鄉下的妹子太便宜，一次四個都要了[12P]

stcar

good good support

dadiaoguang

谢谢

wyp5888

好图，谢谢分享。

wudaode

11

xxp13136

大家好心情

weihai

果您要查看本帖隱藏內容請

q2367975099

看看再说

金正恩

将计就计

zidantiao

真的很不错

kaifka

RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND
GONADOTROPIN
RICHARD C. KLUGO* AND JOSEPH C. CERNY
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan
ABSTRACT
2 f6 H+ P, s; E/ X4 E8 v5 |% r& DFive patients were treated with gonadotropin and topical testosterone for micropenis associated
/ Q* G7 r/ L( \. `; dwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-
5 ^$ K# }/ P  Btropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone
' r( E0 s3 y: I1 t* j% K, {cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average
increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
occurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This
* |  C' q3 O) I/ U; Wstudy suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
" y' l- E( b- ~1 r% @' ~growth. The response appears to be greater in younger children, which is consistent with previ-
ously published studies of age-related 5 reductase activity.
. B. a4 J* p# e, G, C1 z" T; WChildren with microphallus regardless of its etiology will
3 D) b  X. n, I3 Z0 ^require augmentation or consideration for alteration of exter-
nal genitalia. In many instances urethroplasty for hypo-
spadias is easier with previous stimulation of phallic growth.
The use of testosterone administered parenterally or topically
has produced effective phallic growth. 1- 3 The mechanism of
- F& {  W: O- f0 M$ i" O3 Uresponse has been considered as local or systemic. With this
in mind we studied 5 children with microphallus for response
, e1 S* l5 |4 ?9 d/ q$ ?7 I8 o4 `to gonadotropin and to topical testosterone independently.
MATERIALS AND METHODS
4 M% @, x) g, X7 j" b. k# \) n; J0 A/ cFive 46 XY male subjects between 3 and 17 years old were
% F# r6 z- A$ ?' R( u9 i: v  {evaluated for serum testosterone levels and hypothalamic
function. Of these 5 boys 2 were considered to have Kallmann's
! P0 r6 }3 o/ ^5 ^; z' zsyndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
lamic deficiency. After evaluation of response to luteinizing
& ^% M& e* y% ^% W4 m3 Qhormone-releasing hormone these patients were treated with
1,000 units of gonadotropin weekly for 3 weeks. Six weeks
after completion of gonadotropin therapy 10 per cent topical
& X, f# Y' i* [' ]testosterone was applied to the phallus twice daily for 3 weeks.
& x/ p7 N* }: J$ [2 F# M! xSerum testosterone, luteinizing hormone and follicle-stimulat-
7 S3 K- s% O* E# y- S- jing hormone were monitored before, during and after comple-
tion of each phase of therapy. Penile stretch length was
obtained by measuring from the symphysis pubis to the tip of
9 O7 _. G8 z" X+ P1 R& \the glans. Penile circumferential (girth) measurements were
' g0 Y" C. Y( ^7 U: H/ l! Iobtained using an orthopedic digital measuring device (see
( D0 S' Q  m% C1 Y- N8 ~' M; v* wfigure).
RESULTS
Serum testosterone increased moderately to levels between
50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-
) J! H% J$ c$ H7 kterone levels with topical testosterone remained near pre-
treatment levels (35 ng./dl.) or were elevated to similar levels
% N2 G" e% b" @$ rdeveloped after gonadotropin therapy (96 ng./dl.). Higher
. O+ ?. a8 |& z2 Bserum levels were noted in older patients (12 and 17 years old),
* C1 O6 j# K0 C0 h7 Swhile lower levels persisted in younger patients (4, 8, and 10
years old) (see table). Despite absence of profound alterations
of serum testosterone the topical therapy provided a greater
Accepted for publication July 1, 1977. ·
Read at annual meeting of American Urological Association,
2 |2 t  U# R) s9 h) t) f& V' |Chicago, Illinois, April 24-28, 1977.
7 ?; m( b5 O9 |# Y* Requests for reprints: Division of Urology, Henry Ford Hospital,
2799 W. Grand Blvd., Detroit, Michigan 48202.
3 T, G3 l; r# ^2 ?: C$ H* \; |  mimprovement in phallic growth compared to gonadotropin.
Average phallic growth with gonadotropin was 14.3 per cent
increase in length and 5.0 per cent increase of girth. Topical
testosterone produced a 60.0 per cent increase of phallic length
