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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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RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND9 ~* |, u  J/ D- {) ~, Y
GONADOTROPIN
& I5 q' T9 b* i- RRICHARD C. KLUGO* AND JOSEPH C. CERNY) z% p9 Y- E! A, }
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan: i: J4 v) t, D) Z- z
ABSTRACT% P* c5 X& ?8 I; N8 l; k( Z$ B
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
0 E  F) Z6 C8 ?with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-
6 i* F2 S+ U3 V0 htropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone
/ D4 O  V5 _! [$ f- C- Ncream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent. c" F, E+ S4 ~
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent* e( y/ S4 q, V# S* Y
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average
: [. ?( i/ {4 h% Pincrease of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response+ G! [& K1 ?+ J* F/ X. K2 L
occurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This
  H  U3 u( Y8 q- _: B1 H$ H; lstudy suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
4 q6 E' C& A% }) {growth. The response appears to be greater in younger children, which is consistent with previ-
, f4 _# I# _0 `5 z. Zously published studies of age-related 5 reductase activity.
  v* z# L" A5 s/ H/ b7 YChildren with microphallus regardless of its etiology will
& G$ ~! S+ z% d* O8 E5 Arequire augmentation or consideration for alteration of exter-
. U7 b, M" k6 {7 g/ S$ F0 bnal genitalia. In many instances urethroplasty for hypo-
  Y- M$ \9 S0 U( ]7 ?spadias is easier with previous stimulation of phallic growth.
& |1 |- f; A3 B, NThe use of testosterone administered parenterally or topically# T$ b) W9 [- i+ U& Q$ B( b+ a1 s
has produced effective phallic growth. 1- 3 The mechanism of9 g. t! E, I1 x0 H  P6 }3 z2 W
response has been considered as local or systemic. With this
4 i* l8 I9 @; \5 {- O/ l+ ain mind we studied 5 children with microphallus for response
: r5 g. Z1 O# L& r8 z; Q& ato gonadotropin and to topical testosterone independently.
4 \0 Z* B* [0 o' Z$ t" S! P5 KMATERIALS AND METHODS
5 T% o2 C" A) U7 Z1 KFive 46 XY male subjects between 3 and 17 years old were' a$ U6 M0 P1 I0 ?
evaluated for serum testosterone levels and hypothalamic
4 h" H. F- Q' \4 L0 |, t6 lfunction. Of these 5 boys 2 were considered to have Kallmann's
- t4 n' A, x: u' h7 Zsyndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-8 p; V1 ~: t' E# ?" I- b
lamic deficiency. After evaluation of response to luteinizing
- j; X" b2 `' p4 V7 yhormone-releasing hormone these patients were treated with
9 \+ H4 C% E9 p+ J3 b; [8 X1,000 units of gonadotropin weekly for 3 weeks. Six weeks
$ K. ~$ \! h# P! s& T5 B- Z- wafter completion of gonadotropin therapy 10 per cent topical: e* O. G7 ~# G8 [& z, t. r
testosterone was applied to the phallus twice daily for 3 weeks.
6 R- Q, f: P/ \$ ~5 u! }Serum testosterone, luteinizing hormone and follicle-stimulat-4 T8 I5 I; {) a* v% j/ C) W1 z) K
ing hormone were monitored before, during and after comple-4 S3 n7 w% n' `' K# L4 P& M' H
tion of each phase of therapy. Penile stretch length was
! ]4 }8 |  k3 b. V7 S9 Xobtained by measuring from the symphysis pubis to the tip of
8 `* f9 h6 F7 f) j- w/ Dthe glans. Penile circumferential (girth) measurements were
: a6 P3 F0 P# K- c/ A9 Xobtained using an orthopedic digital measuring device (see
7 G, k$ w. X8 P0 f% bfigure).
7 H5 b5 e4 Y7 V0 {/ U8 Q) ]) g% J3 ERESULTS
1 v& w. d* Z6 N$ T& i4 ^( [2 m" HSerum testosterone increased moderately to levels between
4 c5 n! H, m0 C/ x4 F! j8 f50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-
: p1 C4 z7 p9 u: h3 P% b3 s& U) tterone levels with topical testosterone remained near pre-
9 }7 o9 [9 q& N1 s# Ctreatment levels (35 ng./dl.) or were elevated to similar levels
7 h& i- e( l" F& B% h/ q. Q- [0 fdeveloped after gonadotropin therapy (96 ng./dl.). Higher6 p$ G- L7 r8 b; U1 S! e
serum levels were noted in older patients (12 and 17 years old),
5 ^* x- P0 m# e. O; m8 B/ G# O8 h% C$ Mwhile lower levels persisted in younger patients (4, 8, and 10% G. B2 B/ G8 ?0 @0 s; H& i
years old) (see table). Despite absence of profound alterations
( x: f( u2 Q; C) O6 hof serum testosterone the topical therapy provided a greater
4 N" B9 N/ B! ~0 Z9 N& |Accepted for publication July 1, 1977. ·! k' r5 J2 H2 T7 a
Read at annual meeting of American Urological Association,
3 l& P5 v/ [9 U* p0 j0 KChicago, Illinois, April 24-28, 1977.6 V& `% J  d8 @
* Requests for reprints: Division of Urology, Henry Ford Hospital,0 ?" V7 Y' f0 P# ?" T6 b  _) H
