- 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- _( `: I7 m% m- G( d. X
GONADOTROPIN5 u/ T; [: g% m' M& [
RICHARD C. KLUGO* AND JOSEPH C. CERNY9 h. M) J7 J# u
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan; e1 x1 o0 K7 R# A8 Q v: Q
ABSTRACT* _8 w% z S1 c! C4 }, ^
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
/ R' ^9 x3 s" y2 t3 V E$ mwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-4 X( J& d. n1 ~/ }
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone3 V, D& P2 Z y$ q# V+ u( o, X$ u
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent' Z2 @- M$ J; y; I0 V9 ~
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent
. T( ~3 z4 V) b! K3 C% k5 zincrease in length and 5.0 per cent increase of girth. Topical testosterone produced an average i& ] a" r; Y2 h5 `# E
increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response/ ~1 {3 `1 i0 u2 j- S
occurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This3 j2 P2 V% K2 t: G% g: ]( y
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
: E9 {, X% d5 A# R2 dgrowth. The response appears to be greater in younger children, which is consistent with previ-9 m/ d: F$ W' U- ?8 v. j6 Q
ously published studies of age-related 5 reductase activity.$ f2 _7 y; U, o7 O8 B
Children with microphallus regardless of its etiology will5 t# Q" C7 n6 L, f7 M! F* O; G
require augmentation or consideration for alteration of exter-& K: r0 S" [$ R
nal genitalia. In many instances urethroplasty for hypo-
/ N! J( F: P# X' ~/ q8 `4 rspadias is easier with previous stimulation of phallic growth.3 L% G- ]; @8 {' G# P: {5 f1 u
The use of testosterone administered parenterally or topically
6 V& a5 A: y _% Z: Shas produced effective phallic growth. 1- 3 The mechanism of
6 M( |: w7 O- @, oresponse has been considered as local or systemic. With this+ t5 A7 U# _3 w: h% Y0 k
in mind we studied 5 children with microphallus for response
& G8 V) D$ D; Q* ?) x$ J7 ~to gonadotropin and to topical testosterone independently.
( T: \7 ^; j' WMATERIALS AND METHODS
- m! c* J, U# S3 `# o2 {/ R4 rFive 46 XY male subjects between 3 and 17 years old were- W$ S# {+ g( r- F* C
evaluated for serum testosterone levels and hypothalamic
4 E' v8 ]! D- }6 p5 c6 e# bfunction. Of these 5 boys 2 were considered to have Kallmann's
7 w' ?8 x3 h" @syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
1 ~% A3 g3 u% }0 L: @lamic deficiency. After evaluation of response to luteinizing% F u) w& g$ t( o1 F1 s
hormone-releasing hormone these patients were treated with4 w7 a) Q4 n5 G3 U I: \
1,000 units of gonadotropin weekly for 3 weeks. Six weeks* U4 D J; [! `9 K9 m0 Q
after completion of gonadotropin therapy 10 per cent topical
% Q1 w" T* c' b, c8 ]: C- mtestosterone was applied to the phallus twice daily for 3 weeks.
' S' H6 i* O9 \* |" \4 vSerum testosterone, luteinizing hormone and follicle-stimulat-& v% c+ X7 |& M! q
ing hormone were monitored before, during and after comple-
- q; o- \9 F9 H _, n' dtion of each phase of therapy. Penile stretch length was* e+ _: A6 G$ _ f7 C
obtained by measuring from the symphysis pubis to the tip of
+ Y; S! L$ P) F2 ^4 Ithe glans. Penile circumferential (girth) measurements were
3 I- X# _5 I8 \/ n% z% N" cobtained using an orthopedic digital measuring device (see1 k( D* c; T9 P" T
figure).
