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Sexual Precocity in a 16-Month-Old) j% h& T4 W' c5 c: Y3 I0 k$ D
Boy Induced by Indirect Topical
% @7 D8 u/ |0 R, s R$ b H: l+ X* ^% v. `Exposure to Testosterone
0 `7 i$ k+ G8 |Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2) y# E, V' ]4 C. q) h7 R& L" Z. \$ k
and Kenneth R. Rettig, MD1
' v8 {' [8 a) v: iClinical Pediatrics
: k$ A3 J4 w" {Volume 46 Number 6
( e9 n4 A) {0 @" X4 M1 rJuly 2007 540-543' v6 @. f5 \5 M' T7 |" ?: ^
© 2007 Sage Publications5 d" e( W$ E" v$ k
10.1177/0009922806296651
# A( O- i4 q' r8 g; p* {% Fhttp://clp.sagepub.com; Z) K1 f, j: R
hosted at
4 P" ]: @9 ]! C% Vhttp://online.sagepub.com. j# Q* Y, S6 q2 d9 ]6 B
Precocious puberty in boys, central or peripheral,9 v& q5 X1 H: e7 d, ^
is a significant concern for physicians. Central: v5 D* ^8 M' u
precocious puberty (CPP), which is mediated5 G( e/ p! a2 F! ?* z; D" K7 N
through the hypothalamic pituitary gonadal axis, has
6 [0 y* _0 c0 z/ I/ V4 ca higher incidence of organic central nervous system4 Y' v% Y7 E/ t* D- W' m
lesions in boys.1,2 Virilization in boys, as manifested2 _% a# ~% z3 `' |3 d1 h5 Z5 b
by enlargement of the penis, development of pubic% S" G+ U9 u& x5 D1 o& J5 R# A
hair, and facial acne without enlargement of testi-4 @9 k% l% m, ^( y5 e) ]% o; @
cles, suggests peripheral or pseudopuberty.1-3 We
2 h' D& D$ q+ D6 i" a& u* x/ Preport a 16-month-old boy who presented with the
0 j1 i" A: R; [ D- {2 @* ~2 v Denlargement of the phallus and pubic hair develop-8 `1 I6 C) J- p8 K
ment without testicular enlargement, which was due9 n$ o9 d E" U
to the unintentional exposure to androgen gel used by
) c4 D. h8 S% l+ i2 }- Lthe father. The family initially concealed this infor-8 C7 |0 X. |: U( C
mation, resulting in an extensive work-up for this
1 p+ @" }+ N; j* [child. Given the widespread and easy availability of$ ?9 L# f, f6 k" F5 D
testosterone gel and cream, we believe this is proba-; [3 D1 J4 v9 Z1 d
bly more common than the rare case report in the
5 u% z' W' `% e6 hliterature.4& L" N7 b" u, Y9 t9 w2 I
Patient Report
& v4 d' O4 V8 Y9 F; KA 16-month-old white child was referred to the1 A6 q, Q/ u1 A2 K
endocrine clinic by his pediatrician with the concern+ @" ^: G: A% A; {
of early sexual development. His mother noticed9 {; o- b1 d1 [) t7 M
light colored pubic hair development when he was9 K- g9 j* B0 ?6 B% y
From the 1Division of Pediatric Endocrinology, 2University of% S: w% t% r" d
South Alabama Medical Center, Mobile, Alabama.+ t! r! e. b7 Y; K c
Address correspondence to: Samar K. Bhowmick, MD, FACE,
r, A9 x- I( {# WProfessor of Pediatrics, University of South Alabama, College of
0 q9 w' R' e$ WMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
- T, O7 G8 w. ^; T4 U/ J% b7 `e-mail: [email protected].
5 C" l' h& c* C. _; K4 n oabout 6 to 7 months old, which progressively became) Z0 a, D$ G4 }) |2 o: y
darker. She was also concerned about the enlarge-( v: R0 @: S# h# |0 h1 B8 P) F* w! R
ment of his penis and frequent erections. The child
& C+ l8 Z" J, S+ P5 }5 J2 Hwas the product of a full-term normal delivery, with
8 H# n5 u5 u9 ~5 g- _) j9 [a birth weight of 7 lb 14 oz, and birth length of
) z7 y: p, m4 A, a, z1 ~20 inches. He was breast-fed throughout the first year
% y" L& t! \' s, J2 ?& }# xof life and was still receiving breast milk along with
5 y3 \8 k( ^! y/ Fsolid food. He had no hospitalizations or surgery,
2 y% p+ M& {3 R" ]& ?and his psychosocial and psychomotor development2 u! C4 s; C& N9 H8 }, T
was age appropriate.
