- 註冊時間
- 2023-5-6
- 精華
- 在線時間
- 小時
- 米币
-
- 最後登錄
- 1970-1-1
|
發表於 2025-1-4 03:09:28
|
顯示全部樓層
RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND
# d8 b+ o2 M" G( C8 @GONADOTROPIN
! W6 k" F1 {' X$ Y$ TRICHARD C. KLUGO* AND JOSEPH C. CERNY4 C+ m3 o& S; x- k. A8 j$ n8 a
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan
% [1 t; \8 q# U" k K: \ABSTRACT3 t5 A; w1 P( P/ ^
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
[) y# ?) U4 E/ m9 A. vwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-
. a/ z9 U; p- ?6 C- s$ f, }7 _7 ttropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone
+ T4 K/ N4 ?$ y* X, ]4 z0 vcream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent/ X, Y O% U& E! b7 S
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent
% Y. j" f6 O! z# e3 ]increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average
5 R |. N y' G7 `& Vincrease of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
) c+ Z$ ]1 [% woccurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This3 {. C G3 y; l6 |+ c1 I' y
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile1 G* A! D) J2 \' r6 R+ C
growth. The response appears to be greater in younger children, which is consistent with previ-
0 a( x2 w2 W2 C" P8 Y0 mously published studies of age-related 5 reductase activity.
+ R+ ]" y; E/ |" ^Children with microphallus regardless of its etiology will
% R! T: F( `$ Rrequire augmentation or consideration for alteration of exter- v: `3 y/ s$ [* M+ Q% M
nal genitalia. In many instances urethroplasty for hypo-
# J/ `! w5 p) H- r" qspadias is easier with previous stimulation of phallic growth.
6 I2 W! r1 a* u* g& T0 m) a3 yThe use of testosterone administered parenterally or topically1 O1 i3 ~( E: ^/ r
has produced effective phallic growth. 1- 3 The mechanism of8 {% R' D$ I* Q
response has been considered as local or systemic. With this6 u% @! j# [/ A& a K
in mind we studied 5 children with microphallus for response9 @8 ]! p' J: M Y8 l, B2 Y& Q% h
to gonadotropin and to topical testosterone independently.8 |# y' H# y$ ]$ k. z+ [/ X" N& p2 k
MATERIALS AND METHODS) [- _; a4 T/ V5 n( f- } W/ o& G" v
Five 46 XY male subjects between 3 and 17 years old were1 h7 T. H0 d% w7 ~/ [! ^3 L
evaluated for serum testosterone levels and hypothalamic
# k y+ ]2 P3 Q3 T4 Xfunction. Of these 5 boys 2 were considered to have Kallmann's0 n9 `" F2 x+ c! H0 n- @
syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
8 D9 O- I! T- p+ Alamic deficiency. After evaluation of response to luteinizing
4 b4 [/ f% E% Mhormone-releasing hormone these patients were treated with
) U4 j# r6 e' v/ r& P' K1,000 units of gonadotropin weekly for 3 weeks. Six weeks
) \0 @% `7 J$ ?8 n* x' I6 Eafter completion of gonadotropin therapy 10 per cent topical6 j9 R! o) a3 X8 X
testosterone was applied to the phallus twice daily for 3 weeks.. M) M. [0 g/ x+ r9 k, d7 x
Serum testosterone, luteinizing hormone and follicle-stimulat-
R, J: Q6 o8 v3 k; Eing hormone were monitored before, during and after comple-- ?! p' F0 q- ~1 g
tion of each phase of therapy. Penile stretch length was
' [! b" m( [1 r' w+ ^1 Nobtained by measuring from the symphysis pubis to the tip of" _# O" c/ g! i: U7 x6 ~/ ]
the glans. Penile circumferential (girth) measurements were+ \1 A! c* z* V
obtained using an orthopedic digital measuring device (see
6 \ j3 J0 S& z; i$ Z( gfigure).' S$ B% K3 Q* `
RESULTS
% c" ]) c/ S& }( r/ k7 q6 E( bSerum testosterone increased moderately to levels between
) f) M2 T6 {( ?: F8 J% A; |5 n* E50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-
" ~- c3 k/ b% x9 Q. j" Eterone levels with topical testosterone remained near pre-+ m* z& f9 l/ G4 P! \
treatment levels (35 ng./dl.) or were elevated to similar levels
2 ?" q! \5 N# K, \7 c3 K& s ddeveloped after gonadotropin therapy (96 ng./dl.). Higher1 ~- `0 v7 O$ W V2 H+ r" d+ x
serum levels were noted in older patients (12 and 17 years old),. z% L" c( s7 i, E6 U. I" X
while lower levels persisted in younger patients (4, 8, and 10" a1 `' h2 [7 U5 m p
years old) (see table). Despite absence of profound alterations; Z" x' }+ P4 j, T# P+ u% W* _
of serum testosterone the topical therapy provided a greater) q2 o. Y" e3 l
Accepted for publication July 1, 1977. ·
: r( z; r. ~" FRead at annual meeting of American Urological Association,
7 w. T1 O& t6 j. TChicago, Illinois, April 24-28, 1977.