9 N, k& @0 G: _1 a6 PRESULTS, i, Q6 N5 r' S9 T: @5 t& t2 Z4 e
Serum testosterone increased moderately to levels between
: z# T7 M7 r: o8 {/ R$ M. E6 |50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-* z: Q# z* Y1 k% @
terone levels with topical testosterone remained near pre-, a; u; q' z- i
treatment levels (35 ng./dl.) or were elevated to similar levels
+ u8 ~4 C, p8 l% b( w. M1 Y& tdeveloped after gonadotropin therapy (96 ng./dl.). Higher
+ G7 D# D9 a, @: M# a( Lserum levels were noted in older patients (12 and 17 years old),5 p$ ?) H( t( W5 f. M
while lower levels persisted in younger patients (4, 8, and 10- A& [- {. O' d: N/ V
years old) (see table). Despite absence of profound alterations
% p* w$ g- B- f; cof serum testosterone the topical therapy provided a greater
! I# G( z4 \* f1 e% d4 ]9 c% ]Accepted for publication July 1, 1977. ·+ I4 u! \) w* L- \) D
Read at annual meeting of American Urological Association,
9 _0 w+ O- P _. d3 P0 DChicago, Illinois, April 24-28, 1977.* I' X6 l K6 `2 F- k# x; o \# `
* Requests for reprints: Division of Urology, Henry Ford Hospital,
9 R( o9 K7 f6 H2799 W. Grand Blvd., Detroit, Michigan 48202.$ ?: ]/ r1 V/ [( ~' ~
improvement in phallic growth compared to gonadotropin.6 l* t- v3 [5 L; M$ ]1 h2 _
Average phallic growth with gonadotropin was 14.3 per cent
8 Q7 p, `# S% C) B3 C/ Mincrease in length and 5.0 per cent increase of girth. Topical
+ G u2 s8 [! r8 ktestosterone produced a 60.0 per cent increase of phallic length e; a. U/ _; @3 F( D' k
and 52.9 per cent increase of girth (circumference). The
5 o) S/ Q+ [3 zresponse to topical testosterone was greatest in children be-
( ?- _+ m3 h2 Ftween 4 and 8 years old, with a gradual decrease to age 17% F: T$ D1 u% d, n( B0 b" d
years (see table).
( a+ R8 ~- F5 F3 {+ d4 a% DDISCUSSION
% [: u3 R& ~/ a8 n5 [5 {Topical testosterone has been used effectively by other, {) r4 x8 S* {( u2 L: S7 X( h7 i* I
clinicians but its mode of action remains controversial. Im-
& c! g. e% o* Y3 @mergut and associates reported an excellent growth response
( p2 M& f! }& W s0 u2 B9 Xto topical testosterone with low levels of serum testosterone,. Q* n5 L! ?+ _, i! Q0 e/ D4 c
suggesting a local effect.1 Others have obtained growth re-
3 a2 ^, ^: Z5 _sponse with high. levels of serum testosterone after topical: P N6 J6 r0 h) k7 X. R- N
administration, suggesting a systemic response. 3 The use of% N1 y& {8 e% c; ^' ^, f
gonadotropin to obtain levels of serum testosterone compara-
& N3 `$ I% l8 j) @; ^ble to levels obtained with topical testosterone would seem to' s7 Q3 E$ u Q7 E4 c* E4 a
provide a means to compare the relative effectiveness of5 a9 K+ R# t! v% |8 j
topical testosterone to systemic testosterone effect. It cer-
, X* B- Q" R; ^! m4 r6 [$ Mtainly has been established that gonadotropin as well as par-3 `- c! r% Y) `7 ?
enteral testosterone administration will produce genital
4 S& y* c2 s7 s7 k$ k$ o( Rgrowth. Our report shows that the growth of the phallus was
; z L4 R/ f9 L* isignificantly greater with topical applications than with go- @- x; V4 K: [& b8 [ ?" F8 O
nadotropin, particularly in children less than 10 years old.: y. K0 j1 D: g& E
The levels of serum testosterone remained similar or lower
D- y7 B! ?. ^+ uthan with gonadotropin during therapy, suggesting that topi-
) t* d* _. E' i8 _* H5 bcal application produces genital growth by its local effect as% F: z" C( }& ?8 U
well as its systemic effect.. B0 M7 O; U! V) M3 u
Review of our patients and their growth response related to
; f K( Z9 \7 ?/ V8 l* uage shows a greater growth response at an earlier age. This is: _6 s) y6 K1 `1 z. z/ w* S
consistent with the findings of Wilson and Walker, who
* z. P L& m9 `+ k4 lreported an increased conversion of testosterone to dihydrotes-) b: w* W. Y4 |4 m9 a3 [
tosterone in the foreskin of neonates and infants.4 This activ-+ p1 t, E1 ^7 q+ \1 t8 d
ity gradually decreases with age until puberty when it ap-
0 ?- c# B' R7 p/ S6 _! l ^proaches the same level of activity as peripheral skin. It may# s4 T5 T8 M+ a! W, ~. @
well be that absorption of testosterone is less when applied at8 x: B6 c# c$ y0 ]; p7 E
an earlier age as suggested by lower serum levels in children& a1 \7 v) @3 d8 Z) }
less than 10 years old. This fact may be explained by the
( [' ]/ J. f, A( H) pgreater ability of phallic skin to convert testosterone to dihy-
/ G0 t! C' w+ s- ~. _- d7 Pdrotestosterone at this age. Conversely, serum levels in older) g; A. n; a6 w
patients were higher, possibly because of decreased local! G0 N6 ~# s& {0 ?) d2 B% t) x) E
667: d6 U e% U, c5 u0 M+ h
668 KLUGO AND CERNY
( o* ^% M! [# N9 {6 d, {Pt. Age
( z9 l \+ A5 P6 z# V3 ^) n(yrs.): X' X4 F$ s- V% H: l
Serum Testosterone Phallus (cm.) Change Length4 ~$ Y7 N1 b/ h Q, _, F
(ng./dl.) Girth x Length (%)
0 d, y- M# [& Y7 O+ \48 a4 p% \* i" `/ v' L( M& X; d- f* f
8) w1 J$ T3 G6 `- u! L* a- Z3 \
102 C' Z2 w6 O. d. \6 d
12
0 r! z4 d. n( _1 c% k17, J) \5 X' f9 V7 D
Gonadotropin0 f8 k/ P) x: a) p3 [/ U
71.6 2.0 X 3 16.6- j1 P% `! {7 M4 W: O. Q2 h$ U1 D
50.4 4.0 X 5.0 20.04 D4 t6 Y6 m) F5 n/ ?2 I
22.0 4.5 X 4.0 25.0+ m$ }( s6 u6 Z5 u3 E- Y
84.6 4.0 X 4.5 11.1
6 B$ D7 b9 N2 k ~3 T3 h85.9 4.5 X 5.5 9.0
. w/ m( m4 W1 L0 j3 _* \& {Av. 14.3
. {2 @8 Q8 X s. X/ N0 s& |4% {' @0 Y) r* X2 L4 V+ r: h' @
8
, P7 @" @# v( _$ ~& N8 a o5 @100 a8 t7 V( n! @( D
12
& a9 d1 ?4 y" W5 ^5 q y8 E17
3 @' E: h$ J) x( @) W! WTopical testosterone% U% o, {3 Z) u* m( B$ f
34.6 4.5 X 6.5 85: `' K/ M( P: ]2 P0 }- [
38.8 6.0 X 8.5 70- u% K# g \6 F. P6 ?
40.0 6.0 X 6.5 62.5
) I5 @4 z2 P' d93.6 6.0 X 7.0 55.59 a6 h! O2 F+ c
95.0 6.5 X 7.0 27.2' V5 U& Q" y, ?+ b6 H
Av. 60.0
7 i2 H! G' w3 S4 N. D7 A8 Tavailable testosterone. Again, emphasis should be placed on3 {* F7 \" o0 O/ i
early therapy when lower levels of testosterone appear to5 A/ P0 ~- a. m: K
provide the best responses. The earlier therapy is instituted
, N8 W" B9 r6 i# j/ F+ W8 Gthe more likely there will be an excellent response with low8 ^ U) z1 C, f/ g! h- s) N
serum levels. Response occurs throughout adolescence as" k$ O: y7 I; r: ]" K* X4 ~. ~5 z3 K
noted in nomograms of phallic growth. 7 The actual response
+ e `- @( n. G- X. E& x" a* i9 |to a given serum level of testosterone is much greater at birth+ }5 T, a5 [# I9 c/ M I
and gradually decreases as boys reach puberty. This is most
0 }0 \) I& B! n% i# ^7 Y5 w9 p9 q4 G. Olikely related to the conversion of testosterone to dihydrotes-
: R) P; y/ [* U( V, t0 J! @/ ytosterone and correlates well with the studies of testosterone9 V9 F$ k" ^( @4 y; _* ?8 @2 f
conversion in foreskin at various ages.( T+ c0 p& P0 r0 k3 {$ `
The question arises regarding early treatment as to whether
9 L R+ U$ r- L* F4 d2 K, sone might sacrifice ultimate potential growth as with acceler-
R/ w, w# _0 P! nated bone growth. The situation appears quite the reverse
, p9 h4 T J+ e) ? H! `" kwith phallic response. If the early growth period is not used
: s% ~2 Z% H& Q, Dwhen 5a reductase activity is greatest then potential growth
C+ L6 L* u" L$ y( R% wmay be lost. We have not observed any regression of growth3 t: k) A$ z# w2 @0 z
attained with topical or gonadotropin therapy. It may well5 Y% ^3 t9 q' g
be that some patients will show little or no response to any4 | X. _" N$ T
form of therapy. This would suggest a defect in the ability to
' g, e! r! x9 W7 Aconvert testosterone to dihydrotestosterone and indicate that
. i4 {/ f1 _" c& c" b. Xphallic and peripheral skin, and subcutaneous tissue should' d! L1 u+ H9 g! R+ k B
be compared for 5a reductase activity.' x8 |* V: |2 I, r' d( o. f
A, loop enlarges to measure penile girth in millimeters. B,9 ^8 l) P# w4 Z3 c
example of penile girth computed easily and accurately.3 C. u* f8 ^2 ]+ ^
conversion of testosterone to dihydrotestosterone. It is in this
+ [+ ~6 Z6 M9 q+ e6 H6 K6 B+ C2 rolder group that others have noted high levels of serum( l4 C1 g1 G$ H2 F
testosterone with topical application. It would also appear6 e W9 @: e1 k2 X% V( e: p. @
that phallic response during puberty is related directly to the
4 r* b5 f6 J7 c0 s- @+ lserum testosterone level. There also is other evidence of local3 H6 l# O, N! v; c' P% u C9 v
response to testosterone with hair growth and with spermato-
# @4 K" ~" ~( s& sgenesis. 5• 6
- {! u5 z: W( |* R& IAdministration of larger doses of gonadotropin or systemic5 T3 l3 d2 j) T8 C' b7 B& m+ n9 v
testosterone, as well as topical applications that produce
0 s* N4 i1 N! U3 V! chigher levels of serum testosterone (150 to 900 ng./dl.), will
' B# Y( b- t7 E9 \9 m/ j0 balso produce phallic growth but risks accelerated skeletal
+ j7 Q* b4 b! S. ]- `: F0 H/ ematuration even after stopping treatment. It would appear& X6 `0 d1 [, H/ q# }5 f
that this may be avoided by topical applications of testosterone
! D8 L3 U: S7 mand monitoring of serum testosterone. Even with this control
6 l) s5 T. {( [ N& h( nthe duration of our therapy did not exceed 3 weeks at any
1 t: }3 ]1 b5 T8 s( Ctime. It is apparent that the prepuberal male subject may7 T" i5 v6 n2 U+ b
suffer accelerated bone growth with testosterone levels near
$ B! x- J' _3 ^. z; W200 ng./dl. When skeletal maturation is complete the level of; D& h4 V2 ]6 b! k
serum testosterone can be maintained in the 700 to 1,300 ng./
1 J: Q$ w$ ~, i' d" A2 sdl. range to stimulate phallic growth and secondary sexual
7 v# H3 l& Q2 e6 Pchanges. Therefore, after skeletal maturation parenteral tes-
) b3 c) o( j: Qtosterone may be used to advantage. Before skeletal matura-
. v) N7 o/ ?) U ?& W* H- l4 m/ gtion care must be taken to avoid maintaining levels of serum. C. X9 I8 F; ?7 F" p8 W
testosterone more than 100 ng./dl. Low-dose gonadotropin2 P. L! O# p$ x
depends upon intrinsic testicular activity and may require6 D3 ?' } l: \* }, b8 t
prolonged administration for any response.# V2 R1 e/ T& s7 f9 _$ N
Alternately, topical testosterone does not depend upon tes-
4 ^3 Q% j4 ~. t6 W* @% I ~ticular function and may provide a more constant level of
/ {6 E0 `5 O3 A" {REFERENCES
% ~" j6 ]- V* v# ?3 K. |1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
L& l5 T6 M. J% x* W" HR.: The local application of testosterone cream to the prepub-1 n( C- t7 h1 \0 }* o1 D
ertal phallus. J. Urol., 105: 905, 1971.1 g: T$ b3 Y5 }3 {
2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
) U, M j5 [- p8 |; K/ U9 W Xtreatment for micropenis during early childhood. J. Pediat.,# ~; [7 @7 r0 ^$ K
83: 247, 1973.* Y( r2 Q$ S$ B/ U r
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
+ C7 j# y+ ?' G5 H) Done therapy for penile growth. Urology, 6: 708, 1975.6 q9 c) k6 C) W' Y3 {% i8 l
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
, t1 C1 t- d" F6 g5 Q9 T( ~to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by$ F; r7 S v. u7 p
skin slices of man. J. Clin. Invest., 48: 371, 1969.% {0 E" M5 o" _) i. Z) ?/ A8 ~
5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth* R7 _! j; T! @$ X
by topical application of androgens. J.A.M.A., 191: 521, 1965.
) i9 C. ?2 k4 E+ m ~6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local; x7 P" B, i+ x) F1 h, ?- [# V8 ~
androgenic effect of interstitial cell tumor of the testis. J.# }5 e& B0 T# {$ F! p Z/ d5 ` }0 ]
Urol., 104: 774, 1970.
. Q) v( I6 b) p7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-
. g* M, t% V3 J/ X6 M7 ztion in the male genitalia from birth to maturity. J. Urol., 48: |
|