" R! C, M! C8 e& }The family history was remarkable for the father,
" z* K8 q! C b0 }5 B2 ~2 Y$ {& P% Swho was diagnosed with hypothyroidism at age 16,
: i% U/ K: ]7 f% L4 z+ ?which was treated with thyroxine. The father’s9 ]7 m, w- G X- J& x3 y6 T$ \
height was 6 feet, and he went through a somewhat5 e; p: i" ?0 d. j
early puberty and had stopped growing by age 14." V4 D6 }& ^4 t- X' e8 c
The father denied taking any other medication. The3 G4 b) e1 N# |
child’s mother was in good health. Her menarche
; n% [! t& v ]0 awas at 11 years of age, and her height was at 5 feet0 p! ^; J; Y, u8 p3 `3 u
5 inches. There was no other family history of pre-
+ k- `. S& c8 n$ Y: I+ {7 icocious sexual development in the first-degree rela-8 H4 g% w& q. P, L9 F* V
tives. There were no siblings.
# W2 R& `5 g& N: [Physical Examination
Y& Z8 F x+ N: x/ wThe physical examination revealed a very active,8 A+ V! f2 h- Z" H2 P7 Z
playful, and healthy boy. The vital signs documented
3 ~, v9 Q3 Z- W6 A3 S6 va blood pressure of 85/50 mm Hg, his length was3 X; p/ D# T% v! w* r/ R
90 cm (>97th percentile), and his weight was 14.4 kg
* X$ ?7 s( v% s) g(also >97th percentile). The observed yearly growth1 |; [; B- @) S2 c
velocity was 30 cm (12 inches). The examination of- \9 l# t ~( J: h+ i1 w6 a3 v+ ~
the neck revealed no thyroid enlargement.% ?3 D# m3 I- \
The genitourinary examination was remarkable for3 m) ?5 C, X) F* U* P1 S7 ^
enlargement of the penis, with a stretched length of8 r% Z/ e9 G( k5 c$ T
8 cm and a width of 2 cm. The glans penis was very well& `0 S* w0 l9 U2 Y
developed. The pubic hair was Tanner II, mostly around& n1 h3 ]3 L! v" J# b# U
540. o- [: Z+ ]" P& W# c
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from% U1 D% H$ y) S. s! V# B
the base of the phallus and was dark and curled. The
X" k- k4 L. Z5 A0 y7 m( w Q. |! Ptesticular volume was prepubertal at 2 mL each.* g/ L, u7 t5 y
The skin was moist and smooth and somewhat
* h' P5 f% g$ S. K. b; `oily. No axillary hair was noted. There were no
' g( n$ |/ `+ i& p; \9 `abnormal skin pigmentations or café-au-lait spots.( d- H' L3 I, Q! B
Neurologic evaluation showed deep tendon reflex 2+
9 ]3 M6 p5 _) a/ h) \8 f- b: nbilateral and symmetrical. There was no suggestion
7 m: y$ i. F D# I, p2 wof papilledema.6 l6 ^% y5 e, n" U
Laboratory Evaluation
4 s$ [; r# M- M( |! Z; U% E) B+ C4 O6 rThe bone age was consistent with 28 months by3 x+ ~5 ^4 D# M9 E
using the standard of Greulich and Pyle at a chrono-: L) x. F K4 D. j$ z& C% r
logic age of 16 months (advanced).5 Chromosomal
+ e/ O4 a9 g' f- E! Akaryotype was 46XY. The thyroid function test% k# Z' h! Y3 Z* q; G
showed a free T4 of 1.69 ng/dL, and thyroid stimu-7 a- I( `9 ~1 a+ e' R1 ~, N5 i7 z" ?
lating hormone level was 1.3 µIU/mL (both normal).
