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Sexual Precocity in a 16-Month-Old
; X! ?7 r$ J# p' Y, ABoy Induced by Indirect Topical# Z- _3 m2 C; N9 E
Exposure to Testosterone
: s- ~# o9 V- R+ j2 b' XSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
1 _# _6 _; y, O- J7 R* ^and Kenneth R. Rettig, MD1# {' H0 l# c/ I* s; b
Clinical Pediatrics; L# X5 I9 E9 i c y9 b( n
Volume 46 Number 6
1 Q! T9 O$ b# t1 c' OJuly 2007 540-543: w4 O' v2 p$ t3 T( `
© 2007 Sage Publications4 f- y0 L8 F2 p1 s6 d5 ~
10.1177/00099228062966510 }9 p0 d* k+ N. h: ]4 Q. Z
http://clp.sagepub.com
' N; K( T$ X/ Bhosted at; ?( H) c! {$ S: E S
http://online.sagepub.com& A8 f" }! P; a4 c7 H. x4 ]
Precocious puberty in boys, central or peripheral,
4 M" ^- r2 y/ l9 n0 p6 Xis a significant concern for physicians. Central
, S. e: ?! Z" o6 |3 vprecocious puberty (CPP), which is mediated
2 y0 `) h+ t5 z( o# ?through the hypothalamic pituitary gonadal axis, has
; ^1 b' {7 c2 p3 {a higher incidence of organic central nervous system! i* r: _- h2 e" V% m# \
lesions in boys.1,2 Virilization in boys, as manifested. X1 S: C! I! K2 x3 d
by enlargement of the penis, development of pubic, n0 Q; T/ ^) j- v3 p/ r! d7 ?
hair, and facial acne without enlargement of testi-
1 V5 j( g1 [4 J( h& @ j. tcles, suggests peripheral or pseudopuberty.1-3 We
) q* k7 l8 m/ f- L% oreport a 16-month-old boy who presented with the
/ C) F; J$ [. d, `, t a& D- e- uenlargement of the phallus and pubic hair develop-1 @0 Z8 }6 E" w* N) I/ v
ment without testicular enlargement, which was due4 {7 E8 r0 i! x0 m
to the unintentional exposure to androgen gel used by
; K H y) ~9 ]" `6 `; pthe father. The family initially concealed this infor-+ p, e$ Q% [ ]+ A& ^3 m( ]3 n
mation, resulting in an extensive work-up for this
! d# V5 `& m8 R0 c8 W1 F1 Achild. Given the widespread and easy availability of9 e4 m( p8 D8 E. t4 L! V) E! a5 ^& p4 I
testosterone gel and cream, we believe this is proba-
, Z' v* N8 p3 h. z+ M4 n' y4 ^bly more common than the rare case report in the5 m+ K! \' A2 c" q
literature.4- `7 S d) `: u
Patient Report
/ Z4 c% `5 O- ~7 ~6 n* AA 16-month-old white child was referred to the" v B! k& ~8 y3 Q8 t
endocrine clinic by his pediatrician with the concern" @& ^- W% s( p; a
of early sexual development. His mother noticed/ Y/ z" c7 M4 J7 W: A
light colored pubic hair development when he was
; J3 K9 G4 M; I$ Q- OFrom the 1Division of Pediatric Endocrinology, 2University of" i# M& U. ^7 r+ _
South Alabama Medical Center, Mobile, Alabama.
2 y, H9 G1 _. b# x( u+ W0 UAddress correspondence to: Samar K. Bhowmick, MD, FACE,& ?/ u. V( k4 O3 i' a
Professor of Pediatrics, University of South Alabama, College of3 t: B k8 ]% s; w! E
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;: _6 v3 E& s' E; L7 g- Y
e-mail: [email protected]. d; S1 r/ |5 I- s
about 6 to 7 months old, which progressively became; e+ b9 c% i! Q4 T8 N
darker. She was also concerned about the enlarge-
5 s9 a, B7 o" W, }' X3 j ament of his penis and frequent erections. The child
8 @" z8 p0 ?; _was the product of a full-term normal delivery, with( I6 G! x6 ?8 E. z" l+ H& L
a birth weight of 7 lb 14 oz, and birth length of
3 \# K* V H% h. H$ [% [7 a20 inches. He was breast-fed throughout the first year2 A5 G; Y1 A% O' f
of life and was still receiving breast milk along with' @* t3 E' M, j! U0 \ R4 r
solid food. He had no hospitalizations or surgery,
5 {5 D/ D/ \. c2 ]/ g# pand his psychosocial and psychomotor development
5 |" ~3 H% I! o# I( g! Xwas age appropriate.3 \- S' @: o! X+ u+ z4 w8 S
The family history was remarkable for the father,
U8 m; Z2 T2 twho was diagnosed with hypothyroidism at age 16,
( m9 t5 r$ d6 nwhich was treated with thyroxine. The father’s' j7 x. q! n! N
height was 6 feet, and he went through a somewhat6 N& i/ {) D0 B/ @: Y$ U3 r# B
early puberty and had stopped growing by age 14.
