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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 AND
# R/ S  m% ^4 ?8 I$ U* W' b) yGONADOTROPIN
4 a2 f8 b/ M4 b( W9 u7 hRICHARD C. KLUGO* AND JOSEPH C. CERNY( j4 a8 A5 @; ?. u, J/ w
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan7 y5 O$ L0 `! c+ z/ A
ABSTRACT: r0 s  H3 p4 G! [
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
1 J% |6 R  R% V% c# g5 x8 C% E' fwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-5 b. k0 u, X$ F
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone
5 r( D& R) E- i; t9 `cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent6 u3 L+ o, x0 |  i- y; ?
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent% |- V9 e7 e1 v6 K0 M6 a" `; ~
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average
7 q3 ]- m6 ^/ J" pincrease of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
# T0 l2 K1 S2 U1 b3 `, G3 ooccurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This5 Y& p" V" A( u1 `
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
; g3 Y9 K$ j% o1 dgrowth. The response appears to be greater in younger children, which is consistent with previ-
: t1 R% q* m' q- L9 G5 }ously published studies of age-related 5 reductase activity.
' a0 {' b4 s1 AChildren with microphallus regardless of its etiology will
: @; c: j- W  C8 H3 d4 crequire augmentation or consideration for alteration of exter-0 h* n! E5 X- a9 x0 ]5 V( a, x9 Z
nal genitalia. In many instances urethroplasty for hypo-4 r- v. G* M' v4 {
spadias is easier with previous stimulation of phallic growth.
% {2 A( G9 Q9 i( x1 iThe use of testosterone administered parenterally or topically
! _# O0 W) W% L1 T4 f. I6 ?has produced effective phallic growth. 1- 3 The mechanism of/ z# o  B4 c: E3 _9 R; g
response has been considered as local or systemic. With this
' K' W: n3 x' D0 @6 r. }- {in mind we studied 5 children with microphallus for response2 |  j! @$ `2 r6 K( ?+ [. J; c
to gonadotropin and to topical testosterone independently.: w( D5 w6 a8 G2 R) n/ j) {3 V
MATERIALS AND METHODS9 f! h4 N1 f% @- t- U% A. E
Five 46 XY male subjects between 3 and 17 years old were+ _; N9 Z. ~) q& r! t
evaluated for serum testosterone levels and hypothalamic
" V8 A1 k% K+ pfunction. Of these 5 boys 2 were considered to have Kallmann's( P6 ?$ G5 D+ o
syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
' E" b- c0 i; o( M( U# X: w* `lamic deficiency. After evaluation of response to luteinizing4 |- m  n; |  X  p/ r
hormone-releasing hormone these patients were treated with
1 B$ t6 w& ~' @, l1,000 units of gonadotropin weekly for 3 weeks. Six weeks
: {, S7 r0 u% Tafter completion of gonadotropin therapy 10 per cent topical, Z% ^; u8 [/ r( ?8 i& G7 i" O4 T
testosterone was applied to the phallus twice daily for 3 weeks.! \; T5 w( ^( X
Serum testosterone, luteinizing hormone and follicle-stimulat-
9 x7 ^  L0 S  N7 [ing hormone were monitored before, during and after comple-( H8 E2 l) M: w7 j* X8 W* u6 `, \( q
tion of each phase of therapy. Penile stretch length was
8 x  A! Y8 g  y( gobtained by measuring from the symphysis pubis to the tip of% p2 v" T$ q( n" F
the glans. Penile circumferential (girth) measurements were% D' W: `1 v7 D* ?4 H
obtained using an orthopedic digital measuring device (see& m- c0 P* c* e$ q
figure).
% D6 `# x+ `3 HRESULTS
0 c' h. [* Q$ J# j' H1 ^Serum testosterone increased moderately to levels between
: d6 N2 X! U: F6 h' K4 G50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-+ P) ^' s2 }4 }. d( M9 ]+ y2 l7 V0 J
terone levels with topical testosterone remained near pre-
0 A" K9 j/ N! a, f" otreatment levels (35 ng./dl.) or were elevated to similar levels
$ g7 C- h$ M( r7 v8 pdeveloped after gonadotropin therapy (96 ng./dl.). Higher9 s0 v! ]) V- G0 X2 Y' c
serum levels were noted in older patients (12 and 17 years old),
# p6 [& {& l2 f4 zwhile lower levels persisted in younger patients (4, 8, and 10
8 i& u; v6 |* U6 X# p$ M2 u# }. zyears old) (see table). Despite absence of profound alterations
" |7 X9 C& a- T: L. V1 W% hof serum testosterone the topical therapy provided a greater8 {9 P' ^  M; z' X* _" v, f; z- g
Accepted for publication July 1, 1977. ·
: y( m' i9 N: M" r* j1 [, eRead at annual meeting of American Urological Association,% P6 `8 n" _) k
Chicago, Illinois, April 24-28, 1977.8 i/ l5 K  x5 |/ Y
* Requests for reprints: Division of Urology, Henry Ford Hospital,
- W. r+ X7 r8 R) L. I, w' \2799 W. Grand Blvd., Detroit, Michigan 48202./ |" v; {& F( Y. d! h
improvement in phallic growth compared to gonadotropin.+ @# E4 @7 H2 ^: r2 R5 @
Average phallic growth with gonadotropin was 14.3 per cent
- ^: ?) p. i$ s7 a8 ~increase in length and 5.0 per cent increase of girth. Topical3 x5 e! e* V! }7 I7 i: ?# V
testosterone produced a 60.0 per cent increase of phallic length
5 j5 o0 e, j3 f5 h4 m& A: gand 52.9 per cent increase of girth (circumference). The) v! N- f) x( j  p* I% N3 d9 `/ ~. x0 r9 a
response to topical testosterone was greatest in children be-
9 J% E* [/ A4 \7 N- Q, Mtween 4 and 8 years old, with a gradual decrease to age 17( v" i' j6 i. e1 q) e5 P
years (see table).1 j7 j2 S5 L0 a- W7 l! j
DISCUSSION7 X2 X/ n' D+ d' r2 e  J/ ?5 B
Topical testosterone has been used effectively by other
- H6 `3 A' U0 r% |+ Dclinicians but its mode of action remains controversial. Im-" q$ d% w/ J( X' k6 V; E' ]
mergut and associates reported an excellent growth response2 ?3 p! e$ m' R: M; a; Q
to topical testosterone with low levels of serum testosterone,
! e% o( _: U$ j8 L1 P% wsuggesting a local effect.1 Others have obtained growth re-
9 ?& I5 ~' x" c, X- d# X2 ssponse with high. levels of serum testosterone after topical; L- |, Z/ b3 h3 A2 y
administration, suggesting a systemic response. 3 The use of, X& D6 c+ h: ?2 p" X, f9 q
gonadotropin to obtain levels of serum testosterone compara-
! D" X  B) p: ]( p( Dble to levels obtained with topical testosterone would seem to
7 m- h% @4 u  B, V! }provide a means to compare the relative effectiveness of9 `! W) B. v: r2 _
topical testosterone to systemic testosterone effect. It cer-2 g2 g. Y( [9 g8 o- D& A5 K2 f
tainly has been established that gonadotropin as well as par-
% Z0 Z$ N2 m7 _, oenteral testosterone administration will produce genital
4 N- ^$ g8 R. ]" ygrowth. Our report shows that the growth of the phallus was
$ C* n- U$ j* Vsignificantly greater with topical applications than with go-9 u  t" p: v" j
nadotropin, particularly in children less than 10 years old.
8 U8 K& s" E" G; H1 gThe levels of serum testosterone remained similar or lower8 I, h" h8 q4 _+ \  m& t( F- n
than with gonadotropin during therapy, suggesting that topi-  X8 d$ E! Q# j9 C5 ~
cal application produces genital growth by its local effect as
9 T: w- M$ L! L3 uwell as its systemic effect.
4 {6 b) N  M, u$ [' e+ T+ ^Review of our patients and their growth response related to
# n5 z. b) E9 b5 i0 Wage shows a greater growth response at an earlier age. This is
  I# ~8 s& H9 _6 E7 Z& L  D7 V# V$ Gconsistent with the findings of Wilson and Walker, who
) K- q3 q  Z) V  t2 H# xreported an increased conversion of testosterone to dihydrotes-
3 Z+ r9 e" I/ w4 _! ~+ y/ btosterone in the foreskin of neonates and infants.4 This activ-
. `% f4 R# y/ O  t7 i0 D; r$ N/ \8 dity gradually decreases with age until puberty when it ap-4 r; E# I) V) V! C% m* p2 l
proaches the same level of activity as peripheral skin. It may0 i0 F5 C2 ~' `' n; H
well be that absorption of testosterone is less when applied at
# k& \! ?0 Y) {; O0 _$ |- @9 Van earlier age as suggested by lower serum levels in children2 r( x$ g( k5 t# v( |6 \/ S: H
less than 10 years old. This fact may be explained by the/ v2 d7 {& o+ v/ d( F" Q# r5 w9 D
greater ability of phallic skin to convert testosterone to dihy-
% G, o- b$ ?' V* `7 A4 d' j! Odrotestosterone at this age. Conversely, serum levels in older
* Z# U# _( R( O7 ^" k; g# }/ ?patients were higher, possibly because of decreased local
" b4 \7 f. \3 r. E667
$ ]2 H, I2 s2 `, z* S8 [668 KLUGO AND CERNY
5 K. Y- x- }+ i8 Z" N, @9 Y  a5 BPt. Age  x- b5 W6 v+ e  [; {& O
(yrs.)
/ A1 L$ f% R) b6 }9 \Serum Testosterone Phallus (cm.) Change Length. o: w9 f- p+ N% m) b( w
(ng./dl.) Girth x Length (%)' C4 d$ H3 f' p* f; W
4
. |* ~% L$ Z) g4 w/ @) D8
4 I6 n3 E! i2 i1 {$ w, ^  m5 h# T! _10
5 j( z2 Q5 p# v% O6 o' `! @124 L& M2 Z, R5 @( O/ f- s& f
17( E5 P1 E' C) Z+ r1 t! i5 U
Gonadotropin% V) t! s  T" p$ ]) U1 B8 C
71.6 2.0 X 3 16.62 U0 h7 c& U0 _2 [4 m0 V
50.4 4.0 X 5.0 20.0. m1 k7 o  A2 K4 P
22.0 4.5 X 4.0 25.0
! {0 F' e; z) h7 y' e" m84.6 4.0 X 4.5 11.12 O' V$ `0 B; Y2 k4 r  z! k1 ]5 Q' T
85.9 4.5 X 5.5 9.0
4 g) {4 W; q3 bAv. 14.3- ~  c3 ?& M# q; q, {4 T4 o& @
4' y: |& ~. O) b5 {
8/ I+ N8 b# x8 A2 `# s% i2 T- u9 O
10# A$ ], a" z; E
12
, f4 T0 h$ U+ K! }4 r178 P1 C# C$ t+ `8 x! k! ^
Topical testosterone2 g* v$ A- b8 O7 R7 l& Q/ Q( i; m& ]
34.6 4.5 X 6.5 85# \6 m. a. \- ]4 B
38.8 6.0 X 8.5 70- \! ]) J; e% X. C3 D
40.0 6.0 X 6.5 62.5* z* A/ y$ D- _7 f( _
93.6 6.0 X 7.0 55.55 u3 \0 t1 P) J7 f7 b, z! Y: z# Z- f
95.0 6.5 X 7.0 27.23 C8 r; D% V# J
Av. 60.0. V5 R2 s5 U0 l, u3 g
available testosterone. Again, emphasis should be placed on
; `$ F5 F/ f. L* b0 gearly therapy when lower levels of testosterone appear to
/ f# O% ~0 e5 n- jprovide the best responses. The earlier therapy is instituted- `* r8 n" J2 B# \* c* O8 f
the more likely there will be an excellent response with low' r+ H" y" r- X/ s2 j
serum levels. Response occurs throughout adolescence as
4 A# M' X% B5 [/ w9 Q; z( ]+ A: enoted in nomograms of phallic growth. 7 The actual response
* }9 [8 f! T' n9 `( ^to a given serum level of testosterone is much greater at birth
& i0 w$ ]3 ^# p0 x0 cand gradually decreases as boys reach puberty. This is most
9 s- j/ h4 k7 X" R4 mlikely related to the conversion of testosterone to dihydrotes-& W2 n2 _# `- d6 N0 ?% b
tosterone and correlates well with the studies of testosterone
# L. e0 K/ C7 ~* l+ v" T) K  Qconversion in foreskin at various ages.
. y' w- ^+ z& U3 ?/ D; ZThe question arises regarding early treatment as to whether0 k1 s" F* K8 X, U
one might sacrifice ultimate potential growth as with acceler-8 M+ d( g3 G( ?2 {2 U0 s$ k
ated bone growth. The situation appears quite the reverse# M4 O! u8 w5 X$ K: s
with phallic response. If the early growth period is not used+ @# c2 q7 T( I6 O! J/ c
when 5a reductase activity is greatest then potential growth) a6 P$ O) d5 t& ]
may be lost. We have not observed any regression of growth
# t5 {4 ^7 y5 V% L# I& h3 U5 dattained with topical or gonadotropin therapy. It may well: s! a, S  q( R0 f
be that some patients will show little or no response to any
8 B4 a; K5 ]; Y9 }, Oform of therapy. This would suggest a defect in the ability to1 |3 R' I1 m6 t2 P. `
convert testosterone to dihydrotestosterone and indicate that
( v9 v: S/ c9 I! F" `/ i; r; Bphallic and peripheral skin, and subcutaneous tissue should
  `+ H- h, ^0 `4 p; Ybe compared for 5a reductase activity.6 c1 n4 F" j5 K8 ]9 d* @
A, loop enlarges to measure penile girth in millimeters. B,8 b- p9 S# `3 O' B! p" u& i& A5 o
example of penile girth computed easily and accurately.  V+ q3 X7 F: s1 ^! z( z1 T
conversion of testosterone to dihydrotestosterone. It is in this- x4 L3 A' r" W( j3 V2 [
older group that others have noted high levels of serum: Q3 o$ R: a8 v+ T0 R0 e3 o
testosterone with topical application. It would also appear
! N, M: S# ]3 }- n0 ?& X# kthat phallic response during puberty is related directly to the
  [1 G& I0 U/ u# B- pserum testosterone level. There also is other evidence of local$ u) _2 U6 U/ h6 I
response to testosterone with hair growth and with spermato-: t( f0 X" ^2 E& q. m, m. @9 a% t( `; k. |
genesis. 5• 6
; I: @4 ?- o: ~# ]1 p9 z6 q* WAdministration of larger doses of gonadotropin or systemic9 I- {# _- c1 s( A. Q0 s
testosterone, as well as topical applications that produce  u5 K5 U2 n) d- m
higher levels of serum testosterone (150 to 900 ng./dl.), will# X: d1 h- w# `1 |
also produce phallic growth but risks accelerated skeletal* h, H4 _1 j( s
maturation even after stopping treatment. It would appear
5 r. g! t" ~& l* m; Uthat this may be avoided by topical applications of testosterone
9 e. Q3 s. g( X! }6 L" {and monitoring of serum testosterone. Even with this control
7 G1 b3 H3 d9 wthe duration of our therapy did not exceed 3 weeks at any& @) Y  l9 b( A1 F
time. It is apparent that the prepuberal male subject may
  p7 H4 {6 j3 i5 }* s6 J/ x0 usuffer accelerated bone growth with testosterone levels near1 V$ \( t1 k8 b
200 ng./dl. When skeletal maturation is complete the level of/ H  O. R9 `% R' m/ S9 ?" ?; x8 d: x
serum testosterone can be maintained in the 700 to 1,300 ng./
3 Q' e* d8 Q( ddl. range to stimulate phallic growth and secondary sexual
: b5 t1 e' u: ^( hchanges. Therefore, after skeletal maturation parenteral tes-; |% Y% N8 [) _1 c4 J
tosterone may be used to advantage. Before skeletal matura-
/ J1 d, i6 a+ @4 Etion care must be taken to avoid maintaining levels of serum
, f1 d( s, x& }4 W9 f; Mtestosterone more than 100 ng./dl. Low-dose gonadotropin
$ O- i! @' M: I1 ?- {depends upon intrinsic testicular activity and may require
4 m* F' ~1 X4 H& O6 x) p7 C6 Aprolonged administration for any response.
/ f1 G/ x% ]' X# h. cAlternately, topical testosterone does not depend upon tes-: m3 P. C- G5 ]3 s- }! ]  v% a9 ^+ c
ticular function and may provide a more constant level of, y$ H8 q' S' m' J
REFERENCES$ S; N/ H8 Z% S+ F1 T: w$ z, b
1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
* X* ~- h% U% Y0 E1 TR.: The local application of testosterone cream to the prepub-
1 i# J! _! G- Vertal phallus. J. Urol., 105: 905, 1971.% G0 E8 ^' x0 r! c& e2 y
2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone3 G' |+ ^+ z" a, P% j/ f$ ]( y
treatment for micropenis during early childhood. J. Pediat.,
  j  q+ |! `& u. [3 |83: 247, 1973.
' I! _4 o9 t+ l7 P& I0 I: M8 U3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-. m' G" F# x" p4 X+ I% _
one therapy for penile growth. Urology, 6: 708, 1975.: n' q0 l* i8 m- G; L
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone, d$ N- v" A0 f0 A) w- u* G7 G2 v5 D5 ?/ e
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
# x$ @2 Q; Z( }: ^) Tskin slices of man. J. Clin. Invest., 48: 371, 1969.
. c6 S0 g& y, Z7 `0 K6 y5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth
5 `7 L+ t! H9 O4 E& [) Aby topical application of androgens. J.A.M.A., 191: 521, 1965.
7 l' b4 h1 y2 S& N( }: Q5 v6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
0 h4 l& d" T* C9 uandrogenic effect of interstitial cell tumor of the testis. J.
2 v; V& _( z; L+ S1 }- }: [Urol., 104: 774, 1970.
7 v& c5 M8 q- \5 ~- m: E7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-) v2 S$ P/ n9 l1 X7 G5 q6 A. F) G
tion in the male genitalia from birth to maturity. J. Urol., 48:
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