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Sexual Precocity in a 16-Month-Old
% }( J& @) ^8 o4 P* aBoy Induced by Indirect Topical
m" `1 }6 T, U0 QExposure to Testosterone
8 ]# ^4 R7 N( |. ?Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2; r" j7 C2 Q0 ~% M8 d: s! F5 l
and Kenneth R. Rettig, MD1# W9 V0 z' ^8 J$ @3 O: q' Q! _
Clinical Pediatrics+ p8 J2 L% s l3 C" ]# J3 ]
Volume 46 Number 62 @% H7 d/ c/ L
July 2007 540-543- ?; Q M) M# K5 y6 j
© 2007 Sage Publications
& @) n T. _; I* f! M; H% T10.1177/0009922806296651$ k" T% Y; l7 n# e( G
http://clp.sagepub.com
+ z$ i1 r/ ~/ x! Ahosted at
8 F+ }0 m/ u- Qhttp://online.sagepub.com
; D/ q% S' l% D1 q5 v2 H7 gPrecocious puberty in boys, central or peripheral,$ z/ Z& Z! ?! p/ f% h
is a significant concern for physicians. Central
2 x) H( V: X5 j6 P- C5 e* X vprecocious puberty (CPP), which is mediated
) E& P" d# O3 ?. X1 x Cthrough the hypothalamic pituitary gonadal axis, has U6 V L* i( X
a higher incidence of organic central nervous system
. r8 o# g& w H4 q9 r- Flesions in boys.1,2 Virilization in boys, as manifested
! t! ~6 ^, V+ v' ]5 k, \ p; q% U) hby enlargement of the penis, development of pubic+ j; _( s8 f- Y! Q! m; }
hair, and facial acne without enlargement of testi-
$ P2 ], s; ~# K1 @% acles, suggests peripheral or pseudopuberty.1-3 We! T3 X: _1 @6 C5 h5 ?; N
report a 16-month-old boy who presented with the; @- p- _# S4 B, ?: K+ s$ Z: G
enlargement of the phallus and pubic hair develop-
' I) o% G0 Q$ ]4 vment without testicular enlargement, which was due4 H5 N: ^. B+ A5 p/ z
to the unintentional exposure to androgen gel used by% i. W1 w* d) W4 n" z
the father. The family initially concealed this infor-
' ?& |3 ]& p% C2 [* y% T: @mation, resulting in an extensive work-up for this/ R- q9 K# H, W; v( ~. u
child. Given the widespread and easy availability of8 ~. z: Y3 b# r& F. ]$ S# b$ z
testosterone gel and cream, we believe this is proba-
( x4 s) F9 }4 A4 }% Nbly more common than the rare case report in the l* i# [2 k0 B8 U4 K m- }
literature.4
; O3 X1 Z: Q" u; H# W' G3 pPatient Report8 g. S1 T. D! `# N0 _' n: G3 G" p/ g
A 16-month-old white child was referred to the
0 u; e, g- J* L5 |: Pendocrine clinic by his pediatrician with the concern
; m7 f v' D0 Uof early sexual development. His mother noticed
$ j8 a6 c7 Q" L+ M% p* A% {light colored pubic hair development when he was
' K( J3 ^, p/ _3 {) q* dFrom the 1Division of Pediatric Endocrinology, 2University of% ?- k; q% g: y( y6 k
South Alabama Medical Center, Mobile, Alabama.7 o4 u: U0 U+ v+ N5 g
Address correspondence to: Samar K. Bhowmick, MD, FACE,( K3 z2 v; h+ ~
Professor of Pediatrics, University of South Alabama, College of
% C; l9 z0 Q" l; mMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
# ^+ {( k8 E! b- M/ u3 @e-mail: [email protected].* D6 J ?! h. Z5 t0 u2 d
about 6 to 7 months old, which progressively became. ]+ s' w. f2 |4 h5 ~! I2 O) q
darker. She was also concerned about the enlarge-
' k2 \5 o( U; x* i/ w" X5 q9 ~: Nment of his penis and frequent erections. The child
4 {) C! X5 t, a, Y- owas the product of a full-term normal delivery, with
" H, U4 y5 \5 Ea birth weight of 7 lb 14 oz, and birth length of
" r. H- k- F, ]20 inches. He was breast-fed throughout the first year
( C/ G/ J' s& U8 dof life and was still receiving breast milk along with
# m( o" H$ d" a! Dsolid food. He had no hospitalizations or surgery,
4 ?8 w; {' d* ^& d eand his psychosocial and psychomotor development
4 R/ ^* s6 @3 E; W7 |) Zwas age appropriate.5 P' N- i. p( Q- {/ \, D
The family history was remarkable for the father,
1 k4 O u0 f t0 Twho was diagnosed with hypothyroidism at age 16,
7 B. S$ }# a4 X7 \( pwhich was treated with thyroxine. The father’s, q, z x" m( X/ A3 q# b x0 i+ ~
height was 6 feet, and he went through a somewhat
! d3 ~# D" m+ O5 N/ qearly puberty and had stopped growing by age 14.
$ h: ^) U. x( H8 `$ f7 ^The father denied taking any other medication. The3 J/ a0 B! n) }% u" v
child’s mother was in good health. Her menarche
4 ?8 D8 W" z7 [7 ]1 o2 y4 k5 s8 Lwas at 11 years of age, and her height was at 5 feet3 E6 ]% a1 y+ r2 `+ Q
5 inches. There was no other family history of pre-
+ `3 ^" K4 q1 acocious sexual development in the first-degree rela-# s0 S' t) a% n K: b$ N9 c
tives. There were no siblings.
& X- H# S/ v. N" ZPhysical Examination
4 B! H6 z" x+ g6 FThe physical examination revealed a very active,
6 u3 c# Z6 C, ]1 C7 i' @, h" S+ M8 xplayful, and healthy boy. The vital signs documented! @: z+ C1 E! l+ D% ^' R r5 K
a blood pressure of 85/50 mm Hg, his length was
7 K* W( H3 {2 G _( M4 O: @) Y90 cm (>97th percentile), and his weight was 14.4 kg
: P+ o) ?- m+ D' s/ w" W(also >97th percentile). The observed yearly growth
5 z4 A! |9 M1 k. Q% C: Pvelocity was 30 cm (12 inches). The examination of, X- L1 S' }6 G" ^. V/ ?9 }
the neck revealed no thyroid enlargement.! @) ?8 G6 L# t+ P3 g" U$ h
The genitourinary examination was remarkable for
- o4 ^0 q- w4 L3 z' [$ E. i. d' d2 zenlargement of the penis, with a stretched length of
/ z, Y; o5 }* C8 cm and a width of 2 cm. The glans penis was very well
* Z5 ?, y4 [- {9 ldeveloped. The pubic hair was Tanner II, mostly around
1 x+ g+ k4 o0 R! k" Y6 ~, j540! [1 Z# j$ D9 Q
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
+ ]- s+ F& g+ r) D( d8 Ythe base of the phallus and was dark and curled. The: h$ a" r- I! {6 W% w. L
testicular volume was prepubertal at 2 mL each.
, j* A/ \8 w, n! cThe skin was moist and smooth and somewhat
4 f: w6 F( h! [6 Ooily. No axillary hair was noted. There were no
0 |6 L# v: n: a! t$ mabnormal skin pigmentations or café-au-lait spots. Y& P' d6 H g1 w$ ]0 D
Neurologic evaluation showed deep tendon reflex 2+
/ t4 }3 N: Q* Ubilateral and symmetrical. There was no suggestion6 p& l. Q( Z* T7 z/ p: I% {
of papilledema.7 L7 _+ t: x/ A+ P( q, H
Laboratory Evaluation/ x5 C4 c" u8 e6 E
The bone age was consistent with 28 months by# E5 `4 M5 ~" V2 R
using the standard of Greulich and Pyle at a chrono-$ {* u2 u) ?) a5 l w" l' ~9 a/ B4 F. v
logic age of 16 months (advanced).5 Chromosomal, h3 t2 u+ f% X* x$ S7 J
karyotype was 46XY. The thyroid function test
# s6 L! \ [: a) jshowed a free T4 of 1.69 ng/dL, and thyroid stimu-! }6 V9 K& G; P( X7 N2 i+ X
lating hormone level was 1.3 µIU/mL (both normal).
