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Sexual Precocity in a 16-Month-Old. S% V. @) m2 k! Y. X; E
Boy Induced by Indirect Topical W! ~) r; [" Q! g# D
Exposure to Testosterone
* a% H' K. e. s E# M9 r9 K4 J( Q% x ZSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
6 n; ~1 R, r, V( ]8 W) o2 Vand Kenneth R. Rettig, MD1
: z) [6 n/ o* h4 l" R" [( h3 cClinical Pediatrics W" c5 I5 b/ H
Volume 46 Number 6- N! e; f4 i2 i8 X
July 2007 540-5439 @* G5 y% i, d1 e7 I0 y
© 2007 Sage Publications4 D' x! J2 M" w+ K. s9 Q
10.1177/00099228062966514 o7 ]& u0 g( |4 k2 M) X4 R( b
http://clp.sagepub.com$ H: d& g& m& X
hosted at4 {1 _; ]' N8 A: V
http://online.sagepub.com
- U. d: t. d6 }* O dPrecocious puberty in boys, central or peripheral,
5 j* b! ~+ D! F) a' j3 T, pis a significant concern for physicians. Central
4 W2 R# j+ h+ v+ X' \6 Eprecocious puberty (CPP), which is mediated7 `' E# {* b5 ]5 G1 e
through the hypothalamic pituitary gonadal axis, has# S- \3 } g. b E
a higher incidence of organic central nervous system
3 t2 H9 [5 |: I4 plesions in boys.1,2 Virilization in boys, as manifested0 f0 s1 T! Z# ^! j' J" r
by enlargement of the penis, development of pubic
) p% I1 J* `* e; A! shair, and facial acne without enlargement of testi-& {7 W: K- ~6 _2 B) W
cles, suggests peripheral or pseudopuberty.1-3 We
% I% R6 R, m: u9 \+ @5 h" X. Nreport a 16-month-old boy who presented with the- v9 s9 w- v( h' p
enlargement of the phallus and pubic hair develop-! ~4 k q+ a( [' g% ?
ment without testicular enlargement, which was due1 y# c/ K0 A: D8 H
to the unintentional exposure to androgen gel used by
+ Z) F+ G. P+ @: L! p fthe father. The family initially concealed this infor-- c1 U6 D% ~; W. x
mation, resulting in an extensive work-up for this
) ^' x8 m4 f9 N5 y0 I; Rchild. Given the widespread and easy availability of
$ \" w% T! \/ l1 T# q' Ktestosterone gel and cream, we believe this is proba-
, o2 B- X) E1 Z0 n4 J" d& {bly more common than the rare case report in the3 o9 Z$ R, b9 {/ {
literature.4
$ K! `, q* n/ R9 U* `2 H! W' @Patient Report4 j+ ?1 m1 R$ r
A 16-month-old white child was referred to the1 o9 U! C7 h: j8 y' _; P) ?
endocrine clinic by his pediatrician with the concern" l! r( t" Y8 e, M* _
of early sexual development. His mother noticed& N. r7 `2 i% r6 a# h# d6 X4 d$ C6 T, m
light colored pubic hair development when he was w. a0 D V% J* V& G# f% A
From the 1Division of Pediatric Endocrinology, 2University of4 ^1 l, E4 F9 s4 V% V6 \, S( t* T
South Alabama Medical Center, Mobile, Alabama.
. y3 ~/ ]( F) U: O0 p4 l6 [8 ]Address correspondence to: Samar K. Bhowmick, MD, FACE,
6 O9 y5 ]/ C8 h( o; K; qProfessor of Pediatrics, University of South Alabama, College of5 g, b0 W& j" S7 U" j# l
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;% s7 z' g! H5 r% I3 j
e-mail: [email protected].
% J" d( Y% R& @* z% Zabout 6 to 7 months old, which progressively became4 \6 J2 [4 [; E& G n' ^
darker. She was also concerned about the enlarge-
+ T; B3 ]. W5 ^! ~ment of his penis and frequent erections. The child+ e. X+ A' G: o; }* \5 q
was the product of a full-term normal delivery, with# w9 a$ G$ O0 s7 _' s/ y. ?
a birth weight of 7 lb 14 oz, and birth length of6 ~2 {. R, e9 ?2 c/ _
20 inches. He was breast-fed throughout the first year
, I7 l, `2 n7 }/ cof life and was still receiving breast milk along with
& V. {% j5 }+ o3 Z" d9 M7 Dsolid food. He had no hospitalizations or surgery,# x+ Y* l' l7 L5 \
and his psychosocial and psychomotor development& Q/ M1 b% L4 d, ?& a5 p& x
was age appropriate.