6 v& F! ~- {, N* N* t, x7 h( g* Requests for reprints: Division of Urology, Henry Ford Hospital,. x1 c% K ]( ^4 [; }, U
2799 W. Grand Blvd., Detroit, Michigan 48202.
- ^& J+ m! f# W. l" iimprovement in phallic growth compared to gonadotropin.
9 p$ q- \1 r$ ?+ y8 [9 z$ `Average phallic growth with gonadotropin was 14.3 per cent
5 \6 j6 ]* q- U( yincrease in length and 5.0 per cent increase of girth. Topical
( @$ t9 @- }5 G ^6 ]testosterone produced a 60.0 per cent increase of phallic length
$ a" O& I. u* @" ?+ ]4 L1 ]/ Xand 52.9 per cent increase of girth (circumference). The6 u3 ~- ^3 |( }
response to topical testosterone was greatest in children be-
3 M0 c5 c0 N8 F* c9 A/ e: Z( ntween 4 and 8 years old, with a gradual decrease to age 17
; [9 g! y2 m( c" S) gyears (see table).
9 e2 t6 m# o7 f4 v( u0 Y. BDISCUSSION( [ U0 o# W+ Y8 j- l+ Y4 R0 u
Topical testosterone has been used effectively by other
) w+ X3 n1 e }4 Wclinicians but its mode of action remains controversial. Im- S8 L" m$ u5 Y
mergut and associates reported an excellent growth response4 v* X- _: I1 o4 A2 @3 R+ o
to topical testosterone with low levels of serum testosterone,
& a& w+ ~7 s5 ^8 H$ t0 |7 nsuggesting a local effect.1 Others have obtained growth re-+ O' p0 L x1 y/ F' p z5 U
sponse with high. levels of serum testosterone after topical
1 }3 m. ^/ F7 E- T4 vadministration, suggesting a systemic response. 3 The use of
/ s- S# H' a* wgonadotropin to obtain levels of serum testosterone compara-" ?0 ?* Q0 w- g' ?* @' e
ble to levels obtained with topical testosterone would seem to
& S# e" h G& W6 Pprovide a means to compare the relative effectiveness of
0 q3 I* _* q& ?: o: C% Itopical testosterone to systemic testosterone effect. It cer-) L2 [. k! {0 y9 |% N
tainly has been established that gonadotropin as well as par-9 A @6 a" m4 r' g( t- T# ]
enteral testosterone administration will produce genital, j3 w$ k5 k& j5 w# [0 G
growth. Our report shows that the growth of the phallus was! u8 O# V& s" g0 l
significantly greater with topical applications than with go-2 [" G8 S" X4 H8 o. _
nadotropin, particularly in children less than 10 years old.4 Z# J8 \* l; \. p
The levels of serum testosterone remained similar or lower7 d+ y @: r/ B6 {
than with gonadotropin during therapy, suggesting that topi-1 f- ]* i- t/ \/ g" g/ S/ m
cal application produces genital growth by its local effect as
. K% p% }& m, a% b5 Awell as its systemic effect.: U; L. E' `" `1 W
Review of our patients and their growth response related to# l) S/ e% o/ O7 S4 q4 t
age shows a greater growth response at an earlier age. This is8 N* U6 J# C7 _# R3 T
consistent with the findings of Wilson and Walker, who7 s; s% }( i* v7 ~( Q% {
reported an increased conversion of testosterone to dihydrotes-
y7 S& E( z1 H6 utosterone in the foreskin of neonates and infants.4 This activ-: u- c; k: h8 t& h2 J q) O
ity gradually decreases with age until puberty when it ap-
# a6 `. Y/ j$ J! L/ n: Q: Jproaches the same level of activity as peripheral skin. It may R: p- B1 `9 T3 p
well be that absorption of testosterone is less when applied at
* d/ D$ y9 V4 i; Pan earlier age as suggested by lower serum levels in children& }+ q; B7 [* O% M1 w" E! g, G- i/ \
less than 10 years old. This fact may be explained by the
' c9 P0 R8 `1 s6 |greater ability of phallic skin to convert testosterone to dihy-
# @1 J4 A: B+ R. f7 sdrotestosterone at this age. Conversely, serum levels in older. O: O6 |1 w0 ]+ C# E
patients were higher, possibly because of decreased local. W, ]" z& J, S' @0 J9 m$ u; I
667% G% \9 x+ u4 p! o9 l* P$ T& g( Y
668 KLUGO AND CERNY
( V9 Z( n- ]6 a3 w3 K& r7 UPt. Age% U4 k; R) L5 V7 `1 B
(yrs.), L. r1 C! J" u3 c
Serum Testosterone Phallus (cm.) Change Length$ ^. K; o I1 |6 ~1 {7 y" ?
