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鄉下的妹子太便宜,一次四個都要了[12P]

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大家好心情
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RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND: e9 |9 l2 G% j$ Z8 y- {
GONADOTROPIN4 _! E2 a  V* r5 A4 u3 Y
RICHARD C. KLUGO* AND JOSEPH C. CERNY* O1 B* @+ o! P
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan
* M& m# c% p" k3 \5 ?3 m  c# wABSTRACT2 s  A" }; G9 @, M
Five patients were treated with gonadotropin and topical testosterone for micropenis associated  P# g1 F: y" D5 j6 H& T, d
with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-
4 c) i, ^% N$ s* Ltropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone
6 x4 S) b/ Q" }: x7 p0 fcream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent& q' F  j- U2 h0 T3 s/ y5 p
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent% S# h5 ]8 d0 w. p" @4 H. w; Y
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average3 m1 e4 ]. D) _
increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
8 H. w) V0 l7 x* t6 P) {. E- n, Voccurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This
+ n4 o/ f% ^) @0 \& D) i& Mstudy suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
6 [, X  g5 K0 b+ T/ G$ `7 }growth. The response appears to be greater in younger children, which is consistent with previ-
  ?0 o0 g& ]: V9 Z9 Kously published studies of age-related 5 reductase activity.
7 U  o1 U1 \1 N) h/ M8 XChildren with microphallus regardless of its etiology will2 q2 C! M0 p# [& ~- b
require augmentation or consideration for alteration of exter-
* K( v0 U# g/ j* Nnal genitalia. In many instances urethroplasty for hypo-
# T5 m) I  E3 ?9 T( o; `& yspadias is easier with previous stimulation of phallic growth.$ F+ ~0 ]" n, F) @/ w, j8 j  n/ l7 \
The use of testosterone administered parenterally or topically
  A: Y, Q# f+ V* ]has produced effective phallic growth. 1- 3 The mechanism of/ e0 ]' R0 ~; R: G) J
response has been considered as local or systemic. With this
9 {9 p! v  p8 q% Rin mind we studied 5 children with microphallus for response
8 g. E& R$ b' ^2 Yto gonadotropin and to topical testosterone independently.
9 B: H2 O5 V$ VMATERIALS AND METHODS8 f+ U( [( {+ f8 ?) J& X2 C
Five 46 XY male subjects between 3 and 17 years old were$ o4 r6 ~$ _& i/ R8 A; V6 K# J
evaluated for serum testosterone levels and hypothalamic
4 y. D* Z; L/ f/ Ufunction. Of these 5 boys 2 were considered to have Kallmann's* s6 M  A# Q( y) w, S
syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
- A, z& l8 c- _# ~) g# Ulamic deficiency. After evaluation of response to luteinizing
$ X4 L1 u* Q2 ?. j, Ahormone-releasing hormone these patients were treated with
0 w. |6 z  C1 ^$ _0 G6 d1,000 units of gonadotropin weekly for 3 weeks. Six weeks
: B0 t* ~' o1 V1 E/ Jafter completion of gonadotropin therapy 10 per cent topical/ J# @' v/ ?$ p2 Q
testosterone was applied to the phallus twice daily for 3 weeks.
. X4 ~, @9 f% m" e; V+ p9 T- oSerum testosterone, luteinizing hormone and follicle-stimulat-) n' i0 [* h  _$ T- Q( t9 V" G
ing hormone were monitored before, during and after comple-' P. z( J! u4 R
tion of each phase of therapy. Penile stretch length was
! Y. S( _/ [. b' P1 J' eobtained by measuring from the symphysis pubis to the tip of
) j2 E8 n! M  M1 {/ r/ zthe glans. Penile circumferential (girth) measurements were
0 S  K  K9 J4 {obtained using an orthopedic digital measuring device (see
5 y8 n9 Q  h7 Ifigure).
2 s" h( r5 |( s+ N# Z( iRESULTS
* V: A- x! e7 W4 x) Q, ]- _& F  nSerum testosterone increased moderately to levels between
9 p' }/ q6 ]! o50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-0 y' i" x4 u  R% f+ [1 y
terone levels with topical testosterone remained near pre-
- Y4 Y& H% a: ^7 I" Z$ A, Itreatment levels (35 ng./dl.) or were elevated to similar levels
1 j* @1 F% t% F# f" @developed after gonadotropin therapy (96 ng./dl.). Higher
$ e8 z  ~& T, t2 @" Dserum levels were noted in older patients (12 and 17 years old),
6 F  l- c8 k8 S. d/ \, C% s: }" vwhile lower levels persisted in younger patients (4, 8, and 10! k1 o; e2 B; d8 t+ y  d5 J8 T# [
years old) (see table). Despite absence of profound alterations! f: [, Z! i  W
of serum testosterone the topical therapy provided a greater
6 w9 o2 v3 [1 A( rAccepted for publication July 1, 1977. ·
- C" a" D  g( C/ [8 T, ^Read at annual meeting of American Urological Association," o9 h' B# J/ x/ X( l" U. P
Chicago, Illinois, April 24-28, 1977.