; ^: o5 L0 }+ _6 h3 J1 ZThe family history was remarkable for the father,
7 R/ Z3 b1 ?0 [4 R2 C. xwho was diagnosed with hypothyroidism at age 16,: y# Q8 r" a9 a/ J4 O4 _) O
which was treated with thyroxine. The father’s' y0 S: @, t" Y) D ?6 X# c
height was 6 feet, and he went through a somewhat$ \/ s5 k$ g: t5 G: i
early puberty and had stopped growing by age 14.- _3 b! ]) S0 l& u+ r% A- J: R/ B
The father denied taking any other medication. The8 P: z; c. D# X6 I* e; W1 ^9 k+ @
child’s mother was in good health. Her menarche
5 s" a @5 ]7 xwas at 11 years of age, and her height was at 5 feet
- D6 t0 W/ G/ [4 M- K5 W5 inches. There was no other family history of pre-2 u+ _+ W8 L, ]+ L _: @3 Z
cocious sexual development in the first-degree rela-
: C6 o% X; \- G: ]3 etives. There were no siblings.
4 Z" m2 r4 I) K1 [Physical Examination; E/ m5 M$ C; s3 P4 Q) k
The physical examination revealed a very active,, S5 I. y& j/ w/ F8 r3 g5 c
playful, and healthy boy. The vital signs documented8 t {) d+ a( a# r; B% E
a blood pressure of 85/50 mm Hg, his length was$ k: A: O1 F8 @2 \# j* ~
90 cm (>97th percentile), and his weight was 14.4 kg. B- c! ^% n! V/ ^9 G
(also >97th percentile). The observed yearly growth
2 y% B- F/ w0 V% _, evelocity was 30 cm (12 inches). The examination of
/ h) w; s' A4 s9 Qthe neck revealed no thyroid enlargement.
5 z1 P0 D) u9 S- _) @9 K' i2 JThe genitourinary examination was remarkable for
3 K+ @# m- o4 B: \" m% J, `enlargement of the penis, with a stretched length of
, R" T6 _5 E' r& u% K8 y8 cm and a width of 2 cm. The glans penis was very well
1 z7 \/ J! R: p0 z& O( k1 ldeveloped. The pubic hair was Tanner II, mostly around# h9 x9 W% ~3 }6 ~
540' O. \' d$ {' p. |% S
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
1 f1 E: O! D: S8 E# ]& }the base of the phallus and was dark and curled. The
+ M i6 [3 i I5 h" Q' Utesticular volume was prepubertal at 2 mL each.
9 @- T& g6 \. ^3 {The skin was moist and smooth and somewhat M1 F- q0 C9 b5 a4 ?
oily. No axillary hair was noted. There were no
# e; R1 C; V+ w7 Yabnormal skin pigmentations or café-au-lait spots.. w3 v9 d6 n' O" r9 E' _" W3 \; g
Neurologic evaluation showed deep tendon reflex 2+
6 R% R5 U& g) ubilateral and symmetrical. There was no suggestion
' b. I0 N/ }! x: s$ H' Iof papilledema.