and 52.9 per cent increase of girth (circumference). The
7 c( G/ I6 F9 R1 l# Sresponse to topical testosterone was greatest in children be-
tween 4 and 8 years old, with a gradual decrease to age 17
years (see table).
4 h; O' Q# w4 TDISCUSSION
Topical testosterone has been used effectively by other
) [* }6 k4 D) N$ b2 v& {- c) Fclinicians but its mode of action remains controversial. Im-
mergut and associates reported an excellent growth response
' X8 j5 C; T7 }1 M9 t: Mto topical testosterone with low levels of serum testosterone,
' X6 ~9 k' `; e  y6 Lsuggesting a local effect.1 Others have obtained growth re-
  k; b" h$ G, i5 i& E! C+ G3 _sponse with high. levels of serum testosterone after topical
administration, suggesting a systemic response. 3 The use of
5 B; |$ ]/ k: \/ `" L0 @gonadotropin to obtain levels of serum testosterone compara-
9 o; W& m* V$ j2 Able to levels obtained with topical testosterone would seem to
$ M' l5 w; m( _4 Uprovide a means to compare the relative effectiveness of
topical testosterone to systemic testosterone effect. It cer-
tainly has been established that gonadotropin as well as par-
! B$ u* e" V& L! C; L: j2 Genteral testosterone administration will produce genital
( _" R7 F! {0 O! m  Ygrowth. Our report shows that the growth of the phallus was
significantly greater with topical applications than with go-
nadotropin, particularly in children less than 10 years old.
/ d' F, v2 U1 `# n$ q( \( x" ~The levels of serum testosterone remained similar or lower
than with gonadotropin during therapy, suggesting that topi-
cal application produces genital growth by its local effect as
; a6 y- C0 L2 H% c* X) ~well as its systemic effect.
Review of our patients and their growth response related to
age shows a greater growth response at an earlier age. This is
consistent with the findings of Wilson and Walker, who
2 y# g9 H9 ^7 n, t4 [reported an increased conversion of testosterone to dihydrotes-
tosterone in the foreskin of neonates and infants.4 This activ-
' f( M1 B/ [# D6 X$ Zity gradually decreases with age until puberty when it ap-
! D- ?+ h1 e& e) p5 \proaches the same level of activity as peripheral skin. It may
well be that absorption of testosterone is less when applied at
an earlier age as suggested by lower serum levels in children
less than 10 years old. This fact may be explained by the
greater ability of phallic skin to convert testosterone to dihy-
drotestosterone at this age. Conversely, serum levels in older
patients were higher, possibly because of decreased local
. P6 I( Q" m4 H8 d; j667
668 KLUGO AND CERNY
+ l, O$ c' m! ^5 ^! QPt. Age
(yrs.)
; ^& V5 R4 i1 [: [5 r7 Q. Z" \$ WSerum Testosterone Phallus (cm.) Change Length
2 D; \1 u, A& N  \& N(ng./dl.) Girth x Length (%)
! \$ Y* Y7 q. j: Y* d4
8
# s1 S; c9 O  G# Q* D10
5 M, c7 [- K" p& ^12
17
0 O1 h7 H7 C& M  c% d5 w4 H6 HGonadotropin
9 Z+ h+ A0 B, E8 J7 P. ?# i  P71.6 2.0 X 3 16.6
50.4 4.0 X 5.0 20.0
& x5 g; s2 J! ^% S- O  t22.0 4.5 X 4.0 25.0
84.6 4.0 X 4.5 11.1
: B& D1 K: T& b. O. L. _6 ~) J85.9 4.5 X 5.5 9.0
0 x* b8 a' _5 B/ \Av. 14.3
4
8
$ v* }1 M' m8 a* {. W! w* z10
8 `# g" P: ?5 V! Q  X6 d) z12
17
Topical testosterone
6 e5 w* t. W' A6 d34.6 4.5 X 6.5 85
38.8 6.0 X 8.5 70
* m, g8 x+ r9 I( d/ @- d40.0 6.0 X 6.5 62.5
93.6 6.0 X 7.0 55.5
95.0 6.5 X 7.0 27.2
' M7 W1 L* ^0 R3 i( qAv. 60.0
available testosterone. Again, emphasis should be placed on
3 z6 q$ X5 j6 f  D- T% W( @early therapy when lower levels of testosterone appear to
* R, R) b% Q  t# R+ g/ h6 ?provide the best responses. The earlier therapy is instituted
the more likely there will be an excellent response with low
! E& Y1 w! i1 l7 b' aserum levels. Response occurs throughout adolescence as
noted in nomograms of phallic growth. 7 The actual response
' f6 i4 p* D! Q) Y2 J3 \% Oto a given serum level of testosterone is much greater at birth
' i, _1 K7 P6 A0 fand gradually decreases as boys reach puberty. This is most
( q6 N+ ]6 I( B- e; A( @9 |. `/ llikely related to the conversion of testosterone to dihydrotes-
0 K* C9 l1 n  h; Q: g5 ?tosterone and correlates well with the studies of testosterone
; X4 j0 W$ Q3 L- gconversion in foreskin at various ages.
