鄉下的妹子太便宜，一次四個都要了[12P]

stcar

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dadiaoguang

谢谢

wyp5888

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wudaode

11

xxp13136

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weihai

果您要查看本帖隱藏內容請

q2367975099

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金正恩

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zidantiao

真的很不错

kaifka

RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND
1 F/ o; L( W, K$ r1 ]$ _6 sGONADOTROPIN
' Z8 E" [; z$ e: \5 |+ U+ z) oRICHARD C. KLUGO* AND JOSEPH C. CERNY
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan
ABSTRACT
  a. u6 g8 g7 ~( c0 TFive patients were treated with gonadotropin and topical testosterone for micropenis associated
with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone
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
% }$ K& a/ |* `0 o, ]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
0 ^6 a. g5 P- A1 F8 b  ostudy suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
2 C0 g! Q( l6 O! g# ygrowth. The response appears to be greater in younger children, which is consistent with previ-
ously published studies of age-related 5 reductase activity.
# C8 o! e& s! i' t: n/ tChildren with microphallus regardless of its etiology will
6 s3 r" J- f% J/ Prequire augmentation or consideration for alteration of exter-
0 O" T- A, K3 b- e; S; o3 P( ynal genitalia. In many instances urethroplasty for hypo-
spadias is easier with previous stimulation of phallic growth.
The use of testosterone administered parenterally or topically
) x6 i1 C/ E8 }5 O! Hhas produced effective phallic growth. 1- 3 The mechanism of
% O! N$ g& n9 c4 p9 I% \- G( Rresponse has been considered as local or systemic. With this
in mind we studied 5 children with microphallus for response
7 h! B9 I0 _6 o3 f# P9 t4 i  \to gonadotropin and to topical testosterone independently.
MATERIALS AND METHODS
; O9 ~5 a! R+ B+ w; ~Five 46 XY male subjects between 3 and 17 years old were
evaluated for serum testosterone levels and hypothalamic
- ^6 G' \2 `, z; ^) M* A( @$ [. dfunction. Of these 5 boys 2 were considered to have Kallmann's
syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
lamic deficiency. After evaluation of response to luteinizing
+ j5 H. M8 Y+ g: xhormone-releasing hormone these patients were treated with
9 B$ T, f5 |$ l9 z' v0 C: w1,000 units of gonadotropin weekly for 3 weeks. Six weeks
' c# l: y5 W" u' n0 L, U% ?after completion of gonadotropin therapy 10 per cent topical
testosterone was applied to the phallus twice daily for 3 weeks.
Serum testosterone, luteinizing hormone and follicle-stimulat-
+ \) \; x7 |- ?* D: y3 @/ Ving hormone were monitored before, during and after comple-
9 {+ h, \$ }8 r' a/ c! q1 U  N7 v- Stion of each phase of therapy. Penile stretch length was
obtained by measuring from the symphysis pubis to the tip of
; s, @9 A2 U: H$ X2 ethe glans. Penile circumferential (girth) measurements were
& @( [9 Z! L- A* O  w1 B! Tobtained using an orthopedic digital measuring device (see
figure).
3 w+ e& f* g; s/ B5 d0 [8 Z2 uRESULTS
Serum testosterone increased moderately to levels between
7 D% i  R& s4 P" i50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-
terone levels with topical testosterone remained near pre-
treatment levels (35 ng./dl.) or were elevated to similar levels
developed after gonadotropin therapy (96 ng./dl.). Higher
+ K! z3 U" Q4 X2 p+ @5 o0 Gserum levels were noted in older patients (12 and 17 years old),
while lower levels persisted in younger patients (4, 8, and 10
* |2 m# ]4 v" r5 C( jyears old) (see table). Despite absence of profound alterations
" T; {: ]* j/ J7 iof serum testosterone the topical therapy provided a greater
Accepted for publication July 1, 1977. ·