! F" M% T2 G3 A3 wThe father denied taking any other medication. The! R$ |7 C8 F8 f7 c- W8 i4 ^
child’s mother was in good health. Her menarche& Q& {2 C" k$ f4 j& b
was at 11 years of age, and her height was at 5 feet O) s$ G8 Z7 t) L1 h
5 inches. There was no other family history of pre-, v# x* [4 E& q9 u- W6 f
cocious sexual development in the first-degree rela-9 Q N2 Y3 Z2 R* N
tives. There were no siblings.
, T2 ~* w) B0 x H) c0 k4 h$ V" IPhysical Examination, N% e; m9 A/ t
The physical examination revealed a very active,
( \1 w7 y! U( c: K' d2 gplayful, and healthy boy. The vital signs documented v( L1 b% T5 m
a blood pressure of 85/50 mm Hg, his length was
# |" @+ ]3 C$ {90 cm (>97th percentile), and his weight was 14.4 kg! }0 o- o( Q( W
(also >97th percentile). The observed yearly growth
# q0 A h) \6 N6 s6 Z6 pvelocity was 30 cm (12 inches). The examination of" J+ i$ i( V7 D; r; d( v$ ~( m
the neck revealed no thyroid enlargement.' F) m7 K' d, x+ x; y: p
The genitourinary examination was remarkable for
+ x+ h( Z& `" c1 W/ K8 Tenlargement of the penis, with a stretched length of
+ f2 O5 B, ]& G. B" s( l8 cm and a width of 2 cm. The glans penis was very well( Q9 S& ~! w' }
developed. The pubic hair was Tanner II, mostly around
! A. V( Q( T8 a, r& a540/ B: `& _, R2 R' l$ B. r. z
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
7 [9 ]1 v* _5 C2 F2 gthe base of the phallus and was dark and curled. The
2 T( X! E9 y5 l3 |! J5 `testicular volume was prepubertal at 2 mL each.- ^* f: l6 K1 b0 m2 a
The skin was moist and smooth and somewhat
. c$ R) v+ @4 W1 `" S! R3 Z7 Doily. No axillary hair was noted. There were no, q" ]8 N1 { X; ?" Y$ G% F& t9 f
abnormal skin pigmentations or café-au-lait spots.( q$ X0 |6 F) W0 g
Neurologic evaluation showed deep tendon reflex 2+9 b% H/ _# \; f6 e
bilateral and symmetrical. There was no suggestion, S: M; `4 H2 \/ X( r
of papilledema.