9 O" y. H' K8 q2 h4 T$ f* Requests for reprints: Division of Urology, Henry Ford Hospital,
2 }6 B" t6 d9 H) s; ?2799 W. Grand Blvd., Detroit, Michigan 48202." W. w3 W# X4 H' t  l5 i
improvement in phallic growth compared to gonadotropin.* R) A! ~$ Y! U" m
Average phallic growth with gonadotropin was 14.3 per cent0 z* R( k; w  {1 ?2 m
increase in length and 5.0 per cent increase of girth. Topical* E2 q0 E, e7 _
testosterone produced a 60.0 per cent increase of phallic length
; b3 q) V& F- q$ z& Y; rand 52.9 per cent increase of girth (circumference). The
& U; Z$ B2 O( R' f8 yresponse to topical testosterone was greatest in children be-
" @9 X% |' ^1 T- E- Xtween 4 and 8 years old, with a gradual decrease to age 17
3 d- U" [2 {, H  s* |years (see table).- m- c" ?7 Y1 o
DISCUSSION! l2 O) c2 [9 P
Topical testosterone has been used effectively by other
: m- J7 O& ~3 ?  I- Bclinicians but its mode of action remains controversial. Im-  r; q- B+ g8 c3 r5 i! X. s4 Z
mergut and associates reported an excellent growth response
" A9 D* |" r! Z: U( A6 y$ t8 cto topical testosterone with low levels of serum testosterone,
) R# V7 V1 D; k% `1 C" Osuggesting a local effect.1 Others have obtained growth re-
# y) r9 {. r' m0 e6 O5 _# J5 W: K" v( ysponse with high. levels of serum testosterone after topical
8 Z( f/ ^2 Q9 M' w% k: j' Kadministration, suggesting a systemic response. 3 The use of
$ r# }) c! L6 w% p! wgonadotropin to obtain levels of serum testosterone compara-
1 {4 s. R/ }& n6 q; s+ g3 }ble to levels obtained with topical testosterone would seem to0 n9 j" h$ D& Y
provide a means to compare the relative effectiveness of4 W0 d. p4 J5 P# Y0 Q# k
topical testosterone to systemic testosterone effect. It cer-. [  ^3 K/ h1 v" S/ ]5 o( ?0 V
tainly has been established that gonadotropin as well as par-
6 t- `3 _4 g1 s9 Renteral testosterone administration will produce genital
7 m' D* {6 r. A5 \* J. a- \8 Kgrowth. Our report shows that the growth of the phallus was
" P: p" \- R) `% Y8 E+ M( u6 Osignificantly greater with topical applications than with go-
+ o! `- F, `) Xnadotropin, particularly in children less than 10 years old.
8 J" ?3 K' c- R" g& nThe levels of serum testosterone remained similar or lower
; t  V" i: k* j% Dthan with gonadotropin during therapy, suggesting that topi-- a4 Z6 q* y, H( P; _5 G
cal application produces genital growth by its local effect as5 T* Z3 c' U. D8 W  X
well as its systemic effect.; C$ k0 {) [' N$ @
Review of our patients and their growth response related to5 F7 b2 Z% N+ s# z( ]4 ?; [+ x
age shows a greater growth response at an earlier age. This is1 N" ]' u. S4 e% W3 _" S1 |
consistent with the findings of Wilson and Walker, who, A* Z3 Q3 q0 p& O, V) P' W- y$ Q
reported an increased conversion of testosterone to dihydrotes-! n" t  ?0 S1 c5 w. P
tosterone in the foreskin of neonates and infants.4 This activ-1 I7 w' v' ^% h$ W# ~
ity gradually decreases with age until puberty when it ap-/ W+ X% D. H7 L2 L: J
proaches the same level of activity as peripheral skin. It may, g/ X; X8 A: g' `& f. K
well be that absorption of testosterone is less when applied at0 l8 [$ r8 Z/ v  e" `7 N
an earlier age as suggested by lower serum levels in children* `1 D3 ?; X7 |; Q7 p