2 f/ s- y2 M* {The concentrations of serum electrolytes, blood
. K$ N' n( g5 Y u1 nurea nitrogen, creatinine, and calcium all were
/ |( }; C9 N; M6 h$ p2 b& ]/ u% }within normal range for his age. The concentration
( F* B- ^7 ?6 C4 Z6 S! m0 E! Z+ P& M- _9 Vof serum 17-hydroxyprogesterone was 16 ng/dL
! W. u9 y Q' K* s7 G2 j+ ?(normal, 3 to 90 ng/dL), androstenedione was 209 x5 r' J5 K1 Q4 V2 W) N, ~/ s# d/ _2 @
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-' n* O3 x( l5 J- v' v; I
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
4 I/ Q% v5 }- s' wdesoxycorticosterone was 4.3 ng/dL (normal, 7 to) c- g$ }) o$ T& h8 M7 c: e
49ng/dL), 11-desoxycortisol (specific compound S)& ^* h9 V' P, P: ~' `
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-# u# G" N7 [+ u- ?. p
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
! ? |6 T/ O9 g* o9 d, ftestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
" C+ C/ }7 e+ T' qand β-human chorionic gonadotropin was less than- @+ K" o' ^: C9 S
5 mIU/mL (normal <5 mIU/mL). Serum follicular
8 S& N0 S6 m0 P* O9 Mstimulating hormone and leuteinizing hormone, _# W+ Y/ K0 d( s5 c2 V
concentrations were less than 0.05 mIU/mL+ D6 u7 U0 L7 a0 y/ i' R2 f
(prepubertal).1 @8 A3 @% c ^
The parents were notified about the laboratory$ ]9 B8 y( H: u& L0 G7 J- k% B
results and were informed that all of the tests were
( ]7 `* k7 ?$ m8 D2 enormal except the testosterone level was high. The g* ]1 }2 r3 k# [2 q6 f4 ^
follow-up visit was arranged within a few weeks to! n: X0 k( }* Y9 f- y. {
obtain testicular and abdominal sonograms; how-, Z* N( t. Q* {2 g
ever, the family did not return for 4 months.; e% @7 [$ v) }
Physical examination at this time revealed that the
3 N* K6 m5 u' z( N7 Pchild had grown 2.5 cm in 4 months and had gained8 z; t, t- J- N- z7 K; W3 D3 p
2 kg of weight. Physical examination remained
1 V5 {& O6 J5 L5 k0 n9 runchanged. Surprisingly, the pubic hair almost com- C: j$ L$ _; V d
pletely disappeared except for a few vellous hairs at, f. I3 V1 P: H) n0 |- t" d6 Z
the base of the phallus. Testicular volume was still 2
) w* r# ?7 s% U% u0 KmL, and the size of the penis remained unchanged.
/ w) e* q# e! ~1 RThe mother also said that the boy was no longer hav-
! f ?) d& e; D. g+ e; Y& z) @: c0 king frequent erections.
2 E$ e+ a! K$ ~1 jBoth parents were again questioned about use of8 g, P+ [8 y- ?/ I$ n/ M0 b( n
any ointment/creams that they may have applied to
+ z; [/ k |1 Ethe child’s skin. This time the father admitted the' O0 m, ]' I8 J3 D) S
Topical Testosterone Exposure / Bhowmick et al 541
+ C8 ~3 q6 E- s& D& n" duse of testosterone gel twice daily that he was apply-
# |1 L1 |" |& N X+ l! o" x4 F: Ning over his own shoulders, chest, and back area for
6 u ]0 F5 w+ v7 z% z4 Pa year. The father also revealed he was embarrassed
: m) n' I8 ~: F" V! a4 qto disclose that he was using a testosterone gel pre-
! @3 R$ `( S* @$ ?scribed by his family physician for decreased libido4 x r8 B, S V9 R! {4 i( z( T* x1 @
secondary to depression.5 o3 A) U8 F8 r: K; ~" ?