?: i, y- @1 R1 A: N+ KLaboratory Evaluation
- U9 K2 Y d ~" u, rThe bone age was consistent with 28 months by( J8 [$ ?6 s, x1 S) q. G
using the standard of Greulich and Pyle at a chrono-: x9 q1 c% d4 e. \& F# Y% u4 M# _
logic age of 16 months (advanced).5 Chromosomal
. L7 D' U7 A& G8 ^9 t/ M5 T! Y8 Wkaryotype was 46XY. The thyroid function test6 c' l r/ ~, Y0 y5 ^% J- G S# b
showed a free T4 of 1.69 ng/dL, and thyroid stimu-2 U$ z2 H0 D& r7 a
lating hormone level was 1.3 µIU/mL (both normal)." X0 l6 `: }, l
The concentrations of serum electrolytes, blood
9 J8 \" D5 H3 F, q* h2 hurea nitrogen, creatinine, and calcium all were
" F4 w1 {! O& c3 Y9 e! M+ R' fwithin normal range for his age. The concentration+ H4 O: h, i" D* s+ q) `1 j6 z
of serum 17-hydroxyprogesterone was 16 ng/dL
8 t8 F+ Y8 h- P9 o' A" e(normal, 3 to 90 ng/dL), androstenedione was 205 \9 W: @8 f {7 d, s2 H k
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
" N, u; |& W. p# k/ \6 x+ cterone was 38 ng/dL (normal, 50 to 760 ng/dL),7 z& Y2 W# q" a% Z C" |5 M
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
; B8 L5 Z! M h- J49ng/dL), 11-desoxycortisol (specific compound S)
) L/ p' V$ D! v0 Ewas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
# a0 U8 k0 H) \0 Utisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total5 v) m) ] `7 m) m% } B$ b! o" d* Q6 ~
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
* ^8 ?. H/ l; }and β-human chorionic gonadotropin was less than' m) T( `! [6 c, h+ v* M7 d
5 mIU/mL (normal <5 mIU/mL). Serum follicular' p* D- a- o0 d% S: U: U
stimulating hormone and leuteinizing hormone# {/ R/ @. Y& S( ]& P D
concentrations were less than 0.05 mIU/mL
1 J8 U% B/ f9 n/ S+ t3 \(prepubertal).
: j7 y' F+ M1 }! p1 a% B4 M% jThe parents were notified about the laboratory
5 t0 s1 l4 q6 B4 {0 j0 E% eresults and were informed that all of the tests were$ }% n6 e9 n' Q) q# v6 V* U7 r
normal except the testosterone level was high. The% m2 T# i* U6 E& K* W9 X. G
follow-up visit was arranged within a few weeks to
' A! Y0 ]. i0 xobtain testicular and abdominal sonograms; how-* g. k6 g+ O+ {
ever, the family did not return for 4 months.; |( t1 @1 s7 l; i% z* r
Physical examination at this time revealed that the- j6 ^2 ~' T' A. z
child had grown 2.5 cm in 4 months and had gained
4 g* M; t+ S% A* R2 q6 Q2 kg of weight. Physical examination remained
( i3 f/ X% i3 }% ^' l2 [7 ounchanged. Surprisingly, the pubic hair almost com-
0 Q+ K6 u5 Z- p9 z1 L4 O qpletely disappeared except for a few vellous hairs at& m. R3 p4 G Y5 f8 D7 w: T* D& R
the base of the phallus. Testicular volume was still 2/ l- R, @* X: b$ ^/ [3 x# O
mL, and the size of the penis remained unchanged.
! h; U3 ~% `. p" JThe mother also said that the boy was no longer hav-
5 N0 o9 y1 h* V+ i$ d8 {ing frequent erections.
7 l3 R/ ?: X& B9 c6 Y. b, a/ `Both parents were again questioned about use of; J5 Q, H4 `, o* y. |
any ointment/creams that they may have applied to/ S7 e- V$ ^. w2 @2 w8 L( { t
the child’s skin. This time the father admitted the4 v2 b9 T4 P/ c, c0 l% W
Topical Testosterone Exposure / Bhowmick et al 541/ X C: i! U5 M2 c& z
use of testosterone gel twice daily that he was apply-
2 C+ G5 {2 Y' t& Ning over his own shoulders, chest, and back area for
8 @; l* ~+ b* ]: Wa year. The father also revealed he was embarrassed
8 g1 F" T% l3 a! ^1 P0 zto disclose that he was using a testosterone gel pre-6 g6 W8 `' ~" `' c
scribed by his family physician for decreased libido: s% G' t; C. N) i& x: ~( I$ n
secondary to depression.+ O- Y2 R2 `9 Z( a) y
The child slept in the same bed with parents.
9 Y7 I, n2 S: rThe father would hug the baby and hold him on his
$ {7 p/ T7 b# v% f/ n* M+ C7 q! s pchest for a considerable period of time, causing sig-0 c( G2 ~( J1 C# ~: b& u8 y, S- j
nificant bare skin contact between baby and father.& b; `0 t# c; v1 m7 L# l
The father also admitted that after the phone call,* \2 U6 q' V4 ]4 l% @7 s0 V
when he learned the testosterone level in the baby$ q) L; `0 L' ]- S
was high, he then read the product information% ^; S0 S* W8 W/ u* d
packet and concluded that it was most likely the rea-
. m/ j! V2 I0 y/ g6 c3 r5 {son for the child’s virilization. At that time, they/ `7 S1 e% q) p
decided to put the baby in a separate bed, and the
8 O( j6 V1 ]" z8 l+ N M3 pfather was not hugging him with bare skin and had
1 T. g8 c- l1 e7 U# f+ Sbeen using protective clothing. A repeat testosterone
O& P# k' l7 T5 O# j \test was ordered, but the family did not go to the5 h/ R& [. A: B
laboratory to obtain the test.
( V& Q, k7 q) }' ]1 MDiscussion
1 z3 L2 B0 E; Q$ m, l& F, `Precocious puberty in boys is defined as secondary
) p8 d$ i/ I' Z7 {; }sexual development before 9 years of age.1,4! |7 ~- o9 ` Z q" _
Precocious puberty is termed as central (true) when" Y! r& I& Y: S4 o8 n o6 I2 o6 L
it is caused by the premature activation of hypo-( _2 }/ U+ D6 [0 [1 n2 f
thalamic pituitary gonadal axis. CPP is more com-: x! Y5 e# a* e3 r* k6 V
mon in girls than in boys.1,3 Most boys with CPP! V9 N4 K# A/ |
may have a central nervous system lesion that is/ ^& x0 [/ Z' X7 ^* I
responsible for the early activation of the hypothal-
8 `/ t4 B$ Q. `0 Tamic pituitary gonadal axis.1-3 Thus, greater empha-
$ Q) Z) m% C' \9 asis has been given to neuroradiologic imaging in
3 r+ V! ]8 E6 Yboys with precocious puberty. In addition to viril-
' U5 v J% i f" S5 j, Rization, the clinical hallmark of CPP is the symmet-
, ~0 P- H! @# v; d' o" `rical testicular growth secondary to stimulation by5 t J _7 `+ e: [, W& P2 f7 G
gonadotropins.1,3- b3 ]; X: B) i0 a
Gonadotropin-independent peripheral preco-
. k6 o5 y/ k. ^: R% T- O: scious puberty in boys also results from inappropriate
9 B0 d; M% u3 z: Bandrogenic stimulation from either endogenous or1 T, e8 U: |/ n
exogenous sources, nonpituitary gonadotropin stim-4 w( f- s& V# _* W8 r
ulation, and rare activating mutations.3 Virilizing
( v! X* g9 \0 z$ kcongenital adrenal hyperplasia producing excessive& G1 Q, S" V+ W1 t4 n
adrenal androgens is a common cause of precocious$ a0 J! T, M# H! f" L! u
puberty in boys.3,42 \0 ^1 w; Q% ^! n7 p/ p
The most common form of congenital adrenal1 L7 j, l7 @) y7 Z
hyperplasia is the 21-hydroxylase enzyme deficiency.
0 A8 @! K- G C" v: i. r. kThe 11-β hydroxylase deficiency may also result in8 r* i; z& m- i) s
excessive adrenal androgen production, and rarely,- F- X4 Y; }; l0 E n1 ^
an adrenal tumor may also cause adrenal androgen9 i9 Z! x# h. S2 P# h" v
excess.1,3) o8 F$ J, u2 ? o6 |1 A6 _
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, I- ]$ L4 d4 a) X( m, E, g542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
! _ d+ [ d8 S! L3 D H2 xA unique entity of male-limited gonadotropin-
% R& A1 X8 s1 \- T1 ~independent precocious puberty, which is also known
- ]+ R# Z; w4 _6 Kas testotoxicosis, may cause precocious puberty at a; ^) r9 g% W; A, h# a6 Z
very young age. The physical findings in these boys& t0 L) `% x& Y0 R! \7 q% H
with this disorder are full pubertal development,
7 s* j% [" X2 {" {- ^including bilateral testicular growth, similar to boys
1 ~' E* b% h5 D# u7 R* h" Q2 xwith CPP. The gonadotropin levels in this disorder* b5 A, Y: w A; H: x9 w
are suppressed to prepubertal levels and do not show' S7 L& M" m0 q; ~, E: |# x
pubertal response of gonadotropin after gonadotropin-
1 i, H0 \9 n( K b3 S0 z% wreleasing hormone stimulation. This is a sex-linked3 X: {9 F. f" B4 o3 z
autosomal dominant disorder that affects only* d+ m; f3 V* C/ c+ k
males; therefore, other male members of the family5 O& ^7 V2 R+ x8 u" c
may have similar precocious puberty.3* @; r. c; N+ [$ h
In our patient, physical examination was incon-. E! j4 @5 S, _ s+ _' O1 M/ q( q/ B. K
sistent with true precocious puberty since his testi-
1 E( p; y* M Z* c0 r1 T5 f9 q) |* Y: scles were prepubertal in size. However, testotoxicosis
! U' I7 Y9 h+ L$ }0 G& xwas in the differential diagnosis because his father d* L3 f- A% {/ p+ t# e# k8 ?; G
started puberty somewhat early, and occasionally,# y" n$ ]' f+ i" f$ P
testicular enlargement is not that evident in the
6 v" w1 ~$ k" K) p, `2 {beginning of this process.1 In the absence of a neg-
+ H" [5 m1 L; hative initial history of androgen exposure, our( r& x: E" y# P6 p. j. _3 D
biggest concern was virilizing adrenal hyperplasia," u3 ^- _$ L3 `
either 21-hydroxylase deficiency or 11-β hydroxylase4 P- c: w( k! A5 O1 e* ^$ X8 s
deficiency. Those diagnoses were excluded by find-* Q4 V* x% y7 h c/ x6 T
ing the normal level of adrenal steroids.7 l4 p0 [" R* q' T. [6 h$ x# n
The diagnosis of exogenous androgens was strongly4 x5 R' y" u7 ~+ X. J
suspected in a follow-up visit after 4 months because+ G; H9 b/ c4 a. k g
the physical examination revealed the complete disap-- n) i) H# `7 Z1 A3 M6 B$ E8 ?
pearance of pubic hair, normal growth velocity, and7 |& S0 T3 O2 x. u1 s
decreased erections. The father admitted using a testos-4 O) [" l! C4 p9 e/ k( a( o
terone gel, which he concealed at first visit. He was- u* }4 E* w/ Y
using it rather frequently, twice a day. The Physicians’
. a/ o! z! J0 g% i( `$ ~2 VDesk Reference, or package insert of this product, gel or
5 Q# b. E4 w3 H1 w) ]% k; {; Fcream, cautions about dermal testosterone transfer to
3 T. F) x2 j( v) S' K9 t8 T1 _+ yunprotected females through direct skin exposure.) n' g7 ]3 O1 Y2 B1 M) t9 G
Serum testosterone level was found to be 2 times the+ _1 f3 f0 W) \- b
baseline value in those females who were exposed to$ L& Q+ H [ g9 L6 v
even 15 minutes of direct skin contact with their male
0 g6 `/ u! g2 y1 |8 F- n5 bpartners.6 However, when a shirt covered the applica-' ~# t- M) f) y' }# Y) V5 [
tion site, this testosterone transfer was prevented.( O( n$ B. p1 R
Our patient’s testosterone level was 60 ng/mL,
$ z* d$ T2 P$ P2 E, M$ iwhich was clearly high. Some studies suggest that
; q+ Y8 S3 l* }" H# t1 M$ Udermal conversion of testosterone to dihydrotestos-
% m/ m8 [+ l$ j( Z' Uterone, which is a more potent metabolite, is more% @' ^$ F6 F8 y& ?; o# a
active in young children exposed to testosterone2 w( B+ U5 u6 [0 E
exogenously7; however, we did not measure a dihy-
) K. S; p: F3 F/ U6 Y+ u7 Wdrotestosterone level in our patient. In addition to
9 y% o Q$ }* T( o" ?3 dvirilization, exposure to exogenous testosterone in
3 Q8 Z' |6 i N5 r: q8 fchildren results in an increase in growth velocity and1 F7 _$ {3 J8 a4 [; @
advanced bone age, as seen in our patient.
* y! i& Z/ M6 k9 @) v a, hThe long-term effect of androgen exposure during7 i/ ~/ g: N' ^% O$ z+ f2 M, t
early childhood on pubertal development and final
) |% b. k# x4 S$ I4 U5 l/ [2 zadult height are not fully known and always remain
9 Q3 |0 X) s0 y( ia concern. Children treated with short-term testos-
2 }6 A+ P9 R9 C2 {3 Xterone injection or topical androgen may exhibit some) b' @$ _$ D z: N: p( Z' H
acceleration of the skeletal maturation; however, after& v& N2 h# T, Q( e6 I! [ I
cessation of treatment, the rate of bone maturation9 E& ~9 S* q0 [2 }
decelerates and gradually returns to normal.8,9
# a. c; V: b# S' }There are conflicting reports and controversy
# P2 R9 C4 O0 {9 Cover the effect of early androgen exposure on adult
% }; }# d. M5 V7 W" P" t; Jpenile length.10,11 Some reports suggest subnormal
2 d9 P* f: X; y+ ^( e- v0 T0 hadult penile length, apparently because of downreg-) J1 k3 P8 t8 k% U' k$ l. {
ulation of androgen receptor number.10,12 However,( A0 ` ]& S; a6 w6 a
Sutherland et al13 did not find a correlation between
6 D' i5 F9 c! W& {- b: ~0 e# [childhood testosterone exposure and reduced adult# X( o% E. y. b0 N C
penile length in clinical studies.
& r$ }. H# A+ p( sNonetheless, we do not believe our patient is
5 S3 c9 O: M" ~0 c' k8 B0 Ngoing to experience any of the untoward effects from3 \ A, [# K; r: Q
testosterone exposure as mentioned earlier because
: b, `+ ~4 g5 E. o4 ]# k z) {the exposure was not for a prolonged period of time.4 _7 A6 O( y$ \9 m9 X+ L t8 z: z+ m
Although the bone age was advanced at the time of9 B Z7 A! R; c/ L/ Q) }
diagnosis, the child had a normal growth velocity at
9 R' a' U6 ~, J. s! g9 R; m0 Jthe follow-up visit. It is hoped that his final adult
$ F3 }7 T6 m I& jheight will not be affected.
& ^% g" H+ G6 Z) Q- gAlthough rarely reported, the widespread avail-. K! ]# H8 h! s! N5 T
ability of androgen products in our society may
8 S! p1 T+ Y, ?indeed cause more virilization in male or female7 `0 d! M5 _2 j* E2 y/ _ p
children than one would realize. Exposure to andro-: H( A: W/ x& V4 T1 C; j" Y
gen products must be considered and specific ques-
; r4 ~ W( l2 [ e! Q" @& Xtioning about the use of a testosterone product or, U- l g2 Q/ G( I
gel should be asked of the family members during
4 ?: N* j' u9 _$ F" }, Mthe evaluation of any children who present with vir-$ C( I# w9 Q$ G: v
ilization or peripheral precocious puberty. The diag-
8 c* Q4 K6 X6 ]: r( Wnosis can be established by just a few tests and by, q1 }! p( z% ^0 v* B& G6 V1 r
appropriate history. The inability to obtain such a3 m) c# z: p# _" w J$ O- _. m
history, or failure to ask the specific questions, may
0 c3 D/ G$ T6 z3 ^1 R$ s6 v4 h/ z) Presult in extensive, unnecessary, and expensive
9 s3 _9 l7 [/ ~& n+ `: ~* U& B" winvestigation. The primary care physician should be5 z1 ]$ C! N2 N1 |( F
aware of this fact, because most of these children9 p* N, o2 w& U* k0 z- l
may initially present in their practice. The Physicians’) @1 P' L0 ?( t( j" |
Desk Reference and package insert should also put a
6 S3 y2 y# I- j0 Y# r9 iwarning about the virilizing effect on a male or+ {' ^/ ?% |+ I$ w' ~' ^4 \
female child who might come in contact with some-- r1 [' r, G) w
one using any of these products.
6 l, K) a/ i3 VReferences3 m0 t0 O$ _3 Y6 E% B3 x
1. Styne DM. The testes: disorder of sexual differentiation& W, ?( [; H8 b1 K3 `- n- u
and puberty in the male. In: Sperling MA, ed. Pediatric; n* V/ t0 J1 n& @% `0 F
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
. I& F1 B2 K9 l+ ^2002: 565-628.
, U5 s/ q4 k& O9 C2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
8 z6 m* l) ^% F. g% o' h1 Kpuberty in children with tumours of the suprasellar pineal |
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