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鄉下的妹子太便宜,一次四個都要了[12P]

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good good support
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大家好心情
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果您要查看本帖隱藏內容請
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RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND
6 t1 c4 U" b2 M) f, a3 XGONADOTROPIN2 B! R0 u( {) ]/ M* W. B
RICHARD C. KLUGO* AND JOSEPH C. CERNY
/ c1 D! @% f1 |; r# dFrom the Division of Urology, Henry Ford Hospital, Detroit, Michigan
/ T1 j" d2 Z& N; LABSTRACT6 _1 o- l8 `7 e* E( d: ?, y: U# N8 q" x* r
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
1 o' I( a4 r2 u! kwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-* c# a: S/ d& |' s6 Q8 ~/ n
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone( `& K$ B2 U% |7 {
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent3 i. h5 i' Z% @' V% |
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent
  C1 c7 C+ y0 `' C1 q  r# yincrease in length and 5.0 per cent increase of girth. Topical testosterone produced an average7 ^6 G; O; }5 D$ Y7 g
increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
- {& V* P" |! s& Noccurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This2 i+ J7 l  j6 t6 B: Q8 L! o' o
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile! E6 a" P( o* `- ]( p0 N" h
growth. The response appears to be greater in younger children, which is consistent with previ-& @; W8 A0 ^* K  s4 Z: u
ously published studies of age-related 5 reductase activity.
7 [- ^% d1 i) ?Children with microphallus regardless of its etiology will, U, P) d# f4 n: ]
require augmentation or consideration for alteration of exter-
  V. |1 `2 l: l. F. {; Jnal genitalia. In many instances urethroplasty for hypo-3 \& h% |. X1 Y
spadias is easier with previous stimulation of phallic growth.
% |$ u; i& B+ B& B' sThe use of testosterone administered parenterally or topically
4 w7 d. r8 t8 ?0 ^# _7 [has produced effective phallic growth. 1- 3 The mechanism of9 n9 P% j0 l0 V) X1 q& S% @
response has been considered as local or systemic. With this$ C0 E- a- ?# \- j
in mind we studied 5 children with microphallus for response& {2 {0 v( C$ i8 m- @% W
to gonadotropin and to topical testosterone independently.
; Y7 Y, M" Q5 C5 S6 q% ~MATERIALS AND METHODS
6 m' z/ Z( v3 y0 m$ y0 NFive 46 XY male subjects between 3 and 17 years old were  N( b  K+ W! a* u
evaluated for serum testosterone levels and hypothalamic
# ]* m7 _' L9 lfunction. Of these 5 boys 2 were considered to have Kallmann's% L' Z! I. \  [7 h- g1 J
syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-; O. M; l6 }! G
lamic deficiency. After evaluation of response to luteinizing& q7 V2 e1 A; r0 E7 u0 t
hormone-releasing hormone these patients were treated with
3 ?- f8 G' ^7 _9 D1,000 units of gonadotropin weekly for 3 weeks. Six weeks
" E4 q1 H+ z$ y% A3 Vafter completion of gonadotropin therapy 10 per cent topical+ [8 C) g$ d2 V- P# i% u
testosterone was applied to the phallus twice daily for 3 weeks.
: D. C4 v& ?6 Y! Y+ eSerum testosterone, luteinizing hormone and follicle-stimulat-
9 n: |9 `- N6 J  h# Aing hormone were monitored before, during and after comple-" h* ]1 i$ k* Y2 C6 a/ W
tion of each phase of therapy. Penile stretch length was
6 o* z/ w9 k% u- A* }" o5 Lobtained by measuring from the symphysis pubis to the tip of. E. U7 O& C  n# c
the glans. Penile circumferential (girth) measurements were# M2 z& M* M3 T6 \
obtained using an orthopedic digital measuring device (see
9 G2 E6 b- K( @" V) Jfigure).% t, t6 }6 A! C; o* _
RESULTS2 T/ F0 g# M* C+ @
Serum testosterone increased moderately to levels between$ W; l4 W/ m% P. {/ v5 ?  [
50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-6 w3 x" I/ E% G# T3 j4 m: \
terone levels with topical testosterone remained near pre-
( A7 V+ [8 a& K: h0 o' mtreatment levels (35 ng./dl.) or were elevated to similar levels
0 y* p% M5 a. w; B/ G$ Ddeveloped after gonadotropin therapy (96 ng./dl.). Higher
4 ^4 d1 ], G1 U5 X* R8 c, Tserum levels were noted in older patients (12 and 17 years old),
; M4 Y3 {( R0 D0 j5 W) Gwhile lower levels persisted in younger patients (4, 8, and 10. w/ ]/ o6 w* S' }& C  {0 v( W2 S
years old) (see table). Despite absence of profound alterations
6 y% G/ z/ _4 l- p7 lof serum testosterone the topical therapy provided a greater
% b$ G# [. W/ e6 F. k3 a5 ?5 N2 @Accepted for publication July 1, 1977. ·
+ }4 _, n% y2 q+ w6 ~Read at annual meeting of American Urological Association,
: P7 }% h: Z) m/ K  }  O' OChicago, Illinois, April 24-28, 1977.
