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RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND0 J$ G- N, S" G& h: S0 Z
GONADOTROPIN
5 w/ G) s3 l4 [% D2 M: dRICHARD C. KLUGO* AND JOSEPH C. CERNY% R, q# h$ t" u' x+ ^
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan$ Z e% A. J# |" g& M' ?, W7 c
ABSTRACT2 G1 s2 |, C) S$ I/ J+ N* s
Five patients were treated with gonadotropin and topical testosterone for micropenis associated A9 t( t2 D$ [4 x) i
with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-$ I% Y% w2 f2 O
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone+ ] p, E( @5 o/ B% E# I
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent: ]4 F# W8 |& r" @
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent
8 X# s$ q" o: Bincrease in length and 5.0 per cent increase of girth. Topical testosterone produced an average: C* `4 _) C6 J0 T9 H9 N8 K, U* B% Y
increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
6 S, I8 G8 z) `: E2 Xoccurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This( S0 a) ^0 p2 ^0 Y
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
7 o9 f8 \1 Q6 o X) z) igrowth. The response appears to be greater in younger children, which is consistent with previ-
4 X; @! B, }9 m6 j8 y/ [/ ^9 Mously published studies of age-related 5 reductase activity.0 e# {5 t9 Z2 U( A I+ h: Z0 H
Children with microphallus regardless of its etiology will
+ Y. t$ r4 ~8 d5 J/ brequire augmentation or consideration for alteration of exter-9 V) P" i% i. N: _, [
nal genitalia. In many instances urethroplasty for hypo-
* w& t- G: O% L1 yspadias is easier with previous stimulation of phallic growth.4 L/ Q# ~1 r6 `) [+ B/ r
The use of testosterone administered parenterally or topically4 R: c) M- d. R- B& s
has produced effective phallic growth. 1- 3 The mechanism of. N. d0 n8 C6 Z8 N. T/ r
response has been considered as local or systemic. With this0 t b: a+ n2 a# ]
in mind we studied 5 children with microphallus for response
( @5 L) N1 m& T/ ~to gonadotropin and to topical testosterone independently.
; m, {! J0 k5 G$ A9 t" eMATERIALS AND METHODS1 J3 y# t. R1 I% z3 R
Five 46 XY male subjects between 3 and 17 years old were' J) f" g, r4 ]4 V
evaluated for serum testosterone levels and hypothalamic/ w/ R) Q) N4 |6 l0 y
function. Of these 5 boys 2 were considered to have Kallmann's0 z* W+ P% g6 ^; \
syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
' N0 H. D" f( Klamic deficiency. After evaluation of response to luteinizing
, i0 H% u' @( h/ y' }+ Vhormone-releasing hormone these patients were treated with+ W( F; B6 T) s3 i( k5 ~3 {8 d9 h
1,000 units of gonadotropin weekly for 3 weeks. Six weeks
0 s/ I$ i1 F; O1 v3 ~3 |5 ]* Y4 Fafter completion of gonadotropin therapy 10 per cent topical
4 c; W; M! ~( Q# h1 _testosterone was applied to the phallus twice daily for 3 weeks.
- ]' @4 N/ ]5 S) C/ n xSerum testosterone, luteinizing hormone and follicle-stimulat-" H" ]2 L: X; C$ S; n
ing hormone were monitored before, during and after comple- f& t* L1 E7 A
tion of each phase of therapy. Penile stretch length was
# X S& i, L9 O, ~- M7 i% ^obtained by measuring from the symphysis pubis to the tip of" e- i9 f% M- C6 j& P( q
the glans. Penile circumferential (girth) measurements were4 R k7 D5 z: s( k
obtained using an orthopedic digital measuring device (see
5 P6 ^% a' R9 {/ B4 s: Ufigure).% C5 M* N5 J! r6 M0 y9 }* b* ^3 b- C
RESULTS' o2 s2 |! m" k% i
Serum testosterone increased moderately to levels between( a1 w, R: T0 ^6 ^
50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-" ?# l' i) D% l# f( F
terone levels with topical testosterone remained near pre-: f) i1 w @% L
treatment levels (35 ng./dl.) or were elevated to similar levels
6 q3 z# `0 m" ~' B) N5 C: Gdeveloped after gonadotropin therapy (96 ng./dl.). Higher' v: C- f0 Y# Z w2 u
serum levels were noted in older patients (12 and 17 years old),
2 U- g+ [; H5 s' Jwhile lower levels persisted in younger patients (4, 8, and 10
7 b: t. v J3 s) W& d0 V0 F& hyears old) (see table). Despite absence of profound alterations
( {: {* I! r: n1 Y% y3 t2 ~6 A+ rof serum testosterone the topical therapy provided a greater
2 w. Y2 E& k& n5 |1 M/ qAccepted for publication July 1, 1977. ·
3 e- \$ n( b: W$ Q& [2 v5 G5 VRead at annual meeting of American Urological Association,
6 Q. y, _5 [* kChicago, Illinois, April 24-28, 1977.
2 Q; y! N' T2 ]0 i) S/ d* Requests for reprints: Division of Urology, Henry Ford Hospital,* Z( ?+ y3 z* T3 S# ]4 O# U
2799 W. Grand Blvd., Detroit, Michigan 48202.
1 ]& k; I' k' i7 Eimprovement in phallic growth compared to gonadotropin.
. B4 E* G" p; \1 ]" cAverage phallic growth with gonadotropin was 14.3 per cent
' Y, X! j- m) i# F( Kincrease in length and 5.0 per cent increase of girth. Topical+ h7 S1 t" ?/ q% d" ?% z1 Y
testosterone produced a 60.0 per cent increase of phallic length0 A' E) S) b& _. P. L. o# [0 T0 s' ^8 v2 a
and 52.9 per cent increase of girth (circumference). The
! g& ]3 ~# u7 U' [* uresponse to topical testosterone was greatest in children be-
6 J9 D `8 H- `; |7 j5 ^" Wtween 4 and 8 years old, with a gradual decrease to age 17/ ^) c9 |; @. B. a9 ~4 \
years (see table).
4 `( t8 m+ t/ {3 fDISCUSSION
7 J5 C. N. {9 h2 \5 {1 U7 ZTopical testosterone has been used effectively by other, [2 S. [ ~/ U& Y
clinicians but its mode of action remains controversial. Im-1 G' g v0 Q1 ]7 {: d0 v( T
mergut and associates reported an excellent growth response1 y* z* N' W0 @3 G
to topical testosterone with low levels of serum testosterone,2 b/ o3 T$ {% V9 N: H
suggesting a local effect.1 Others have obtained growth re-* S; G# R% B8 p, b6 N4 D
sponse with high. levels of serum testosterone after topical
; J. Q6 t7 n' T3 B |administration, suggesting a systemic response. 3 The use of
: V+ R! L# Y2 T/ N, C$ Fgonadotropin to obtain levels of serum testosterone compara-* L; l) E3 m2 j7 {6 _
ble to levels obtained with topical testosterone would seem to; \" y. {1 \. \& Z4 Z
provide a means to compare the relative effectiveness of& ^9 Q4 G/ @" l: F" I3 t1 o
topical testosterone to systemic testosterone effect. It cer-7 F8 E3 J% x, O" D! }
tainly has been established that gonadotropin as well as par-3 }1 u0 v4 s; Y, I3 N2 z
enteral testosterone administration will produce genital
- i4 {& j2 E$ Q2 n% B7 k: a/ dgrowth. Our report shows that the growth of the phallus was& o$ W* B+ e$ e
significantly greater with topical applications than with go-- u. t0 v* \, z. Y7 ]$ a3 L. f
nadotropin, particularly in children less than 10 years old.+ J; J; |, P3 D: V5 d" K
The levels of serum testosterone remained similar or lower) z2 r% g D- b5 I% {: F1 o
than with gonadotropin during therapy, suggesting that topi-- v0 C& ?2 Y% A2 s) p1 O8 y( W& {- ^4 P! n
cal application produces genital growth by its local effect as
3 G0 }& j1 D. o7 ?( m8 gwell as its systemic effect.. c) F* _ z2 f- A. Y
Review of our patients and their growth response related to/ s' M6 f+ v: f8 J
age shows a greater growth response at an earlier age. This is
' L, r5 y6 c8 @consistent with the findings of Wilson and Walker, who
+ \# Z3 b! p% ]; h# X/ o Y: Qreported an increased conversion of testosterone to dihydrotes-' x) U. k: N( m$ ^8 F# w
tosterone in the foreskin of neonates and infants.4 This activ-
/ m5 q' \* V2 W) e- P7 i2 yity gradually decreases with age until puberty when it ap-
5 v4 k( l. C( i2 a' \9 qproaches the same level of activity as peripheral skin. It may
. d8 I" w# N* h" ^5 K- g! B' d2 S2 Uwell be that absorption of testosterone is less when applied at
5 s. o: N& ?8 J7 n5 Nan earlier age as suggested by lower serum levels in children# m' Z1 L5 i0 i
less than 10 years old. This fact may be explained by the
9 }% W4 g0 ]5 Hgreater ability of phallic skin to convert testosterone to dihy-0 o! v& u, n2 i$ M
drotestosterone at this age. Conversely, serum levels in older( A" s9 s+ M& L8 @
patients were higher, possibly because of decreased local6 c4 n3 D+ F7 W" H! { S, _* @
6676 E O+ Y8 n8 n2 c5 q2 }
668 KLUGO AND CERNY
* {' ^8 w9 R4 g7 _5 i* _8 CPt. Age1 e! q1 |! z, z) X' P y. T
(yrs.)
/ l4 W( ] ^# p. B) Q- `- YSerum Testosterone Phallus (cm.) Change Length7 H. ~9 q# f/ T; C) J+ x" m. D
(ng./dl.) Girth x Length (%)
5 d1 u% w3 t6 |8 B8 r4
4 I; ~$ [" i! q8
0 L( b8 P- u% X10
4 ~. G: T3 p8 Y+ E9 f" u9 u ?121 Z. l: k1 V6 [6 z
17$ m0 @* q: Y8 o! O3 V4 d
Gonadotropin! G. Z" l; [! C' C
71.6 2.0 X 3 16.6
; D& w6 H, b* v50.4 4.0 X 5.0 20.0 ^# F0 U+ M. s/ [8 A
22.0 4.5 X 4.0 25.0
5 c5 z' ?3 @. f( D2 Q5 R" }84.6 4.0 X 4.5 11.1
\' C$ B% E" C( ^8 f. R7 d85.9 4.5 X 5.5 9.0
, S Z, S" H0 _7 j9 N$ fAv. 14.3
! H+ U. B0 f. e8 A F+ G8 D, w. k49 K" [* }0 j/ I0 S7 N# `* a
8
3 I3 p- V6 g( e& n( p9 K0 n102 @7 a- ?6 k. I: H% Z% j
12% y: h' z0 X& s- `' V3 E' b
17( y( r% d. H( G
Topical testosterone. r! d* ~8 I% z2 d! l1 A0 ^
34.6 4.5 X 6.5 85
- _8 V8 I7 [% s: b& x1 @38.8 6.0 X 8.5 70
1 F; n I9 V% H% y40.0 6.0 X 6.5 62.5
" @8 z# Q+ N' T. _9 ~! f93.6 6.0 X 7.0 55.5" p/ H' p: ~1 \! D; k3 H! s
95.0 6.5 X 7.0 27.2
& L, D; F6 k7 k; VAv. 60.0# S- \! @6 N' T4 Q4 N
available testosterone. Again, emphasis should be placed on
. \6 O i% Y5 k2 Xearly therapy when lower levels of testosterone appear to# S0 w* t) |2 Z5 f! Y! T B
provide the best responses. The earlier therapy is instituted
, z# x* g* q' O# W" Uthe more likely there will be an excellent response with low
% A$ b6 X' S8 U3 ]9 {' @serum levels. Response occurs throughout adolescence as$ y3 O; O0 k p
noted in nomograms of phallic growth. 7 The actual response' M& j; w @5 G& e W+ x" s
to a given serum level of testosterone is much greater at birth
1 u. S8 r! C8 y- v( sand gradually decreases as boys reach puberty. This is most
6 {' e' w5 ]. w. Y4 dlikely related to the conversion of testosterone to dihydrotes-
2 m. d: L8 y2 Z0 X+ v" {tosterone and correlates well with the studies of testosterone
% m! z" }1 w& @3 E# R# oconversion in foreskin at various ages.) ?5 c9 v( w+ @
The question arises regarding early treatment as to whether
s- q3 P( _# vone might sacrifice ultimate potential growth as with acceler-
* L) P8 w( _- y8 A: L, `ated bone growth. The situation appears quite the reverse
+ J' x1 Q% A4 c2 {3 N1 ~4 v$ T3 Zwith phallic response. If the early growth period is not used; s p R4 ]# O9 E" }3 X; I
when 5a reductase activity is greatest then potential growth0 I8 A: K w% b5 O4 K5 R" [' r7 X) u
may be lost. We have not observed any regression of growth
# ` h7 s5 F% ^7 uattained with topical or gonadotropin therapy. It may well2 K3 R _8 R+ v/ y0 ]" D5 {. R- Y
be that some patients will show little or no response to any
8 l8 A) ] j Q4 ?; _form of therapy. This would suggest a defect in the ability to. z4 R# H5 n$ j( Z7 ^/ |
convert testosterone to dihydrotestosterone and indicate that
( l8 M3 ?8 t g1 l3 s) O/ }+ jphallic and peripheral skin, and subcutaneous tissue should; S2 u. @6 V1 L0 q4 N$ }
be compared for 5a reductase activity.
3 B( E+ z) x/ Y) I# {- B$ A- [A, loop enlarges to measure penile girth in millimeters. B,
+ j: a& s+ X5 N" Zexample of penile girth computed easily and accurately." `% K- W7 X3 @# X0 d# U" T+ p
conversion of testosterone to dihydrotestosterone. It is in this0 u/ K% q% Q0 ~! y' M
older group that others have noted high levels of serum
- \4 R0 M# D% ]' R7 \testosterone with topical application. It would also appear/ ^4 ^8 R/ d5 v+ N! @: d. C
that phallic response during puberty is related directly to the4 N4 I2 g& n) @) O: @
serum testosterone level. There also is other evidence of local/ v9 F, Z( H5 T* a8 j2 b3 Z8 ]
response to testosterone with hair growth and with spermato-: _ [0 Z: d) {5 I* u
genesis. 5• 6
/ F+ M# y5 Z, C; k0 M! u0 N6 EAdministration of larger doses of gonadotropin or systemic1 @$ G+ h0 A9 C
testosterone, as well as topical applications that produce5 ^$ D' u( u, \" B0 t7 F' }3 z, Q1 E" p
higher levels of serum testosterone (150 to 900 ng./dl.), will
0 `# W4 R8 Y9 z- A A, palso produce phallic growth but risks accelerated skeletal, _7 O( x5 Y& N9 v
maturation even after stopping treatment. It would appear; t! t+ C# ~1 g2 O
that this may be avoided by topical applications of testosterone
4 \# v( j% p( _and monitoring of serum testosterone. Even with this control! [& ~% F9 ]! Z/ D6 y* W6 j/ ^
the duration of our therapy did not exceed 3 weeks at any
$ p% [3 b0 J2 t& M: c- \4 I- x% dtime. It is apparent that the prepuberal male subject may5 T5 F5 C* M& n* l
suffer accelerated bone growth with testosterone levels near
! Q/ }7 a2 b! g8 R! r0 X200 ng./dl. When skeletal maturation is complete the level of2 A( I4 g, l+ V
serum testosterone can be maintained in the 700 to 1,300 ng.// I7 P* J$ c3 D2 H, h V, x3 h
dl. range to stimulate phallic growth and secondary sexual
1 l! G4 s7 R$ P1 T6 J. wchanges. Therefore, after skeletal maturation parenteral tes-# b4 j& c* y! s
tosterone may be used to advantage. Before skeletal matura-# r0 r9 t% }1 K
tion care must be taken to avoid maintaining levels of serum
) p5 V/ m0 a8 Qtestosterone more than 100 ng./dl. Low-dose gonadotropin8 Z7 n/ G$ M$ c3 {3 T
depends upon intrinsic testicular activity and may require
; c9 r) O4 }- v k" D5 z3 xprolonged administration for any response.0 h# y6 A! n) [7 a& i2 Y1 k% Q
Alternately, topical testosterone does not depend upon tes-
4 {* g& Z9 v* E4 N- }+ ?7 `ticular function and may provide a more constant level of4 _( d9 R- W* M7 X
REFERENCES
- \, ^; w( T, c% M; ~! n1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,1 A, R, g! o: K3 k2 ~! V" t5 i
R.: The local application of testosterone cream to the prepub-
( I2 u- b5 G3 ^$ i jertal phallus. J. Urol., 105: 905, 1971.
. H& P& S: d) L$ {' M2 w! l' I2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone4 K/ o: R7 k1 b3 q/ X
treatment for micropenis during early childhood. J. Pediat.,
- W0 N4 L1 N6 x; u; Z83: 247, 1973.
" f$ k l8 ~6 T: B, }. f" H3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
. {6 V2 I9 v6 A$ S3 j; F7 ~0 q0 Uone therapy for penile growth. Urology, 6: 708, 1975.# b, H- y- p8 K% s
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
( X2 i# {; o: l- q* {1 F$ Kto 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
* j: ` t$ A6 _3 S; |. pskin slices of man. J. Clin. Invest., 48: 371, 1969.& a3 k: `* u% x
5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth
/ [" W- {. I" X7 I* Jby topical application of androgens. J.A.M.A., 191: 521, 1965./ c6 p3 Y' u( X* Z9 T
6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
+ |. @( L4 E6 O0 }7 G" G# Dandrogenic effect of interstitial cell tumor of the testis. J.# ]% Z p$ b7 x M& K
Urol., 104: 774, 1970.
8 P3 s2 N9 {( l7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-4 h. O0 g5 L0 c$ y# @3 f1 ^2 V
tion in the male genitalia from birth to maturity. J. Urol., 48: |
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