- 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
# A4 H+ j, m( R# vGONADOTROPIN
2 g5 _& i# y+ h6 GRICHARD C. KLUGO* AND JOSEPH C. CERNY9 d1 l! C' z, k
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan7 f) k( b5 v. E, |
ABSTRACT% ?. y' `, F6 O1 H& D: \6 x
Five patients were treated with gonadotropin and topical testosterone for micropenis associated7 I4 F3 M+ ^- N% u {- a8 w
with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-
: A4 H; D# I4 P* |" I0 A( ^tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone
3 s7 T* Y$ S8 i" p. _cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent# k( l+ ^2 \ U/ S4 J
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent
: d% ~: \+ i2 j3 N+ i5 h/ \5 i# Y6 Eincrease in length and 5.0 per cent increase of girth. Topical testosterone produced an average
+ M2 I8 c" H, L0 v" r" J' m" cincrease of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response( _, q* R% K+ D3 F0 a" A/ c
occurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This% W7 i3 w* j" g6 ?0 h! s
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile! D+ S& m$ U i. x) ^6 A0 E! {
growth. The response appears to be greater in younger children, which is consistent with previ-7 ?) t" ^; k% z( m0 u/ W* D5 W- G
ously published studies of age-related 5 reductase activity.
- z# H/ m+ g; r7 e4 |8 RChildren with microphallus regardless of its etiology will
' T) _1 q; L, w. `+ I5 Krequire augmentation or consideration for alteration of exter-5 m/ o% A, ?+ r2 S, `% a: W$ _
nal genitalia. In many instances urethroplasty for hypo-
& R b& v) R9 i: S+ Jspadias is easier with previous stimulation of phallic growth.
# d7 H. S; P+ [8 NThe use of testosterone administered parenterally or topically/ Z% q0 E& H- k& O M% S1 \9 P
has produced effective phallic growth. 1- 3 The mechanism of9 ]8 O5 `4 Z" }+ r6 T0 H* c( Y K
response has been considered as local or systemic. With this
5 ]5 T. ~ w0 w1 o( a8 o% M3 E/ \8 Zin mind we studied 5 children with microphallus for response
1 C |1 ^: i+ O3 H1 {4 D* Z; dto gonadotropin and to topical testosterone independently.
5 R4 d4 q8 I/ U; N7 f2 y' GMATERIALS AND METHODS6 [9 k" f* ?( s. Z
Five 46 XY male subjects between 3 and 17 years old were& {& P$ _; z6 b O( Z. M( ^
evaluated for serum testosterone levels and hypothalamic2 S. x5 W7 C" J# o
function. Of these 5 boys 2 were considered to have Kallmann's2 y8 O) \& ~4 F2 w4 F r
syndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-
# T$ C7 w- K- ~. Alamic deficiency. After evaluation of response to luteinizing, r) |) [/ S/ ~6 H
hormone-releasing hormone these patients were treated with% W, Z9 x# R+ L" W8 ~
1,000 units of gonadotropin weekly for 3 weeks. Six weeks# f5 H; v4 D2 M2 y
after completion of gonadotropin therapy 10 per cent topical
2 P# Q% a* |- Ltestosterone was applied to the phallus twice daily for 3 weeks.& h( C n' }. D" ~4 {5 w8 O4 Z
Serum testosterone, luteinizing hormone and follicle-stimulat-
) ~! d# Q6 C: X# I' k( _ing hormone were monitored before, during and after comple-1 M5 ]- @9 `7 `2 c h5 u$ M' e
tion of each phase of therapy. Penile stretch length was; C- l; Q/ W' @& ^8 {- W" h7 K' q
obtained by measuring from the symphysis pubis to the tip of$ }- }2 d7 I; w
the glans. Penile circumferential (girth) measurements were; l+ v) O' L/ H2 Y) t4 b; Q
obtained using an orthopedic digital measuring device (see
& _3 L7 N, k7 h% H( B$ M: {figure).