The child slept in the same bed with parents.' J0 i2 ?3 ^9 C4 |) P# X
The father would hug the baby and hold him on his
. o' T; j) n1 @0 bchest for a considerable period of time, causing sig-' w6 D! I. f, a; D! R# k
nificant bare skin contact between baby and father.7 q. x6 R+ @' `1 X+ Z% B' I
The father also admitted that after the phone call,' \4 g" J& h. U& B
when he learned the testosterone level in the baby
8 W' L) e3 j5 X& P& ~0 ~was high, he then read the product information2 x5 m7 o% W0 V# t; ^
packet and concluded that it was most likely the rea-6 S# P3 S+ q0 ^1 M0 X
son for the child’s virilization. At that time, they9 U% x0 O5 g, S4 _8 }; g
decided to put the baby in a separate bed, and the; X" u& h2 m. z4 n2 ?# F
father was not hugging him with bare skin and had
* }3 S' @2 O7 W, w G4 w; Vbeen using protective clothing. A repeat testosterone
& D3 m$ w Y% Q$ D6 e4 e( A' Htest was ordered, but the family did not go to the
5 ^. t, j7 O, V* F. xlaboratory to obtain the test.# W% R7 p% m @# I$ @. P( x
Discussion' e3 o! i- I5 V4 S% ], v
Precocious puberty in boys is defined as secondary9 B+ V/ e8 {1 b# p7 h
sexual development before 9 years of age.1,4
8 X; I5 D9 T8 ?0 p7 j6 FPrecocious puberty is termed as central (true) when
& T0 g( u( T4 ^2 O& D! yit is caused by the premature activation of hypo-3 b0 I& L4 k9 n3 {. C4 z6 N) @
thalamic pituitary gonadal axis. CPP is more com-
: E4 E8 O, N; Z) ?0 ~2 Y$ d0 @mon in girls than in boys.1,3 Most boys with CPP. U! N# O; c J+ }0 q) F
may have a central nervous system lesion that is% o5 F% R& R7 l! v" Y
responsible for the early activation of the hypothal-
0 m. h Z& G$ M7 _2 D) m6 R7 g) i7 Samic pituitary gonadal axis.1-3 Thus, greater empha-! ]3 [0 ]4 C' q
sis has been given to neuroradiologic imaging in9 C2 b, d9 A/ @ U
boys with precocious puberty. In addition to viril-) i: U5 R. A# I; n" I5 J
ization, the clinical hallmark of CPP is the symmet-
* m9 E, ]' J: f+ }+ Krical testicular growth secondary to stimulation by
& V3 p+ @$ e. {: e5 agonadotropins.1,35 u) g( z: D- V8 a# M& r+ y
Gonadotropin-independent peripheral preco-
% T; n5 d W6 L5 pcious puberty in boys also results from inappropriate
0 S. M; V1 U/ u# d, Vandrogenic stimulation from either endogenous or
% v6 c$ q n' z# j0 aexogenous sources, nonpituitary gonadotropin stim-
1 K( Q3 H% z K" P! x- Bulation, and rare activating mutations.3 Virilizing) X8 H0 V) o2 j( `8 }6 Z
congenital adrenal hyperplasia producing excessive8 A' t. f$ Z' I7 W0 S, j- } c
adrenal androgens is a common cause of precocious
/ y/ }6 `4 [; h! @8 n: Xpuberty in boys.3,4
" o4 f3 f( ? F9 u5 {, c% T9 l# ~$ nThe most common form of congenital adrenal0 l! u$ ~0 [/ C' k( s I
hyperplasia is the 21-hydroxylase enzyme deficiency.
