- 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
% s: V* N2 C. T0 b! X) ]2 E8 }/ jGONADOTROPIN* h, Q7 N3 h# z! Y/ W+ J
RICHARD C. KLUGO* AND JOSEPH C. CERNY
, L& Q' ~2 ]" `+ A* g4 KFrom the Division of Urology, Henry Ford Hospital, Detroit, Michigan
- f) Z+ t$ ~- Q9 e7 HABSTRACT/ [3 ]: u- K2 ?5 b
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
! L. i2 K% j! a2 H1 e& Z- g: ^ dwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-9 L' j8 R3 ?* f
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone( x; P5 }6 K3 I, m& r( v5 v- ]
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent% Y. I {' O1 H3 `( N
for both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent
f; Z$ h5 P( p8 o9 @7 vincrease in length and 5.0 per cent increase of girth. Topical testosterone produced an average6 p9 T! k' k3 q- A" A
increase of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response
: D6 O. P# [: S# I* xoccurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This9 F! m$ h+ k$ }! g
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
! X. r3 H& y" `$ hgrowth. The response appears to be greater in younger children, which is consistent with previ-
; o# w& v% r. j! oously published studies of age-related 5 reductase activity.' j9 |! P0 N; o- W
Children with microphallus regardless of its etiology will
3 v! U. S/ y$ x; h# f/ S7 `require augmentation or consideration for alteration of exter-
& ]# Z( |4 H$ c$ T7 ?nal genitalia. In many instances urethroplasty for hypo-
v) _2 `, t% ] Q2 e" B4 h' q% Xspadias is easier with previous stimulation of phallic growth.
+ \) q$ e8 ?; X: IThe use of testosterone administered parenterally or topically
P, T3 u% X( h4 N. h2 X; bhas produced effective phallic growth. 1- 3 The mechanism of
2 S; G" I: y+ |' i' g6 g6 D; s% Uresponse has been considered as local or systemic. With this
( f; k+ [5 X+ j' L K/ Q- e+ o$ E3 bin mind we studied 5 children with microphallus for response, C4 ?( Z a0 w6 `) h: d5 Q
to gonadotropin and to topical testosterone independently. W* }9 R' V3 A; e/ N
MATERIALS AND METHODS7 s" y8 G+ u4 a! _- k
Five 46 XY male subjects between 3 and 17 years old were
& G( u2 p2 J1 ?" t# |8 @( Yevaluated for serum testosterone levels and hypothalamic+ W/ C7 |! v0 e; o) D( U" _& K
function. Of these 5 boys 2 were considered to have Kallmann's
4 ? I2 v$ \* c5 J6 f, Dsyndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-% f) [5 ^- `- y; e& x, q: G
lamic deficiency. After evaluation of response to luteinizing
: m) i# k( G1 ~6 [6 X7 ohormone-releasing hormone these patients were treated with2 {4 }! \6 r- _, D9 |/ Y3 P
1,000 units of gonadotropin weekly for 3 weeks. Six weeks f j R' F( E6 g7 S
after completion of gonadotropin therapy 10 per cent topical I3 \, { }! c) g# a) u( c* g
testosterone was applied to the phallus twice daily for 3 weeks.0 X1 x9 \* j3 n' a7 }+ A; ]
Serum testosterone, luteinizing hormone and follicle-stimulat-# i. [1 H H( ?$ [6 x- H7 c
ing hormone were monitored before, during and after comple-9 ]9 v( w/ n0 i4 [9 ~( Z
tion of each phase of therapy. Penile stretch length was3 d) h l6 y6 C, s1 p! A
obtained by measuring from the symphysis pubis to the tip of; \9 w# j8 }3 i
the glans. Penile circumferential (girth) measurements were
: Q R+ N) w7 u9 xobtained using an orthopedic digital measuring device (see R& U7 D- u, G2 j- O
figure).
/ K" ]; J) S3 w4 q9 U. mRESULTS1 ~- Q4 i1 F% T0 d. Q- H6 O
Serum testosterone increased moderately to levels between( N: M4 G r3 d' i9 J, \6 r" l
50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-
7 W9 ~5 p4 \! bterone levels with topical testosterone remained near pre-. O" _' _9 R4 K5 v/ I
treatment levels (35 ng./dl.) or were elevated to similar levels
L2 J- u+ q: c+ ^, I$ r4 mdeveloped after gonadotropin therapy (96 ng./dl.). Higher
$ u, _9 P' w( j/ V: Cserum levels were noted in older patients (12 and 17 years old),; K, W; d1 u8 E7 ~: D) B' z
while lower levels persisted in younger patients (4, 8, and 10" m! q- J) r$ \, Z- b2 e6 O% E
years old) (see table). Despite absence of profound alterations7 _! ?/ v5 G3 u N9 T/ r% V
of serum testosterone the topical therapy provided a greater
: t4 }/ X7 Z: m( {Accepted for publication July 1, 1977. ·
" d7 l. J+ Y4 R6 F- h+ ~, ERead at annual meeting of American Urological Association,: K: E t; o. E: X b
Chicago, Illinois, April 24-28, 1977.+ f) T0 H' b0 X2 B0 d0 S( V' H
* Requests for reprints: Division of Urology, Henry Ford Hospital,
+ [! |/ t9 E; v9 p4 E: [( ?% A- P2799 W. Grand Blvd., Detroit, Michigan 48202.
6 _$ u5 Z/ f% t( ]- q! Nimprovement in phallic growth compared to gonadotropin.6 R/ Z# I$ B7 ^5 j S
Average phallic growth with gonadotropin was 14.3 per cent
* ^' Z Y$ p& g$ W; R0 cincrease in length and 5.0 per cent increase of girth. Topical
( ]9 @9 z& g% C- H' k1 Dtestosterone produced a 60.0 per cent increase of phallic length0 }9 d8 m! D& c) ?4 L8 p. u7 j
and 52.9 per cent increase of girth (circumference). The
& h' L: x# K; }6 vresponse to topical testosterone was greatest in children be-% X0 ^3 S: |! G; ], o+ |7 S
tween 4 and 8 years old, with a gradual decrease to age 17
" I5 \7 y; H) @' g! qyears (see table).
5 F/ ]! K0 N. M2 T' eDISCUSSION+ g P+ y! z! S2 u) ~( s
Topical testosterone has been used effectively by other
% `6 }" l# R& u$ \ |& k$ {* ]1 Wclinicians but its mode of action remains controversial. Im-+ G5 _ Y5 P: o# A; `8 B( g6 M
mergut and associates reported an excellent growth response8 ` z( k" g6 M) U
to topical testosterone with low levels of serum testosterone,3 E* y6 N. l* \0 x3 _0 Q! k% }
suggesting a local effect.1 Others have obtained growth re-
$ c& Z& _5 u8 O) A& H9 a$ }, d* }sponse with high. levels of serum testosterone after topical1 Y' g& X @! p1 Y
administration, suggesting a systemic response. 3 The use of
. Q. H6 }1 @0 J' Ggonadotropin to obtain levels of serum testosterone compara-
9 G( O8 {4 z' P9 ]* {, t5 Uble to levels obtained with topical testosterone would seem to
9 ~& e# o( b7 ]% S: Bprovide a means to compare the relative effectiveness of
3 Q: M5 I$ ^1 P! _* Ctopical testosterone to systemic testosterone effect. It cer-2 \$ z" E6 I/ v2 _9 |+ v$ ~1 B" P5 s
tainly has been established that gonadotropin as well as par-
) Q9 w- i+ y- A/ H# |( v6 `enteral testosterone administration will produce genital/ B/ S% `+ H r9 [+ _4 C( g
growth. Our report shows that the growth of the phallus was
, H; D- E9 J) Fsignificantly greater with topical applications than with go-
! y( C! r8 ^# }" Q+ C$ R1 k5 Onadotropin, particularly in children less than 10 years old.
9 {5 Y5 b* e1 J1 wThe levels of serum testosterone remained similar or lower' p% R c( _, w- ?6 F
than with gonadotropin during therapy, suggesting that topi-/ P; j6 y7 U2 w( o0 \
cal application produces genital growth by its local effect as* c9 V( Y# C5 w x* Q4 ~
well as its systemic effect.
4 V5 B* j( M; K5 N( }4 S" `Review of our patients and their growth response related to
. N( @; O, @/ p+ F. w- J& bage shows a greater growth response at an earlier age. This is
9 u. `' ^ @1 \( i6 Mconsistent with the findings of Wilson and Walker, who
8 D, z" W, i; {reported an increased conversion of testosterone to dihydrotes- \1 T b( O% {/ G$ c* i6 a
tosterone in the foreskin of neonates and infants.4 This activ-" `7 |# f% I" p+ h7 y
ity gradually decreases with age until puberty when it ap-' ~7 b( N8 B& {: I+ M+ t
proaches the same level of activity as peripheral skin. It may
1 H* L2 D7 l& {( iwell be that absorption of testosterone is less when applied at
R# o5 |( y: g5 B/ H3 u# y; K/ w/ _an earlier age as suggested by lower serum levels in children
4 B+ h8 {- f9 F* [less than 10 years old. This fact may be explained by the" b+ _: u e" q
greater ability of phallic skin to convert testosterone to dihy-- d8 k1 Z, X9 G- f" `) z" V
drotestosterone at this age. Conversely, serum levels in older& N, H: @3 R% y( a: G: Z, _% O1 U
patients were higher, possibly because of decreased local/ `$ f1 J7 B4 u" P3 G
667! e" W6 d2 S! c0 T) \. S9 U
668 KLUGO AND CERNY
# M' B/ X0 X* XPt. Age. c$ _; w! Y- A/ P. R( k' B! W
(yrs.)