2799 W. Grand Blvd., Detroit, Michigan 48202.  u/ I( U; |% m4 ?
improvement in phallic growth compared to gonadotropin.
) I7 e. p% U; W) K% d- E4 uAverage phallic growth with gonadotropin was 14.3 per cent! A- [" b/ }  \9 j7 D. M# j
increase in length and 5.0 per cent increase of girth. Topical
+ G: w* o1 F/ P; w8 L9 z/ Ntestosterone produced a 60.0 per cent increase of phallic length
$ Y7 D8 d2 X( zand 52.9 per cent increase of girth (circumference). The$ I* l/ Y' w7 z# }/ }! u3 A: R' S! d
response to topical testosterone was greatest in children be-
% z. k/ I5 b, X1 v/ E; jtween 4 and 8 years old, with a gradual decrease to age 17( T  ?- ^+ ]0 I0 Z4 U
years (see table).3 M1 K7 B# `% E; E  t# }
DISCUSSION
' s8 q4 p: B/ NTopical testosterone has been used effectively by other& d4 R/ ]6 L" @3 C4 M1 I- |
clinicians but its mode of action remains controversial. Im-5 _5 V  S2 @2 x% G+ I
mergut and associates reported an excellent growth response
; W0 V9 Z, a+ T! u: |* m! Q4 gto topical testosterone with low levels of serum testosterone,
4 S) n, C4 A. l- U- O: csuggesting a local effect.1 Others have obtained growth re-
( [$ N, g, \5 ^& G% u( msponse with high. levels of serum testosterone after topical5 I2 y4 _2 V$ [* a& |% i
administration, suggesting a systemic response. 3 The use of
6 s2 S5 ^' f* a4 \. c1 `  _gonadotropin to obtain levels of serum testosterone compara-( _+ S. @: K) N# A; W7 u4 d1 D
ble to levels obtained with topical testosterone would seem to
6 `% z4 E/ n# \1 @: c3 }provide a means to compare the relative effectiveness of! e1 l, _, ]7 a5 a1 O
topical testosterone to systemic testosterone effect. It cer-* f) O, i3 c+ V; p
tainly has been established that gonadotropin as well as par-
* ~; F7 O7 v$ b5 A' p9 B4 Denteral testosterone administration will produce genital9 [  V6 }5 x6 A8 v& V
growth. Our report shows that the growth of the phallus was1 g6 d2 O: z9 J( M( H
significantly greater with topical applications than with go-5 ?. F, R  g% y! C  N9 `9 S
nadotropin, particularly in children less than 10 years old.
% p% p" c" C* ~; UThe levels of serum testosterone remained similar or lower. D* S! m. L# o1 r, N
than with gonadotropin during therapy, suggesting that topi-% \, K# F: e' @% B; i
cal application produces genital growth by its local effect as
- ], z- h4 A. E  f7 rwell as its systemic effect.
) V% o6 @% w" j1 @: `6 X, hReview of our patients and their growth response related to
8 q; p! i  N6 uage shows a greater growth response at an earlier age. This is
8 ?/ B/ a/ K+ B  u6 {9 h7 u; b" R- Oconsistent with the findings of Wilson and Walker, who
) I+ q  @( {7 j3 x) r% @reported an increased conversion of testosterone to dihydrotes-
0 N' a  e# J8 I( i# g  I) N: ztosterone in the foreskin of neonates and infants.4 This activ-
$ _: k: m! |7 nity gradually decreases with age until puberty when it ap-+ b$ Q4 T) V: J; T# T
proaches the same level of activity as peripheral skin. It may6 c! @" C* g5 s& `. i( ?
well be that absorption of testosterone is less when applied at
+ |2 ?2 Q: t3 Jan earlier age as suggested by lower serum levels in children
# m: l; y, c2 ]" s# Q8 K) v3 {less than 10 years old. This fact may be explained by the# I* Y  {# w( ]
greater ability of phallic skin to convert testosterone to dihy-
& a! f$ O9 E1 @1 k* [drotestosterone at this age. Conversely, serum levels in older0 X, M. Z! H. `; O
patients were higher, possibly because of decreased local
$ u6 I) F  E  O, ?6676 u, Z/ [4 a. Z7 r1 N. r2 A# E. K
668 KLUGO AND CERNY
2 ]- x" }' X8 X$ e* {Pt. Age; Y( b/ Q7 {0 A( N
(yrs.)* T) u7 b! u( P' d1 z
Serum Testosterone Phallus (cm.) Change Length
( d7 q: G6 }7 c) D+ P: P(ng./dl.) Girth x Length (%)7 V% C. {1 i1 w
4
6 G0 J0 n8 m2 i% y4 Y8; U& z: u5 a; L, p7 K* Z
10
7 W6 K$ `" u7 \" V% s  |12" t# G/ P, ]: _8 \" f5 K
17
- u! R: P$ w  }! JGonadotropin
9 d: e# G8 \! O71.6 2.0 X 3 16.6, G1 w1 U9 A4 y; h9 f
50.4 4.0 X 5.0 20.0  k+ o% N( F9 B; l* w
22.0 4.5 X 4.0 25.0
1 V# ]' @  m6 l84.6 4.0 X 4.5 11.1
2 K; ]" u; O1 M4 _. V- p$ W! H$ b2 J" S85.9 4.5 X 5.5 9.0/ a  k6 Q! t. G  T. c( o% @
Av. 14.3
; C. |) R# i8 V2 Q- S" H4 m49 D% J3 B" @# H  C" }5 E. O; o
87 p  ~5 z6 k2 L, B( w
10
9 E1 u7 f9 [# f& V# W% O121 f7 @2 W: D; F% @/ Z. z
17, [4 O$ P5 w4 l! d
Topical testosterone
2 S1 t0 i/ Q6 S; s* _34.6 4.5 X 6.5 85- \1 k" v8 P7 f' ~; v
38.8 6.0 X 8.5 70
- `6 `4 y% ]. O5 B! T40.0 6.0 X 6.5 62.5
" F2 Q) z: d7 ~9 C' T! l93.6 6.0 X 7.0 55.5& V! N! f! E- E! g3 t, T5 ^
95.0 6.5 X 7.0 27.2) Q0 b3 n, B  w% Q4 q
Av. 60.0
0 @7 x7 V2 s# ]8 c5 {0 _$ k$ _3 B$ ~( bavailable testosterone. Again, emphasis should be placed on1 P1 D( `2 e7 N/ d5 T. H' S
early therapy when lower levels of testosterone appear to) N; I; y  t' P) u$ s) x
provide the best responses. The earlier therapy is instituted
8 A' a7 s6 s8 Zthe more likely there will be an excellent response with low
0 s- F+ h  s7 [2 x8 Cserum levels. Response occurs throughout adolescence as, u# H6 U. s' N6 w
noted in nomograms of phallic growth. 7 The actual response
/ T. k" h7 f! c% G  @to a given serum level of testosterone is much greater at birth
0 ^1 o$ X7 s! B1 O+ ~and gradually decreases as boys reach puberty. This is most: m8 t5 Z; H9 A" P9 x* i
likely related to the conversion of testosterone to dihydrotes-2 F6 O2 G" W  E  Y1 _3 h/ L5 U
tosterone and correlates well with the studies of testosterone! _, l4 z% {2 s" N# X4 u
conversion in foreskin at various ages.0 @( Q4 k5 ?4 ]& ~4 H
The question arises regarding early treatment as to whether& f) E; p7 z& F$ B
one might sacrifice ultimate potential growth as with acceler-6 q6 d$ p1 y$ _
ated bone growth. The situation appears quite the reverse
2 z, q2 ?2 \1 Y$ L, Hwith phallic response. If the early growth period is not used/ ~( W$ O* m, \! V6 `9 M
when 5a reductase activity is greatest then potential growth: u- d- N; k3 p2 K  ]3 o( ?
may be lost. We have not observed any regression of growth
9 |# U: A& a% G3 K& q! vattained with topical or gonadotropin therapy. It may well6 d9 @& l% n3 x* m3 T( x- |
be that some patients will show little or no response to any; c& H# K) p; @  S' `  P$ }
form of therapy. This would suggest a defect in the ability to
; i2 K1 b$ W  X% S; d( uconvert testosterone to dihydrotestosterone and indicate that% d- O  P3 B$ x% z: m
phallic and peripheral skin, and subcutaneous tissue should
4 r8 V) F/ H% v! N$ ?& Ibe compared for 5a reductase activity.$ b+ X8 W% o; v0 s0 i8 g5 K! j( ?
A, loop enlarges to measure penile girth in millimeters. B,
3 r* `& Z1 h( T6 r4 N; s8 Xexample of penile girth computed easily and accurately.. U8 o  h2 g9 v
conversion of testosterone to dihydrotestosterone. It is in this" ]2 t! _, D7 _$ V
older group that others have noted high levels of serum6 Z. h  j# n9 @* U1 S
testosterone with topical application. It would also appear/ p% Y, z- s# m9 M0 ^2 j) k
that phallic response during puberty is related directly to the$ h; Z0 x+ g$ k7 i
serum testosterone level. There also is other evidence of local7 x* t# f0 E+ M( d$ @
response to testosterone with hair growth and with spermato-- a, o; n1 ?( ]& R) n4 V! c- }
genesis. 5• 67 c- V/ N5 T0 f, y
Administration of larger doses of gonadotropin or systemic
! }. r* Z6 n' X1 e' v  utestosterone, as well as topical applications that produce) p! X, H+ G+ A! ?' h8 S' V: K
higher levels of serum testosterone (150 to 900 ng./dl.), will1 k9 l; K, |$ h! v7 g' s
also produce phallic growth but risks accelerated skeletal
3 y. _* q& m  \5 c9 G$ ~/ |maturation even after stopping treatment. It would appear/ O5 k/ ~/ d3 f0 s1 ^4 W) X
that this may be avoided by topical applications of testosterone, j$ \! S+ l% Y" l
and monitoring of serum testosterone. Even with this control! ^( D6 x5 Z8 d( N# y) H
the duration of our therapy did not exceed 3 weeks at any; ~- L6 G8 G; Q' |' r
time. It is apparent that the prepuberal male subject may( I8 V$ ]3 ]" t
suffer accelerated bone growth with testosterone levels near, ?0 z- U+ [; w. e5 R( }2 H) _$ u6 r
200 ng./dl. When skeletal maturation is complete the level of
6 B1 I/ \: m$ i- t/ R* {serum testosterone can be maintained in the 700 to 1,300 ng./3 `/ e/ R0 y& D% X. \
dl. range to stimulate phallic growth and secondary sexual
. ?( {5 J  E1 w7 Pchanges. Therefore, after skeletal maturation parenteral tes-4 k- l, F% d* t9 I" a; Q% s* _
tosterone may be used to advantage. Before skeletal matura-
4 p" [, z  t$ O4 t/ X  [0 ption care must be taken to avoid maintaining levels of serum
8 a0 {0 r; N4 Z6 Q' v1 Itestosterone more than 100 ng./dl. Low-dose gonadotropin" `3 F; z2 r& q2 `- t
depends upon intrinsic testicular activity and may require% v; X7 a4 P3 x7 O4 H
prolonged administration for any response.
1 E! d% C6 g4 @8 G% EAlternately, topical testosterone does not depend upon tes-
7 \1 ~2 H  N2 v6 fticular function and may provide a more constant level of
2 C2 K- k/ K0 d# _: q! A7 D* n# \REFERENCES$ S3 U' U% M3 Z0 W$ P7 ~2 R
1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
  `8 n- e& X& N& i" T, uR.: The local application of testosterone cream to the prepub-: l: a/ m6 e! U: X6 Y
ertal phallus. J. Urol., 105: 905, 1971., z& F  Y. \( X
2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
& n  M# E- H: Qtreatment for micropenis during early childhood. J. Pediat.,
% g* f" w- H  \8 r) Z& p1 O83: 247, 1973.% N! l- H# ]% m1 g  I
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-1 ?9 ?& u# `4 O5 A
one therapy for penile growth. Urology, 6: 708, 1975.; K. `, i0 }( b" |/ B6 F4 k
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone. h+ P- h# L9 l9 k
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by% H' x8 K1 b" R& g
skin slices of man. J. Clin. Invest., 48: 371, 1969.
% H  j6 m( T( L5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth6 `3 T$ r1 h7 |) ]. p  Q5 L; U
by topical application of androgens. J.A.M.A., 191: 521, 1965.' P0 m- |4 Q* v2 X2 [
6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local* `9 f/ u% T% @, O) \
androgenic effect of interstitial cell tumor of the testis. J.
1 P# V7 v+ {" HUrol., 104: 774, 1970.
" ?/ o# C, L9 e2 ~+ F5 z, m5 |7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-7 N; R$ o. E( D" ^, n4 k1 g& h% `
tion in the male genitalia from birth to maturity. J. Urol., 48:
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