The question arises regarding early treatment as to whether
( C9 V- e' c, l$ m1 None might sacrifice ultimate potential growth as with acceler-
$ ?  O5 y6 D( A% u' [# tated bone growth. The situation appears quite the reverse
with phallic response. If the early growth period is not used
9 d# a" N; g9 E/ N! ^& gwhen 5a reductase activity is greatest then potential growth
may be lost. We have not observed any regression of growth
attained with topical or gonadotropin therapy. It may well
' u, K' _( b  q, e3 dbe that some patients will show little or no response to any
, ?& L3 J; m- t8 ]7 m# Nform of therapy. This would suggest a defect in the ability to
convert testosterone to dihydrotestosterone and indicate that
* O# \7 H1 |4 k2 ephallic and peripheral skin, and subcutaneous tissue should
be compared for 5a reductase activity.
6 g; G$ j8 f8 \: iA, loop enlarges to measure penile girth in millimeters. B,
example of penile girth computed easily and accurately.
' b# ~, B3 k& D5 Pconversion of testosterone to dihydrotestosterone. It is in this
older group that others have noted high levels of serum
testosterone with topical application. It would also appear
) }  Q5 R2 N- [6 i& m. _, T1 D7 Sthat phallic response during puberty is related directly to the
serum testosterone level. There also is other evidence of local
response to testosterone with hair growth and with spermato-
genesis. 5• 6
6 b" o; \% \. l2 D" [- B3 SAdministration of larger doses of gonadotropin or systemic
testosterone, as well as topical applications that produce
& ~+ o! J5 h+ T, O9 p0 khigher levels of serum testosterone (150 to 900 ng./dl.), will
; a! P+ Q7 M! I1 P: ~also produce phallic growth but risks accelerated skeletal
maturation even after stopping treatment. It would appear
that this may be avoided by topical applications of testosterone
' Z0 F( y- p  c" Eand monitoring of serum testosterone. Even with this control
4 f+ C. l2 j9 s- q- H, c, Xthe duration of our therapy did not exceed 3 weeks at any
1 q2 e, h/ E" `) G1 ^, o3 Ztime. It is apparent that the prepuberal male subject may
; H# k8 E+ s- l0 L9 rsuffer accelerated bone growth with testosterone levels near
# W% l- R5 j* e, S6 i200 ng./dl. When skeletal maturation is complete the level of
serum testosterone can be maintained in the 700 to 1,300 ng./
  O" h( E) g" x+ I& d" U5 vdl. range to stimulate phallic growth and secondary sexual
. R7 T  E) u0 q' _changes. Therefore, after skeletal maturation parenteral tes-
tosterone may be used to advantage. Before skeletal matura-
tion care must be taken to avoid maintaining levels of serum
' M& K$ }( ?# T# z# Mtestosterone more than 100 ng./dl. Low-dose gonadotropin
+ d. \7 P% e1 ^8 S, T/ {9 gdepends upon intrinsic testicular activity and may require
2 A2 c# q7 E4 cprolonged administration for any response.
" `8 E8 P! I. Y  qAlternately, topical testosterone does not depend upon tes-
ticular function and may provide a more constant level of
! v, [3 c0 L% V; Z+ SREFERENCES
1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
$ o7 @' v2 l6 r* }R.: The local application of testosterone cream to the prepub-
6 S3 X4 S7 P! ^ertal phallus. J. Urol., 105: 905, 1971.
2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
/ E& I1 O: k6 m: S, _treatment for micropenis during early childhood. J. Pediat.,
( n- k6 Q5 D* S# N  D- l: ?# H83: 247, 1973.
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
one therapy for penile growth. Urology, 6: 708, 1975.
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
  c% ?" f# ~  S$ f5 Y6 cto 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
& b1 ?6 J( H) a' Pskin slices of man. J. Clin. Invest., 48: 371, 1969.
5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth
: u5 O1 t2 @; f: N! X: Eby topical application of androgens. J.A.M.A., 191: 521, 1965.
: R$ D/ m4 k- p6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
androgenic effect of interstitial cell tumor of the testis. J.
Urol., 104: 774, 1970.
4 }; N" ~  ?& C' l4 @4 S" X6 c2 I7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-
8 N0 l7 ?4 g* K2 |% X7 b9 t, t- ation in the male genitalia from birth to maturity. J. Urol., 48: