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RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND
' u, O m) M9 ~( T. N2 u; uGONADOTROPIN. p$ ~; g6 Y* L9 x/ f
RICHARD C. KLUGO* AND JOSEPH C. CERNY# n( p/ ?$ Z! x% m
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan: Q2 h5 n* L3 ?9 A5 x4 L# v
ABSTRACT
2 C! n. {0 a# o6 pFive patients were treated with gonadotropin and topical testosterone for micropenis associated
* Q: X% o( a! `3 ]( Xwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-7 o0 F: `, C% d; z
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone( N2 b/ J- w' h7 x5 r
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent
& |! Y6 |2 a% C7 w: e6 P. Tfor both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent! J8 ]1 p* W* y9 u V% R4 @
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average
5 i% B) H' s1 P, f$ Sincrease of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
& ?! t Z- [% k9 {& c* doccurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This
' ]9 k3 g2 X1 M/ _study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile0 H! B( c M d% R
growth. The response appears to be greater in younger children, which is consistent with previ-& Y. B' m' K7 V9 a; a; a& P7 v
ously published studies of age-related 5 reductase activity.
+ z: Z" X4 x5 K5 J2 {Children with microphallus regardless of its etiology will* U, Y6 Y8 V6 N
require augmentation or consideration for alteration of exter-
. u8 k5 X, [. H8 Snal genitalia. In many instances urethroplasty for hypo-
4 V/ B& |* {0 T L' k! S6 a& tspadias is easier with previous stimulation of phallic growth.
2 q" ~+ x+ O( i7 Q1 f5 uThe use of testosterone administered parenterally or topically
& F* G3 u4 k; t' Q+ c9 V# O/ ^has produced effective phallic growth. 1- 3 The mechanism of( x( D S; a6 o8 j" ]% s( x
response has been considered as local or systemic. With this
1 @: {; }# O: \in mind we studied 5 children with microphallus for response5 Z: g- Q* X* O5 C9 S, z% y. V% Y
to gonadotropin and to topical testosterone independently.% {1 @( D# q! j) h: R2 V
MATERIALS AND METHODS5 j% m6 [- z6 n0 a( V' ~, p
Five 46 XY male subjects between 3 and 17 years old were Z4 Y5 d( P0 O& \ F
evaluated for serum testosterone levels and hypothalamic
: P- ?4 G0 M9 _function. Of these 5 boys 2 were considered to have Kallmann's
$ J3 T; f9 ^3 O9 esyndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
# l, E5 h( k" A5 H6 Rlamic deficiency. After evaluation of response to luteinizing
. v/ E2 a2 |7 E/ d4 Nhormone-releasing hormone these patients were treated with$ g H" d; s' _! [- [3 T7 O# ~
1,000 units of gonadotropin weekly for 3 weeks. Six weeks2 h8 x( R$ X" t) `0 A& L2 t; I
after completion of gonadotropin therapy 10 per cent topical! P) B/ A$ Q* D# `" _1 d$ [
testosterone was applied to the phallus twice daily for 3 weeks.& m! N) H+ e9 l" N+ h) X
Serum testosterone, luteinizing hormone and follicle-stimulat-# F; G4 p q$ k7 ^
ing hormone were monitored before, during and after comple-) f% U4 M7 u' |0 q5 ^" E' c9 B
tion of each phase of therapy. Penile stretch length was$ q$ `/ x+ [" @+ @
obtained by measuring from the symphysis pubis to the tip of
6 c4 o4 H2 I- [' M- p4 f. ]the glans. Penile circumferential (girth) measurements were
8 C1 j6 S+ [: g; o7 }. C/ hobtained using an orthopedic digital measuring device (see% o( r5 U7 ?! @
figure).
0 k' f# L- j; u4 GRESULTS
& h! g6 {. f: C: X8 {8 tSerum testosterone increased moderately to levels between- A& ?/ f; O( H9 a6 ]! k
50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-
3 X0 ~; W) j# [terone levels with topical testosterone remained near pre-
% ~) a! n# m5 z! _4 s2 Q7 Ctreatment levels (35 ng./dl.) or were elevated to similar levels9 U9 Z6 V% w$ m" D2 M% \7 G& h
developed after gonadotropin therapy (96 ng./dl.). Higher) }# j# K: P* o! ]
serum levels were noted in older patients (12 and 17 years old),. f# m& B3 P: G, T7 M1 n
while lower levels persisted in younger patients (4, 8, and 10/ p, c6 j5 | h" O+ T3 j
years old) (see table). Despite absence of profound alterations
+ U: c$ ]& \/ f+ c: r! h, e4 Lof serum testosterone the topical therapy provided a greater- ^% t G" @ K3 R1 u
Accepted for publication July 1, 1977. ·
+ X( e5 ~* v3 E& y6 }% N$ @. wRead at annual meeting of American Urological Association,6 f8 a. V e S$ w8 P
Chicago, Illinois, April 24-28, 1977.( P; j# x5 Y7 `3 P7 [7 @2 C5 R
* Requests for reprints: Division of Urology, Henry Ford Hospital,
9 o/ h8 |4 R: y o2799 W. Grand Blvd., Detroit, Michigan 48202.; Q- ]: u/ V! Z- `. v/ t& ?: j
improvement in phallic growth compared to gonadotropin.
