- 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/ R p" R0 Y+ H- W' P
GONADOTROPIN# z6 o* e" W! t& u O/ j
RICHARD C. KLUGO* AND JOSEPH C. CERNY4 B0 Q, S" n& e2 G
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan* z1 [4 `* D* j' E, s& _4 u" V0 S
ABSTRACT/ y9 _' p9 O3 E) d0 X9 J, |
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
# R" G8 L; v. @. X& `% l( Q; Dwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-8 g6 a" }$ w! P) g; ?
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone( Y w3 w; w2 r9 V% m
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent
% \7 T. y. u8 k, Yfor both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent" x+ M6 a: `* O- @: ^1 p0 |$ [
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average; O; {/ G3 j, T4 B( Q
increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response# k6 y4 j% p; ?& @8 M$ p* J6 ^1 [$ M; w
occurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This, m: a K7 @/ R& N6 p" {* ~
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile2 f/ g# e7 u1 ]4 \
growth. The response appears to be greater in younger children, which is consistent with previ-- D3 u5 \2 a4 `' J3 B8 o4 X
ously published studies of age-related 5 reductase activity.
' e' z2 k% n2 f' n, e1 L+ u- @Children with microphallus regardless of its etiology will
# {# l) f# t, ?require augmentation or consideration for alteration of exter-
" L% t c0 N7 qnal genitalia. In many instances urethroplasty for hypo-
9 m7 N9 p( a1 M; e' wspadias is easier with previous stimulation of phallic growth.: s: A1 J8 B7 u, c+ P
The use of testosterone administered parenterally or topically% n+ w! f4 a( O$ e, P1 T! ^5 Q4 x! V% d: G
has produced effective phallic growth. 1- 3 The mechanism of- l6 y" o- P+ q/ ]- M" V3 I
response has been considered as local or systemic. With this
0 i5 e0 }& `5 \4 }2 Z" }in mind we studied 5 children with microphallus for response
" N" T! _" X4 Y6 cto gonadotropin and to topical testosterone independently." X% c; K# L' d" F3 K) T
MATERIALS AND METHODS
) @6 i! y' |. e! c# L# `Five 46 XY male subjects between 3 and 17 years old were
6 v: m6 N( ~3 Y( U4 Xevaluated for serum testosterone levels and hypothalamic- C4 Q8 p# x1 k6 a/ h
function. Of these 5 boys 2 were considered to have Kallmann's& ]$ o) @, B8 ?! H1 f2 T
syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
' { U' t3 ?0 ]( A& f8 Y! Wlamic deficiency. After evaluation of response to luteinizing3 J3 o4 v! h& Q( {
hormone-releasing hormone these patients were treated with; I$ n S( U0 E5 W& ~+ ~& L
1,000 units of gonadotropin weekly for 3 weeks. Six weeks. B9 v, t1 g$ ^
after completion of gonadotropin therapy 10 per cent topical, L4 q8 F8 F0 w# L+ ^# T) _
testosterone was applied to the phallus twice daily for 3 weeks.6 ~+ l+ k0 t% I4 w
Serum testosterone, luteinizing hormone and follicle-stimulat-$ I6 P7 R$ K" v" J
ing hormone were monitored before, during and after comple-
. s: |/ D& t; {: }- C, ation of each phase of therapy. Penile stretch length was' U3 {4 a3 l9 G
obtained by measuring from the symphysis pubis to the tip of {* j( n- K7 ]( n- K# f
the glans. Penile circumferential (girth) measurements were
, f: D1 G1 k2 E$ y [- @! G6 iobtained using an orthopedic digital measuring device (see
- Y! N0 q4 u- {4 Y* p' g: xfigure).
. o' U% C5 a( A5 \RESULTS
, ?* L; u2 \$ u1 PSerum testosterone increased moderately to levels between
/ Q. b* O0 s2 s0 h" g# f2 M50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-8 l5 X6 F* d6 O
terone levels with topical testosterone remained near pre-
3 Z# n) ~5 k& C0 g5 Mtreatment levels (35 ng./dl.) or were elevated to similar levels
# |3 D0 c) H! ?* u/ q3 `developed after gonadotropin therapy (96 ng./dl.). Higher2 k$ Y0 `; F' o: {
serum levels were noted in older patients (12 and 17 years old),
4 e+ q" c, w8 Q; o) m( L0 Gwhile lower levels persisted in younger patients (4, 8, and 10
+ w, M3 f$ S; Y+ m4 Z- x/ Eyears old) (see table). Despite absence of profound alterations) m6 f' T0 d. P% X R
of serum testosterone the topical therapy provided a greater5 U5 z4 W3 _$ Q5 f2 P
Accepted for publication July 1, 1977. ·- q3 k( s* e- d' x& N
Read at annual meeting of American Urological Association," C' R, \2 J5 u* _! p
Chicago, Illinois, April 24-28, 1977., j" x, a( N( {
* Requests for reprints: Division of Urology, Henry Ford Hospital,
0 [; y% Y. p+ f- [2799 W. Grand Blvd., Detroit, Michigan 48202.