1 `" N( Z, \$ r) q ]2 a/ z; u9 [Laboratory Evaluation
% v% V- L A$ P0 ]2 Y6 |% x9 `* hThe bone age was consistent with 28 months by
7 T/ M- I0 K4 x8 busing the standard of Greulich and Pyle at a chrono-1 k* u/ E3 D3 t
logic age of 16 months (advanced).5 Chromosomal
) j' k- `4 }) Akaryotype was 46XY. The thyroid function test
5 w6 ^0 F! D* O8 r- ?, Yshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
* I: K$ o9 a% g4 e. V1 f& V- hlating hormone level was 1.3 µIU/mL (both normal).' q! G6 [8 x T$ o
The concentrations of serum electrolytes, blood
0 p4 N' u) I# @# Yurea nitrogen, creatinine, and calcium all were
1 K# k$ j+ W2 L& d$ ^- Z' I% Kwithin normal range for his age. The concentration4 Y$ p7 ]( i0 C5 @# \' g
of serum 17-hydroxyprogesterone was 16 ng/dL: _, _. T1 X* v2 `
(normal, 3 to 90 ng/dL), androstenedione was 208 U; l. C- m4 X. Q; i
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-# m* I" o- V( a4 i3 R8 }3 P+ x
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
9 I5 v8 D( h2 q) e: z0 idesoxycorticosterone was 4.3 ng/dL (normal, 7 to% A5 m& ]7 I Z, ~4 w
49ng/dL), 11-desoxycortisol (specific compound S)
3 `$ h0 }, C) G* O/ J1 w/ H" t; A8 Xwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-$ O. }" l3 G" d; a2 T7 K
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
- P: a. U% A, [& S$ C/ a- ]testosterone was 60 ng/dL (normal <3 to 10 ng/dL),% }5 y& ?$ h- J y' R7 `
and β-human chorionic gonadotropin was less than
, z& z3 w9 P" h5 mIU/mL (normal <5 mIU/mL). Serum follicular
8 t2 k ]4 G% C. pstimulating hormone and leuteinizing hormone
8 l, z6 x) k7 _& ~. L* _! F4 Jconcentrations were less than 0.05 mIU/mL% Y6 M1 ?+ Z* C& x, p. N" |! j1 P& k+ }
(prepubertal).- o8 b- ~: b. |: f7 M- L
The parents were notified about the laboratory0 H( T% ^1 ^: m, W
results and were informed that all of the tests were9 y4 K# {: F/ n" q2 D: i
normal except the testosterone level was high. The
`" S, ]! K7 G! I& U9 h7 s( Hfollow-up visit was arranged within a few weeks to
f/ e8 W- ^7 d$ G) \4 mobtain testicular and abdominal sonograms; how-
: k H) N! W+ n+ y) {ever, the family did not return for 4 months.4 s0 _1 i3 e! Q
Physical examination at this time revealed that the
) P2 I( [4 s# e) n% pchild had grown 2.5 cm in 4 months and had gained/ y0 d/ e" g" F' C; C
2 kg of weight. Physical examination remained9 h. e% y4 k% t, M5 @* I" E
unchanged. Surprisingly, the pubic hair almost com-
$ @& m ?+ u3 Y; n: o8 lpletely disappeared except for a few vellous hairs at* k+ }& s+ i/ S
the base of the phallus. Testicular volume was still 2
! W m3 N9 X1 E* p8 O3 m( k9 O+ ZmL, and the size of the penis remained unchanged.
& E* ^/ @5 A8 O* t. w( o: _+ uThe mother also said that the boy was no longer hav- n( _, a$ I* F5 G8 ^* I
ing frequent erections.
1 `+ c3 Z: d; k" R# z7 W5 S0 p; q2 C+ FBoth parents were again questioned about use of
8 j9 W: ^ I; K+ ]any ointment/creams that they may have applied to
# W/ q! F( X- `the child’s skin. This time the father admitted the& V" O1 U) C0 y9 q0 W( K2 N
Topical Testosterone Exposure / Bhowmick et al 541: W$ l( z$ h ` S3 X
use of testosterone gel twice daily that he was apply-/ R U, r- B4 Z5 L4 M$ x
ing over his own shoulders, chest, and back area for
5 h- ~3 n* N) I' |# P! N& Y. Wa year. The father also revealed he was embarrassed
. s! ^# f S x; B" `1 Lto disclose that he was using a testosterone gel pre-# }+ {/ W9 P# v4 S! m
scribed by his family physician for decreased libido
! S: i( [8 Y9 S1 \/ A/ isecondary to depression.8 d( e# S( \# m
The child slept in the same bed with parents.
3 i. R7 a, B- h0 j9 S$ [0 Q* a" WThe father would hug the baby and hold him on his
3 o% n, f- O/ M) Schest for a considerable period of time, causing sig-
2 G+ R- u- t, k* Jnificant bare skin contact between baby and father." s3 p4 \4 I! c6 `, s8 K6 u7 k
The father also admitted that after the phone call,; m" y% V$ A: G: a
when he learned the testosterone level in the baby
/ X! x1 {. A m+ K, zwas high, he then read the product information* L; y2 q2 I% ?$ @) [
packet and concluded that it was most likely the rea-
- @. K+ _! ~7 x1 {! r& d6 } S) Dson for the child’s virilization. At that time, they! D; k' ~- m7 k$ u
decided to put the baby in a separate bed, and the7 M- F! v9 E# U7 h$ E; p$ r1 m) Y( h
father was not hugging him with bare skin and had
) w' ?4 F$ U. W- N, U' w1 r' P0 Bbeen using protective clothing. A repeat testosterone/ A/ T6 o+ b1 e" i0 {# n
test was ordered, but the family did not go to the
3 }( K% s" P, a1 Q1 U: llaboratory to obtain the test.
3 n' P& c5 M( w1 ODiscussion+ j: Y W, q" c3 e+ U! E0 c. H
Precocious puberty in boys is defined as secondary
, Y1 ?1 u9 I% v; u, {+ vsexual development before 9 years of age.1,48 i5 ]4 e9 }, ^" P- f: U5 F
Precocious puberty is termed as central (true) when& b ^/ Q+ s- g/ S9 f: a
it is caused by the premature activation of hypo-
! }/ K" U1 j7 Q0 E& x+ c* n. C( [thalamic pituitary gonadal axis. CPP is more com-
; j* t- q) d) |4 d, amon in girls than in boys.1,3 Most boys with CPP6 g" w+ F3 G# u; w) v3 Z
may have a central nervous system lesion that is' K' |! Y9 ]- N4 V# e
responsible for the early activation of the hypothal-
1 Q4 Z% x% k, R9 Bamic pituitary gonadal axis.1-3 Thus, greater empha-
9 }4 u/ R, {2 O( I2 Asis has been given to neuroradiologic imaging in9 z2 [- X6 v" x5 O2 T
boys with precocious puberty. In addition to viril-+ d* \$ {& T2 A, Y @
ization, the clinical hallmark of CPP is the symmet-1 Z5 @5 c* R; v! I0 J
rical testicular growth secondary to stimulation by
. Z" s9 ~8 b- T' e% Kgonadotropins.1,3& P$ N0 r6 b, \2 l- o4 n0 t
Gonadotropin-independent peripheral preco-
& D$ ^4 a/ ]$ @2 mcious puberty in boys also results from inappropriate; g$ m0 E! ^) J9 ]2 |2 F) A
androgenic stimulation from either endogenous or0 |& Q; O" i/ Z/ v1 q
exogenous sources, nonpituitary gonadotropin stim-
! L! d! Q* @1 h8 F7 z8 p' {ulation, and rare activating mutations.3 Virilizing. d* z& y5 S3 Q! I& g
congenital adrenal hyperplasia producing excessive# _5 d* C: |5 ?9 ]
adrenal androgens is a common cause of precocious
6 r% `- c. _, `5 N# X, mpuberty in boys.3,42 S3 d; L$ t8 n. q9 \
The most common form of congenital adrenal
: _# G; l$ F. w/ h" Hhyperplasia is the 21-hydroxylase enzyme deficiency.
# e3 M8 c( V$ a* C7 ^6 {0 t$ WThe 11-β hydroxylase deficiency may also result in( Z5 u3 o( Q( K0 d; V, n
excessive adrenal androgen production, and rarely,
0 Z. I3 ~% x8 k' T) S" Dan adrenal tumor may also cause adrenal androgen5 [9 j: I; w& n) q
excess.1,3
( M* u# A9 E) X* o0 a7 y" `at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from: X$ f$ O1 N1 R$ k7 A5 V9 V
542 Clinical Pediatrics / Vol. 46, No. 6, July 20075 S* o- a3 m+ V( q2 q3 E
A unique entity of male-limited gonadotropin-$ ^; D3 x) j+ p/ U9 q4 y
independent precocious puberty, which is also known5 w6 n2 L5 X" W1 w% i6 Q
as testotoxicosis, may cause precocious puberty at a
; W( J7 a. b1 y* hvery young age. The physical findings in these boys
6 V/ [5 X% G# F. N7 wwith this disorder are full pubertal development,6 O4 _' t2 o! d
including bilateral testicular growth, similar to boys: V' @6 d6 o# ?" a4 j% J# {1 b2 V. q
with CPP. The gonadotropin levels in this disorder
/ O3 U) I3 d% {( Ware suppressed to prepubertal levels and do not show
2 a5 V: o( q3 }( Kpubertal response of gonadotropin after gonadotropin-, Y8 Z, d* e7 [
releasing hormone stimulation. This is a sex-linked
8 U, J4 ^: e! Qautosomal dominant disorder that affects only
0 q* N; f1 S. |9 C7 X0 k+ M4 hmales; therefore, other male members of the family
- \' c& u" D& t" {, B& Jmay have similar precocious puberty.3+ W) s$ {, c: _9 K
In our patient, physical examination was incon-) D2 y7 i; C# w7 W5 V1 r8 r- I7 v" [
