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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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真的很不错
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RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND
  d! X: }! [3 j9 wGONADOTROPIN: L# z0 U3 [6 K! e( P( Z
RICHARD C. KLUGO* AND JOSEPH C. CERNY. g9 b" A0 t0 U0 p. |. i
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan
# ~  P5 r* q6 I3 g5 U" E3 K; c0 \/ O0 QABSTRACT
: T1 h  }7 B& n/ Z5 iFive patients were treated with gonadotropin and topical testosterone for micropenis associated
3 I8 D# N: f) A; Y3 Gwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-# ~: O% ?. r3 F+ c& O8 F9 e8 L5 S
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone& ?6 B; J' M9 A' ]( {
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent
* C7 y" h& G# o" R* ~. s0 H  ofor both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent: b: ~0 _3 C( G- ]
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average
- g! _" ?4 j# A* y, Qincrease of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response, `! t5 c1 h  D' R* I# l0 [- b5 Y
occurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This
) ^, {: }1 x: E5 m+ Kstudy suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
  {/ d0 ^5 D  a2 H9 t7 A4 v- ]- X( v  Qgrowth. The response appears to be greater in younger children, which is consistent with previ-- ?$ ]1 ^) X& j0 ^( e6 q% z* i
ously published studies of age-related 5 reductase activity.4 D9 w. _3 a0 \1 _
Children with microphallus regardless of its etiology will
' d: i; s  _/ M# }) ~' Drequire augmentation or consideration for alteration of exter-
& o9 U+ ?7 g) a  ?1 Y# u8 |nal genitalia. In many instances urethroplasty for hypo-5 {' e" b0 Z  t9 |
spadias is easier with previous stimulation of phallic growth.
. x- A5 h: U' AThe use of testosterone administered parenterally or topically
" v; G3 u; M; t5 M6 W  F  w2 N9 vhas produced effective phallic growth. 1- 3 The mechanism of3 J) k  f( |5 v
response has been considered as local or systemic. With this
7 W/ v% S' T5 A- B: h# Kin mind we studied 5 children with microphallus for response
' P, x1 z" Q: Z$ Uto gonadotropin and to topical testosterone independently.$ y, d) l* Y, g( T
MATERIALS AND METHODS
* x9 z1 q! g! e7 m3 UFive 46 XY male subjects between 3 and 17 years old were4 B2 z) f& F! c: C+ k8 h
evaluated for serum testosterone levels and hypothalamic; S. \+ _& E" m  b* Q# |7 u+ b& x
function. Of these 5 boys 2 were considered to have Kallmann's
1 ?' e5 [' l) w3 O: bsyndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-7 u  `( Y; e  X: v
lamic deficiency. After evaluation of response to luteinizing
8 P' t' h' X( r! F$ `hormone-releasing hormone these patients were treated with
; ~$ P! i: g5 E0 u1,000 units of gonadotropin weekly for 3 weeks. Six weeks
7 v4 A4 Y# i2 L6 e( d3 A  pafter completion of gonadotropin therapy 10 per cent topical
4 r( C/ t4 i3 r7 f3 stestosterone was applied to the phallus twice daily for 3 weeks.
, h! L$ U% h, ]9 QSerum testosterone, luteinizing hormone and follicle-stimulat-4 p4 c2 o/ `2 P
ing hormone were monitored before, during and after comple-- V# @6 x$ C5 L( z
tion of each phase of therapy. Penile stretch length was9 }3 w# s1 l0 r+ a. M5 _
obtained by measuring from the symphysis pubis to the tip of$ p/ v, ^- [5 R7 F; Q# O4 ~
the glans. Penile circumferential (girth) measurements were4 k8 a, \- G  l3 e
obtained using an orthopedic digital measuring device (see$ H8 f7 D; a1 c# |3 J1 Q2 J
figure).' T2 r8 a- B5 }) b* Q7 j, [# j8 j
RESULTS- f, \  J9 W2 r' B" R6 d; r+ s
Serum testosterone increased moderately to levels between
; x2 u# h% o5 c! g* S50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-
7 C' ?! m5 h6 ?3 aterone levels with topical testosterone remained near pre-# z4 r( j5 K6 A/ ?
treatment levels (35 ng./dl.) or were elevated to similar levels
, q2 F. {* e8 Wdeveloped after gonadotropin therapy (96 ng./dl.). Higher
* G/ [2 b6 x! |1 _$ Hserum levels were noted in older patients (12 and 17 years old),
8 W2 W2 {# a2 O: s; y. |( f9 Wwhile lower levels persisted in younger patients (4, 8, and 10
( T$ |; w2 W( c. yyears old) (see table). Despite absence of profound alterations
! o% f  I" L2 ~4 r  Y* Pof serum testosterone the topical therapy provided a greater
8 t  |! V% @' R7 u: TAccepted for publication July 1, 1977. ·
2 h0 \* {6 F6 y/ \4 XRead at annual meeting of American Urological Association,
* q* I1 \5 I# V& v3 U: \Chicago, Illinois, April 24-28, 1977.