1 ^: }' i9 V8 N ? L" iimprovement in phallic growth compared to gonadotropin.' t4 @) p$ p3 R' {2 {- |- k* @
Average phallic growth with gonadotropin was 14.3 per cent4 ~- D9 u) B- K F; `2 E
increase in length and 5.0 per cent increase of girth. Topical
3 ~: M9 ~& q+ R5 Y/ G1 ~6 mtestosterone produced a 60.0 per cent increase of phallic length$ c, x/ X! \3 \, y4 ~
and 52.9 per cent increase of girth (circumference). The- D, e% S& y4 t9 z# L
response to topical testosterone was greatest in children be-
, v' G- N5 b2 K# p! _! qtween 4 and 8 years old, with a gradual decrease to age 171 P P' j; d( w. r; N0 o
years (see table).+ P! j$ {' v1 L0 L6 y. b& ~
DISCUSSION
& A% X% K) s7 b' [1 O$ |9 zTopical testosterone has been used effectively by other2 O/ `9 K5 c% o2 q" _) p
clinicians but its mode of action remains controversial. Im-
( w0 B0 {! v( |* b$ L. n, Qmergut and associates reported an excellent growth response9 Z0 M( h" }9 ?2 E* N
to topical testosterone with low levels of serum testosterone,+ `1 z8 z0 U) w! q# N! [3 z
suggesting a local effect.1 Others have obtained growth re-
8 M* `- m# p$ V* osponse with high. levels of serum testosterone after topical
, R' V# e. [" p' O: A2 |6 Wadministration, suggesting a systemic response. 3 The use of
( E# K3 w" b# r) M- ^gonadotropin to obtain levels of serum testosterone compara-5 Z) s8 J3 E7 p
ble to levels obtained with topical testosterone would seem to/ B+ @' M, {+ V2 w) i9 L$ O
provide a means to compare the relative effectiveness of# n3 H9 o% H. M3 M) j7 _) R# f- j
topical testosterone to systemic testosterone effect. It cer-$ U2 J4 r1 s% u1 T
tainly has been established that gonadotropin as well as par-' N! P& _4 B* w) n% w
enteral testosterone administration will produce genital
& z6 W2 O7 m7 c6 S+ _. egrowth. Our report shows that the growth of the phallus was# g) G# ^/ l% ^# @: Q" x
significantly greater with topical applications than with go-
9 |: l# _% f5 |! @nadotropin, particularly in children less than 10 years old.8 P1 a* e: a$ L& A4 \! b: j- L
The levels of serum testosterone remained similar or lower
3 E8 [6 @$ Z$ ^3 }than with gonadotropin during therapy, suggesting that topi-* ]. R9 B p8 O( N
cal application produces genital growth by its local effect as8 s0 X( f/ \5 Q; E8 U2 O' E4 s0 E, A
well as its systemic effect.
% c) f, T5 Q8 S4 r4 b) U: C' o9 WReview of our patients and their growth response related to
; z$ ]8 ?6 M6 g! x0 g$ {% } K fage shows a greater growth response at an earlier age. This is7 Y/ Y5 o' m# m/ V; ?( [# f
consistent with the findings of Wilson and Walker, who7 J$ f# ]; e9 _
reported an increased conversion of testosterone to dihydrotes-3 o- ^, e, E9 F* G" u2 F' C
tosterone in the foreskin of neonates and infants.4 This activ-
* M6 e* S. T. D$ \: J+ B, yity gradually decreases with age until puberty when it ap-$ z6 g3 F0 o- f6 k- _2 C. n
proaches the same level of activity as peripheral skin. It may2 K7 l1 G) X( a8 y; d
well be that absorption of testosterone is less when applied at7 V) j# O1 q. _- _" D" f I, F' \
an earlier age as suggested by lower serum levels in children9 _) {$ R7 h% o$ j2 `
less than 10 years old. This fact may be explained by the
n: B5 i/ x8 I B) ]' h" O0 S+ Rgreater ability of phallic skin to convert testosterone to dihy-
, g+ s$ Q# B0 a3 @/ f$ Edrotestosterone at this age. Conversely, serum levels in older
% D/ j- |1 ~# p( F% |( y7 vpatients were higher, possibly because of decreased local
* [5 N5 I/ m, p' @' d$ p: F! D667
. A4 n, u3 \2 T1 M668 KLUGO AND CERNY5 B$ O& P! C, `- y
Pt. Age# l# Y+ \# M8 L, N1 X' ^: U6 `0 \
(yrs.)
