- 註冊時間
- 2023-5-6
- 精華
- 在線時間
- 小時
- 米币
-
- 最後登錄
- 1970-1-1
|
發表於 2025-1-4 03:09:28
|
顯示全部樓層
RESPONSE OF MICROPENIS TO TOPICAL TESTOSTERONE AND
! M5 I1 R9 g+ Q1 }7 eGONADOTROPIN
, ?' c d w5 r2 K1 p. wRICHARD C. KLUGO* AND JOSEPH C. CERNY
: |# B3 t! s! w& aFrom the Division of Urology, Henry Ford Hospital, Detroit, Michigan7 q* Q. f# u9 ]% K8 D% a* M2 w
ABSTRACT I+ w, F- Q6 H# t- b
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
; F K* B. H: }9 G5 H! twith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado- k3 C' u, v# e
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone
2 y5 E' I' S9 x0 q7 bcream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent
, k0 Q6 z4 Z5 C# W: w$ y2 rfor both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent
1 o% @& J6 ^1 Y; i: l1 j* Y. Mincrease in length and 5.0 per cent increase of girth. Topical testosterone produced an average
* D( G8 ~0 e, t; S. ]increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
; i# J5 t! E$ O. t zoccurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This/ ?; m" Q& i+ N+ |7 X
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
4 e( L) \9 k% C$ lgrowth. The response appears to be greater in younger children, which is consistent with previ-
! x6 c! H- ^ C' x3 ~, m2 J; @' a) r+ A+ Lously published studies of age-related 5 reductase activity.( M' `7 y- _+ k
Children with microphallus regardless of its etiology will, t k2 }5 [- m5 h- f; y
require augmentation or consideration for alteration of exter-: Z+ k9 O8 D9 L2 H k
nal genitalia. In many instances urethroplasty for hypo-
7 j5 W+ }- V% x6 U- k& ^- jspadias is easier with previous stimulation of phallic growth.
; k/ [4 _/ N8 b3 cThe use of testosterone administered parenterally or topically
) g( W1 o2 U" N, q* A* O1 S- Chas produced effective phallic growth. 1- 3 The mechanism of) B* x! n4 a1 Z% J# P
response has been considered as local or systemic. With this
0 Q6 K. _; T( `1 T; L7 l( Q. [1 Rin mind we studied 5 children with microphallus for response4 {! o2 [$ x6 o$ k
to gonadotropin and to topical testosterone independently. ~2 F* o& {( g% Y" e# J J
MATERIALS AND METHODS% V, r" v+ }' v/ G2 E+ S& S( e0 Q- h: ^
Five 46 XY male subjects between 3 and 17 years old were. E6 r( q5 U% |" `6 ~+ H
evaluated for serum testosterone levels and hypothalamic
* M7 e3 a! g6 s7 F' ]function. Of these 5 boys 2 were considered to have Kallmann's
& N+ L* z* w, B& ?syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
0 s& M8 D" n4 p, u! k* F; Zlamic deficiency. After evaluation of response to luteinizing
. i) D: R- `8 F4 d4 Chormone-releasing hormone these patients were treated with
9 A: W0 g7 ^8 p# l1,000 units of gonadotropin weekly for 3 weeks. Six weeks2 l$ F- K e% \, F
after completion of gonadotropin therapy 10 per cent topical
2 { l3 e: z! S2 k, Otestosterone was applied to the phallus twice daily for 3 weeks.* r; j) H! n( w/ L" _$ \( |
Serum testosterone, luteinizing hormone and follicle-stimulat-
0 n, H# X ]" F- _4 B/ j0 Cing hormone were monitored before, during and after comple-
0 [% p3 k4 e* ?6 s: }2 z9 {. vtion of each phase of therapy. Penile stretch length was) x8 y# V0 ?' }- O
obtained by measuring from the symphysis pubis to the tip of
1 F) p* \* \- Ithe glans. Penile circumferential (girth) measurements were
; e: r2 h/ S' M6 W# K% iobtained using an orthopedic digital measuring device (see5 I& a+ i6 A7 z' T
figure).! K, L4 k' s2 h3 q9 f
RESULTS
! U" I7 G3 R* H7 \Serum testosterone increased moderately to levels between
- j) i% V9 o- E7 x/ d5 Z50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-0 `: G' T% z4 C. V9 P& X# @2 S
terone levels with topical testosterone remained near pre-
- U3 d3 W$ p* x; r1 V/ X7 \treatment levels (35 ng./dl.) or were elevated to similar levels& d, d1 K8 [, O* L o- J
developed after gonadotropin therapy (96 ng./dl.). Higher k ^6 b/ t6 R" }
serum levels were noted in older patients (12 and 17 years old),3 y6 W$ _. A" D. |; o& Y) L u
while lower levels persisted in younger patients (4, 8, and 10; y+ a; k7 W; Y: ^& ?0 N
years old) (see table). Despite absence of profound alterations+ @" M/ J0 G0 G
of serum testosterone the topical therapy provided a greater. Q- Q& h/ j& q, t. o0 u
Accepted for publication July 1, 1977. ·
, o# p4 Q" s# k# K- r# iRead at annual meeting of American Urological Association,