sistent with true precocious puberty since his testi-
, f/ A9 m' E! A# M! C$ kcles were prepubertal in size. However, testotoxicosis
: g' ?' C4 |$ t# } owas in the differential diagnosis because his father
1 m5 I" _; T0 Bstarted puberty somewhat early, and occasionally,
, w5 u3 m! q$ v+ G0 a, ztesticular enlargement is not that evident in the
4 P, |& @9 P4 X+ Y( O& Vbeginning of this process.1 In the absence of a neg-. l% M* B9 F+ H! Y( ?4 Z- ?
ative initial history of androgen exposure, our
& t6 Z0 I, t. ^biggest concern was virilizing adrenal hyperplasia,, \) z5 y$ k& i* }2 `- L9 S* f: v
either 21-hydroxylase deficiency or 11-β hydroxylase2 @# U5 i! V5 k7 m1 T
deficiency. Those diagnoses were excluded by find-: h9 `% N! J( b" W \
ing the normal level of adrenal steroids.
. L; t1 c5 Z/ |) rThe diagnosis of exogenous androgens was strongly
% D" N1 q4 E* @( D0 t3 b: S- asuspected in a follow-up visit after 4 months because: i. G3 n5 Y `1 C& |% p0 u
the physical examination revealed the complete disap-
8 J \9 m0 w7 k opearance of pubic hair, normal growth velocity, and6 W( r- C& g( }
decreased erections. The father admitted using a testos-9 s; R! I0 x0 I
terone gel, which he concealed at first visit. He was
, n* s. N7 b* R8 W) Iusing it rather frequently, twice a day. The Physicians’) L0 I2 D; O( z9 ]/ J/ j
Desk Reference, or package insert of this product, gel or
- d: {! b4 h7 ccream, cautions about dermal testosterone transfer to% Q& j/ d8 | d( M6 t
unprotected females through direct skin exposure.
) o4 R) z$ J3 E6 i& SSerum testosterone level was found to be 2 times the( ?! h( G! F L- ^2 W
baseline value in those females who were exposed to- K, ]: t/ R3 S4 i9 V
even 15 minutes of direct skin contact with their male9 X) i/ U4 q5 U6 m
partners.6 However, when a shirt covered the applica-
! }% A+ C; {" [( `3 R- Stion site, this testosterone transfer was prevented.% ?; k9 A* @* d, b9 k
Our patient’s testosterone level was 60 ng/mL,+ z. d/ ~8 j8 |4 y/ ?+ w4 O& F& z
which was clearly high. Some studies suggest that
, i9 H: W3 e9 Q5 M! `# {' ddermal conversion of testosterone to dihydrotestos-
" X% q& R0 F) \) e- y. }terone, which is a more potent metabolite, is more
' H: ~% Z$ r4 B. ^3 [. n6 hactive in young children exposed to testosterone
. v: e9 L( ~6 F1 }4 m- @& B9 \* Bexogenously7; however, we did not measure a dihy-0 j+ ^$ {" z* w/ X: t
drotestosterone level in our patient. In addition to, X* h3 |2 V: n/ U3 O
virilization, exposure to exogenous testosterone in( B( L/ U. H" T4 v
children results in an increase in growth velocity and% r8 S( O; R: I- ~' [* m6 U" E1 C5 o
advanced bone age, as seen in our patient.' N& ~. v" r: u! L& C1 P
The long-term effect of androgen exposure during; w. S( |* D5 b, |% e' W( }! k9 T3 b
early childhood on pubertal development and final+ e5 H( Q& V' C0 e! x
adult height are not fully known and always remain3 Z6 `# v' K3 Q) j7 n
a concern. Children treated with short-term testos-0 m( E1 V3 J9 ^0 G0 \3 C
terone injection or topical androgen may exhibit some. E. W2 R3 G- Y5 v
acceleration of the skeletal maturation; however, after+ t; @& E2 s: w8 Y
cessation of treatment, the rate of bone maturation2 A# W" C; ^4 D& h6 ^( _
decelerates and gradually returns to normal.8,9, R+ z2 D" N% J) V9 q+ E
There are conflicting reports and controversy
9 G- @* ]0 K. l# u( i( Bover the effect of early androgen exposure on adult
, U k. J9 d2 qpenile length.10,11 Some reports suggest subnormal
7 s1 F. f% g2 A) u- C# zadult penile length, apparently because of downreg-
" Z1 o0 P" z5 s! q% A( U- B9 g/ @' Bulation of androgen receptor number.10,12 However,. @$ s8 @- \0 \+ |( o
Sutherland et al13 did not find a correlation between
: X+ N) q% G+ j$ fchildhood testosterone exposure and reduced adult
+ n7 |2 @4 n7 h6 T$ @penile length in clinical studies.