less than 10 years old. This fact may be explained by the. }( n1 j9 J! o+ T" L! G2 G5 }! `
greater ability of phallic skin to convert testosterone to dihy-
! {5 m3 z) k) f- m2 adrotestosterone at this age. Conversely, serum levels in older4 A& Z. D' |% ]. ]+ {4 T' I
patients were higher, possibly because of decreased local
! ?, K, w: O) N  k) Y% d667' H2 R- E4 @$ E+ z4 s' [
668 KLUGO AND CERNY
6 V0 j, C3 V/ ~' \# wPt. Age
7 N6 F2 P" q* R0 A6 |) |( {: h(yrs.). f5 O/ m& x- ^& d5 B
Serum Testosterone Phallus (cm.) Change Length
' B' v! O- c# @$ B/ a9 x(ng./dl.) Girth x Length (%)
) t3 y! M- p, k3 H9 q4 T. r4
# r; g: v. m: _3 ~; k8
& L  H; u  K6 K10
* X& h1 {6 U, [$ T6 d: t126 i! p( D! r, y6 T6 I7 {
17
! [6 e  H  Y2 w- H" U4 pGonadotropin
$ T$ v. E) i& k& k71.6 2.0 X 3 16.6
4 o. n0 j  S9 y: a# A2 D50.4 4.0 X 5.0 20.0% A  F8 O8 M# g. Z1 ], V5 h
22.0 4.5 X 4.0 25.0
. a/ X* ^" h; g, Y' s84.6 4.0 X 4.5 11.1
, K$ q+ [! K, k* L" Z6 d- {; p  ]85.9 4.5 X 5.5 9.08 {8 @/ r2 B, F# J3 y7 K
Av. 14.3
9 b) ]; ?" D" w" g1 ?4+ I& w  h% p1 N+ {
8
& _" Z7 y- O' b+ m8 ?, k, D( s10
5 c  n- Q# c( B( i+ Z9 |" i# k120 `$ I5 [, `( T* J3 ]3 h
17
! z, h! B6 K2 ]5 s) y# |Topical testosterone
3 G0 b5 z8 p8 L+ c- X. U34.6 4.5 X 6.5 85" Q) X4 T+ [4 e7 n7 ]% Y# N& u9 A
38.8 6.0 X 8.5 70
# B9 i+ o5 u6 v6 K. [40.0 6.0 X 6.5 62.50 Z3 b+ S+ L7 l% P9 ^; N
93.6 6.0 X 7.0 55.5; l! Q2 H: L$ _( J
95.0 6.5 X 7.0 27.2
1 s* s9 i2 r( A0 S  n* rAv. 60.0; [3 ]1 s5 v/ u* \7 n" f/ S2 p
available testosterone. Again, emphasis should be placed on8 ^/ i& V4 a1 X$ s7 {
early therapy when lower levels of testosterone appear to
& j* ], i: l1 y( ]; V5 V! Q9 Z5 Sprovide the best responses. The earlier therapy is instituted& k3 O4 k  ^, e) m( @5 I  F1 ^
the more likely there will be an excellent response with low
5 Z+ O) D& X# v; Rserum levels. Response occurs throughout adolescence as
( L0 A, i; }, l1 N) Fnoted in nomograms of phallic growth. 7 The actual response
6 x1 M+ C  O3 A. s! hto a given serum level of testosterone is much greater at birth
4 \8 g/ \; C4 e6 Yand gradually decreases as boys reach puberty. This is most! W; d  |5 W: `: z
likely related to the conversion of testosterone to dihydrotes-
6 o. O  \2 S. r& N7 m$ Jtosterone and correlates well with the studies of testosterone
5 N- Z5 C% P& D- H/ d9 vconversion in foreskin at various ages.
( k) p" M8 M) w8 D- h' J, ZThe question arises regarding early treatment as to whether
' n! n- T0 |0 \one might sacrifice ultimate potential growth as with acceler-1 T6 J0 J& p. J" X
ated bone growth. The situation appears quite the reverse
6 @0 k0 E* n9 c- J( F  b, w  n9 J0 vwith phallic response. If the early growth period is not used, ^+ V3 a! M, R/ L5 u0 J
when 5a reductase activity is greatest then potential growth% [( b2 o* Y1 w7 U9 [2 P
may be lost. We have not observed any regression of growth
4 o9 E" M9 ^4 ^7 N1 D& A; lattained with topical or gonadotropin therapy. It may well
/ ^! w! ?/ g5 V0 d6 lbe that some patients will show little or no response to any/ a' D6 I- B- P
form of therapy. This would suggest a defect in the ability to
' J# U' S2 z$ P- T6 i7 bconvert testosterone to dihydrotestosterone and indicate that; Y/ t; y* w& Q0 t4 N6 P
phallic and peripheral skin, and subcutaneous tissue should5 \: l& d1 t; @+ j& a) J) i
be compared for 5a reductase activity.
$ y0 |( {9 s3 ~* F, _% _A, loop enlarges to measure penile girth in millimeters. B,
6 ^5 J; G) z  ^7 R, Aexample of penile girth computed easily and accurately./ I0 L8 R3 ]% q$ [& l
conversion of testosterone to dihydrotestosterone. It is in this
' t5 j& p2 p( `) C( Golder group that others have noted high levels of serum
$ [& ]& {% ?/ U" [$ h7 mtestosterone with topical application. It would also appear0 g0 j" |: D* d3 D5 M3 y2 Y. ?
that phallic response during puberty is related directly to the% b- w# C4 V! a! s
serum testosterone level. There also is other evidence of local7 c& B9 a8 |' G" D. a. n
response to testosterone with hair growth and with spermato-
( X' o$ j! i5 M) v& e- x* Qgenesis. 5• 6+ A, @) C# [* ^6 f' n
Administration of larger doses of gonadotropin or systemic
, H/ e, w% U, S/ F8 l& Q3 Jtestosterone, as well as topical applications that produce
' H  \0 ]! w9 g' y5 l) Ehigher levels of serum testosterone (150 to 900 ng./dl.), will/ t/ I: E4 N/ z8 P7 R  m
also produce phallic growth but risks accelerated skeletal, a# V$ Y7 z8 z% z+ I9 g
maturation even after stopping treatment. It would appear
6 X& t2 f, y9 ]$ k6 _4 hthat this may be avoided by topical applications of testosterone. U9 x! x. n- f* k5 Q# g* C6 v
and monitoring of serum testosterone. Even with this control
7 R# `9 Z' E2 m3 ^# @, d6 ^- v6 J" Zthe duration of our therapy did not exceed 3 weeks at any6 z- ?) T( m/ E+ r9 y) ^
time. It is apparent that the prepuberal male subject may) T2 R2 l4 _0 L; b* o, i
suffer accelerated bone growth with testosterone levels near$ d. [! Q5 G; Y. Y+ d  P, `8 N
200 ng./dl. When skeletal maturation is complete the level of
1 k( u6 g0 }; h8 Q3 Q% Kserum testosterone can be maintained in the 700 to 1,300 ng./5 l; T$ [' b0 J! W5 K" R+ @
dl. range to stimulate phallic growth and secondary sexual# j; J3 J" F5 C2 P; ?: Q$ `
changes. Therefore, after skeletal maturation parenteral tes-: k' ?) `" l; V; Z% j
tosterone may be used to advantage. Before skeletal matura-
! a: z/ [8 O9 T' @% l( i0 Ftion care must be taken to avoid maintaining levels of serum; q* {5 M8 R4 Y  I4 }& |+ {( g# y
testosterone more than 100 ng./dl. Low-dose gonadotropin
8 n' b( [8 |$ Q) K- P  X1 [3 ldepends upon intrinsic testicular activity and may require% P( L; k0 p! R& j/ A
prolonged administration for any response.
5 J1 p0 u; V. J2 W1 \! v" T. O' \8 VAlternately, topical testosterone does not depend upon tes-" U! \3 R3 |: F! T" C+ b& k; _  Z
ticular function and may provide a more constant level of
* z7 ~, o  F0 `: ZREFERENCES/ m. t! \( }1 s: c% w
1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
  @  M( U' ?8 C4 Q9 wR.: The local application of testosterone cream to the prepub-
) B* c  V7 P/ l/ c) p. e8 i' k" W/ ]$ M4 hertal phallus. J. Urol., 105: 905, 1971.4 C- H; Y/ ^- P6 J' E& M& t
2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone2 S$ A" S2 I' D4 T
treatment for micropenis during early childhood. J. Pediat.,: P0 q0 @1 Y2 i1 K+ d4 U' z! R
83: 247, 1973.
: i$ Q4 X" V6 p' h  u3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
! s7 K; G$ i. O& Y, G" g5 rone therapy for penile growth. Urology, 6: 708, 1975.% g" c( W) T1 p: q# |
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
) v5 ]6 Q1 H8 Jto 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
" x; a0 ]; D8 Z' |5 lskin slices of man. J. Clin. Invest., 48: 371, 1969.4 x9 G* X8 B* {( B) x4 n: [, w
5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth5 g0 t& A1 {: f3 S8 j/ V. N
by topical application of androgens. J.A.M.A., 191: 521, 1965./ j4 ~' e! h! l& K2 Z2 K1 r
6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
* C. |( B0 l- B6 d" e5 Jandrogenic effect of interstitial cell tumor of the testis. J.
- T5 G: i  q" ]Urol., 104: 774, 1970.' ~' v; l& e1 D1 j+ F+ r
7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-
6 H9 z: \) n& l$ i! etion in the male genitalia from birth to maturity. J. Urol., 48:
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