(ng./dl.) Girth x Length (%)
( @$ I5 c, l" y4
; F1 L3 ?2 A/ |! `) z8
) f- J# ~+ M3 Q( _, A% c10) V) P( f* {$ L! |/ }) K
12) O& u1 K% H- Q8 W
17
, b4 V8 z& `( h7 ?, h3 }Gonadotropin: e/ A# ^" q+ f( |3 K1 s
71.6 2.0 X 3 16.6! \) O1 c7 ~0 s' c9 ^
50.4 4.0 X 5.0 20.0, [6 a. h- A! L" S0 [
22.0 4.5 X 4.0 25.0
5 s% b4 q$ M) w. g8 @84.6 4.0 X 4.5 11.1
+ u# O3 f) l2 w85.9 4.5 X 5.5 9.0% W& r' N. N. {" { C# i
Av. 14.3
3 m9 K# X: V& F4
, F" W D* i) J8
+ J3 _* ?. _1 i7 L9 M) O100 ~( U0 K7 q- X" E% p: V
12
7 y4 Q' L8 R; Y: B; ?: x177 a' F" E. {1 [/ m2 _
Topical testosterone& V5 x0 ?; o7 t6 H1 \
34.6 4.5 X 6.5 85
( N4 o8 E1 F% {) @' v# ^- O" h38.8 6.0 X 8.5 70; J. S" ^$ e+ g9 n3 u
40.0 6.0 X 6.5 62.5
! C( k- Q$ i' _. W* w' i/ t% k93.6 6.0 X 7.0 55.5. p* p8 B( `% B. E% T, I
95.0 6.5 X 7.0 27.2
: y9 \ X4 z" @! o' u4 tAv. 60.0 B. c$ d; A; V8 z# e
available testosterone. Again, emphasis should be placed on
+ `4 I6 a' \0 D" v* Z. [" e) z+ Kearly therapy when lower levels of testosterone appear to5 I* p- }* ~7 H2 r4 a- i7 m4 R
provide the best responses. The earlier therapy is instituted& s+ b0 X! [& U# }/ u% H2 G# S6 W4 a
the more likely there will be an excellent response with low3 h7 O# {2 B' A$ y
serum levels. Response occurs throughout adolescence as# @( X! k' X0 y/ O9 r
noted in nomograms of phallic growth. 7 The actual response) r# P- N5 T2 j
to a given serum level of testosterone is much greater at birth
7 r9 Y; V0 {: qand gradually decreases as boys reach puberty. This is most% }& D2 i, q" B3 t
likely related to the conversion of testosterone to dihydrotes-2 H8 [( `! _& f& n
tosterone and correlates well with the studies of testosterone
* I! [6 R. D, C' R2 O, \conversion in foreskin at various ages.& ]+ K7 [6 Q* I. k
The question arises regarding early treatment as to whether
* v2 W- S# f; @$ ione might sacrifice ultimate potential growth as with acceler-5 a u, E0 \, l' l
ated bone growth. The situation appears quite the reverse2 \6 Z+ U0 q$ l( r
with phallic response. If the early growth period is not used
- Z5 ? u4 [' A4 mwhen 5a reductase activity is greatest then potential growth
( X: G& I% B$ _may be lost. We have not observed any regression of growth* y7 d! z, a) i
attained with topical or gonadotropin therapy. It may well
* p$ ~9 {8 u8 A0 ], Kbe that some patients will show little or no response to any
, s. U0 F8 d O# O+ fform of therapy. This would suggest a defect in the ability to
+ l+ S- V. d7 w) Y, Z9 Qconvert testosterone to dihydrotestosterone and indicate that
' r- K8 u7 k9 B6 ~3 d5 Sphallic and peripheral skin, and subcutaneous tissue should9 S7 \; b; U0 _; d3 {: R: F: n
be compared for 5a reductase activity.