# g5 k& L. [8 IRead at annual meeting of American Urological Association,
* B' M6 Z' a) N) q( AChicago, Illinois, April 24-28, 1977.
* Requests for reprints: Division of Urology, Henry Ford Hospital,
4 ^, L3 h/ e0 D2799 W. Grand Blvd., Detroit, Michigan 48202.
improvement in phallic growth compared to gonadotropin.
Average phallic growth with gonadotropin was 14.3 per cent
( e) K1 Z3 c8 W0 E/ M( V: Zincrease in length and 5.0 per cent increase of girth. Topical
testosterone produced a 60.0 per cent increase of phallic length
: Z3 N) D9 O; j6 w& L* H3 j* k* Gand 52.9 per cent increase of girth (circumference). The
response to topical testosterone was greatest in children be-
3 i* r$ j  n; ?4 g# W( dtween 4 and 8 years old, with a gradual decrease to age 17
8 v) h3 s2 u6 c7 oyears (see table).
DISCUSSION
' ^2 f$ e% e; F( o: C: WTopical testosterone has been used effectively by other
clinicians but its mode of action remains controversial. Im-
5 h% I* M6 m! t) f5 Imergut and associates reported an excellent growth response
to topical testosterone with low levels of serum testosterone,
suggesting a local effect.1 Others have obtained growth re-
sponse with high. levels of serum testosterone after topical
" a% S+ |7 s: G6 b4 e- Hadministration, suggesting a systemic response. 3 The use of
& a* P* u% s' A7 r: jgonadotropin to obtain levels of serum testosterone compara-
  I, \$ \- m6 ~2 r. s6 j* Eble to levels obtained with topical testosterone would seem to
1 [* I. u2 p/ W# l$ {& Iprovide a means to compare the relative effectiveness of
topical testosterone to systemic testosterone effect. It cer-
# n7 i$ l- R3 H# c; `* mtainly has been established that gonadotropin as well as par-
enteral testosterone administration will produce genital
  R9 X: S( Q7 Qgrowth. Our report shows that the growth of the phallus was
7 F7 E4 H: E- e! s& n; _3 X, Gsignificantly greater with topical applications than with go-
' w; C9 r4 N: j- cnadotropin, particularly in children less than 10 years old.
6 H1 K' f& U; M7 `7 a# r$ V8 HThe 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
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 C$ K1 Z- f! i, S5 breported an increased conversion of testosterone to dihydrotes-
tosterone in the foreskin of neonates and infants.4 This activ-
* x% C, q0 a. C1 C, S, |ity gradually decreases with age until puberty when it ap-
' \4 F' I) b2 E' j2 L: x. R  _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
6 D8 b2 o* {3 ]. \. a) B, a8 \patients were higher, possibly because of decreased local
% _" a+ i$ Q, m) o" e! s9 D; f667
668 KLUGO AND CERNY
Pt. Age
(yrs.)
+ U/ ^9 z9 Z* `# i2 R6 GSerum Testosterone Phallus (cm.) Change Length
(ng./dl.) Girth x Length (%)
4
8
10
. l3 d8 ?5 ?3 F12
17
( \0 a: b# T* m0 O& `1 W$ @% ?Gonadotropin
' h4 a; @! [$ y+ W' R71.6 2.0 X 3 16.6
9 v! N% n7 ^7 `7 T) a7 c  `2 d50.4 4.0 X 5.0 20.0
22.0 4.5 X 4.0 25.0
84.6 4.0 X 4.5 11.1
' m! Q% i% I0 G9 [! ~85.9 4.5 X 5.5 9.0
Av. 14.3
4
8
10
12
17
, ?- [1 r5 Q! g8 ETopical testosterone
6 o* C% v5 A, j34.6 4.5 X 6.5 85
0 `; }6 X* {0 {% b3 G3 m/ f38.8 6.0 X 8.5 70
40.0 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
Av. 60.0
available testosterone. Again, emphasis should be placed on
, f( C  z& y/ r9 ]$ uearly therapy when lower levels of testosterone appear to
provide the best responses. The earlier therapy is instituted
) A2 R7 t. W/ h. ithe more likely there will be an excellent response with low
serum levels. Response occurs throughout adolescence as
3 g/ M7 t# N' g$ u9 ynoted in nomograms of phallic growth. 7 The actual response
to a given serum level of testosterone is much greater at birth
and gradually decreases as boys reach puberty. This is most
likely related to the conversion of testosterone to dihydrotes-
3 d3 |' l5 F  o' M8 Ktosterone and correlates well with the studies of testosterone
conversion in foreskin at various ages.