2 E1 U: A5 F9 [; w- `RESULTS* f+ A) ?' ]/ O2 r1 b8 A
Serum testosterone increased moderately to levels between
, d0 n9 p- K* X5 J! D1 F50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-
+ V5 @& J& W. cterone levels with topical testosterone remained near pre-
, Y* b: W \; e4 Jtreatment levels (35 ng./dl.) or were elevated to similar levels% U8 I, }( Z& f- m
developed after gonadotropin therapy (96 ng./dl.). Higher
' O4 _! z+ w& {" a8 @serum levels were noted in older patients (12 and 17 years old),
, W0 _1 ~1 x$ a( Zwhile lower levels persisted in younger patients (4, 8, and 10
2 ]+ V) Y; \' _& F' E- B+ k3 vyears old) (see table). Despite absence of profound alterations7 e& i7 o$ A/ ~! [
of serum testosterone the topical therapy provided a greater3 v+ z' b% ]4 F8 `4 [; Y
Accepted for publication July 1, 1977. ·
0 Q. Z; d$ D3 ~& t& ^4 vRead at annual meeting of American Urological Association,4 C, r/ q" [. y3 Y: y( N3 V
Chicago, Illinois, April 24-28, 1977.4 o- t, m0 f, s; g2 } O
* Requests for reprints: Division of Urology, Henry Ford Hospital,. N& M8 I# w s0 e
2799 W. Grand Blvd., Detroit, Michigan 48202.
6 z k( s+ ~9 Eimprovement in phallic growth compared to gonadotropin.
1 Y% e; z% l3 p' ~; V9 nAverage phallic growth with gonadotropin was 14.3 per cent2 s+ V2 K& f4 z) J7 n% s0 b2 _
increase in length and 5.0 per cent increase of girth. Topical) f1 j$ R. L% i& [; g' K0 |
testosterone produced a 60.0 per cent increase of phallic length( E# a/ h8 } ^- O1 I$ R Y
and 52.9 per cent increase of girth (circumference). The' C% B6 e3 }4 d; x
response to topical testosterone was greatest in children be-" n4 h3 Y% U X" _3 ^
tween 4 and 8 years old, with a gradual decrease to age 17+ R) [4 x6 o+ g& K7 H6 R4 M
years (see table).
& l$ S6 W* p' h3 e' }) a4 [DISCUSSION# e4 M( z; y: O' G
Topical testosterone has been used effectively by other% P- }: D! K1 Z: L
clinicians but its mode of action remains controversial. Im-
1 c9 s3 F* f& Qmergut and associates reported an excellent growth response0 E8 U! R3 S) u* c* T2 ^
to topical testosterone with low levels of serum testosterone,
% m6 z4 x0 `7 p, n. c0 ?8 E4 l& Ksuggesting a local effect.1 Others have obtained growth re-
, P1 |* @. z% f5 Dsponse with high. levels of serum testosterone after topical
! | e6 X6 m* [/ V, m' d( i( zadministration, suggesting a systemic response. 3 The use of4 ^; h) k0 c$ k$ r z
gonadotropin to obtain levels of serum testosterone compara-
/ `" F* P( i- Cble to levels obtained with topical testosterone would seem to# y8 } v) Z- B5 _
provide a means to compare the relative effectiveness of
. m8 v8 A1 ]) ztopical testosterone to systemic testosterone effect. It cer- b2 D8 d4 t0 J4 K
tainly has been established that gonadotropin as well as par-
[7 ~6 h; K: Z! m1 Zenteral testosterone administration will produce genital! W! }. Z; m4 y/ F
growth. Our report shows that the growth of the phallus was
- e- b% L1 R: ^) e# G, [significantly greater with topical applications than with go-
B# j! }, g$ ^' X+ W& G. `nadotropin, particularly in children less than 10 years old.
' X$ F. E& r& P) c6 K& ?( ~The levels of serum testosterone remained similar or lower
' F$ w1 r' e4 B4 ^$ p# t, {. xthan with gonadotropin during therapy, suggesting that topi-- S3 [( o6 M- R3 R$ R9 ?6 f8 U
cal application produces genital growth by its local effect as
s J: n3 ?! V5 L" pwell as its systemic effect.. T! |" W0 b* X- Z
Review of our patients and their growth response related to7 b" C0 y+ W5 y' A; u5 _
age shows a greater growth response at an earlier age. This is
8 y) W0 |: |8 d% I, K( v% Yconsistent with the findings of Wilson and Walker, who
! }" {% ?+ ]( b m, {reported an increased conversion of testosterone to dihydrotes-
i; S) Q7 G0 Q: ?9 ` ztosterone in the foreskin of neonates and infants.4 This activ-4 P% E) g w7 ]) w Q3 K
ity gradually decreases with age until puberty when it ap-
$ A$ H. ]2 O1 r$ Gproaches the same level of activity as peripheral skin. It may3 T9 c0 O, h2 N& [
well be that absorption of testosterone is less when applied at
1 s; t! ]( v) C# Aan earlier age as suggested by lower serum levels in children
! \/ q- p4 Z4 h( @less than 10 years old. This fact may be explained by the8 I3 u% s) s* M! b# ^
greater ability of phallic skin to convert testosterone to dihy-/ F3 h; [" A8 v p- r
drotestosterone at this age. Conversely, serum levels in older! m( s/ |# c$ F8 g8 Z
patients were higher, possibly because of decreased local0 J8 Z1 S8 H5 Y+ i4 L5 A