/ h" l8 b" k, `$ ?. y$ Y; lSerum Testosterone Phallus (cm.) Change Length
3 h0 U- j* ]$ D4 ^(ng./dl.) Girth x Length (%)5 P1 M% t* y8 O5 X
4
8 B. x) M) ~0 B1 g" w: [, Y+ T8
! O( C2 Q+ Y+ m. Y8 E) |10: `0 }0 x0 [4 ?' W! c
120 v) L, P. G0 h a7 W
17) m. s. C- ?) b' B$ [
Gonadotropin+ h/ u" D+ u2 O! N( a) W6 \+ H
71.6 2.0 X 3 16.6
9 m3 D8 Z$ _3 g6 [50.4 4.0 X 5.0 20.0
8 f: ?0 A4 _& [+ g" H22.0 4.5 X 4.0 25.0
* `* g( X, w# Z$ v1 b8 l5 v84.6 4.0 X 4.5 11.1
* e: _6 i2 X4 y/ r5 F& j$ N85.9 4.5 X 5.5 9.0 r2 X; d8 X+ b) n5 z# h
Av. 14.3
! v& x/ j' K. m1 M' K0 b# F. K4 X4
" j: f$ T+ R5 l8# i- M* R0 X7 _7 F( }
10
- S p- C J; K% q+ l/ _7 M12
D5 G4 u7 ?8 n2 T" }' M% f17) |) q& _, }% r
Topical testosterone/ \& b! Q3 w" D& @
34.6 4.5 X 6.5 85
( F' t% k8 J Q: E9 Y* ?7 W38.8 6.0 X 8.5 708 ^- H9 W/ d+ U6 k" ]
40.0 6.0 X 6.5 62.5' D. D s# s# P3 R! }
93.6 6.0 X 7.0 55.53 a9 ?+ v) |+ K" P6 |) v6 @
95.0 6.5 X 7.0 27.22 |. N/ h% r2 I8 b8 g9 H% _
Av. 60.00 Y4 q* R' i# m$ {$ `* i. Z
available testosterone. Again, emphasis should be placed on% y9 H# z0 G2 o* G
early therapy when lower levels of testosterone appear to. `0 |* x* t! s* O
provide the best responses. The earlier therapy is instituted/ q2 q) c5 q9 V. c! c
the more likely there will be an excellent response with low
: ~" S! U' S. D% j' i0 Gserum levels. Response occurs throughout adolescence as
" a- ^- p& i1 Qnoted in nomograms of phallic growth. 7 The actual response( o1 \5 ~; ^6 H" l
to a given serum level of testosterone is much greater at birth) {( z, f* v& I' C& W
and gradually decreases as boys reach puberty. This is most
/ F) v3 j6 B" Z y2 vlikely related to the conversion of testosterone to dihydrotes-
9 Y% o- y0 e4 ytosterone and correlates well with the studies of testosterone
1 |% q4 v4 Y0 [' hconversion in foreskin at various ages.
9 B4 m% k5 p% a, ?1 _8 FThe question arises regarding early treatment as to whether4 h2 s0 [4 m& P: {) K$ c
one might sacrifice ultimate potential growth as with acceler-
& }& S' P( t6 D$ aated bone growth. The situation appears quite the reverse
9 R8 Y9 s8 S9 O7 \8 zwith phallic response. If the early growth period is not used9 M8 }! ]5 T- p8 E9 }! F; w
when 5a reductase activity is greatest then potential growth* G' q! x# S% p; @& I* c
may be lost. We have not observed any regression of growth
: G" e$ z8 _3 S4 I- Q' ], X4 b3 uattained with topical or gonadotropin therapy. It may well1 Y g( C& l. ^9 g' g1 M
be that some patients will show little or no response to any
- R6 d. E2 ^5 O- `" Z/ Iform of therapy. This would suggest a defect in the ability to
6 D" {. ~! n( O! z! r% bconvert testosterone to dihydrotestosterone and indicate that6 V$ ~5 ?5 P |
phallic and peripheral skin, and subcutaneous tissue should
' c/ d: d" ~% h x8 z( [be compared for 5a reductase activity.
4 i& J* g' |0 Q, c7 z3 pA, loop enlarges to measure penile girth in millimeters. B,
Z& z i1 d2 G5 K, |" W6 o( c* Iexample of penile girth computed easily and accurately.
! X5 ]% b4 F0 j. S- |! ?conversion of testosterone to dihydrotestosterone. It is in this0 i7 C @' @: Z# o9 O1 D
older group that others have noted high levels of serum
) X- o4 @0 n/ x! w5 |# |testosterone with topical application. It would also appear
. c: O+ r1 L1 O6 @) O$ Y) ?: jthat phallic response during puberty is related directly to the
9 J2 ]6 c# c0 A @/ wserum testosterone level. There also is other evidence of local
q' J+ D& J; Eresponse to testosterone with hair growth and with spermato-+ J" j6 p1 M" C, ~3 R# s2 ]
genesis. 5• 6/ E$ g8 Y4 d7 f( A9 Y
Administration of larger doses of gonadotropin or systemic2 z/ I9 w5 @( I+ {# O8 z
testosterone, as well as topical applications that produce
' X' I6 _& T+ k$ X, k! Qhigher levels of serum testosterone (150 to 900 ng./dl.), will( c$ |. D: V# y$ `9 A6 g7 ~, o( \
also produce phallic growth but risks accelerated skeletal
( {2 n. ~- [4 _maturation even after stopping treatment. It would appear
8 q7 l& u" k# X% N3 p" b/ _1 k! r) rthat this may be avoided by topical applications of testosterone
4 x5 o, c- B- q9 [. |/ J$ V9 uand monitoring of serum testosterone. Even with this control
+ a0 a0 n& x p, |0 [% E+ Z4 \the duration of our therapy did not exceed 3 weeks at any. b4 S+ F2 {( T; h# R
time. It is apparent that the prepuberal male subject may
- i. w% p p- S2 o# [ k# t# psuffer accelerated bone growth with testosterone levels near
5 W3 ]! U# i4 S, F) v8 S200 ng./dl. When skeletal maturation is complete the level of$ ?$ _- p. @ M
serum testosterone can be maintained in the 700 to 1,300 ng./
7 z: a' y% T- W" z2 j# _0 P- ^dl. range to stimulate phallic growth and secondary sexual
1 r3 Z3 _6 f. ]$ L2 T+ {; D% Qchanges. Therefore, after skeletal maturation parenteral tes-
" V4 l/ p8 F, @tosterone may be used to advantage. Before skeletal matura-3 a- T( C, {) w2 T
tion care must be taken to avoid maintaining levels of serum+ c9 n1 T# ]0 b+ m
testosterone more than 100 ng./dl. Low-dose gonadotropin" j: p7 l% i6 e5 ?( x$ |& `3 R
depends upon intrinsic testicular activity and may require! p; o2 ~" k' }8 [) b8 s
prolonged administration for any response./ ?. D. c9 L2 p* @. W; S% Q% ^
Alternately, topical testosterone does not depend upon tes-
' q+ K& k, R0 @8 o& q" J! E9 A0 fticular function and may provide a more constant level of
; Z4 D* [( e e- S# x6 V% WREFERENCES
4 e/ `7 e, }4 u' R# M1 M1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
9 W$ W/ M# X4 v9 H5 ~R.: The local application of testosterone cream to the prepub-# x' _2 j2 f; x, k
ertal phallus. J. Urol., 105: 905, 1971.
( [8 q' O2 c3 e2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
( `: M' x, I6 |& S( Y* U( g; S: Jtreatment for micropenis during early childhood. J. Pediat.,' ]0 `+ m& F$ s# [* Q
83: 247, 1973.
1 T* u, M- s% R, v; v3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
1 |9 ~8 G5 T+ ~; Sone therapy for penile growth. Urology, 6: 708, 1975.
: [/ y, H& q' K5 Q' d4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
! z7 Q) ?* v: Z+ F4 wto 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by; Q9 \4 Y, C0 \8 [) u
skin slices of man. J. Clin. Invest., 48: 371, 1969.
1 V3 Z& P* @2 B6 Y; z# ^7 b8 M' t7 Z5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth" |8 }3 g+ D8 P- @
by topical application of androgens. J.A.M.A., 191: 521, 1965.1 r0 _9 E& N% Z( x; |
6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local# X H3 O1 C7 x6 h
androgenic effect of interstitial cell tumor of the testis. J.
. b* L" W H3 w4 T9 |, p) D( ?Urol., 104: 774, 1970.% U8 K: K8 M3 x! L) N
7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-7 D4 ]9 W* u4 F: g
tion in the male genitalia from birth to maturity. J. Urol., 48: |
|