1 G- c5 H& T: V' Q( l0 [! g5 f6 k: ]Chicago, Illinois, April 24-28, 1977.
) r0 K, M9 P3 S- K1 [* Requests for reprints: Division of Urology, Henry Ford Hospital,. O1 G* {8 V+ j- r5 m4 K
2799 W. Grand Blvd., Detroit, Michigan 48202.1 i. f, G* n2 S0 k6 P6 v
improvement in phallic growth compared to gonadotropin.
2 M) r! \! D, XAverage phallic growth with gonadotropin was 14.3 per cent
: m1 ?( X' A7 m, Zincrease in length and 5.0 per cent increase of girth. Topical8 q8 `/ t: @, J& I2 G
testosterone produced a 60.0 per cent increase of phallic length
! C, L' P1 n" \& p# V" band 52.9 per cent increase of girth (circumference). The% k" O5 W5 Y# u+ g) O; B
response to topical testosterone was greatest in children be-- l+ q Q) j; |- H Z! o+ F
tween 4 and 8 years old, with a gradual decrease to age 172 Y6 J! d% [1 Q* t J" {5 o
years (see table).
% n1 M/ g4 r% u1 uDISCUSSION
) p" [% O* N; @1 a o* W+ fTopical testosterone has been used effectively by other# ]8 l! c; L |& O3 b* g9 K! F5 @
clinicians but its mode of action remains controversial. Im-- V8 p& g% K. l+ E- m
mergut and associates reported an excellent growth response
3 k- `. I* H) G* Q! d0 G1 Vto topical testosterone with low levels of serum testosterone,
4 m- K8 c6 h6 U* Q' H/ xsuggesting a local effect.1 Others have obtained growth re-6 N* N) h( X. t6 |
sponse with high. levels of serum testosterone after topical _, n7 z9 H- }+ Z; D/ P
administration, suggesting a systemic response. 3 The use of1 f4 l# j7 f0 U4 F. t- E' e9 x
gonadotropin to obtain levels of serum testosterone compara-
4 E7 z) ?! _; ^2 z0 g/ l, A5 pble to levels obtained with topical testosterone would seem to l p# e) _( k& H# h) c9 j
provide a means to compare the relative effectiveness of( `- b! R( }' T
topical testosterone to systemic testosterone effect. It cer-- V% e; H5 t8 M
tainly has been established that gonadotropin as well as par-
+ x, L2 L4 H5 J/ e8 p$ u2 D- Renteral testosterone administration will produce genital
9 z/ D2 }( [; d2 Xgrowth. Our report shows that the growth of the phallus was
% m: Y) C8 F- hsignificantly greater with topical applications than with go-
% u6 y! x! C; T7 E$ @nadotropin, particularly in children less than 10 years old.
* I: e* x. r& | ~7 C6 r+ KThe levels of serum testosterone remained similar or lower* t% a( Y0 o$ t1 ?6 @5 A
than with gonadotropin during therapy, suggesting that topi-0 b7 T9 ^" `; s8 n5 X
cal application produces genital growth by its local effect as
- F" W0 j: C; e e7 Swell as its systemic effect.5 F% ~6 X9 Q) q* Q$ R8 {
Review of our patients and their growth response related to1 H; k- ?+ I0 |
age shows a greater growth response at an earlier age. This is0 L3 x, Y: s3 Q' {
consistent with the findings of Wilson and Walker, who+ V0 o! P1 @6 r ^) O
reported an increased conversion of testosterone to dihydrotes-
3 X8 O+ V! ?# h( N, Btosterone in the foreskin of neonates and infants.4 This activ-- e% x# D+ x) a2 E
ity gradually decreases with age until puberty when it ap-
% y: i( j; H" t% p* _proaches the same level of activity as peripheral skin. It may
; g) F. f( S d1 U7 @1 Xwell be that absorption of testosterone is less when applied at, p. L4 y3 d& S3 |: `7 O8 R
an earlier age as suggested by lower serum levels in children5 Q, H% |- i- `% ?4 p6 Q
less than 10 years old. This fact may be explained by the
" p! V* l: a5 e' I5 |' T' ^$ |' pgreater ability of phallic skin to convert testosterone to dihy-! r& b/ v, q7 K2 U
drotestosterone at this age. Conversely, serum levels in older* n) q) q* ^- i$ k
patients were higher, possibly because of decreased local+ q7 U& f! g* u/ @! t* D
667; ^" [- j! \. ?& D2 @
668 KLUGO AND CERNY) z5 n A% u$ J+ N2 x
Pt. Age& H- P2 ^4 R7 O0 l' o: X
(yrs.)
