- 註冊時間
- 2023-5-6
- 精華
- 在線時間
- 小時
- 米币
-
- 最後登錄
- 1970-1-1
累計簽到:5 天 連續簽到:1 天
|
發表於 2025-1-4 03:09:28
|
顯示全部樓層
RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND
+ W5 b$ B$ u" ?* [8 Q) w hGONADOTROPIN
8 H. A% ~4 o s+ W$ B6 N* m+ eRICHARD C. KLUGO* AND JOSEPH C. CERNY
0 U# N+ G! [1 |4 g% r+ R# y3 xFrom the Division of Urology, Henry Ford Hospital, Detroit, Michigan
; w5 \; r' q+ x: f1 AABSTRACT0 x6 Z( d: y j% d5 |( S
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
% Q1 t: ~- A+ D' o1 @: nwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-
8 k* X1 E; W8 Z+ g8 s2 T3 qtropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone- I" H8 P) |9 y) A: o+ |+ p; a5 D# X& G
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent
3 X' Y6 m9 P p* J6 k7 l/ L( C0 Kfor both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent. p2 A* G) b* _9 e8 ]
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average
& o% q4 M& ^; L- \! I+ `increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
. s1 j' _! m, w# _1 z+ u! q# ~occurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This% G k. r" [. I
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
( Q) k9 J1 s1 S1 X: v* z2 Bgrowth. The response appears to be greater in younger children, which is consistent with previ-9 r! K5 P4 {- [% [+ [6 {0 y, v" A2 q% M
ously published studies of age-related 5 reductase activity.
* U7 T* f# d; p0 t) C3 q6 UChildren with microphallus regardless of its etiology will
) `8 j# r0 G4 M$ g: Crequire augmentation or consideration for alteration of exter-
2 q" p) V' @( A1 z xnal genitalia. In many instances urethroplasty for hypo-) d3 w% Z1 [- M, I, i2 E
spadias is easier with previous stimulation of phallic growth.. H5 Y) x) z! j, z' K$ T/ V
The use of testosterone administered parenterally or topically
" ]$ G5 a- Z7 Z* Phas produced effective phallic growth. 1- 3 The mechanism of- @8 t% p* W( }. v
response has been considered as local or systemic. With this6 L, N. g8 t5 O B2 l I
in mind we studied 5 children with microphallus for response+ ]! {5 I2 V H# V1 x a
to gonadotropin and to topical testosterone independently.
9 O% A! m2 V; ~! F8 PMATERIALS AND METHODS
, }, U. X' X' G6 ^% J; X lFive 46 XY male subjects between 3 and 17 years old were
. y/ n! V3 L5 ~1 b5 kevaluated for serum testosterone levels and hypothalamic/ w* N; _; O( }) _) v9 ?0 d# w# D
function. Of these 5 boys 2 were considered to have Kallmann's
/ z) i6 u3 J3 B0 ysyndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-9 B9 S- q* H n7 U
lamic deficiency. After evaluation of response to luteinizing( G0 ~7 H- N; @+ Q( m7 D# K+ t
hormone-releasing hormone these patients were treated with
9 F/ t1 U7 j U# W; G4 O; F& o1,000 units of gonadotropin weekly for 3 weeks. Six weeks* l+ ~2 Y* I1 b5 d& {
after completion of gonadotropin therapy 10 per cent topical2 w% }) F- C8 x2 d8 b
testosterone was applied to the phallus twice daily for 3 weeks.
