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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
( K  i* T8 o" A! d( g  E! d. wGONADOTROPIN( ]7 S* m- i7 H1 ?% Y# I4 a: A
RICHARD C. KLUGO* AND JOSEPH C. CERNY
6 ]/ ~; ?! `; `  l& o1 PFrom the Division of Urology, Henry Ford Hospital, Detroit, Michigan* j7 R& c0 }% k0 t1 i' J4 W+ \8 V5 I# s
ABSTRACT; h$ c9 w2 O) d; |: p- ~
Five patients were treated with gonadotropin and topical testosterone for micropenis associated7 J/ R- `8 v& F% i+ f  A. J
with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-: [/ l7 C2 s  B
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone" x5 f% u, _3 j: ^2 |* I5 x; p4 |
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent# \* i. z4 B# S( H2 _( Y8 t& B9 C
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent! G! a1 i/ B  {* k
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average$ G. ?# _1 o( R6 Z$ @6 l
increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
7 w! O( ^9 a( e5 ~4 ]7 \- Loccurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This
/ v1 J% H% ~  Sstudy suggests that 10 per cent topical testosterone cream twice daily will produce effective penile4 E3 p7 Z5 c+ E) _2 B& J5 J6 y
growth. The response appears to be greater in younger children, which is consistent with previ-( d% e% s' c4 b: |& p3 p2 G7 k1 ~
ously published studies of age-related 5 reductase activity.! M/ j. u2 t# q9 E$ O
Children with microphallus regardless of its etiology will6 w5 C1 S8 N1 v" o6 W9 |
require augmentation or consideration for alteration of exter-5 O7 T: i) ]( p- u0 ?' o
nal genitalia. In many instances urethroplasty for hypo-
# }4 l8 {5 M) s0 aspadias is easier with previous stimulation of phallic growth.
4 R  k; j+ m' \: j4 @& cThe use of testosterone administered parenterally or topically& B) p+ H# P# ?$ X5 C$ y
has produced effective phallic growth. 1- 3 The mechanism of
$ i1 [* X3 W; W  J' `1 Cresponse has been considered as local or systemic. With this
- N2 P- K! M2 r6 h+ a& F+ Fin mind we studied 5 children with microphallus for response* I! F' U& u# R% Z, j
to gonadotropin and to topical testosterone independently.) G& \. q; z- i0 v, b- w5 L* e0 l
MATERIALS AND METHODS( v2 [0 {# H0 K( \: e7 g
Five 46 XY male subjects between 3 and 17 years old were( H+ o& d6 D4 L) U  H6 k% O. q
evaluated for serum testosterone levels and hypothalamic
+ `, e5 d1 o, M& a2 Kfunction. Of these 5 boys 2 were considered to have Kallmann's% R, B2 S( T( r, k  z; ~+ G$ S2 `
syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
) n# v; {% C  q9 W& v0 e  blamic deficiency. After evaluation of response to luteinizing- {6 I- a# s7 R
hormone-releasing hormone these patients were treated with
6 s, h2 |, I% `1,000 units of gonadotropin weekly for 3 weeks. Six weeks
7 [5 l9 d* x2 a6 Zafter completion of gonadotropin therapy 10 per cent topical
) X# h# i" L% n  Ftestosterone was applied to the phallus twice daily for 3 weeks.0 U& p6 e- f. z5 l% h7 x+ w
Serum testosterone, luteinizing hormone and follicle-stimulat-
4 C7 v( N1 y9 J" j/ ]( Oing hormone were monitored before, during and after comple-& G& D' [- Z0 J# p/ m7 @) [
tion of each phase of therapy. Penile stretch length was1 C' U" K8 ^& K: G/ p& z/ T% j3 N
obtained by measuring from the symphysis pubis to the tip of# B- x( I2 R/ C* L2 e& D1 n( ~
the glans. Penile circumferential (girth) measurements were
. k: z/ R6 q- u* ^+ X5 K$ hobtained using an orthopedic digital measuring device (see/ H) o( S% W' K$ e
figure).2 Z( ^5 N' G- U) f0 t/ C1 G) S
RESULTS& z) p& T5 z( O7 u* O2 J/ [. w
Serum testosterone increased moderately to levels between+ C2 O( K$ }& b7 }! R& K2 ]4 m
50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-& F$ T( O2 o  _) E# {/ |
terone levels with topical testosterone remained near pre-* ~4 N8 b- y3 C2 |- l9 E+ t
treatment levels (35 ng./dl.) or were elevated to similar levels( f* ^3 Q6 P, L/ Z: `8 g
developed after gonadotropin therapy (96 ng./dl.). Higher
" \  x+ v2 V0 Kserum levels were noted in older patients (12 and 17 years old),! E% H. n) r- v8 A8 h
while lower levels persisted in younger patients (4, 8, and 10$ s$ A" E$ f4 W2 x& M+ ?5 f
years old) (see table). Despite absence of profound alterations5 }+ C8 R/ p  |8 e
of serum testosterone the topical therapy provided a greater( u$ J, x$ a( p, t1 \- C1 d! W1 q5 \
Accepted for publication July 1, 1977. ·; S7 j* o( r" k7 ?
Read at annual meeting of American Urological Association,6 w  w) H- y- A+ E
Chicago, Illinois, April 24-28, 1977." \+ p, ^: x% O/ h% g! {9 Q
* Requests for reprints: Division of Urology, Henry Ford Hospital,# ]/ j6 b3 t: l5 n" l6 {3 n
2799 W. Grand Blvd., Detroit, Michigan 48202.
# l4 [) m0 |: z* n9 p) t5 p% y% \improvement in phallic growth compared to gonadotropin.2 Z' Y' m9 t9 x; I0 Q% v. W, V
Average phallic growth with gonadotropin was 14.3 per cent; g( K& ]- j. C, |9 ~. M
increase in length and 5.0 per cent increase of girth. Topical
1 @! {, @% b! O& ~; gtestosterone produced a 60.0 per cent increase of phallic length
% V6 S% B+ b7 |and 52.9 per cent increase of girth (circumference). The; ]& b7 t# u9 e
response to topical testosterone was greatest in children be-
' o. Z& }# z9 E+ i% n+ g! k) U  btween 4 and 8 years old, with a gradual decrease to age 17
: ~# s+ Y, E0 E8 n2 _years (see table).% h) h* a& b  q
DISCUSSION
" `) Y3 M+ P8 sTopical testosterone has been used effectively by other
8 U3 |+ L6 q+ \# P" P. O6 t$ C5 jclinicians but its mode of action remains controversial. Im-0 e$ w( ]( S* H) u( E1 P
mergut and associates reported an excellent growth response8 x$ D- D% V% B! b: ~9 _1 `* h
to topical testosterone with low levels of serum testosterone,
( c: m* d. \' y- v- f( V3 Wsuggesting a local effect.1 Others have obtained growth re-
( c* j8 X7 v; J1 t3 Y9 }/ asponse with high. levels of serum testosterone after topical
8 I; {' p: C+ M. i1 x8 `administration, suggesting a systemic response. 3 The use of
; u6 t; g8 e# h) d( r# F3 ?gonadotropin to obtain levels of serum testosterone compara-7 F8 I$ W: G  `+ X2 ?
ble to levels obtained with topical testosterone would seem to
( O, F5 A# b- F; Q* `2 `- R* Qprovide a means to compare the relative effectiveness of' y/ |+ i) ~  t0 j
topical testosterone to systemic testosterone effect. It cer-7 t1 _8 {/ Y1 W6 X2 f
tainly has been established that gonadotropin as well as par-
: Q4 x5 F0 a: G$ O4 }enteral testosterone administration will produce genital
1 R. Q' a, _0 L1 \, z) Mgrowth. Our report shows that the growth of the phallus was
6 p9 Z! L7 }, W0 x5 b7 k6 j4 q6 ysignificantly greater with topical applications than with go-
) N* k) m3 f2 K- Lnadotropin, particularly in children less than 10 years old.2 H! l5 b& h9 E; ^3 K8 w/ S( s
The levels of serum testosterone remained similar or lower# _. D$ z9 [& R# b. I- m% E
than with gonadotropin during therapy, suggesting that topi-: P" V7 _) ?/ O: d4 D. [. I
cal application produces genital growth by its local effect as
9 r. [% I- Y; U; i! H$ F4 xwell as its systemic effect.* k$ G7 o# G5 @4 n7 _" {! G
Review of our patients and their growth response related to0 p$ T3 b- E# y% D7 ^
age shows a greater growth response at an earlier age. This is
7 T- @- T) {$ `consistent with the findings of Wilson and Walker, who
2 v; I) W: B. H! N1 creported an increased conversion of testosterone to dihydrotes-
+ l2 F8 L' N/ g' a* q5 j1 Htosterone in the foreskin of neonates and infants.4 This activ-! Q8 `6 J' m5 G/ ~, L. {
ity gradually decreases with age until puberty when it ap-) c/ n7 u0 U5 E* h1 \4 J; W/ ]
proaches the same level of activity as peripheral skin. It may! ]  a7 ^7 p3 y
well be that absorption of testosterone is less when applied at
8 x( G6 Q, s2 |# K  H+ p- W) ean earlier age as suggested by lower serum levels in children  \$ B5 Y1 ?/ a, W! k
less than 10 years old. This fact may be explained by the
0 {# }* S4 N( r+ J4 [  Dgreater ability of phallic skin to convert testosterone to dihy-
7 g5 y7 F5 i: W+ z1 o$ mdrotestosterone at this age. Conversely, serum levels in older
* b! y3 |3 M" o9 M5 r9 ?patients were higher, possibly because of decreased local5 P3 c, t6 C; {4 \
667
& b6 `* w# L8 `. w668 KLUGO AND CERNY. O0 C8 M, n$ `% E" b6 q0 z. [" w
Pt. Age
; R4 y. r! v; r# g(yrs.)
3 B$ W* o% p! V7 E+ |Serum Testosterone Phallus (cm.) Change Length
+ o1 S$ \; z" Q& i/ G  W: N(ng./dl.) Girth x Length (%)
$ F/ H; m) k' b" S4* J7 F% X- ]+ L, @# `3 d9 E; J
8/ i- w8 q% ~4 P  u. B' C( ^
10) \$ ]$ \  K3 c/ U+ X4 W' r4 ?
12  ]5 G8 ^( s3 f, I! {; g
17
4 M7 i6 F( J' y0 B; gGonadotropin' N1 V; r' \7 ]; b: G' @# C3 _/ ~
71.6 2.0 X 3 16.6
- ]  E2 C. g- l4 ]5 p50.4 4.0 X 5.0 20.0
+ _' [4 j: M( |4 w! \22.0 4.5 X 4.0 25.08 D; f( `9 Y; A( i
84.6 4.0 X 4.5 11.16 `5 l! J! d( X- e# v+ ~- ~4 d
85.9 4.5 X 5.5 9.0
) C* A: }2 z4 Z/ x! DAv. 14.3
9 i1 Y: g/ ~. V% H3 a40 Y9 u# D& n4 i/ F/ m$ c
8" ^4 U  W+ a) S
10
  z% y5 }' J) G6 ]12
  `) \- \* F, R! i1 p178 {, A6 T0 G$ V: R7 e
Topical testosterone1 L" D" e/ ~7 p
34.6 4.5 X 6.5 85
6 j3 L1 f6 W+ m+ R38.8 6.0 X 8.5 70! A& F5 }4 B0 W" I8 {
40.0 6.0 X 6.5 62.59 }9 P! `, J3 [; R6 `
93.6 6.0 X 7.0 55.5( H* a8 G8 B" P. Q# {5 n
95.0 6.5 X 7.0 27.2
8 S( g: ?2 t' b* p3 _- IAv. 60.0
0 q' A2 s- _% U5 Cavailable testosterone. Again, emphasis should be placed on2 f1 a1 w& p) u+ k
early therapy when lower levels of testosterone appear to
# i7 i. n4 q' |) |' Eprovide the best responses. The earlier therapy is instituted2 A  e0 W. z. k1 t$ W
the more likely there will be an excellent response with low
4 W9 x! b' J: }' i- g% @serum levels. Response occurs throughout adolescence as* O: S! [% T; R$ E$ [# _
noted in nomograms of phallic growth. 7 The actual response
9 w, T: \" v$ S, m0 O9 D* mto a given serum level of testosterone is much greater at birth
7 Z2 ^1 U: w  F: P& I& s! b( jand gradually decreases as boys reach puberty. This is most/ v+ Z: d- D6 p$ U4 q. X
likely related to the conversion of testosterone to dihydrotes-1 h, ^8 J  e& K/ n. k$ {, A3 F9 f
tosterone and correlates well with the studies of testosterone; F9 Z% B2 T$ M! m
conversion in foreskin at various ages.3 H) o3 Y% d7 D4 {& B4 W! M$ d
The question arises regarding early treatment as to whether
% M- `3 Q$ C0 @$ `, f8 Tone might sacrifice ultimate potential growth as with acceler-
& e' s! y4 f  q' `0 E+ t3 k: [& gated bone growth. The situation appears quite the reverse
3 ^8 H  |  m4 wwith phallic response. If the early growth period is not used
( M# \4 q( r2 `when 5a reductase activity is greatest then potential growth
$ a9 R4 S- u$ j- u9 j$ z* u( umay be lost. We have not observed any regression of growth4 q. d" j5 A) P. S# C7 m7 M
attained with topical or gonadotropin therapy. It may well
# ~1 d9 x# Q5 x0 A9 t. w+ L; S7 Ybe that some patients will show little or no response to any( Y1 o6 h; z' M) F: m3 q( Y: U; X
form of therapy. This would suggest a defect in the ability to) f( @6 t6 x0 w4 s
convert testosterone to dihydrotestosterone and indicate that$ ~3 ]) F% t, ~
phallic and peripheral skin, and subcutaneous tissue should8 Y0 O/ W: {2 s8 H% F
be compared for 5a reductase activity.
& m1 z7 n8 j7 E- s/ g1 WA, loop enlarges to measure penile girth in millimeters. B,
/ V; G7 s4 f5 b/ m; M# [6 ]example of penile girth computed easily and accurately.9 Z! c# s. ^* X- R
conversion of testosterone to dihydrotestosterone. It is in this2 Z" W; _' K' y* l) S' R- c
older group that others have noted high levels of serum
& l' G' B: b; c" A. t, @: mtestosterone with topical application. It would also appear& B0 @7 ^0 ?9 J! W7 j
that phallic response during puberty is related directly to the
( D5 t" Q8 Q# V% w9 o7 g' _3 Rserum testosterone level. There also is other evidence of local( S8 q3 e$ W: Z& _
response to testosterone with hair growth and with spermato-
8 S: a, l  `; n, Agenesis. 5• 6
3 x9 l* [, G& @# o4 Z. x  ]/ rAdministration of larger doses of gonadotropin or systemic/ _8 W2 [* A% R1 O' Q- \
testosterone, as well as topical applications that produce
- V# A- x9 W2 h: z- S) uhigher levels of serum testosterone (150 to 900 ng./dl.), will. y$ `. F$ Z" S7 d% R+ N
also produce phallic growth but risks accelerated skeletal
* Z" K. Z# Z  q/ c3 d8 J3 u9 Umaturation even after stopping treatment. It would appear
9 P6 l* R, N9 l5 I3 C0 vthat this may be avoided by topical applications of testosterone
; }$ n6 L8 Q) u4 Y) g4 Y, v4 land monitoring of serum testosterone. Even with this control: x% V0 ^  u# W
the duration of our therapy did not exceed 3 weeks at any2 Z/ U- V0 ~8 @% Q1 d& a8 s- T
time. It is apparent that the prepuberal male subject may4 H7 m8 k+ y0 q
suffer accelerated bone growth with testosterone levels near
1 q5 c  ?. L& k200 ng./dl. When skeletal maturation is complete the level of- z% V4 O8 _# P, ]% [( T1 d
serum testosterone can be maintained in the 700 to 1,300 ng./. N% R. N3 p: z
dl. range to stimulate phallic growth and secondary sexual
- y# @/ }6 T1 o9 Z3 j& ~& f+ p# {4 ^changes. Therefore, after skeletal maturation parenteral tes-
; Z+ E5 V: Q$ e! b% q2 [tosterone may be used to advantage. Before skeletal matura-4 ]; a0 V9 X- N
tion care must be taken to avoid maintaining levels of serum
" [# b3 T5 P1 I5 t" c; Y# r- Rtestosterone more than 100 ng./dl. Low-dose gonadotropin3 V/ ?4 R/ {1 m3 y/ v
depends upon intrinsic testicular activity and may require( a1 j0 O0 z3 k! d' q: G1 s
prolonged administration for any response.4 f9 S& C, ^; Z* K
Alternately, topical testosterone does not depend upon tes-
: ^* z# ~, I9 ~+ qticular function and may provide a more constant level of  X& M0 f7 m7 m4 c  }8 B; h3 E- Z8 b
REFERENCES6 h/ N, W" n9 H
1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
! Q. a6 r4 W" V6 c3 c+ b/ ER.: The local application of testosterone cream to the prepub-
; f7 a, G) A7 j3 iertal phallus. J. Urol., 105: 905, 1971.
  j: d, x% o$ m2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
1 m- w( ?1 y+ |* |' k- t' xtreatment for micropenis during early childhood. J. Pediat.,# L* W5 V* O% o/ X0 u; S: _
83: 247, 1973.1 f) J+ r! h0 ~$ P  b+ p
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-( |+ y8 b. O9 V5 N! A; U7 }6 ^
one therapy for penile growth. Urology, 6: 708, 1975.
4 K' H. `0 @6 n+ y8 n) t4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
0 e% _+ n3 ?$ P/ cto 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
7 {' v3 S, Z% F. \" x+ [skin slices of man. J. Clin. Invest., 48: 371, 1969.
2 O7 L% {: J6 }5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth
% N& q6 I% ~; Bby topical application of androgens. J.A.M.A., 191: 521, 1965.
  ?% }) w8 M: e/ n9 l5 a" G  d7 Q$ p6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local4 P; H7 A  P8 ^0 }) U# K1 b
androgenic effect of interstitial cell tumor of the testis. J.6 H3 n- S4 J9 i8 N0 Z0 m/ }5 W5 Y
Urol., 104: 774, 1970.
" K/ [6 c. }+ F- ?4 P4 c& [7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-" K+ W5 A0 ?* ]" T5 Q
tion in the male genitalia from birth to maturity. J. Urol., 48:
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