& s3 g1 ~# n4 S0 z, S% ySerum Testosterone Phallus (cm.) Change Length
' k+ E: R0 M6 [) L3 V/ b& {3 R(ng./dl.) Girth x Length (%)) C" {# k# K- d# O- c' J& g
4, Q+ a' e: E/ O0 {7 J+ q- c: q, q
8/ O% \* M- g+ X: O: M
10( ]. p! B9 n c
12
# x0 a" z1 r5 [( t/ G- t l17( b2 q+ d) c# c
Gonadotropin
3 H5 w, D5 u1 U71.6 2.0 X 3 16.6
$ ]* W( G7 Z/ `6 |& k0 ~, M! p50.4 4.0 X 5.0 20.0
4 l. r* b. {0 ^" p" x3 s22.0 4.5 X 4.0 25.0* _" U# e3 X# \- r9 ~: t* K
84.6 4.0 X 4.5 11.1
7 M! O9 F3 P0 f- _6 B) l6 ~9 Y85.9 4.5 X 5.5 9.0/ A) F& l! O* d
Av. 14.3( L/ s l2 ]& t/ V5 b2 w' Q
4
! ]; k w3 Q4 n- A8- A* l% E; `! U* S( O8 ]8 R) t
100 C! i+ K; B- e& o
12
0 m3 }9 J/ @7 S# F17
6 Z$ _2 I( G! G! f! Y8 LTopical testosterone$ v! p! y9 S; A- g8 D) }
34.6 4.5 X 6.5 85
! R! i7 j8 g3 U; N" ^& I+ V38.8 6.0 X 8.5 70
( T. O8 O T( ~4 {9 |: B: u40.0 6.0 X 6.5 62.5: _2 S1 D/ q9 j5 Z
93.6 6.0 X 7.0 55.5% H, ]. z9 d# i5 {; w5 ]
95.0 6.5 X 7.0 27.24 }. K; N/ H+ [! T3 \
Av. 60.0
7 n. M4 }; T% j* o7 aavailable testosterone. Again, emphasis should be placed on+ m) S; u% N d* ]
early therapy when lower levels of testosterone appear to: a% W% u8 \+ Q. j# n) K- _: h: c
provide the best responses. The earlier therapy is instituted% O# k% Y1 P: \& l
the more likely there will be an excellent response with low
4 z0 i# b: N, R* F: oserum levels. Response occurs throughout adolescence as
) A) E. e. v' `2 H' `noted in nomograms of phallic growth. 7 The actual response! E0 o$ \& p5 U7 {
to a given serum level of testosterone is much greater at birth7 W( Y0 d# t( S$ ?' n; D( H( K
and gradually decreases as boys reach puberty. This is most
$ x! q: O3 I! T9 x# h- \likely related to the conversion of testosterone to dihydrotes-" b! _+ g( X% m
tosterone and correlates well with the studies of testosterone
, K# i: C" `3 G8 L& Rconversion in foreskin at various ages.& a O! `& c, j5 d. Q. ~
The question arises regarding early treatment as to whether4 W3 j' A9 e5 M$ p# U# ?
one might sacrifice ultimate potential growth as with acceler-
! k7 Z& [: s6 t3 A# t5 Xated bone growth. The situation appears quite the reverse
8 M. c* d3 D* X* p5 Qwith phallic response. If the early growth period is not used
; ]# [ R; T% f) `0 }3 H9 S* A0 ^) Kwhen 5a reductase activity is greatest then potential growth% l0 u* ]1 I+ U) z5 h
may be lost. We have not observed any regression of growth: s, a o. b+ p, g ]
attained with topical or gonadotropin therapy. It may well' S4 K* h* m5 e" Y; ^, p
be that some patients will show little or no response to any3 c- T9 b% u5 `
form of therapy. This would suggest a defect in the ability to
+ s0 e/ W: \& @2 z! ]convert testosterone to dihydrotestosterone and indicate that! S U& V& ^0 H; L, R' h
phallic and peripheral skin, and subcutaneous tissue should6 z% k; D3 G) R- m, ?
be compared for 5a reductase activity.* j2 G! s: H4 P! h( w2 z' c/ f
A, loop enlarges to measure penile girth in millimeters. B,
* c5 c, m* ^3 u0 b: Texample of penile girth computed easily and accurately.
3 _9 G: l( G3 ^7 ~# I# _conversion of testosterone to dihydrotestosterone. It is in this+ J2 G# J; N4 z4 `- Z$ _
older group that others have noted high levels of serum
- O! O9 q& V' a& vtestosterone with topical application. It would also appear
8 r/ W/ p4 D$ mthat phallic response during puberty is related directly to the; e: b9 F8 y7 l2 D6 w" [
serum testosterone level. There also is other evidence of local6 Z" w) `% Q2 L' Q a, Q! {
response to testosterone with hair growth and with spermato-
! ~5 L* l9 F/ }+ xgenesis. 5• 6" Q# ]5 h, y+ V/ e4 R, T4 `
Administration of larger doses of gonadotropin or systemic0 i% Z1 }- o. Q+ T7 _: B4 u
testosterone, as well as topical applications that produce7 U( m" p6 ^7 M" h" x
higher levels of serum testosterone (150 to 900 ng./dl.), will' K9 X# g7 `+ N9 D5 b, S5 Z/ f
also produce phallic growth but risks accelerated skeletal. h( y* E& o" Z/ i
maturation even after stopping treatment. It would appear9 H' I ]$ z" a* Q. Z% W0 y/ C" N
that this may be avoided by topical applications of testosterone
( ]% j- M2 f& u* hand monitoring of serum testosterone. Even with this control
4 c2 n7 W' [* D5 Z+ q5 u- A% Fthe duration of our therapy did not exceed 3 weeks at any9 C+ d) o8 Y- `! ?2 q
time. It is apparent that the prepuberal male subject may7 T4 {) G W2 U, w2 e
suffer accelerated bone growth with testosterone levels near. U% |( q. T9 ]
200 ng./dl. When skeletal maturation is complete the level of
8 n( I, @0 T* q* B* J! i, I& j: ]serum testosterone can be maintained in the 700 to 1,300 ng./0 O4 d1 O9 K1 q* D
dl. range to stimulate phallic growth and secondary sexual
/ r' u/ ^2 I/ P! \6 A+ S. }# v% Pchanges. Therefore, after skeletal maturation parenteral tes-# Q; y, P" X5 k0 m' n/ y
tosterone may be used to advantage. Before skeletal matura-8 e/ v0 L4 E% f9 l! u0 m ]
tion care must be taken to avoid maintaining levels of serum
/ N9 Q$ U' H1 K1 S0 h) W9 Stestosterone more than 100 ng./dl. Low-dose gonadotropin
5 ^8 h* r; r! m. T k: @# Ldepends upon intrinsic testicular activity and may require8 c6 q4 i# H `8 w
prolonged administration for any response.* G2 s @3 k. H8 t8 A
Alternately, topical testosterone does not depend upon tes-
4 b6 I& M. a, S0 A1 |ticular function and may provide a more constant level of
6 n! T5 P; r$ K1 _; X6 L% v& ^REFERENCES: L* Y1 w3 K* Q3 K
1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
( T. c2 E( q8 ^1 ]( [8 s! l* [R.: The local application of testosterone cream to the prepub-! J4 C, @- o2 H7 d
ertal phallus. J. Urol., 105: 905, 1971.
' A2 d! }7 n- o1 V W7 b; d2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
/ F+ {! J& Q! m5 B, e; v7 y2 }treatment for micropenis during early childhood. J. Pediat.,) f( O# o5 w" z8 m# m; c# s
83: 247, 1973.! _2 ^ s: F0 ?" D- u* g, l( u
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-5 M5 r9 _1 G9 T6 n9 s" J* l
one therapy for penile growth. Urology, 6: 708, 1975./ U( g8 L% a* y6 d9 [
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone8 U/ ?$ s- r7 N' s, _. N+ u, t
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
$ T' Q' T: r) I# @6 l4 gskin slices of man. J. Clin. Invest., 48: 371, 1969.
! E. @. k# I! c( Q0 l! ~5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth: O6 v A8 q" i6 j7 x/ r
by topical application of androgens. J.A.M.A., 191: 521, 1965.4 k5 `1 @ N, v$ C) }2 `% S' ]
6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
5 C$ N! ]# I6 S, p: Tandrogenic effect of interstitial cell tumor of the testis. J.
+ c( [- r" g" m1 e! XUrol., 104: 774, 1970.
; Y* O/ W# F: }7 s5 K; N2 I/ R7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-
3 M c3 N _* @% stion in the male genitalia from birth to maturity. J. Urol., 48: |
|