' B1 H, ~) n$ O2 y* R+ LSerum testosterone, luteinizing hormone and follicle-stimulat-
H# H. c) @6 m% ving hormone were monitored before, during and after comple-
# t# t2 R9 N5 \% ?2 ytion of each phase of therapy. Penile stretch length was
3 Z8 e9 U$ G4 o6 d! _obtained by measuring from the symphysis pubis to the tip of5 s1 K5 M! o% U5 o: F
the glans. Penile circumferential (girth) measurements were
- t0 X3 F& W" l: C7 p' @8 [obtained using an orthopedic digital measuring device (see }2 h! u- `( O3 ]) L( F9 S& W
figure)., Y& C5 L- M& B8 V9 z. |$ z
RESULTS D" B* ~& o1 D: l {9 K$ p+ [
Serum testosterone increased moderately to levels between/ T9 T- L9 o m
50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-
5 f: s8 B) m, J- |! iterone levels with topical testosterone remained near pre-( x' x2 R1 k2 a$ ]: _* }
treatment levels (35 ng./dl.) or were elevated to similar levels
: j6 P: P( M/ @$ A. N/ K4 i, ddeveloped after gonadotropin therapy (96 ng./dl.). Higher
, ^2 l k, L' x5 h% S: @. h( Userum levels were noted in older patients (12 and 17 years old),8 i2 e; a) I( Z/ E& Q6 n4 A \
while lower levels persisted in younger patients (4, 8, and 10
/ N C. w& ~8 syears old) (see table). Despite absence of profound alterations
/ w" h1 f' l- Q$ ?% vof serum testosterone the topical therapy provided a greater$ B; z, x' @) h2 S8 E" s
Accepted for publication July 1, 1977. ·# j. U! D" i: w% p
Read at annual meeting of American Urological Association," G2 @4 I4 U* [( a) h- p
Chicago, Illinois, April 24-28, 1977.7 I5 R5 [9 W7 \! v- B9 d
* Requests for reprints: Division of Urology, Henry Ford Hospital,
' w. Y1 B6 h8 Q! ~+ e2799 W. Grand Blvd., Detroit, Michigan 48202.) i. n$ O. @2 g- O, U3 ~8 H
improvement in phallic growth compared to gonadotropin.0 {3 H5 j: L) r" h- h+ j3 U
Average phallic growth with gonadotropin was 14.3 per cent+ k- n' `0 ^( p" l- ]7 z9 \2 V
increase in length and 5.0 per cent increase of girth. Topical7 J+ ?: L/ h$ [6 D7 X+ J2 m6 k
testosterone produced a 60.0 per cent increase of phallic length
6 R( I# Q4 A. F+ s/ Sand 52.9 per cent increase of girth (circumference). The; t! ?+ t, G4 p$ U+ W, v4 _3 y2 i
response to topical testosterone was greatest in children be-
! h0 z0 _/ o0 m, z) ^ L, Ptween 4 and 8 years old, with a gradual decrease to age 17- I0 j: c4 C7 h' x5 x& W
years (see table).
% r" B1 }" s8 h( C+ V, }DISCUSSION3 f0 P3 u" Q) X: Z
Topical testosterone has been used effectively by other6 }3 u" B* \; K. d; q4 x
clinicians but its mode of action remains controversial. Im-3 V9 y. T. W" a4 }0 e+ } @8 J
mergut and associates reported an excellent growth response: g) f3 d1 y6 u x/ U( m4 t
to topical testosterone with low levels of serum testosterone,
- f5 i& Y, q: R2 i3 A2 zsuggesting a local effect.1 Others have obtained growth re-: j5 s" W$ |: }9 e2 J
sponse with high. levels of serum testosterone after topical/ j- f1 {* {/ x8 v$ _
administration, suggesting a systemic response. 3 The use of# F+ R5 o' ], J0 g
gonadotropin to obtain levels of serum testosterone compara-
+ o, K! Z( v# y0 r) \: B/ zble to levels obtained with topical testosterone would seem to! u2 Y# W( B0 x7 i+ h
provide a means to compare the relative effectiveness of
) f) ?% [1 c# Z1 o. V D4 Z! \topical testosterone to systemic testosterone effect. It cer-
7 Z( k' I4 U! rtainly has been established that gonadotropin as well as par-0 g# C& k" _! S7 S! @" t
enteral testosterone administration will produce genital
3 w, [. Y3 B- ~ `1 M2 Lgrowth. Our report shows that the growth of the phallus was
" A9 g L6 Q8 j* t' |/ \significantly greater with topical applications than with go-
1 g: f1 |5 `5 y0 B; Pnadotropin, particularly in children less than 10 years old.& ?# ^. x6 T7 A
The levels of serum testosterone remained similar or lower/ p1 P) i' `8 u
than with gonadotropin during therapy, suggesting that topi-# V4 I$ h/ R& |
cal application produces genital growth by its local effect as$ `9 K$ c5 [" e, c& O6 A
well as its systemic effect.
- V* w' x5 P( ^3 P [# bReview of our patients and their growth response related to$ W l ], m# X$ s5 ]/ |* G7 p
age shows a greater growth response at an earlier age. This is3 `! f# b" E/ J. z
consistent with the findings of Wilson and Walker, who
- w8 A% d8 ?+ S2 |, Breported an increased conversion of testosterone to dihydrotes-9 z. z4 x4 ^, f/ t
tosterone in the foreskin of neonates and infants.4 This activ-1 Z0 ]2 N/ d2 A8 E. z, p
ity gradually decreases with age until puberty when it ap-
, P1 G# U- [! B: L1 `proaches the same level of activity as peripheral skin. It may
/ e* G$ w3 C# lwell be that absorption of testosterone is less when applied at7 h Q4 s/ \0 z( D5 U) |
an earlier age as suggested by lower serum levels in children
9 H& Z G$ g1 dless than 10 years old. This fact may be explained by the
% |5 y% _- L% w( y/ G! i1 A2 dgreater ability of phallic skin to convert testosterone to dihy-
. A! P# v) V! _* W( X8 q) c# h( h5 ddrotestosterone at this age. Conversely, serum levels in older/ ]8 X; K1 F9 d1 B- K& O6 p$ P
patients were higher, possibly because of decreased local
" H' [6 B) }1 S1 N) r8 g667. h- {- d- Z3 @7 m5 c2 q: w! u
668 KLUGO AND CERNY2 Q; I% W% o" r4 N- e
Pt. Age
+ W) x1 D, N% `$ c3 z: N5 V(yrs.)6 x% l, \7 M* x# _% g7 F
Serum Testosterone Phallus (cm.) Change Length
' i; P# p, b' X0 Q9 {(ng./dl.) Girth x Length (%)* p1 T" i/ ^5 A
4* A4 H, h9 H7 S0 `
8 [4 d8 W( [# G9 d
10
3 \6 @- ]9 g( g' e. g; E/ \125 V; ]6 x4 F% Y& _7 {3 x! }
17
. X+ n' ?! g/ |6 FGonadotropin" A: ^) | A1 j0 U- h! I5 ^
71.6 2.0 X 3 16.61 T) {/ e7 [: S3 W
50.4 4.0 X 5.0 20.0
, m( V- \5 \5 K5 P3 O& W22.0 4.5 X 4.0 25.0# s2 |$ A, y; d) b5 s8 E- _( c
84.6 4.0 X 4.5 11.1# k: N( j- Q4 p; v! L
85.9 4.5 X 5.5 9.02 L1 n7 g4 i }' c
Av. 14.3
0 C# `# @* q3 b1 j7 b4
1 u) C5 ~6 u! u, V- I8! D: m" k& l5 M% A
10 P; E+ z# [0 `* \, D# ?7 o9 R
125 Y% J8 A6 u, U' l! p; d
173 }+ d& D7 g( f" u) n
Topical testosterone
, L5 \/ P+ W, k7 i34.6 4.5 X 6.5 85( z6 c, U+ k: B
38.8 6.0 X 8.5 70
0 j! } s+ a* N* M: R. N40.0 6.0 X 6.5 62.5# ^$ Z5 j+ N/ U& G: D: \2 q7 L0 k
93.6 6.0 X 7.0 55.5
/ @+ L7 v4 k( ~, A6 m, j95.0 6.5 X 7.0 27.25 S5 w0 }! Z# h2 _# R E: f
Av. 60.0
% a J/ x3 M2 x" L# ]1 f2 ]available testosterone. Again, emphasis should be placed on P. Z! D% M% W/ k' f
early therapy when lower levels of testosterone appear to( m0 ^& p0 ]# L3 P7 S6 @
provide the best responses. The earlier therapy is instituted
# t9 c( J$ {2 L: J6 U# v5 q0 b3 Ethe more likely there will be an excellent response with low
3 |6 z/ e$ i& P5 Q# [# T- tserum levels. Response occurs throughout adolescence as% e4 w; X [1 e7 M" \. O" ]' A
noted in nomograms of phallic growth. 7 The actual response$ S; L! n7 A1 E/ e3 O# g
to a given serum level of testosterone is much greater at birth
- c0 R) z1 D- fand gradually decreases as boys reach puberty. This is most1 {0 Y) N* O7 i
likely related to the conversion of testosterone to dihydrotes-( F0 f" w7 R+ D! j: e
tosterone and correlates well with the studies of testosterone
4 m0 d- x( Y, b# k, [6 `conversion in foreskin at various ages.