! X1 f/ \; b8 _# O* [2 C1 n8 D* Requests for reprints: Division of Urology, Henry Ford Hospital," K* L2 L" u/ {+ T
2799 W. Grand Blvd., Detroit, Michigan 48202.
7 h/ H  k. P: Bimprovement in phallic growth compared to gonadotropin.
, J: d# u% \( N9 G9 ]Average phallic growth with gonadotropin was 14.3 per cent
2 ]* H0 }9 X. Q$ N1 Q) Z6 }increase in length and 5.0 per cent increase of girth. Topical/ ^9 f/ C: A; n8 Q0 G
testosterone produced a 60.0 per cent increase of phallic length" {: `) R- x5 {* Q3 `6 y! S. w
and 52.9 per cent increase of girth (circumference). The8 P& J$ U2 E( |, G3 P6 T
response to topical testosterone was greatest in children be-
" d% w7 J/ _% s4 l- H- U4 `8 R" rtween 4 and 8 years old, with a gradual decrease to age 17
# Y7 z' i. u3 G0 X1 w. pyears (see table).
- ~: `9 `/ j9 n) N/ kDISCUSSION6 |: n4 n2 D- ?
Topical testosterone has been used effectively by other
, i1 w' C7 d% jclinicians but its mode of action remains controversial. Im-
( {9 S0 [+ {. h; }+ {$ ]5 S" \mergut and associates reported an excellent growth response
4 M6 v6 w& j' m. E& V/ Hto topical testosterone with low levels of serum testosterone,& E9 U! A' P% i! Y" F
suggesting a local effect.1 Others have obtained growth re-4 w: @' C+ U) K1 T( y6 E
sponse with high. levels of serum testosterone after topical
0 @) Q% F; q* O) Xadministration, suggesting a systemic response. 3 The use of0 b+ J7 q9 S& F; X
gonadotropin to obtain levels of serum testosterone compara-3 C4 A9 y$ S3 o5 }% P9 Z) {* k
ble to levels obtained with topical testosterone would seem to$ Y% `/ f4 I( }4 S
provide a means to compare the relative effectiveness of
9 _) |3 M+ C+ D9 E+ S; Stopical testosterone to systemic testosterone effect. It cer-
9 K+ V8 f9 p2 Y( ntainly has been established that gonadotropin as well as par-
' A+ P8 i8 M& q4 E0 w0 r: C0 G9 @enteral testosterone administration will produce genital' n+ F# s5 r: E1 X" [9 z5 A9 X
growth. Our report shows that the growth of the phallus was
% O4 X7 w" r6 W  }; J: t, Ysignificantly greater with topical applications than with go-
* b4 G' j; v& \: {nadotropin, particularly in children less than 10 years old.+ T$ U7 f: Y0 w, E/ o3 t, J! ?4 p
The levels of serum testosterone remained similar or lower( d: V7 h2 P3 S) O* m& z2 e
than with gonadotropin during therapy, suggesting that topi-
6 A. j0 O. n7 t; @- b$ a& C% Xcal application produces genital growth by its local effect as6 U* I/ n% r4 D$ G& }3 T9 I
well as its systemic effect.
+ D, F2 o5 I9 c6 }* {; cReview of our patients and their growth response related to8 S1 g$ Z8 b' P  E% l* ]- L
age shows a greater growth response at an earlier age. This is% A3 j$ t! k6 y! q, t- q
consistent with the findings of Wilson and Walker, who
' v3 y$ u" k  R) i- B5 }7 b$ G9 Sreported an increased conversion of testosterone to dihydrotes-
) N2 L% A* V5 {9 P8 s  A* `tosterone in the foreskin of neonates and infants.4 This activ-
$ A. `# O' B: R$ g. x# Zity gradually decreases with age until puberty when it ap-
1 `4 h# X  N& h* Wproaches the same level of activity as peripheral skin. It may1 D! c3 }/ K- T
well be that absorption of testosterone is less when applied at
9 ?( ^* |) ~4 Z( n* G  tan earlier age as suggested by lower serum levels in children- H/ W  G+ b5 }
less than 10 years old. This fact may be explained by the4 j8 d7 N0 r, |$ v
greater ability of phallic skin to convert testosterone to dihy-/ i# ?3 X' c6 ^! h- \6 e& I
drotestosterone at this age. Conversely, serum levels in older
0 B( x; I& a0 o, S  `$ y$ o- ]' Spatients were higher, possibly because of decreased local
% a" z, p4 f3 z9 s% y- ~667" o0 K# @9 S5 z$ K9 ?7 O
668 KLUGO AND CERNY
! H2 t% z: Q6 d3 o9 A  @Pt. Age4 R1 A' y/ c' q* D1 O1 ], X/ n. H
(yrs.)
* e  r: P. f; M: dSerum Testosterone Phallus (cm.) Change Length
! F+ N1 g6 l* D(ng./dl.) Girth x Length (%)# o: e. `" o" g) g7 c- o0 F5 N2 @. M
4
6 y6 Y% w3 r0 N82 V. x8 S9 |* C9 u
10/ ?1 r/ ?% S' n( H% r$ m* f/ f* k
12
) O# n$ p; l3 H5 g8 L' x17. I/ Q! @* j7 I
Gonadotropin
' T- p" q& T+ n! c, c/ i4 o71.6 2.0 X 3 16.60 V- ]$ P, c4 N9 Q3 {, k
50.4 4.0 X 5.0 20.0
! Q+ f8 P( e; o* ^$ v9 z6 q* b22.0 4.5 X 4.0 25.0
: r9 l! A/ b: N# ~* {( h84.6 4.0 X 4.5 11.1* t0 ]- z! ~# v" B0 m- I. r5 a
85.9 4.5 X 5.5 9.0
8 R: A5 }0 {" ~7 F8 ^Av. 14.3' v# ]7 [' Z4 a/ @3 u% W/ g
4
" Z  ?. |2 c4 U* }1 e8 I8
" s( b: j" O- h- o10* T% x5 E/ [' l/ P  N% W
122 @6 l4 o" S3 }# T
173 `& q( f: N4 V  V0 ?3 M
Topical testosterone
$ f/ Y+ s" w) B" L1 k34.6 4.5 X 6.5 855 \2 B0 V+ ~  G
38.8 6.0 X 8.5 70. B9 U- ]* R0 _8 B
40.0 6.0 X 6.5 62.5% i! X# S9 H* s. H. n
93.6 6.0 X 7.0 55.5
, S- j/ V* T8 X95.0 6.5 X 7.0 27.2
5 i& v4 c8 j0 d2 \! D4 p; U7 }Av. 60.0
7 n# _6 X6 s5 h3 d& L3 B4 c$ savailable testosterone. Again, emphasis should be placed on# h0 k% k2 ?  N+ L* m7 w& Y7 A+ t8 m
early therapy when lower levels of testosterone appear to& h5 D: e* `- l# k( V* ]3 ?; v6 a; _
provide the best responses. The earlier therapy is instituted
$ s% P5 b  R+ P5 \the more likely there will be an excellent response with low
8 `+ J! R* X: Zserum levels. Response occurs throughout adolescence as
0 H6 k4 L( u6 |$ l+ Xnoted in nomograms of phallic growth. 7 The actual response6 f2 V# H* U: Z# D- I6 r
to a given serum level of testosterone is much greater at birth' o: V( h2 Z' f' }
and gradually decreases as boys reach puberty. This is most
, V  T: K8 L1 |3 o6 @) i" alikely related to the conversion of testosterone to dihydrotes-
) m/ {4 q- T, P9 H  M) [tosterone and correlates well with the studies of testosterone; u" L1 c7 P( L3 q; S  |" m* @
conversion in foreskin at various ages.$ j) h2 H3 d( P! ~) v; b9 g
The question arises regarding early treatment as to whether
: Q; j" K& H0 d9 Rone might sacrifice ultimate potential growth as with acceler-
* }* E( F  ]3 Wated bone growth. The situation appears quite the reverse
0 H/ X+ M8 n5 ewith phallic response. If the early growth period is not used3 W- g" J7 d1 w1 S3 o
when 5a reductase activity is greatest then potential growth; I7 N0 f+ z# `
may be lost. We have not observed any regression of growth6 V% M; U# G8 s. k, J+ S
attained with topical or gonadotropin therapy. It may well& {: z0 n, I8 t8 b- X! J7 C
be that some patients will show little or no response to any
8 O: ^) a; u' Bform of therapy. This would suggest a defect in the ability to
1 U- z1 O7 ]% j0 }, a$ y  q) }" Wconvert testosterone to dihydrotestosterone and indicate that  A* ~7 Z+ O% V. M7 b( W3 f: X
phallic and peripheral skin, and subcutaneous tissue should
+ i. L1 D! P3 A/ q* H9 ^4 \be compared for 5a reductase activity.* c3 Y* @) D7 m6 O+ m1 N' }9 U
A, loop enlarges to measure penile girth in millimeters. B,
" `( a  W4 X- uexample of penile girth computed easily and accurately.. M9 e) c- \, B
conversion of testosterone to dihydrotestosterone. It is in this
- @; `2 i& d* _: Nolder group that others have noted high levels of serum3 T! T# e; f+ `9 _/ w! y; J
testosterone with topical application. It would also appear, p# D- T) g  w; Z9 j+ Y* B, [
that phallic response during puberty is related directly to the
' q3 k' U$ D/ e% T8 @' m+ Z3 Dserum testosterone level. There also is other evidence of local4 t2 C1 j% q  E
response to testosterone with hair growth and with spermato-
9 V) a$ Y: ?% egenesis. 5• 6" h: H* H; J( T4 D4 @4 c3 d1 E
Administration of larger doses of gonadotropin or systemic! d) d2 u' q9 J- V
testosterone, as well as topical applications that produce
, D% X, }$ \( c# L' d8 O) T% T6 F! _higher levels of serum testosterone (150 to 900 ng./dl.), will
+ X& \+ J- ]: z* g( f6 Valso produce phallic growth but risks accelerated skeletal
5 R' H- F" e+ X; ?' A' c* x4 nmaturation even after stopping treatment. It would appear
2 p" i9 v& j; C7 z# k3 ~that this may be avoided by topical applications of testosterone
; ?9 y+ H- t1 ]. ]4 l6 w, F7 hand monitoring of serum testosterone. Even with this control4 {% P4 h, |. I. Z
the duration of our therapy did not exceed 3 weeks at any
) v" A7 H4 C" S3 m& j+ ntime. It is apparent that the prepuberal male subject may' H2 \, g; [8 s! l4 O% l  C9 Z
suffer accelerated bone growth with testosterone levels near% U2 q  Z! ]: F
200 ng./dl. When skeletal maturation is complete the level of, _! ^, ^. }1 t6 a6 }' Q9 |
serum testosterone can be maintained in the 700 to 1,300 ng./
3 L8 B+ _5 R3 B' K3 _dl. range to stimulate phallic growth and secondary sexual
+ x# a$ O9 Z8 p- j( h. l5 bchanges. Therefore, after skeletal maturation parenteral tes-' b/ |9 {7 Y: u  {/ x: E1 \9 t
tosterone may be used to advantage. Before skeletal matura-
0 ?6 ]7 \! H/ V1 I0 T( Ation care must be taken to avoid maintaining levels of serum" {0 U! p4 x. ^$ _1 h( z
testosterone more than 100 ng./dl. Low-dose gonadotropin
7 V0 R0 ?! P# G  f0 I( v! x9 Zdepends upon intrinsic testicular activity and may require' J9 b( R0 I7 h4 ?; K& o) o7 _
prolonged administration for any response.
6 ^" f/ Y* ~+ i9 ?( W1 qAlternately, topical testosterone does not depend upon tes-
" X( V5 U5 s' h& B: Xticular function and may provide a more constant level of% a0 D1 S- B' x- X( V: p; n8 ?5 s. {
REFERENCES/ ^5 }8 S7 V" v7 c+ g
1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,5 j2 s: t4 J: Q! ?0 c" _5 z
R.: The local application of testosterone cream to the prepub-
4 O& O! y1 s( U4 \* _8 [* S6 B# u1 R1 tertal phallus. J. Urol., 105: 905, 1971.
) ?; e, i$ C, L" l' r# U8 Y2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone- x, }2 G, j* ]9 d
treatment for micropenis during early childhood. J. Pediat.,
0 j/ h$ A& @1 h1 _; @1 |83: 247, 1973.5 z* r  r' e. Y; Q- s
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-" k: r  Y) J" R6 W; P% t
one therapy for penile growth. Urology, 6: 708, 1975.
6 `8 R; ]3 P2 v  K# a4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
; x: ~5 Z( B; j. ^to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
" A7 L4 v) k2 i6 Y, n) gskin slices of man. J. Clin. Invest., 48: 371, 1969.
$ u: W8 E4 {& B) R0 m% Z: \$ b0 x5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth
6 Y6 T) P3 E5 }0 Qby topical application of androgens. J.A.M.A., 191: 521, 1965.
  n( Y: f" ]1 h% w6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
( K. ~$ D' b7 d! eandrogenic effect of interstitial cell tumor of the testis. J.9 I( F! o8 j* |  r5 Q% S8 I
Urol., 104: 774, 1970.
, @+ L) J, \; b6 H7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-& M1 n& \! |9 z- g. `1 Q" o
tion in the male genitalia from birth to maturity. J. Urol., 48:
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