3 l! ~" M9 ]! g0 z2 _+ |5 N! AAverage phallic growth with gonadotropin was 14.3 per cent
$ o! }* O' s. }" S+ Wincrease in length and 5.0 per cent increase of girth. Topical6 P7 @* s7 k2 F l6 z
testosterone produced a 60.0 per cent increase of phallic length
" y! J( ?: E3 G4 P( wand 52.9 per cent increase of girth (circumference). The
% z6 ~# q3 k: x2 g9 N. |6 t7 U# {response to topical testosterone was greatest in children be-
a \' v3 t( b% o# ptween 4 and 8 years old, with a gradual decrease to age 17
) ~; K k+ m* G! w* }" hyears (see table).
3 ]( g5 i, p( Z' n9 [DISCUSSION
7 ^$ P4 r4 c* HTopical testosterone has been used effectively by other$ C: Y' m: [ f* F C
clinicians but its mode of action remains controversial. Im-
' l) E' _+ _8 u' kmergut and associates reported an excellent growth response+ s- a" O% j# p& z U5 {. u$ ~
to topical testosterone with low levels of serum testosterone,
3 k2 x# ^7 A! c$ }! B* ]" Ysuggesting a local effect.1 Others have obtained growth re-
; D8 i! M' q' e3 P3 hsponse with high. levels of serum testosterone after topical4 T: K* }+ N! m: x l6 s
administration, suggesting a systemic response. 3 The use of
6 }. g6 p8 U; d# D: Kgonadotropin to obtain levels of serum testosterone compara-9 V9 }9 k5 B( n6 r
ble to levels obtained with topical testosterone would seem to# Y& x/ C% U/ i# }
provide a means to compare the relative effectiveness of* l) _5 B/ x3 W7 m* m; N
topical testosterone to systemic testosterone effect. It cer-; r; ]- Q8 f1 v+ x
tainly has been established that gonadotropin as well as par-- @! m2 S# C: S F9 `
enteral testosterone administration will produce genital
% L; `" Z, ^, H1 N: wgrowth. Our report shows that the growth of the phallus was
+ g- D0 N; d# Z' osignificantly greater with topical applications than with go-- `/ h# L( w I! d3 D) X* c
nadotropin, particularly in children less than 10 years old.& N! a. h$ N2 A+ y: h5 k# O" x' m
The levels of serum testosterone remained similar or lower2 g: J7 S8 R+ @" F# m
than with gonadotropin during therapy, suggesting that topi-( D' H7 P$ O, [; O
cal application produces genital growth by its local effect as
. g ^6 \, [) {# R. v7 k; l7 e$ qwell as its systemic effect.
. |4 f; m# c, S( ~5 K2 }Review of our patients and their growth response related to. a, [' W4 `$ U: v4 S, b- |: F8 Q
age shows a greater growth response at an earlier age. This is+ ]- G% @+ W8 b) [4 x
consistent with the findings of Wilson and Walker, who6 G! r$ |: w7 P0 d6 Z* z5 z" `5 p
reported an increased conversion of testosterone to dihydrotes-
8 g& b( r. M" j1 Htosterone in the foreskin of neonates and infants.4 This activ-
$ b2 N# S0 i1 P" e' w, I; }9 ]( X7 }9 gity gradually decreases with age until puberty when it ap- s! D$ T; U0 J8 b4 M: W
proaches the same level of activity as peripheral skin. It may
2 K* n6 ^0 c3 @7 O+ G: }) twell be that absorption of testosterone is less when applied at
+ T5 I, p4 o' |5 r) M3 d7 H2 @an earlier age as suggested by lower serum levels in children
, z2 U' c4 H- @3 P+ b+ Qless than 10 years old. This fact may be explained by the# A S" V9 l/ y! f
greater ability of phallic skin to convert testosterone to dihy-- x4 E9 H- }9 [( r$ e* u. o4 X
drotestosterone at this age. Conversely, serum levels in older
4 U7 k' W& L$ e/ W9 apatients were higher, possibly because of decreased local$ j: y1 e' |! C N& h# E1 S
667
% M w/ c1 i0 [/ K: p3 [& ]668 KLUGO AND CERNY9 I: m# _7 x( o2 H+ D5 O+ k
Pt. Age2 @3 A* U( G# L$ Y/ R6 c/ P5 H* H
(yrs.)
; J$ b4 c+ {$ H z# H% n6 JSerum Testosterone Phallus (cm.) Change Length: i1 v" N+ N) N6 K F
(ng./dl.) Girth x Length (%)
3 X$ j0 f& u+ P5 Q J8 x8 C4
$ j6 o0 V- B7 ?2 S- t( Y) x( e8
( w4 x+ E. [! u- F# ^0 b10
+ x" w- T' f" q+ f0 J6 i12) |9 T! L1 ?% z0 n
17
# V q( @4 g! _6 `" {Gonadotropin! U. g! i( D8 V% a
71.6 2.0 X 3 16.6
0 [: H1 `4 S5 W3 V; P. z, `0 J50.4 4.0 X 5.0 20.0- I7 h* L2 W# L7 N% M2 o
22.0 4.5 X 4.0 25.07 }, b6 R% T% s. A
84.6 4.0 X 4.5 11.1
+ X1 l& x# |/ y$ a/ ?85.9 4.5 X 5.5 9.0
* @/ y1 N" H( n$ zAv. 14.3+ m: {& @! _ A0 e
4
- K% B0 q8 _4 z9 i* T G( p! d- d& m8# e) c9 |: G2 m: w; b8 ]0 A/ X% g' v
105 D7 w! a2 U3 s, ]8 a+ J6 y
121 J& _: k- |1 s9 D/ z
17
: w! B/ h# y2 r- A% o" ?$ G3 t; `Topical testosterone( \! P3 c6 K+ D' b1 t% a3 p! K
34.6 4.5 X 6.5 85
* {* p. f/ q4 H9 o38.8 6.0 X 8.5 70
9 X! d2 u$ }& P3 @0 w' Z$ t: w3 b( h40.0 6.0 X 6.5 62.5
( Y8 M6 I. j* H" r C6 o1 z93.6 6.0 X 7.0 55.5
! ^% e3 A; g2 s6 z95.0 6.5 X 7.0 27.2
: i) m* i% K4 w0 P& Z! d0 kAv. 60.0
" q) A& I; O/ x" p! Oavailable testosterone. Again, emphasis should be placed on+ U* R! ^8 c" J7 [$ I; r8 H
early therapy when lower levels of testosterone appear to4 E' n/ e# m5 O7 Z1 i$ o
provide the best responses. The earlier therapy is instituted
2 ]8 J8 R) h/ I8 t. o% hthe more likely there will be an excellent response with low2 |8 _2 q5 X, b+ P5 ?! r5 }
serum levels. Response occurs throughout adolescence as( r& j2 f6 S+ e4 {+ I2 o
noted in nomograms of phallic growth. 7 The actual response0 {2 ~; q3 X3 Q) ]1 ?" B/ e* Z1 U$ S9 S
to a given serum level of testosterone is much greater at birth
8 t) z7 V q$ [9 k6 sand gradually decreases as boys reach puberty. This is most
7 {3 ]. l8 ?) Y C7 V. b$ _likely related to the conversion of testosterone to dihydrotes-( y- z2 K. M) p: l
tosterone and correlates well with the studies of testosterone
$ v$ h& J4 `8 x. Qconversion in foreskin at various ages.: f6 k/ t3 H/ G( z6 @- ]5 z
The question arises regarding early treatment as to whether
+ W; a' o1 o5 w8 None might sacrifice ultimate potential growth as with acceler-
+ u9 p+ ^( s2 z0 c/ Rated bone growth. The situation appears quite the reverse
% z, N% j: ^: A7 E: A* o4 F: Fwith phallic response. If the early growth period is not used
2 j( F6 }/ e+ W$ |7 z6 C5 _when 5a reductase activity is greatest then potential growth7 o8 U2 @2 D; {2 h) p
may be lost. We have not observed any regression of growth- D& Q9 f; x' w
attained with topical or gonadotropin therapy. It may well
& Q( ~8 o$ y$ `6 ]be that some patients will show little or no response to any
( d/ r. i4 O* H% ]3 \form of therapy. This would suggest a defect in the ability to
5 M: k! v7 k6 u; V" \convert testosterone to dihydrotestosterone and indicate that
& v w: ?& F$ C. i4 pphallic and peripheral skin, and subcutaneous tissue should" Z2 u: \; l3 Z- y/ k( i
be compared for 5a reductase activity.
& j6 h1 n# G, o2 h8 Z" K& |0 {! CA, loop enlarges to measure penile girth in millimeters. B,2 C) f7 G9 k- [1 E) X1 E: U
example of penile girth computed easily and accurately.
& p# q. g& Z# O# e( Hconversion of testosterone to dihydrotestosterone. It is in this1 |, T# A+ _# J( ^! f/ n1 |' P. c8 Y
older group that others have noted high levels of serum
: d6 j) t3 M8 |1 Btestosterone with topical application. It would also appear
6 p3 a% W6 c/ _* a! athat phallic response during puberty is related directly to the/ @& m. V: u+ k. i
serum testosterone level. There also is other evidence of local
8 v6 g8 i: | Y* f6 Jresponse to testosterone with hair growth and with spermato-
3 |/ K' b i1 A7 j: h: Z/ G0 R+ Ggenesis. 5• 6
8 ]2 }- [9 e. g. J6 |' lAdministration of larger doses of gonadotropin or systemic
( C% j9 O9 l7 y, V- t2 q, J4 Htestosterone, as well as topical applications that produce
) w$ ?1 |% B( j$ Ohigher levels of serum testosterone (150 to 900 ng./dl.), will
9 ?' C* x- O& ?0 [& l( [# ialso produce phallic growth but risks accelerated skeletal8 b4 |, [. U; K) [9 v2 _+ [3 u
maturation even after stopping treatment. It would appear
7 c* c1 `" f9 z1 K C3 ^) Tthat this may be avoided by topical applications of testosterone
0 ]0 F, W( N l: eand monitoring of serum testosterone. Even with this control% O1 s3 B# Q# B% n1 a& h
the duration of our therapy did not exceed 3 weeks at any8 U" x2 m' M4 g& R- _
time. It is apparent that the prepuberal male subject may5 \$ W1 H6 L$ a& l3 [
suffer accelerated bone growth with testosterone levels near ~6 X. L% R1 Z& i1 J
200 ng./dl. When skeletal maturation is complete the level of
8 c& N& x, f4 d0 Q) yserum testosterone can be maintained in the 700 to 1,300 ng./
, ^6 B2 ] i8 R, g2 N. Z3 O, Udl. range to stimulate phallic growth and secondary sexual" f: q/ |2 g0 ?) S c$ p+ t! K
changes. Therefore, after skeletal maturation parenteral tes-
# i4 k: h6 @7 H, h; E4 ?tosterone may be used to advantage. Before skeletal matura-# |; H3 T, {8 @; a5 u: Z
tion care must be taken to avoid maintaining levels of serum$ x+ v Q% ]' x& R: |9 B
testosterone more than 100 ng./dl. Low-dose gonadotropin
7 v, n) x; Y! R6 i M8 Pdepends upon intrinsic testicular activity and may require) L, F$ @* C, V5 K0 c) Z& d
prolonged administration for any response.
' \! m4 ^! _$ J$ }8 ~Alternately, topical testosterone does not depend upon tes-
Y \+ W w) V" M( o% xticular function and may provide a more constant level of/ q0 Z) y4 o9 A3 _" M* s# S
REFERENCES
5 t% j- M. Q S' J$ M1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
: F; ?' P' T, FR.: The local application of testosterone cream to the prepub-
( h3 P/ v! y0 Gertal phallus. J. Urol., 105: 905, 1971.( H) F$ o$ M: J) J7 @ A2 U
2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone( V) J# ~4 J" e+ @- ]+ M* s
treatment for micropenis during early childhood. J. Pediat.,
0 T" V1 ?0 o0 N$ J6 \8 n; G83: 247, 1973.) g& q1 d# F$ u
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-8 s% ]1 B5 \+ B3 F7 a
one therapy for penile growth. Urology, 6: 708, 1975.
6 S# D" `6 v! u8 w! J' ^4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone X8 a F+ e4 w( |3 s
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
' j' I( r" w" d3 z) e4 |1 z% V; `skin slices of man. J. Clin. Invest., 48: 371, 1969.
; p) `9 X! Y- D3 ^8 |3 E6 q5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth9 v7 ]: F0 a9 H
by topical application of androgens. J.A.M.A., 191: 521, 1965.
+ g o, r# S. ^ C6 r" b/ S6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
: ~ d4 d/ r8 n- m7 K4 E8 bandrogenic effect of interstitial cell tumor of the testis. J.
$ ~: r) y2 [& T- c( d5 GUrol., 104: 774, 1970.- w/ l2 e9 x4 Q4 u- q& l* F
7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-6 s& g9 T) @$ f& X6 R+ s9 v
tion in the male genitalia from birth to maturity. J. Urol., 48: |
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