8 l" u% R. T0 kNonetheless, we do not believe our patient is
8 o2 Q( |0 P W5 U) wgoing to experience any of the untoward effects from# e1 E5 E9 R! }$ t" ^# A; ]
testosterone exposure as mentioned earlier because
0 s! C' c8 L6 {2 A1 p+ ?' _the exposure was not for a prolonged period of time.
5 z% k' w8 |3 s9 c4 B3 }Although the bone age was advanced at the time of1 ^5 W! H8 t- p" h4 e
diagnosis, the child had a normal growth velocity at# u; Z* }! @( c; V
the follow-up visit. It is hoped that his final adult5 u# O6 f+ N; q
height will not be affected.4 u! A( i2 U" _3 i0 b
Although rarely reported, the widespread avail-
2 g. v/ D! S+ H8 M& p( z: [+ @8 Rability of androgen products in our society may
% B2 t( J7 V# H+ @8 q* @ Uindeed cause more virilization in male or female
5 |9 j/ k T' ?% b: S) Ychildren than one would realize. Exposure to andro-
. ]9 }5 D3 {) |gen products must be considered and specific ques-
) ^* e, E; I6 |tioning about the use of a testosterone product or
; \ `# F0 ~4 ?$ X, F* Pgel should be asked of the family members during
/ o9 Q9 b% ~5 F4 x' L- kthe evaluation of any children who present with vir-
% c, P. F7 L% q2 r4 c2 bilization or peripheral precocious puberty. The diag-
5 P6 L# v/ o7 T8 D; L6 d5 Enosis can be established by just a few tests and by" |2 B* I/ [6 m2 @
appropriate history. The inability to obtain such a
, K& D( Z& K$ lhistory, or failure to ask the specific questions, may
6 D9 B0 @! S: Q/ Z0 Z3 V5 ?+ A$ Lresult in extensive, unnecessary, and expensive
5 i( z& g2 h0 ]9 t' t5 }, Z0 g+ yinvestigation. The primary care physician should be9 s7 N4 p( i) @& j
aware of this fact, because most of these children2 w$ l, B$ [) s) L7 \ m6 M
may initially present in their practice. The Physicians’
0 _3 d Y% j4 h: f9 i! F) I3 m% {3 dDesk Reference and package insert should also put a
; ~, f" J8 ~9 R5 fwarning about the virilizing effect on a male or4 J# K" I2 X* [. @5 r3 B
female child who might come in contact with some-% ]. Y7 M$ _7 x* A( ~- v+ t7 ^+ I
one using any of these products.+ e! U+ E: G; p2 G9 r
References
6 c6 r/ o! ^! j2 c. X$ t1. Styne DM. The testes: disorder of sexual differentiation
9 y& S' q4 K8 B* @9 S) G8 d, y1 Vand puberty in the male. In: Sperling MA, ed. Pediatric( ]: t7 _4 S& ^! L1 v9 V7 M% n
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;$ Q- Q7 [# f/ q n& Z, E
2002: 565-628.
. ?- g( i T' p/ |/ K* q1 |' N2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: B4 Y# _. ~4 M( x. ^/ N3 E
puberty in children with tumours of the suprasellar pineal |
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