: Q6 n5 J+ c) b" W5 n; |) U) a* Requests for reprints: Division of Urology, Henry Ford Hospital,
+ j. \+ `* G1 X. C2799 W. Grand Blvd., Detroit, Michigan 48202.
  c7 K( {4 P5 X; X4 |" q" Vimprovement in phallic growth compared to gonadotropin.; e3 `! k/ Y: Q' d& o& C% f
Average phallic growth with gonadotropin was 14.3 per cent. v- C- I) H6 T- }8 v$ o( X1 r7 r
increase in length and 5.0 per cent increase of girth. Topical% O: `" b5 A% i/ D
testosterone produced a 60.0 per cent increase of phallic length+ k  n; c+ ]% g; ~, w5 ^4 @
and 52.9 per cent increase of girth (circumference). The# L3 v; M5 O- q% A( K. G9 r
response to topical testosterone was greatest in children be-9 ]0 V6 W  t' o
tween 4 and 8 years old, with a gradual decrease to age 17. U1 D9 v2 W; T/ Z' `0 L: ?/ K
years (see table).' b( T2 W; Z5 I7 g
DISCUSSION1 w$ c7 Z/ i- f7 Z' Q( Y0 K. C/ W
Topical testosterone has been used effectively by other& {4 g" C5 @0 E( ~/ D! p
clinicians but its mode of action remains controversial. Im-1 H! y$ l5 Q! |
mergut and associates reported an excellent growth response3 k0 |0 f% o5 Q5 W% \) m" Q
to topical testosterone with low levels of serum testosterone,
* T% c6 v) B/ x3 D6 b9 _. z  Psuggesting a local effect.1 Others have obtained growth re-' C$ n7 k7 L  F
sponse with high. levels of serum testosterone after topical2 P% M* O9 a7 V6 Z$ W" A% z
administration, suggesting a systemic response. 3 The use of
( q2 E. E" b2 i4 jgonadotropin to obtain levels of serum testosterone compara-
) V! e, C2 Y, Zble to levels obtained with topical testosterone would seem to" ]. L/ t$ x3 Z
provide a means to compare the relative effectiveness of
% O$ g0 x" T% ]; ?% Etopical testosterone to systemic testosterone effect. It cer-9 l: i0 {1 X9 y, B* J* v
tainly has been established that gonadotropin as well as par-! C( x( H0 C4 B
enteral testosterone administration will produce genital$ R& P4 k0 {' j
growth. Our report shows that the growth of the phallus was
7 w5 N* o  r5 M  S2 `* Vsignificantly greater with topical applications than with go-
, H: R( o4 t' ]( Ynadotropin, particularly in children less than 10 years old.; g% j/ w( ~3 B! M% a
The levels of serum testosterone remained similar or lower
: y' N1 U/ h3 M) K% xthan with gonadotropin during therapy, suggesting that topi-7 d$ Y/ i6 N2 s8 k3 W6 b% N
cal application produces genital growth by its local effect as
. Y/ V4 r% E+ ?, Ewell as its systemic effect." Y2 Z0 W' \  ~/ E  Q
Review of our patients and their growth response related to1 B0 X- {: q- E: G) F
age shows a greater growth response at an earlier age. This is8 ]& X! b+ ]$ E1 \
consistent with the findings of Wilson and Walker, who
& d6 }% g- x+ q7 M/ Vreported an increased conversion of testosterone to dihydrotes-
: f2 y9 d3 M9 m+ Z- P. Stosterone in the foreskin of neonates and infants.4 This activ-) q5 r2 d4 X" a' F
ity gradually decreases with age until puberty when it ap-
7 P  A# n* N& d& a8 oproaches the same level of activity as peripheral skin. It may, v; B7 U4 U- F9 O2 b; d* L
well be that absorption of testosterone is less when applied at
& T, `, d, H  \, Lan earlier age as suggested by lower serum levels in children2 a# z5 c3 e8 E: @) i7 F/ g; _, Z
less than 10 years old. This fact may be explained by the9 ~" q& M6 O6 D. h
greater ability of phallic skin to convert testosterone to dihy-2 l& L% T/ s% ^9 ?) P0 C2 v6 a
drotestosterone at this age. Conversely, serum levels in older
# k& L, m7 |: tpatients were higher, possibly because of decreased local
4 K" h6 Q& q" b4 i6671 X# y6 N' z; n+ Q  y
668 KLUGO AND CERNY
0 `2 y  f$ X) ^$ y' QPt. Age! c) ~2 o1 M2 d4 G' b  b
(yrs.)