4 r! f8 _! Z. Q6 }) h5 KThe 11-β hydroxylase deficiency may also result in# G" @1 Y2 d( s4 z
excessive adrenal androgen production, and rarely,
5 ?9 ]& E) G4 h2 J# ^0 E, q4 t' h+ dan adrenal tumor may also cause adrenal androgen: z+ M3 T/ M4 V- ~2 n
excess.1,3% L2 x* [( B! R8 o" u
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
0 G! ^* Q- a _4 u1 E2 E542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
9 \4 p) i$ }3 c* F" ~- \5 B. FA unique entity of male-limited gonadotropin-/ t# Z( p) }$ Y6 I0 J3 W
independent precocious puberty, which is also known
% O- e; M0 n. tas testotoxicosis, may cause precocious puberty at a7 x+ v" z8 K# a
very young age. The physical findings in these boys* E1 o+ j, ~5 k# R5 k4 @! o5 y
with this disorder are full pubertal development,
: Q* i# n. u1 p. [3 F' ^including bilateral testicular growth, similar to boys1 O1 k& B: @* P8 }( Z' s
with CPP. The gonadotropin levels in this disorder* v& a% O: C" ]7 \+ u+ r3 G M& u
are suppressed to prepubertal levels and do not show, e/ a7 k/ y* H$ }- f
pubertal response of gonadotropin after gonadotropin-' R7 k) C" Y1 k# f$ {/ s
releasing hormone stimulation. This is a sex-linked
2 ~( N0 x: e2 v! w2 v' G. fautosomal dominant disorder that affects only( [6 e& K- D1 K' v8 u' c
males; therefore, other male members of the family
# T! u' Q$ c4 I+ _7 b2 ]may have similar precocious puberty.3
7 h2 p0 u- I, @In our patient, physical examination was incon-
( g* k2 q P+ X% C2 a: C% X psistent with true precocious puberty since his testi-
& X; z7 s+ C7 Kcles were prepubertal in size. However, testotoxicosis5 x4 E- F' T% P, D9 A
was in the differential diagnosis because his father
% e4 u" {- f& P# D+ X( Z: K- [& `started puberty somewhat early, and occasionally,
7 k3 J* x. k+ V/ X' B7 A1 k& dtesticular enlargement is not that evident in the
) Q, G9 E7 f7 k2 y9 R7 A) s; o2 v3 V- Vbeginning of this process.1 In the absence of a neg-0 P/ |! ^: r9 m: r
ative initial history of androgen exposure, our
2 Q# K5 K7 |$ ~1 H2 `biggest concern was virilizing adrenal hyperplasia,
e" v7 y5 @2 l1 `! `either 21-hydroxylase deficiency or 11-β hydroxylase7 n0 e: o5 W( H* {- D5 j- y
deficiency. Those diagnoses were excluded by find-- }/ ?) f3 s7 R" V- P2 v
ing the normal level of adrenal steroids., e$ c5 c, C. N0 V6 H
The diagnosis of exogenous androgens was strongly9 P2 [1 E6 L2 }7 X3 n2 F
suspected in a follow-up visit after 4 months because) B# p j6 _& H2 ^
the physical examination revealed the complete disap-. t' E7 p$ R8 Q+ S: m- v$ V
pearance of pubic hair, normal growth velocity, and# _8 r" c, @4 O) n$ ^' J
decreased erections. The father admitted using a testos-
- m1 T( O& E* K4 Qterone gel, which he concealed at first visit. He was
; U4 `! z7 C$ b! M2 N" M* uusing it rather frequently, twice a day. The Physicians’" z ?% R! P# E
Desk Reference, or package insert of this product, gel or3 ]% t$ S- u) b! @5 z! r9 C
cream, cautions about dermal testosterone transfer to; R* p5 F& G1 z6 [
unprotected females through direct skin exposure.
. x% z; `& V2 D- }. S" c8 H) OSerum testosterone level was found to be 2 times the# l N" q- Q1 n8 _* P
baseline value in those females who were exposed to
; a$ n, X4 F; V3 B* j; a4 m% Ieven 15 minutes of direct skin contact with their male, S+ q8 J; A$ C. A7 b8 Z0 v; Z- N8 w
partners.6 However, when a shirt covered the applica-
/ p$ }1 U4 C* ]# z/ }7 Xtion site, this testosterone transfer was prevented.1 _7 }% v* a4 A1 |5 ?8 t
Our patient’s testosterone level was 60 ng/mL,
5 } h, e. i% M, z5 X' \which was clearly high. Some studies suggest that. y$ |; j _2 m: z' g* Y
dermal conversion of testosterone to dihydrotestos-4 m& G/ Y* Z8 n$ U: O! Q
terone, which is a more potent metabolite, is more
+ Y4 n9 e6 z$ X7 k# |- E3 Y" ?active in young children exposed to testosterone
/ X" u+ s0 ^ @/ `$ U0 `exogenously7; however, we did not measure a dihy-
; [) y9 e! G! {' F. d% }1 ldrotestosterone level in our patient. In addition to/ h+ t j. S( {% Z# n
virilization, exposure to exogenous testosterone in
2 u! @8 C$ Y$ W' ^children results in an increase in growth velocity and
3 ]1 P" A9 P, v$ Nadvanced bone age, as seen in our patient.
: K& e, V7 Y4 w$ G- M8 BThe long-term effect of androgen exposure during( L0 h& K2 v/ f5 P! w g& _9 u
early childhood on pubertal development and final% U8 F z# K' H
adult height are not fully known and always remain
0 P- s9 h6 @4 f' w+ X& d$ a# \a concern. Children treated with short-term testos-
8 e7 q5 \' _* s1 A& K( l% }( h7 ^- zterone injection or topical androgen may exhibit some
1 `9 G* v. z4 ~* w% J3 cacceleration of the skeletal maturation; however, after) e( `3 ~: Y& H& Z) W
cessation of treatment, the rate of bone maturation
B0 v6 }* o( edecelerates and gradually returns to normal.8,9) k2 m1 F# j h2 K3 l/ o
There are conflicting reports and controversy7 J3 l' S' h5 O9 Q8 ^
over the effect of early androgen exposure on adult
# ~8 y- e0 v* e% t: j# P1 Npenile length.10,11 Some reports suggest subnormal
; c; e [: c5 \" A( _. C0 m% fadult penile length, apparently because of downreg-0 D+ ]8 _, M4 Z5 z
ulation of androgen receptor number.10,12 However,) E* N- a6 e7 o6 C- `& o
Sutherland et al13 did not find a correlation between
9 x; }( X8 z1 H! Z, |childhood testosterone exposure and reduced adult" Y+ {. t/ r) }
penile length in clinical studies. _/ v* A9 f0 B& j
Nonetheless, we do not believe our patient is$ Y, ~- H' e8 N
going to experience any of the untoward effects from
& N+ l% P: L( E% gtestosterone exposure as mentioned earlier because
, m- @5 W0 m5 q! n) O" |7 Dthe exposure was not for a prolonged period of time.
7 n7 C% a- o7 Q. `Although the bone age was advanced at the time of
( X! s" T3 X, v9 [diagnosis, the child had a normal growth velocity at9 d: ~' f' p6 S! l) G' P
the follow-up visit. It is hoped that his final adult/ j, m- U1 A; R; v. a9 x
height will not be affected.
) P$ T' I3 }$ z# {0 f. A3 XAlthough rarely reported, the widespread avail-& o: T2 X( v+ O$ R, T w
ability of androgen products in our society may
$ ~) v2 L% f/ H: tindeed cause more virilization in male or female4 p- n5 _1 M9 q* m
children than one would realize. Exposure to andro-/ m, t; x& e" U: d5 i: ?, p
gen products must be considered and specific ques-+ J4 W+ W* c2 Q6 X- w1 \& o) F
tioning about the use of a testosterone product or
( d( D4 B' b h$ t' }; |2 _gel should be asked of the family members during
/ W# K5 ?8 m4 w9 {the evaluation of any children who present with vir-6 p& c0 L: W' s3 N( m: O4 n' f+ ]8 J* t; x
ilization or peripheral precocious puberty. The diag-
* \4 U/ T' g H1 D& ^; N8 Hnosis can be established by just a few tests and by9 M8 s+ V! m- y. b1 P. V
appropriate history. The inability to obtain such a( E, |% z0 P: C1 E; n7 ~6 I
history, or failure to ask the specific questions, may* t$ n: t8 P5 I) a G
result in extensive, unnecessary, and expensive! A, P* ?* y, f5 ~9 }( |, [+ n# [3 ~
investigation. The primary care physician should be
/ X+ @7 r2 a( m) _' L% naware of this fact, because most of these children* ~% O" v2 A4 j( }' D6 I( ~
may initially present in their practice. The Physicians’6 J# i- r6 x3 p4 U2 a" Q$ J# S/ y
Desk Reference and package insert should also put a& Q( [; P8 O9 f% H" Z
warning about the virilizing effect on a male or
: d: B. q3 c+ y8 z |8 J3 y0 vfemale child who might come in contact with some-4 U v2 j( t6 n4 g$ k
one using any of these products.
% f# |& k8 E! Y' P. XReferences% I! ]( @8 B: ?4 [
1. Styne DM. The testes: disorder of sexual differentiation
; o$ p( l8 C! B) |" H& E' P/ Qand puberty in the male. In: Sperling MA, ed. Pediatric
; I) l$ s/ v$ g& F6 \% wEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
& w/ d& E; _/ M$ M. q p2002: 565-628., R: r3 x& a3 [5 U0 k
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
+ m+ y+ v6 _) g* `" j- M% V7 W! opuberty in children with tumours of the suprasellar pineal |
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