The question arises regarding early treatment as to whether
one might sacrifice ultimate potential growth as with acceler-
ated bone growth. The situation appears quite the reverse
' R; [1 b) J( Twith phallic response. If the early growth period is not used
when 5a reductase activity is greatest then potential growth
may be lost. We have not observed any regression of growth
. S8 C1 u! [) t6 T8 R1 Sattained with topical or gonadotropin therapy. It may well
) f  S( i2 Z. \0 p* jbe that some patients will show little or no response to any
2 f5 {/ t# @1 X1 `% f' V! U- M" Uform of therapy. This would suggest a defect in the ability to
convert testosterone to dihydrotestosterone and indicate that
phallic and peripheral skin, and subcutaneous tissue should
be compared for 5a reductase activity.
7 c' M6 Y8 `, S( _/ s/ yA, loop enlarges to measure penile girth in millimeters. B,
example of penile girth computed easily and accurately.
conversion of testosterone to dihydrotestosterone. It is in this
: ?" P; Y) m/ I. l8 e% F, Tolder group that others have noted high levels of serum
4 H# i0 q# f5 l  c0 v( p# B" gtestosterone with topical application. It would also appear
2 g6 A. v: W% j# f  a! }; Wthat phallic response during puberty is related directly to the
6 C0 D& Z( p/ wserum testosterone level. There also is other evidence of local
. H8 ^- e( B! o: uresponse to testosterone with hair growth and with spermato-
9 }1 ?& o/ k2 x. h+ k/ d" U5 kgenesis. 5• 6
Administration of larger doses of gonadotropin or systemic
7 p9 r$ ]- p3 X/ h8 U/ U, e$ Otestosterone, as well as topical applications that produce
( |9 ?6 m3 n/ U$ Uhigher levels of serum testosterone (150 to 900 ng./dl.), will
also produce phallic growth but risks accelerated skeletal
3 Z* ?( ~  O  H0 O4 C" Omaturation even after stopping treatment. It would appear
that this may be avoided by topical applications of testosterone
and monitoring of serum testosterone. Even with this control
the duration of our therapy did not exceed 3 weeks at any
time. It is apparent that the prepuberal male subject may
3 W; Y4 w5 n. m! n) Z0 l; g+ [7 Xsuffer accelerated bone growth with testosterone levels near
200 ng./dl. When skeletal maturation is complete the level of
serum testosterone can be maintained in the 700 to 1,300 ng./
dl. range to stimulate phallic growth and secondary sexual
changes. Therefore, after skeletal maturation parenteral tes-
2 l! L5 w8 a& w) Z2 ?, ^: }, G+ atosterone may be used to advantage. Before skeletal matura-
tion care must be taken to avoid maintaining levels of serum
testosterone more than 100 ng./dl. Low-dose gonadotropin
depends upon intrinsic testicular activity and may require
" d1 {, B# Z3 E5 q. tprolonged administration for any response.
" H0 g, `7 c6 H* {1 v) z4 ~6 IAlternately, topical testosterone does not depend upon tes-
2 L1 I' M) K% R& V' B( }ticular function and may provide a more constant level of
REFERENCES
& a* A% q9 u3 D7 t1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
R.: The local application of testosterone cream to the prepub-
ertal phallus. J. Urol., 105: 905, 1971.
) M& U9 f3 E& z  U2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
treatment for micropenis during early childhood. J. Pediat.,
) B1 r4 D4 w, o83: 247, 1973.
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
' w4 X' i1 R* C! L$ `0 Qone therapy for penile growth. Urology, 6: 708, 1975.
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
skin slices of man. J. Clin. Invest., 48: 371, 1969.
5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth
6 z4 ~+ v3 ?! {, f, H: Rby topical application of androgens. J.A.M.A., 191: 521, 1965.
6. 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.
7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-
tion in the male genitalia from birth to maturity. J. Urol., 48: