was remarkable for
w3 T7 j# _3 C: Senlargement of the penis, with a stretched length of8 K* ?) |; w- E+ T! a
8 cm and a width of 2 cm. The glans penis was very well
& C# e. j0 O! Xdeveloped. The pubic hair was Tanner II, mostly around
# o6 L/ w! a5 ?% I( H7 h, W% U5401 `. m) |+ d5 X
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
1 R4 U9 W8 ?+ ^( r0 vthe base of the phallus and was dark and curled. The
2 `& j9 ?: I+ g: wtesticular volume was prepubertal at 2 mL each.
2 X0 Q5 p4 r9 ?. n6 q; \- t7 yThe skin was moist and smooth and somewhat8 K* r9 X: g4 w
oily. No axillary hair was noted. There were no9 C% R3 g/ j) D O: m) }& l$ ^9 Y
abnormal skin pigmentations or café-au-lait spots.
) C) Q, C2 n$ F4 |. kNeurologic evaluation showed deep tendon reflex 2+/ T' Y' q# S5 P1 W" m
bilateral and symmetrical. There was no suggestion8 F) G1 m* Y2 D0 b, {
of papilledema.+ e4 M4 C7 K% H( ]0 q( e' |
Laboratory Evaluation
& v) L I- l6 N7 a3 K8 tThe bone age was consistent with 28 months by
?. k+ K: \$ Y) g* P2 \using the standard of Greulich and Pyle at a chrono-
; R+ ]/ x8 N8 Nlogic age of 16 months (advanced).5 Chromosomal
, C& ?4 {. N) m! U1 q @5 ckaryotype was 46XY. The thyroid function test# f" I/ z( N! ^, _& n
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
( H6 t' q) X6 q/ Q; g3 `# V3 {- slating hormone level was 1.3 µIU/mL (both normal).
' ]+ w- F8 V' j9 OThe concentrations of serum electrolytes, blood
) l8 E" b/ }( f6 S; w9 x+ Ourea nitrogen, creatinine, and calcium all were
" i1 }: H2 B9 l( A" rwithin normal range for his age. The concentration7 k* _/ {. Z7 b
of serum 17-hydroxyprogesterone was 16 ng/dL
6 D4 t% v) `( R, b(normal, 3 to 90 ng/dL), androstenedione was 207 i. ^/ o7 w4 S: R( r( A
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-) f: I2 M7 ~1 G+ m8 W/ _
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
7 s8 v: _8 D. |$ Wdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
9 L& ~2 c5 Z: A: N$ h49ng/dL), 11-desoxycortisol (specific compound S)
/ k7 \5 s+ w8 a: l1 N$ }. u" S/ mwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
: ?, k* ]8 g( d8 Z, P4 jtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
# |% C) B4 |- }0 K- g8 btestosterone was 60 ng/dL (normal <3 to 10 ng/dL),. a, t& f, g; ]! ~
and β-human chorionic gonadotropin was less than
3 X1 z& u8 @2 ]" d( z' w5 mIU/mL (normal <5 mIU/mL). Serum follicular) l# O7 r/ ]; T, y; e, J: L! m. ?
stimulating hormone and leuteinizing hormone
5 v: H' u! r2 R( `" t9 z- d+ _7 |concentrations were less than 0.05 mIU/mL
$ t/ [5 o# q6 }% o(prepubertal).
# F" L% ~$ e3 XThe parents were notified about the laboratory
7 I/ {9 ?5 X/ |, ?7 ]& K& y6 s2 i+ eresults and were informed that all of the tests were. q7 {3 X+ Q& K/ r/ o
normal except the testosterone level was high. The$ I( G# j" w% ~: H5 m9 a5 S6 g6 e- m5 t
follow-up visit was arranged within a few weeks to
# o+ w9 ^1 M2 R: f0 m5 ?; o D! L6 cobtain testicular and abdominal sonograms; how-4 y4 g, |! A1 } H, Q, o" A
ever, the family did not return for 4 months.' c/ C( H$ i- H
Physical examination at this time revealed that the: S3 q# w( n. I5 Y* u
child had grown 2.5 cm in 4 months and had gained
+ k2 `) k; I; g8 h( e# O2 kg of weight. Physical examination remained/ V5 R% N+ }7 g4 x1 |# v
unchanged. Surprisingly, the pubic hair almost com-' j$ g, b5 A. [
pletely disappeared except for a few vellous hairs at# C, r( \: \3 u: Y& k$ R8 `
the base of the phallus. Testicular volume was still 2
U7 ~% q2 i3 H: X- imL, and the size of the penis remained unchanged.
p7 F' q& W7 E' S# c% s! wThe mother also said that the boy was no longer hav-
1 f' u+ B: s. K6 Y* Ging frequent erections.
/ C1 X8 t, G& g0 _Both parents were again questioned about use of# v' m9 i$ @6 h# G; y
any ointment/creams that they may have applied to
" I& P. V+ F$ o! H# `6 Kthe child’s skin. This time the father admitted the
6 X8 V. U' [/ w4 \+ S/ fTopical Testosterone Exposure / Bhowmick et al 541
) P* M2 _2 O b# Z' [( t% Ause of testosterone gel twice daily that he was apply-
5 E) ~) I5 _6 _+ ^, R2 Ning over his own shoulders, chest, and back area for) v( D+ a' J& k1 b% O
a year. The father also revealed he was embarrassed
% j, v n5 J' u$ }! q+ Mto disclose that he was using a testosterone gel pre-% M; T% R! Y0 Y2 Y5 E3 E
scribed by his family physician for decreased libido
0 M) q' }6 x$ y9 d- Csecondary to depression., T2 O! U' j/ x U
The child slept in the same bed with parents., [/ @9 E1 F1 U, {) R! x- W
The father would hug the baby and hold him on his
8 h. @, J- q) i/ g) nchest for a considerable period of time, causing sig-0 _5 q" f/ P+ q$ w3 O6 {
nificant bare skin contact between baby and father." w# T* S7 T, `2 V# w" W
The father also admitted that after the phone call,
5 t5 Z( N) X2 }! pwhen he learned the testosterone level in the baby0 L1 g0 l( t- K4 E- x; N
was high, he then read the product information
7 _8 I1 y" V g5 K$ Kpacket and concluded that it was most likely the rea-% g% z7 R& V! t! A) D }
son for the child’s virilization. At that time, they
. n C* i% @3 P" |8 ]decided to put the baby in a separate bed, and the
0 x; F8 [: |; V6 T2 V+ Z) qfather was not hugging him with bare skin and had
/ F8 H( C: a$ Ubeen using protective clothing. A repeat testosterone9 L0 p* h! m8 {$ t8 y: m# {0 A
test was ordered, but the family did not go to the
; ^: {1 _4 u/ ylaboratory to obtain the test.4 z! J- f; n( w5 j
Discussion
1 E* \, L( U" V8 j9 Z- m* p- c; QPrecocious puberty in boys is defined as secondary+ l* a2 O* ^# p4 S* J
sexual development before 9 years of age.1,4
4 V7 v- r( H/ c, p6 i8 f7 g3 KPrecocious puberty is termed as central (true) when
' c3 y' ?; D9 }; t; l+ Iit is caused by the premature activation of hypo-/ `8 b; n( }6 T" D
thalamic pituitary gonadal axis. CPP is more com-
# T2 E8 [/ I) L% }mon in girls than in boys.1,3 Most boys with CPP
% W, A) B9 c/ |: c7 D6 u$ Cmay have a central nervous system lesion that is1 p+ ^& O, ^! ]
responsible for the early activation of the hypothal-
, s1 q! w6 b, j# ~; kamic pituitary gonadal axis.1-3 Thus, greater empha-
7 Q8 P5 {4 r5 csis has been given to neuroradiologic imaging in
$ X& A1 D8 o, l& tboys with precocious puberty. In addition to viril-
' h7 Q; V4 N2 m+ i3 A0 s3 Hization, the clinical hallmark of CPP is the symmet-- o# r5 }; k9 [4 K0 Y1 a7 R, z
rical testicular growth secondary to stimulation by" d, o7 {# ?& Z1 i2 W
gonadotropins.1,3
Q) m* k, a" u9 sGonadotropin-independent peripheral preco-; u! A1 n5 m& _% H4 D! P/ w, i4 G
cious puberty in boys also results from inappropriate. R0 [' l7 u) q9 }
androgenic stimulation from either endogenous or
; q9 {1 D( a. i5 v$ g( p3 y- Gexogenous sources, nonpituitary gonadotropin stim-1 K- R7 \$ o9 O" t6 I& d1 q
ulation, and rare activating mutations.3 Virilizing: e# q, q0 v: @0 l. R( r
congenital adrenal hyperplasia producing excessive% s e) s h( K9 F
adrenal androgens is a common cause of precocious
* `' s3 Z& Z* @7 mpuberty in boys.3,4
! ~4 C; F) j0 t; RThe most common form of congenital adrenal5 X( r( ~0 U4 V; W, P" i- m6 f% r
hyperplasia is the 21-hydroxylase enzyme deficiency.