) Q0 e0 y# `# _7 DA, loop enlarges to measure penile girth in millimeters. B,; \7 j, ^! t4 Q v
example of penile girth computed easily and accurately.
2 b/ V2 I" I/ ^2 Kconversion of testosterone to dihydrotestosterone. It is in this
0 b$ j* A: t! P7 r' jolder group that others have noted high levels of serum
+ k+ ~' Z7 @, d# M" V6 Q0 R, y/ @testosterone with topical application. It would also appear
" I% O* w& b. H9 t5 g) ^that phallic response during puberty is related directly to the& ]3 t" k( j# m3 g) j
serum testosterone level. There also is other evidence of local
# L# ^' j2 N' h& ^, ~$ Sresponse to testosterone with hair growth and with spermato-! D8 Q( i% B1 B4 N$ ~4 S
genesis. 5• 6% r8 h# E+ z1 R& r
Administration of larger doses of gonadotropin or systemic
* e) b* h# [/ v4 b1 Etestosterone, as well as topical applications that produce0 p! I$ Y; O9 U0 S0 t
higher levels of serum testosterone (150 to 900 ng./dl.), will8 f6 H) j( f& S, `8 B
also produce phallic growth but risks accelerated skeletal1 ^ j/ p, \0 s2 p$ h* K
maturation even after stopping treatment. It would appear, g) J$ `! W$ N# y
that this may be avoided by topical applications of testosterone
* w( o3 X' ~* H; ^$ I. W1 Kand monitoring of serum testosterone. Even with this control
( K: j4 k! k& u0 x/ F U4 tthe duration of our therapy did not exceed 3 weeks at any
1 [# m% g0 ]- U. H3 etime. It is apparent that the prepuberal male subject may; X. ^3 J; F E0 k, d
suffer accelerated bone growth with testosterone levels near
" j/ E+ q0 L* Y% `- q200 ng./dl. When skeletal maturation is complete the level of- O8 ?; n' b9 |( Q- R) \
serum testosterone can be maintained in the 700 to 1,300 ng./
, R6 A* F4 _" C2 p4 Q& L- Z4 E+ j" Ddl. range to stimulate phallic growth and secondary sexual
/ |# g+ H) {! n: s# B8 I8 Dchanges. Therefore, after skeletal maturation parenteral tes-
# J* Z$ H8 w- x0 V2 Wtosterone may be used to advantage. Before skeletal matura- |* J1 F( B+ Z& J! \% o: C% e
tion care must be taken to avoid maintaining levels of serum
1 D" [4 v1 M/ {7 q) Ktestosterone more than 100 ng./dl. Low-dose gonadotropin
' m' X/ s" d' u9 c' tdepends upon intrinsic testicular activity and may require
5 ~( f- U5 N* h+ R4 h4 @prolonged administration for any response.8 q( E) ?+ |) L0 H2 x- ] J
Alternately, topical testosterone does not depend upon tes-
/ d2 K& u5 X. p# S$ T+ K% Sticular function and may provide a more constant level of
' V7 g2 d5 e3 M% |. |3 [# qREFERENCES
& H/ a1 ]$ U, ]5 a1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
) k1 G( k( _, O: ER.: The local application of testosterone cream to the prepub-
8 B* Y3 a- O* q C* l. _ertal phallus. J. Urol., 105: 905, 1971.1 o E3 |; r$ e2 ?- U( f
2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone8 O& a* L4 I# B/ ?
treatment for micropenis during early childhood. J. Pediat.,7 ]4 L. K, r3 R. \
83: 247, 1973.! o% K; `, L# l% C) g
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-- _) }3 W( Y* j% c L7 H
one therapy for penile growth. Urology, 6: 708, 1975.
" w4 U# s. L. f' V2 a) } V4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone, j/ j& [2 [+ g: V$ y. F# ~' W+ \* O+ K* P
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
9 N) B' H& `8 ]! `" p. Q3 Lskin slices of man. J. Clin. Invest., 48: 371, 1969.
0 V8 i/ a& g( y% }5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth2 N' X H8 x' A) c. X
by topical application of androgens. J.A.M.A., 191: 521, 1965.( h8 g9 n( I! r/ D. f# ~& J5 T
6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
$ [* V5 A+ M! h* T- g3 Y9 Yandrogenic effect of interstitial cell tumor of the testis. J.
" j# |# f G K( M: m. j# \9 @# ]Urol., 104: 774, 1970.
& h* \; s8 r0 @* e6 A. L. N) Q7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-
& z1 p% ^( W3 _% M* ction in the male genitalia from birth to maturity. J. Urol., 48: |
|