. W$ L( T. L9 ^& J( _; c1 WThe question arises regarding early treatment as to whether
( k6 q3 g& |6 G# Y) |" z4 Y6 done might sacrifice ultimate potential growth as with acceler-
0 D; A5 y3 ?5 o% V7 q' [ated bone growth. The situation appears quite the reverse! Z( c7 m" R( @
with phallic response. If the early growth period is not used8 E+ l; i% a6 a6 o
when 5a reductase activity is greatest then potential growth' A* D* k6 h, z ^+ q8 K
may be lost. We have not observed any regression of growth; C$ \9 r0 R% W5 B: _0 W
attained with topical or gonadotropin therapy. It may well# R5 W) e, ]) W9 u7 [4 w2 H- U
be that some patients will show little or no response to any
/ R7 V/ } B- s5 |" Z+ mform of therapy. This would suggest a defect in the ability to7 o$ `2 e0 ~- ^- c5 t. k
convert testosterone to dihydrotestosterone and indicate that* `, `; s% l3 T$ g; I3 v' B8 p
phallic and peripheral skin, and subcutaneous tissue should3 L0 p8 N" N4 M0 P8 s, T4 X
be compared for 5a reductase activity.# ^) {( j2 M) B
A, loop enlarges to measure penile girth in millimeters. B,1 n, x j; e( f5 v
example of penile girth computed easily and accurately.8 k3 w1 g2 S7 q# H
conversion of testosterone to dihydrotestosterone. It is in this, w8 e' F: {! a( T) ^! q
older group that others have noted high levels of serum) K) G: k# G5 F
testosterone with topical application. It would also appear: r5 k1 B; I' H
that phallic response during puberty is related directly to the$ x0 d: ] _2 m; s+ ~
serum testosterone level. There also is other evidence of local
% v6 E8 R# k. e1 g6 {response to testosterone with hair growth and with spermato-
; h! B7 J* ~! G- b" n* B& ogenesis. 5• 6
1 [- M! Z1 M0 |# g/ @/ ]$ l: hAdministration of larger doses of gonadotropin or systemic2 ?: C2 W3 u: P* [# ~
testosterone, as well as topical applications that produce
4 k* {1 _! \- k9 d- {, _! O/ ghigher levels of serum testosterone (150 to 900 ng./dl.), will
7 h$ N" Q" q# v/ kalso produce phallic growth but risks accelerated skeletal1 y- s+ l$ _9 \' l+ z. f, k
maturation even after stopping treatment. It would appear5 K4 ~2 M& k8 C
that this may be avoided by topical applications of testosterone
6 c$ I, c; f* L( @: R- vand monitoring of serum testosterone. Even with this control
' f# d: Y2 w5 ]/ G3 G' `8 z: lthe duration of our therapy did not exceed 3 weeks at any
; {6 ]" m! O& q: n0 z$ ?. m2 ~% Z, ltime. It is apparent that the prepuberal male subject may
+ C o# k+ J! C9 t2 m8 {8 \suffer accelerated bone growth with testosterone levels near
, Z5 \$ N; k- B+ q, t4 I- p200 ng./dl. When skeletal maturation is complete the level of
6 e$ x, D( \7 m& Z2 C' I) F* zserum testosterone can be maintained in the 700 to 1,300 ng./
9 N5 W/ R; U* M) Rdl. range to stimulate phallic growth and secondary sexual
) B6 ]1 v# ~- o( |( a3 ^changes. Therefore, after skeletal maturation parenteral tes-- U% x/ {. T9 L" |6 Z) P
tosterone may be used to advantage. Before skeletal matura-& j" D% T# |/ X1 P2 w" I
tion care must be taken to avoid maintaining levels of serum- M: y' f% i$ n
testosterone more than 100 ng./dl. Low-dose gonadotropin2 ]) ^3 a+ N+ E6 K8 v3 W
depends upon intrinsic testicular activity and may require
; Q8 h4 N, G* v8 w% {1 yprolonged administration for any response.
$ D) S" W R- d+ NAlternately, topical testosterone does not depend upon tes-4 I3 T! O9 U4 n( C' S1 p0 }1 x
ticular function and may provide a more constant level of
$ \0 E3 N. b; M. M% A6 H' kREFERENCES
, S& a5 v' F( Z; U- I0 c2 a1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,7 [1 H* t; m6 u* x/ i n' s1 x
R.: The local application of testosterone cream to the prepub-. y) c% t2 m6 i0 |$ G
ertal phallus. J. Urol., 105: 905, 1971.5 J. v2 T$ R" B* V4 ~/ Z2 g+ a
2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
' C2 b. C$ r, V2 s! G- u9 Etreatment for micropenis during early childhood. J. Pediat.,8 a \( r/ f. X; }* g( q
83: 247, 1973.3 {; r' g5 W3 E4 F* _" B7 B, P. U/ b3 F
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
8 y3 n) J. \5 v6 J9 n% Qone therapy for penile growth. Urology, 6: 708, 1975.
, w. h' y! w: R8 v$ V( `, K4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone; [, c8 Y4 m+ i$ z
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by3 X- A, y( g3 h* Q* Q- G: p
skin slices of man. J. Clin. Invest., 48: 371, 1969.; }9 Y5 r3 a3 B/ M! \& N
5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth" W( D6 y1 W3 R
by topical application of androgens. J.A.M.A., 191: 521, 1965.
- F& c1 K* t; _6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local f: z% R1 Y E u( N- p! z0 F3 \/ o
androgenic effect of interstitial cell tumor of the testis. J.
; m4 e& u6 |" T% A( m* {Urol., 104: 774, 1970.4 z/ d+ O; K* q) D/ R
7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-
5 b8 c; s7 r4 m' qtion in the male genitalia from birth to maturity. J. Urol., 48: |
|