7 T/ g" M8 g/ m. j" HSerum Testosterone Phallus (cm.) Change Length
! P2 j9 S, `$ O7 }2 Z(ng./dl.) Girth x Length (%)& P( J5 ~5 {& w& |" o$ ]0 L0 f
40 K2 H  r9 z. _; u1 ]4 ~: [
8
( H: h( Z/ J& C5 A( C10  k) ?5 n8 B4 q: U4 a
129 m  w, e5 v$ E3 S6 ?" G  d7 k
177 S, U- n  ^( o" g
Gonadotropin% W, H, C, p, E2 `  _) R
71.6 2.0 X 3 16.61 G' \1 U3 j: Q& Q: }; J
50.4 4.0 X 5.0 20.0
& H2 m9 v7 r, }6 H" N1 M22.0 4.5 X 4.0 25.04 @- J9 J  M: ^8 o
84.6 4.0 X 4.5 11.1" F/ E3 N$ f5 j; g( k
85.9 4.5 X 5.5 9.0
6 W2 h% k% Q# k) T  j4 G6 SAv. 14.33 S1 f' [5 T% a
4
( O3 v7 u0 ^7 z; b! i( n# H8% f: T: ]4 J+ e0 q( |: _
10
1 Y1 W+ p4 y1 [6 \: ~12
5 S# z) d) t+ H3 m& r$ D17
6 I3 |# ]4 [3 O4 UTopical testosterone* j5 Z) T, U( o# N" E3 x; Z8 ?
34.6 4.5 X 6.5 853 i: z1 E( N7 u) s
38.8 6.0 X 8.5 70
( Y) w% |& S8 w; N& C40.0 6.0 X 6.5 62.56 a/ u- ^1 `, t7 w: X  }* q! x
93.6 6.0 X 7.0 55.5
7 y& r9 |& V: ~" `. [. G4 [95.0 6.5 X 7.0 27.2
, u7 n; z2 P+ t8 J/ B5 PAv. 60.0
. i$ |" N4 Y- L7 B% j' B* d, Gavailable testosterone. Again, emphasis should be placed on
$ Y  r0 p2 H. u: f1 ~' V- Z8 \early therapy when lower levels of testosterone appear to% G* O: i! O: N( [4 }' \1 b
provide the best responses. The earlier therapy is instituted  H+ ]: Y$ e: @/ i
the more likely there will be an excellent response with low
7 y* m0 A  [5 }$ G2 B8 U8 gserum levels. Response occurs throughout adolescence as
# @) \: x& k3 ~) w; Znoted in nomograms of phallic growth. 7 The actual response
6 o, |  l: ?2 |to a given serum level of testosterone is much greater at birth
: }; h: `* V7 i* P9 D. n" I; o. kand gradually decreases as boys reach puberty. This is most
% O2 {( Y/ C% u( slikely related to the conversion of testosterone to dihydrotes-4 |6 j$ u% a5 [) b4 Q2 A
tosterone and correlates well with the studies of testosterone
" ]9 o7 Q+ y1 {+ B) Q# J8 Dconversion in foreskin at various ages.
5 {3 S5 [: W7 A+ B0 k$ Q$ v6 cThe question arises regarding early treatment as to whether
+ W+ ]$ v* `, N0 J8 @6 X. {one might sacrifice ultimate potential growth as with acceler-
! ]8 V  @$ m( _# t. ~" l; Rated bone growth. The situation appears quite the reverse
# D- E! j, T/ Y+ h" Mwith phallic response. If the early growth period is not used5 q. K0 G) n( u1 r! z
when 5a reductase activity is greatest then potential growth7 G4 L. w+ A: A( Z
may be lost. We have not observed any regression of growth
) F, a7 \4 d& S" t4 f5 yattained with topical or gonadotropin therapy. It may well
. g' T6 ]' }5 M2 D4 H# s9 v4 B% zbe that some patients will show little or no response to any
$ X; u+ i1 _6 a8 ~: K4 C1 \0 \( _# ~form of therapy. This would suggest a defect in the ability to
2 U: y. }, u. I8 D+ }convert testosterone to dihydrotestosterone and indicate that8 m5 H8 X! K6 S
phallic and peripheral skin, and subcutaneous tissue should
: ^5 ^0 b  P6 C3 m  Ibe compared for 5a reductase activity.
! F9 G3 r, L1 T* j$ uA, loop enlarges to measure penile girth in millimeters. B,
4 M' ?  A5 t1 h  ^0 V# a6 Oexample of penile girth computed easily and accurately.
) Z) |  @3 G) M0 v; w+ `* n5 a+ {conversion of testosterone to dihydrotestosterone. It is in this
, x" w* c0 x# \( holder group that others have noted high levels of serum) Q1 H. x2 n7 x" G/ L
testosterone with topical application. It would also appear
- W' ?8 i" d, Athat phallic response during puberty is related directly to the
  v% @$ K" b0 aserum testosterone level. There also is other evidence of local
4 x' c! y  }8 [! Wresponse to testosterone with hair growth and with spermato-  R8 M# o) H- s1 C
genesis. 5• 6! |9 _$ n: |! ~) |
Administration of larger doses of gonadotropin or systemic
' b* _% E" J. ]1 g8 etestosterone, as well as topical applications that produce
% O4 g) `' {1 e6 j0 }higher levels of serum testosterone (150 to 900 ng./dl.), will
) c. `* r7 ]- E3 r+ d# w1 V+ O- Xalso produce phallic growth but risks accelerated skeletal: ]  t: _' a* S- e' q( B
maturation even after stopping treatment. It would appear' B+ N% H; N3 {! e7 s2 c1 ]
that this may be avoided by topical applications of testosterone* q5 ~0 {  Y" a, N
and monitoring of serum testosterone. Even with this control
7 a0 _0 j! c7 S$ U3 fthe duration of our therapy did not exceed 3 weeks at any# P  C. O8 r5 c( y  w; V0 P
time. It is apparent that the prepuberal male subject may! r, _' ?* X8 O1 v& Q$ |  P; }
suffer accelerated bone growth with testosterone levels near3 k4 d5 `0 L3 ?/ ?; F. \! e
200 ng./dl. When skeletal maturation is complete the level of
& U: j7 }9 ]. pserum testosterone can be maintained in the 700 to 1,300 ng./
: \% s) j! o4 G! pdl. range to stimulate phallic growth and secondary sexual
8 u: ^8 N; \& B4 }' u# Echanges. Therefore, after skeletal maturation parenteral tes-
# H, ?5 V! K/ X% y* _* rtosterone may be used to advantage. Before skeletal matura-
& @1 r' }0 v, ntion care must be taken to avoid maintaining levels of serum8 p8 E% U  i/ ^3 z2 |7 ^
testosterone more than 100 ng./dl. Low-dose gonadotropin
* j( K$ E: a+ ~$ U1 X" zdepends upon intrinsic testicular activity and may require8 G1 m( Q, Y( V, G' X$ b; L& ?
prolonged administration for any response., f1 g$ y0 [6 G' t
Alternately, topical testosterone does not depend upon tes-9 \) `9 A: T4 e3 X7 v
ticular function and may provide a more constant level of
. S; B+ a; S. r1 P# gREFERENCES" O, c" V! S6 t1 @3 t* j# J
1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
+ i$ B1 b6 h1 c7 }( F- E4 F& \R.: The local application of testosterone cream to the prepub-
, x1 E7 p1 y+ c5 C- z  Sertal phallus. J. Urol., 105: 905, 1971.
3 Z+ A: |3 R: y  {4 e* h2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
8 y$ Z5 S/ \' n. Wtreatment for micropenis during early childhood. J. Pediat.,
2 a' L# {! E: W3 o1 J83: 247, 1973.- u! f8 D) }- V  W+ S& c; F! y/ x( e6 J4 Y
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
0 y' I) |/ q* B# I( D7 Oone therapy for penile growth. Urology, 6: 708, 1975.: _9 p9 C9 N8 R# w# C! E
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
1 m. m# _4 [: J" _  W% Sto 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
, r) `9 z: l- hskin slices of man. J. Clin. Invest., 48: 371, 1969.7 _  G9 a$ s/ F5 p
5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth
% z! n1 @$ O/ p" t. m7 zby topical application of androgens. J.A.M.A., 191: 521, 1965.. K! D; N) @4 }7 c# N- Y* ], Z
6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local$ `+ V5 s" R7 o1 o
androgenic effect of interstitial cell tumor of the testis. J.6 i" x/ q8 ~/ N# D. d
Urol., 104: 774, 1970./ l, t' R5 I% }$ L" K
7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-2 s! u# a6 j' i# U' K6 W) F
tion in the male genitalia from birth to maturity. J. Urol., 48:
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