667
; ?5 @& {3 _4 K: V% b9 [668 KLUGO AND CERNY, r5 v$ P" a1 Q
Pt. Age
1 S$ o% b! F) \: b(yrs.)
$ t3 y: V6 j1 }Serum Testosterone Phallus (cm.) Change Length& }2 Q0 Q6 Q/ V- ?$ q
(ng./dl.) Girth x Length (%)3 E ?5 f7 O4 G8 \, X( x
48 _2 p1 J ^+ t0 G6 }: E
8
8 _" b u( Y; F% F10" A. |, R2 J' R! |* b
12
% C3 j0 F- ~ |1 D8 U170 g6 \/ W+ e3 k. a
Gonadotropin- U- y8 a4 W* D/ ^1 J* @$ i* f
71.6 2.0 X 3 16.65 \* f; r, }' {* h6 T
50.4 4.0 X 5.0 20.0
7 e2 x9 H6 F+ U- l' Y+ p22.0 4.5 X 4.0 25.0
5 J8 ?4 y# }7 h84.6 4.0 X 4.5 11.1
e, M7 ]! o2 K/ i0 @/ y85.9 4.5 X 5.5 9.09 G4 K6 a& W& Q# n: o# `
Av. 14.3
" v* e! ?: W. j) W, ^3 J" `( p4
5 H( b x! ?' b1 a, E7 F* l85 M. o. f! x) K6 ]+ i
10, C% I1 I3 X6 o4 L; J
12, H7 N: a" y1 C- O8 }- y7 S
17
" B+ u, }7 L4 X ~" w3 }2 {Topical testosterone
6 k6 S7 d. e, I2 \4 |34.6 4.5 X 6.5 85) q1 `; \7 j1 U! ?# V
38.8 6.0 X 8.5 70" v- _* t8 P) `0 L$ m
40.0 6.0 X 6.5 62.5 d( }! C. a; N% \
93.6 6.0 X 7.0 55.5" S2 ~0 _7 B: b4 D, T2 Z
95.0 6.5 X 7.0 27.2
3 H" ^( \& j8 ?Av. 60.0
9 ] Q+ C/ z2 k/ C( t. ~available testosterone. Again, emphasis should be placed on
( I8 w2 c, [# r9 Uearly therapy when lower levels of testosterone appear to' ~9 I; E9 h/ D6 p
provide the best responses. The earlier therapy is instituted
5 A, O2 a/ c8 fthe more likely there will be an excellent response with low
: l/ o1 Z2 A6 T- d5 vserum levels. Response occurs throughout adolescence as, B$ }/ }1 Z y0 k! B
noted in nomograms of phallic growth. 7 The actual response
. H$ t% O+ d! ?; [; O4 _8 Vto a given serum level of testosterone is much greater at birth
4 s( q# O2 A7 F& R: ~1 r- C: qand gradually decreases as boys reach puberty. This is most
" ~* P$ e. `6 a; W% b6 nlikely related to the conversion of testosterone to dihydrotes-
- f( ]2 b: R& @; A4 ]9 gtosterone and correlates well with the studies of testosterone7 E D1 L- _9 R' `, x) m) k3 v& `2 ?
conversion in foreskin at various ages.
! h% y5 G- N; kThe question arises regarding early treatment as to whether
/ ~# y5 G! f# x, eone might sacrifice ultimate potential growth as with acceler-
/ h3 k. t& c1 \: Pated bone growth. The situation appears quite the reverse6 z$ o7 _- Z* l0 C4 z3 a4 d% ?" X
with phallic response. If the early growth period is not used8 I6 {0 X3 W2 X7 b& l" Y: O+ T
when 5a reductase activity is greatest then potential growth' D0 |0 J P+ \$ H/ G) v w' K, g, R
may be lost. We have not observed any regression of growth
6 C6 Q" N2 M, {; l# E2 jattained with topical or gonadotropin therapy. It may well
1 Y4 w+ R+ o7 C7 M4 ^be that some patients will show little or no response to any
3 e- c9 z$ q; O9 _9 T( k2 x2 nform of therapy. This would suggest a defect in the ability to# @/ ^8 C, U# s9 Y! y5 C
convert testosterone to dihydrotestosterone and indicate that# H: e [+ d" F" L6 \
phallic and peripheral skin, and subcutaneous tissue should) n; u0 J# G' ?2 w( s) ^) O. a
be compared for 5a reductase activity.