2 R; R/ n# Z, G7 q+ [3 zThe 11-β hydroxylase deficiency may also result in% y8 G3 y0 ?( s; |, ]
excessive adrenal androgen production, and rarely,! P' |: d. X+ u& q
an adrenal tumor may also cause adrenal androgen& A3 X% F/ ?6 J- s0 x; T
excess.1,3
( h+ H" h' ~0 _: }9 c e: m4 pat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from! I7 N" I/ e, O: F
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
: S- ]% ^$ w& S c& Y( cA unique entity of male-limited gonadotropin-0 |; B) Q% T x8 D' k$ m% ~0 d
independent precocious puberty, which is also known
) Q; m6 K4 q9 i$ Z7 Qas testotoxicosis, may cause precocious puberty at a, E I- x4 n7 W2 H6 p' z' t
very young age. The physical findings in these boys
' g) I9 l( L5 q# q9 a& G7 pwith this disorder are full pubertal development,
% j) ?. s: \# G) Z6 F6 tincluding bilateral testicular growth, similar to boys
N! p+ h+ i' Y2 v, u( z) Wwith CPP. The gonadotropin levels in this disorder; S% @7 P, Z, a, J A
are suppressed to prepubertal levels and do not show) { q- ~+ V, a0 M. p
pubertal response of gonadotropin after gonadotropin-
C* Z: [& e+ b+ }releasing hormone stimulation. This is a sex-linked$ ~) `9 v/ \( b( g% Z/ H$ h3 ?
autosomal dominant disorder that affects only3 c. |# _# p: {4 i
males; therefore, other male members of the family
& f$ L; I5 _6 q! P0 Hmay have similar precocious puberty.3
3 O/ b* F* ?8 @+ NIn our patient, physical examination was incon-
) t% |* x0 S8 Y! vsistent with true precocious puberty since his testi-
1 W3 h+ z q i% @cles were prepubertal in size. However, testotoxicosis
# n1 O* c4 o% D( G! Rwas in the differential diagnosis because his father- m$ U' a* X) L) T a7 U: [$ R
started puberty somewhat early, and occasionally,
0 @* W: e+ I7 n D7 T9 U5 Ltesticular enlargement is not that evident in the
' Y+ Y- r l6 j, ?, bbeginning of this process.1 In the absence of a neg-3 j5 L8 Q8 ^! X& C' O+ Z! h( L1 l& k: S
ative initial history of androgen exposure, our# @$ D1 ^( d/ q9 O
biggest concern was virilizing adrenal hyperplasia,$ H" x" O3 {: ?& e* u
either 21-hydroxylase deficiency or 11-β hydroxylase# T! m( A! _1 J( V& S- R
deficiency. Those diagnoses were excluded by find-( |/ k5 Y6 U$ `3 }
ing the normal level of adrenal steroids.$ n' ?" i0 @$ X! s1 p6 r
The diagnosis of exogenous androgens was strongly
/ p( {$ ]2 h& Z1 u H3 }, ksuspected in a follow-up visit after 4 months because2 o' F. _0 r Y( G: ]/ X! r, q7 a
the physical examination revealed the complete disap-
; ~% _; Z) I4 ]* G* {& Z8 |% \: x% Ipearance of pubic hair, normal growth velocity, and
$ Y+ @4 f4 U, b B" _8 Ddecreased erections. The father admitted using a testos-
' E9 ^$ A" Z2 I% k- t6 eterone gel, which he concealed at first visit. He was! S% `* @- w& _; i, S; G" H
using it rather frequently, twice a day. The Physicians’
5 k/ x, m, K- t- MDesk Reference, or package insert of this product, gel or
4 ~7 g- O& }3 Y% j8 F" y2 M. o* jcream, cautions about dermal testosterone transfer to
0 C1 H+ ~8 A* p; v6 Q4 uunprotected females through direct skin exposure.
, H0 c+ g8 @: B% K6 ^% k: vSerum testosterone level was found to be 2 times the4 R0 r( L$ N0 f. ]6 \
baseline value in those females who were exposed to
, ~0 h7 e5 g: K- s$ l0 Qeven 15 minutes of direct skin contact with their male
, r w. s; b4 y6 S: `' U2 ~partners.6 However, when a shirt covered the applica-( X% E. R6 w& B( P* H& V0 Y8 j5 m- V
tion site, this testosterone transfer was prevented.
: E. G% L/ D, M& r1 q4 k4 S' TOur patient’s testosterone level was 60 ng/mL,
- V4 s2 Q0 u6 j' w9 m- K3 _$ n1 a! jwhich was clearly high. Some studies suggest that/ e# R& P+ k2 K0 ~! x. D ]! k
dermal conversion of testosterone to dihydrotestos-9 H7 V/ D6 A- }7 S$ M1 E& Q
terone, which is a more potent metabolite, is more# ^3 a) [8 o3 o0 N) e3 \9 [3 A
active in young children exposed to testosterone2 H, g3 \/ u1 q0 Q' P
exogenously7; however, we did not measure a dihy-2 T T1 g# b0 E) H. C2 e% H
drotestosterone level in our patient. In addition to, s9 I6 q. Z# N/ Q7 R6 a
virilization, exposure to exogenous testosterone in
- Q- ]. }! _* W$ M, k, K( L0 rchildren results in an increase in growth velocity and4 I. r+ g" w" n& g2 d: ?2 m
advanced bone age, as seen in our patient.
p5 @ H4 h* A2 T6 N) HThe long-term effect of androgen exposure during
8 L/ n/ p! E$ bearly childhood on pubertal development and final
9 j" M) ]" A# |7 nadult height are not fully known and always remain
" p$ `2 H i! b' t" ia concern. Children treated with short-term testos-
) r5 L4 c# s6 r6 g! p7 ?$ yterone injection or topical androgen may exhibit some" S' ?( H8 F, s }8 b
acceleration of the skeletal maturation; however, after
0 Z0 z0 y8 D1 b8 V6 Tcessation of treatment, the rate of bone maturation
4 o" l- v; J0 L$ s+ l2 W$ N" bdecelerates and gradually returns to normal.8,9
4 ~- Z0 J$ ^& U6 m- JThere are conflicting reports and controversy
& J9 a1 r, V6 n: Y! g. G, i' Fover the effect of early androgen exposure on adult
; @6 ^+ }# U! g& c6 c" Mpenile length.10,11 Some reports suggest subnormal
: u- v' X3 M! |4 F" _adult penile length, apparently because of downreg-0 ?9 E% c/ D* M& w2 [
ulation of androgen receptor number.10,12 However,# Y5 |) v5 ^; W6 Z; j4 T
Sutherland et al13 did not find a correlation between
, l& |. v1 S- J/ {. l: X4 schildhood testosterone exposure and reduced adult/ H, o+ L& q+ I! D% D
penile length in clinical studies.; M3 T/ o5 m- S% K2 L7 k) R+ X, V
Nonetheless, we do not believe our patient is& m; }4 m# m) [' M1 |" x% S
going to experience any of the untoward effects from
$ _5 a. t9 H! ~- R4 o- r: L4 Ktestosterone exposure as mentioned earlier because' K6 d! l: N' Q n6 W% W
the exposure was not for a prolonged period of time.
0 Y" z! q( z' @' I" ^Although the bone age was advanced at the time of
! ~& @: R2 }9 u/ Zdiagnosis, the child had a normal growth velocity at
, j, J; c! T' b, x5 Cthe follow-up visit. It is hoped that his final adult
2 J2 r( O6 H( o7 S' h2 T; Uheight will not be affected.9 ?" T. ?: [" D& O' F9 i( O
Although rarely reported, the widespread avail-
; a$ `- k& q: `/ l" t1 nability of androgen products in our society may, ?7 ~: V+ a+ }" u& K. T
indeed cause more virilization in male or female! J$ t) @7 T; U9 R
children than one would realize. Exposure to andro-
1 w- R& R( r: Xgen products must be considered and specific ques-
* d( V2 l" j2 D# V. qtioning about the use of a testosterone product or
- V( }$ R* y$ d' q2 d. X* Rgel should be asked of the family members during
+ x* a$ i7 s0 Q! R6 Jthe evaluation of any children who present with vir-
' ~3 {) j, z0 ~# t2 H. y6 J- rilization or peripheral precocious puberty. The diag-
1 m- t% T) j P4 Xnosis can be established by just a few tests and by
! h. p& z1 [$ w7 C; i3 uappropriate history. The inability to obtain such a
% a+ N6 ]( ?5 @) {: g0 Q+ Thistory, or failure to ask the specific questions, may9 n5 v, T; q& U1 ^* q) m6 m5 ]
result in extensive, unnecessary, and expensive
5 I! a2 \! q7 ? x$ {- Ginvestigation. The primary care physician should be! ^2 ?) z3 Q: r9 r
aware of this fact, because most of these children: T7 ]8 D$ [# O
may initially present in their practice. The Physicians’2 x" E4 k. }" @( l7 `
Desk Reference and package insert should also put a9 Q1 G j) V# d3 j# |. T% Q3 h* R
warning about the virilizing effect on a male or9 s3 U! G) Z) x9 W
female child who might come in contact with some-
2 C* t. U- G+ t$ j8 A7 |0 ] {one using any of these products.
1 F! @1 R. G8 R3 ]- \# c) DReferences
& x/ B# ?+ x% I! b7 q L1 {$ I8 R1. Styne DM. The testes: disorder of sexual differentiation( Q8 s L+ Q& P2 r. J
and puberty in the male. In: Sperling MA, ed. Pediatric! j' M) m7 ^* B
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
% N7 K {' W0 V7 Y0 {+ d2002: 565-628.7 Y$ D1 M2 t9 v+ H, H
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious; R: i6 I# @. C2 e
puberty in children with tumours of the suprasellar pineal |
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