9 L- Z8 ]% K0 H1 y9 G' t/ yThe concentrations of serum electrolytes, blood) d" a: w7 A. g
urea nitrogen, creatinine, and calcium all were) `& c% r3 l7 @/ Z( M m
within normal range for his age. The concentration
9 t+ a) A0 Z2 G5 e/ I) b% F6 |of serum 17-hydroxyprogesterone was 16 ng/dL4 o9 j, Y8 f" B- D
(normal, 3 to 90 ng/dL), androstenedione was 20! i8 |7 W% l8 {1 `( \2 }
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
( g( i& f7 y) T! E7 H' \( ~+ ^ fterone was 38 ng/dL (normal, 50 to 760 ng/dL),4 l% @) ~3 G; g8 s' J
desoxycorticosterone was 4.3 ng/dL (normal, 7 to" R) {2 q/ |3 g P$ U! p! ]
49ng/dL), 11-desoxycortisol (specific compound S)
- y5 @0 b. @* j% D1 S2 Rwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-7 B8 D, y$ w/ S1 O& e$ K2 b
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
# r0 s1 u% U7 \+ ^4 Ltestosterone was 60 ng/dL (normal <3 to 10 ng/dL),1 _( |9 x$ U% }# `3 U' @
and β-human chorionic gonadotropin was less than9 P9 o0 A. z* m0 Z
5 mIU/mL (normal <5 mIU/mL). Serum follicular
8 X0 _& q8 a9 S" Wstimulating hormone and leuteinizing hormone5 u/ k, A4 _, D& p0 `5 I$ O' e
concentrations were less than 0.05 mIU/mL% d8 \2 k' v \+ f; o
(prepubertal).+ D. i, m, A. Y6 ], W/ N$ }3 s, }, S
The parents were notified about the laboratory
) C1 g7 A6 u' t6 }: z lresults and were informed that all of the tests were
; v) W7 V5 M* ^) @normal except the testosterone level was high. The4 _1 J6 X3 r, f4 K2 r1 D
follow-up visit was arranged within a few weeks to8 n# B$ `/ t7 n! m0 M0 o
obtain testicular and abdominal sonograms; how-
, _* V" W) r* h; a( @! W! ~ever, the family did not return for 4 months.
1 G+ W9 p5 m% ^2 ]6 o% oPhysical examination at this time revealed that the3 Z! U2 y9 H2 ]; f. X
child had grown 2.5 cm in 4 months and had gained
: w* R6 S: b0 g3 v; Q2 w% u+ _2 kg of weight. Physical examination remained
7 ^* j7 G1 ~ m. t, l& hunchanged. Surprisingly, the pubic hair almost com-& e. C9 p$ r D
pletely disappeared except for a few vellous hairs at
$ V+ V2 m1 _4 m4 f0 h2 [, {2 x3 Rthe base of the phallus. Testicular volume was still 2
8 s3 z. R2 h1 NmL, and the size of the penis remained unchanged.
5 v2 ]$ b' J8 X. v( c! i0 i& {3 o; a4 {( dThe mother also said that the boy was no longer hav-9 z! o' A( F3 `: v: n
ing frequent erections.
. V: ]& n# i3 K* \5 k' rBoth parents were again questioned about use of- o( A$ G" i8 O9 U! e
any ointment/creams that they may have applied to# J( \4 C2 G0 G
the child’s skin. This time the father admitted the5 n1 H+ h, A- m# F$ W! g0 Y
Topical Testosterone Exposure / Bhowmick et al 541
" ^/ M$ z6 p: h6 Vuse of testosterone gel twice daily that he was apply-
2 i* x$ N9 ~9 u8 t% G! Fing over his own shoulders, chest, and back area for
* y$ G* Q1 U9 [- ~ {: {a year. The father also revealed he was embarrassed& _3 L; h- |: |( ^1 e: `
to disclose that he was using a testosterone gel pre-* p( o/ x! b$ u( m( C. ?) \8 Y3 j7 Z
scribed by his family physician for decreased libido
: D- }* ?* j8 ^9 i6 Hsecondary to depression." ]) o# R; ?2 x, i# d' Z: a& p5 C% N
The child slept in the same bed with parents.6 V; {8 n7 I( x( D0 m- L" i0 R
The father would hug the baby and hold him on his6 ]' r, W5 J0 ^ K" ~
chest for a considerable period of time, causing sig-5 M! }1 p6 Z( D1 U
nificant bare skin contact between baby and father.
. |. ^# i& n9 N$ `4 IThe father also admitted that after the phone call,
: a8 J5 F( R) M5 Ewhen he learned the testosterone level in the baby
& |3 M3 e' a! K8 H ~# @was high, he then read the product information' r5 f% M7 a+ {# \' p2 ?: \$ U: Z
packet and concluded that it was most likely the rea-
- R2 {# R) [% e ~& Z8 m, ?& ason for the child’s virilization. At that time, they- s- m0 z, i8 u1 [
decided to put the baby in a separate bed, and the
# O% O F% U; P: e9 cfather was not hugging him with bare skin and had4 a* G, t. @" y4 W( l
been using protective clothing. A repeat testosterone. H$ M8 U) v3 z% g: Q& @
test was ordered, but the family did not go to the
9 T5 |1 c! I8 N( U" q" u, W4 Q8 |* Alaboratory to obtain the test.) @6 p, K' g% C) p6 U8 y
Discussion
! v9 ?) d1 G" X) T: PPrecocious puberty in boys is defined as secondary
+ k" T: ~* z, Asexual development before 9 years of age.1,4/ H" f) N- o# g* @; |
Precocious puberty is termed as central (true) when
' M, l8 c7 a" ^8 r1 O" q9 Sit is caused by the premature activation of hypo-+ d/ U8 H" ]6 y, o8 D4 K: _, \+ M
thalamic pituitary gonadal axis. CPP is more com-
2 ?+ F! e0 U2 w( e( I$ Fmon in girls than in boys.1,3 Most boys with CPP/ w; u) y% f2 `/ Z4 C! Y
may have a central nervous system lesion that is/ H0 T+ B( h3 o p
responsible for the early activation of the hypothal-2 j& M$ M" s+ ~' X0 {, c
amic pituitary gonadal axis.1-3 Thus, greater empha-
8 M5 u; D( Z1 W4 i6 `sis has been given to neuroradiologic imaging in2 C5 Y7 s( {0 V# d9 |
boys with precocious puberty. In addition to viril-
7 K( L0 E2 a7 X! b/ ?ization, the clinical hallmark of CPP is the symmet-8 M- o" m! P8 G- x) D; g: [, P
rical testicular growth secondary to stimulation by0 _& F& a7 d7 [) e& z+ b& w% n
gonadotropins.1,3
! Q# q( Z0 l+ ~Gonadotropin-independent peripheral preco-
* o% e G) E0 i/ B1 h4 N' ^ Wcious puberty in boys also results from inappropriate
. W5 N1 O% ~$ h6 w' q) zandrogenic stimulation from either endogenous or
( A1 j' x1 _+ Dexogenous sources, nonpituitary gonadotropin stim-
1 T3 B3 ~* P `5 E9 sulation, and rare activating mutations.3 Virilizing6 w [3 t5 b+ k u
congenital adrenal hyperplasia producing excessive
D) \* J$ W: Q Zadrenal androgens is a common cause of precocious, w1 L- p+ R" g+ g/ d& B7 f3 y
puberty in boys.3,40 p) }1 p6 |! Z: r( C
The most common form of congenital adrenal
7 ?" b6 p6 b$ f* e/ i- @hyperplasia is the 21-hydroxylase enzyme deficiency., {/ N; @# r3 ~! T+ S
The 11-β hydroxylase deficiency may also result in
- u7 q, ?& C* texcessive adrenal androgen production, and rarely,
/ r2 q! i6 L( [& V han adrenal tumor may also cause adrenal androgen
4 G+ o& F7 d8 N* w6 X9 D% O: aexcess.1,3
/ W- ~. L/ k8 zat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, B q4 j, w; u0 t7 h" V" |( r542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
" X4 F) [1 N) c3 C7 f1 T- w# A$ SA unique entity of male-limited gonadotropin-* b: i4 q- Z! | p
independent precocious puberty, which is also known7 F T; ?* q" a( C
as testotoxicosis, may cause precocious puberty at a Q$ I% c1 n# E' i" q
very young age. The physical findings in these boys! `1 B" T% d5 a, A
with this disorder are full pubertal development,! P8 d+ @( U. Y' o2 p) V% ?
including bilateral testicular growth, similar to boys" e/ s! v8 ?) f+ W, Y8 o
with CPP. The gonadotropin levels in this disorder
* X: v o' ^) ^( z9 b+ M; Yare suppressed to prepubertal levels and do not show1 w# N& A( R$ R2 F
pubertal response of gonadotropin after gonadotropin-6 ~, N6 `4 A7 ]3 |
releasing hormone stimulation. This is a sex-linked
* n# v' ?2 k a/ |% c' r) e* u- tautosomal dominant disorder that affects only
9 @# d1 C; p% k0 jmales; therefore, other male members of the family
1 B |# G' q0 J' d, U5 P% Xmay have similar precocious puberty.3
X, B% s' N6 e7 d; M) GIn our patient, physical examination was incon-
) Y8 ~) n9 Q, k ~# g6 z4 Ksistent with true precocious puberty since his testi-
* g& c, ^) T P$ P7 x! Pcles were prepubertal in size. However, testotoxicosis' D$ K0 N) |& Z9 v% r
was in the differential diagnosis because his father
3 v! S8 d$ K8 F1 D% rstarted puberty somewhat early, and occasionally,: R. C2 i% [6 i2 q1 L- d& h
testicular enlargement is not that evident in the% }8 m( b$ ~" ?, C* N
beginning of this process.1 In the absence of a neg-
" n5 f& y6 i0 F1 Aative initial history of androgen exposure, our
' M8 g9 [: l" _biggest concern was virilizing adrenal hyperplasia,2 H3 W' @, s" \2 ?
either 21-hydroxylase deficiency or 11-β hydroxylase M( W4 |3 M |+ U, `) r5 `
deficiency. Those diagnoses were excluded by find-0 q# k6 A: l4 }
ing the normal level of adrenal steroids.- f1 d3 d$ P p/ k' K) c
The diagnosis of exogenous androgens was strongly( \) d) ]" G6 W8 E
suspected in a follow-up visit after 4 months because5 ^2 z- a5 ^. i: [6 y3 j
the physical examination revealed the complete disap-
/ g9 l: K# @( C5 v3 @& }5 j7 \# t4 apearance of pubic hair, normal growth velocity, and+ `6 x, K3 m1 K$ F$ D
decreased erections. The father admitted using a testos- A/ s4 U6 M* @ F) w
terone gel, which he concealed at first visit. He was
9 s* V5 a. M8 A p8 g2 m& A2 S- Busing it rather frequently, twice a day. The Physicians’
! y5 L8 Z4 J2 w5 c+ G2 p4 n" o+ _ CDesk Reference, or package insert of this product, gel or3 H5 v2 b) }" ^ |1 s1 j
cream, cautions about dermal testosterone transfer to5 N* P' P+ j+ z% \6 ~1 e3 ?
unprotected females through direct skin exposure.; z' i4 \; |- [( d
Serum testosterone level was found to be 2 times the) T* c& I6 c, d( w. {. S
baseline value in those females who were exposed to \* N: I. B: u2 w
even 15 minutes of direct skin contact with their male9 w' @7 b$ R: v* k" g! q
partners.6 However, when a shirt covered the applica-
9 i" Z! O9 i1 s) @9 @. ~tion site, this testosterone transfer was prevented.6 a* q G7 `$ i
Our patient’s testosterone level was 60 ng/mL,
+ z) G0 [4 d5 g. Z: H% W9 _ _) hwhich was clearly high. Some studies suggest that
8 r1 G* s$ p9 {+ \ ?' I- wdermal conversion of testosterone to dihydrotestos-) l7 @' N* u4 H( Q+ f6 p ^! T
terone, which is a more potent metabolite, is more
* C4 s& N7 [0 |; R' E6 lactive in young children exposed to testosterone5 g, Z {/ Q9 p
exogenously7; however, we did not measure a dihy-: O) M6 G: k. u$ U' t5 L
drotestosterone level in our patient. In addition to
3 g5 Z# I2 H N$ H) ] Gvirilization, exposure to exogenous testosterone in
9 k, Z# X" @8 Z6 F4 Rchildren results in an increase in growth velocity and+ {; \- c+ b* r5 X( x3 C# `& a
advanced bone age, as seen in our patient.* V% O% d. F5 u! Z3 C7 {, k: O& j
The long-term effect of androgen exposure during, @! P# ~& m5 f2 L
early childhood on pubertal development and final
9 {* j& d, J( x2 n7 e* nadult height are not fully known and always remain
v/ a8 X( A+ b( ba concern. Children treated with short-term testos-
' s1 y V) b; K; aterone injection or topical androgen may exhibit some. H( h% t! K! R. z
acceleration of the skeletal maturation; however, after) o; C' q4 @1 t6 X2 {, V# N; F
cessation of treatment, the rate of bone maturation
1 D% M7 I0 W1 M6 }' p* f. Hdecelerates and gradually returns to normal.8,9
6 c0 K/ g3 F0 ]& C; a- M, _There are conflicting reports and controversy6 O. o3 C3 W, \) t* f
over the effect of early androgen exposure on adult
$ J9 F( a+ e8 h1 I- S/ kpenile length.10,11 Some reports suggest subnormal7 Z/ H# |3 x# b% q) k3 H' U
adult penile length, apparently because of downreg-$ E. t3 W' Q# R4 m7 z
ulation of androgen receptor number.10,12 However,
$ {0 Q6 x, l; [9 ]6 r' ]* K' ySutherland et al13 did not find a correlation between