' `3 K/ E p [4 S4 FA, loop enlarges to measure penile girth in millimeters. B,, e# B$ Y. h1 n
example of penile girth computed easily and accurately.
/ p+ i( t |2 v" n6 \/ ~conversion of testosterone to dihydrotestosterone. It is in this
9 H' F7 S3 S0 Jolder group that others have noted high levels of serum- Q2 \' Z6 e% J
testosterone with topical application. It would also appear/ {8 C, I: e. y
that phallic response during puberty is related directly to the
6 m$ `" G- R, @. T. wserum testosterone level. There also is other evidence of local
6 \, J% `) v7 D& aresponse to testosterone with hair growth and with spermato-9 f" \" Y$ F" ^8 e, G j
genesis. 5• 6
: c. L( u" M7 P- O$ RAdministration of larger doses of gonadotropin or systemic* G! `7 o9 d: l0 L) y0 T* s
testosterone, as well as topical applications that produce
) x5 C4 s! o& B. v. N3 f- r1 r! whigher levels of serum testosterone (150 to 900 ng./dl.), will
8 e, U1 c2 @! ]' k& H! Xalso produce phallic growth but risks accelerated skeletal2 [9 G% J: P( ^
maturation even after stopping treatment. It would appear8 D* N3 m& D; k) |, i
that this may be avoided by topical applications of testosterone0 Q6 F" b- b* Y8 E) m" k; H
and monitoring of serum testosterone. Even with this control
4 [0 b. |; a4 _$ N, V3 s+ ^the duration of our therapy did not exceed 3 weeks at any
/ W5 S+ t) k8 }time. It is apparent that the prepuberal male subject may* K# t/ m, d2 }8 f/ m' F# y
suffer accelerated bone growth with testosterone levels near! R% A8 w" o9 i S6 w1 L
200 ng./dl. When skeletal maturation is complete the level of
. H! s. t- j$ g, m g8 Aserum testosterone can be maintained in the 700 to 1,300 ng./
Y/ Z' f- a8 _: Odl. range to stimulate phallic growth and secondary sexual) O# X2 k9 ]2 m( N- x+ ?
changes. Therefore, after skeletal maturation parenteral tes-
$ V8 b, Z% |, O3 w. |% ~' p: Dtosterone may be used to advantage. Before skeletal matura-9 |% K+ f4 W* t1 y
tion care must be taken to avoid maintaining levels of serum
: I9 ^- B; [) N) `0 b5 G# K' g* Vtestosterone more than 100 ng./dl. Low-dose gonadotropin
( x2 p7 c: F7 F; j* ^depends upon intrinsic testicular activity and may require
$ U+ Y1 ^3 c9 r: z' d% [( O9 r1 ?prolonged administration for any response.
6 t j& k- w( @, H! sAlternately, topical testosterone does not depend upon tes-
* R, u$ Y A& U! C) U) P jticular function and may provide a more constant level of
8 j/ y, i% a- I N8 U7 ?' QREFERENCES
1 m, }( B3 e- X, B6 Y8 }1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
1 m$ F% y/ S, X8 f* xR.: The local application of testosterone cream to the prepub-
: Y) W Y% V6 h) q( b3 mertal phallus. J. Urol., 105: 905, 1971.
% o& x( e( w+ k7 I& I5 S/ r4 P2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
, ]0 ^* l0 @1 V. |( J0 y; M# vtreatment for micropenis during early childhood. J. Pediat.,
! R* [7 X+ q& R* j. Y2 p+ ]( V83: 247, 1973.
1 h* |9 X9 ^: ?- g/ v% E( _3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
M, B7 W( U& S3 `5 k! Jone therapy for penile growth. Urology, 6: 708, 1975.
- E/ {$ Z6 c; P+ R& b8 }# \4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone) m$ n h0 K) E+ w) @
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by: c$ L, w- p; s5 h' G1 y: \4 I
skin slices of man. J. Clin. Invest., 48: 371, 1969.
! u, G: s K( U2 O5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth
0 [& {/ Q( Q, I/ `by topical application of androgens. J.A.M.A., 191: 521, 1965.4 u" Q/ q% v/ S: R; j; Y, B
6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
+ n0 |: R, w- X) z9 i: y( wandrogenic effect of interstitial cell tumor of the testis. J.
$ g. {2 a0 M3 J A7 @) i3 nUrol., 104: 774, 1970.
" _# ]$ s& n u" |7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-4 v% i% w# u! L4 G C# p- s8 z" ?
tion in the male genitalia from birth to maturity. J. Urol., 48: |
|