4 P. B. y4 ^! C+ ^1 H5 [( jchildhood testosterone exposure and reduced adult
7 X: T9 ^1 c6 N6 G" mpenile length in clinical studies.
$ j) _- o' e/ XNonetheless, we do not believe our patient is; t' O3 p2 r3 ^. H* X: R& L
going to experience any of the untoward effects from. q2 F* E, M# [2 g! d
testosterone exposure as mentioned earlier because/ L- r6 t. s0 @: y) M0 l
the exposure was not for a prolonged period of time.& J# R1 ^0 [2 `6 I- a+ j. I+ ^6 ?# _/ e
Although the bone age was advanced at the time of
0 M0 Y" N0 s) r4 _; Ediagnosis, the child had a normal growth velocity at4 P' ~: |! u6 F/ P: S
the follow-up visit. It is hoped that his final adult
! ~8 e/ d9 B, T4 [* F8 v* F# iheight will not be affected.
* f) ^% X' @( N9 k7 s# T, H% QAlthough rarely reported, the widespread avail-- { ^3 ~, Q2 c$ m& ]1 ?# q
ability of androgen products in our society may: O9 ]3 b2 h* _4 D
indeed cause more virilization in male or female
/ a1 N6 s' b8 k1 K x9 bchildren than one would realize. Exposure to andro-5 @3 V# b* g# ^6 Q1 P
gen products must be considered and specific ques-3 I0 P1 j% S& Q% L; A' J
tioning about the use of a testosterone product or
' \: Q9 n- K7 mgel should be asked of the family members during
* y5 O+ o) E2 r7 Q" m! _: fthe evaluation of any children who present with vir-
% y3 N/ ?9 Y& J, h: V# k6 U7 Qilization or peripheral precocious puberty. The diag-
0 f l0 s- u/ K& x5 jnosis can be established by just a few tests and by. b" h# Q% g7 x# @/ y
appropriate history. The inability to obtain such a: d8 f5 Z6 M+ j- y. `2 \
history, or failure to ask the specific questions, may
1 {% J, m0 F$ k2 L5 y- l$ f+ I) rresult in extensive, unnecessary, and expensive
. s) O% v: N6 G$ Einvestigation. The primary care physician should be
; m; Q2 R" S" Y) H- l( z0 H- ~aware of this fact, because most of these children
; [+ f, R n: [7 wmay initially present in their practice. The Physicians’+ x2 f# R+ C$ u, X: O
Desk Reference and package insert should also put a
( r, q7 q. J) c: |warning about the virilizing effect on a male or
+ X) ^ G! f; w- W4 p8 {6 ~female child who might come in contact with some-4 U! W* M1 j3 A3 N" a, y: s6 D
one using any of these products.
9 e! C3 f7 r4 R r3 f L% tReferences
( v) o# O, w9 T5 X- ?1. Styne DM. The testes: disorder of sexual differentiation
8 ?# W# ]# e1 g2 n( m* ^and puberty in the male. In: Sperling MA, ed. Pediatric
, g3 ]. l" s# [( mEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;8 F. D% ^0 w2 U0 A
2002: 565-628.
; j! b% W0 ?8 z8 T2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
9 k" y+ }! T. T% [$ ^, Apuberty in children with tumours of the suprasellar pineal |
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