# r* P% V9 w" Q% LSerum Testosterone Phallus (cm.) Change Length
S4 I6 V# Q8 v {9 N6 `+ `# ]2 X(ng./dl.) Girth x Length (%); k4 P) \; e/ X' p" I
4. ~" B5 h k% K$ N
8
3 Q" U. s" c8 i8 H10- v, t& H" C- J2 w3 x2 \
12( t2 ]0 Q" C# R* S' M
17
, e) u! S! e) o) DGonadotropin2 T' d1 B3 C: [5 A7 [; v
71.6 2.0 X 3 16.63 g3 u: z& e% x& Y/ ]6 ]4 V% d% W: c
50.4 4.0 X 5.0 20.0( ^) N( M! N' {7 j
22.0 4.5 X 4.0 25.0
1 r3 e! h$ v7 Y4 u, k% B84.6 4.0 X 4.5 11.18 M4 w1 p6 ^8 V# f5 I
85.9 4.5 X 5.5 9.0* N1 [, n& K5 t8 D4 {# S9 j
Av. 14.3! F4 \) C' A7 ^
4* V* I a p" k
88 P* [3 F& l! n! W: l4 i
10
; `+ z$ F& D/ }2 S12
0 f, J q/ W5 m8 D8 s3 B+ E; n+ P17
2 u9 H& H" g/ Q. l% @ |" `7 Z, PTopical testosterone
' v& b; q( y) G/ x; M( c34.6 4.5 X 6.5 85
3 H, T( P! t K# I1 k38.8 6.0 X 8.5 70. i9 z: B& K: X3 G# A
40.0 6.0 X 6.5 62.5
$ `: N8 K t5 `7 b' a+ D% O* c8 t93.6 6.0 X 7.0 55.57 X+ t+ t; }3 U, a2 p% N# c
95.0 6.5 X 7.0 27.2$ v, W% _# h# K- k' r9 \8 b1 X8 X
Av. 60.0
- i2 @( h7 @$ G% wavailable testosterone. Again, emphasis should be placed on; j4 ?. q# D( Q
early therapy when lower levels of testosterone appear to
/ \. _+ F0 T, z' ~# j! wprovide the best responses. The earlier therapy is instituted
& S+ Q5 z- T- L+ K8 Sthe more likely there will be an excellent response with low
, x! R' J. P3 ?$ r0 W# Wserum levels. Response occurs throughout adolescence as, b% Y6 w9 Q2 F2 s7 ~
noted in nomograms of phallic growth. 7 The actual response
% M: M! S; e1 Pto a given serum level of testosterone is much greater at birth% Q+ Y* u* F, }9 f Y
and gradually decreases as boys reach puberty. This is most
' {# F. N1 D# @# W7 G" G8 \2 rlikely related to the conversion of testosterone to dihydrotes-/ ^1 I. A0 y+ P( W7 @
tosterone and correlates well with the studies of testosterone
6 V* K$ x5 Y- Z7 p4 a% R8 y# bconversion in foreskin at various ages.
/ |2 ~6 L- t+ v9 l) i5 ]" m* j: @The question arises regarding early treatment as to whether5 [5 q) w$ Q( v* w
one might sacrifice ultimate potential growth as with acceler-
) \1 S# t n$ K9 `ated bone growth. The situation appears quite the reverse
: z [ F* P/ Q5 b' l$ C cwith phallic response. If the early growth period is not used
( H) Q. t( ^; b9 w8 M. ?; lwhen 5a reductase activity is greatest then potential growth
& }* l9 W! J; Mmay be lost. We have not observed any regression of growth X6 c$ t( y" ~2 f% O) }2 M. b8 j
attained with topical or gonadotropin therapy. It may well
" G0 j' O" o* M& f/ }, tbe that some patients will show little or no response to any
O" ], o2 o5 G/ k7 N( Tform of therapy. This would suggest a defect in the ability to
( U$ v- T) t3 h' R" ?convert testosterone to dihydrotestosterone and indicate that
0 A# M/ k9 ?" I7 S/ l! gphallic and peripheral skin, and subcutaneous tissue should0 M2 l4 F: N" D, V7 X
be compared for 5a reductase activity.
$ q' k# F N" J7 y4 Z7 }A, loop enlarges to measure penile girth in millimeters. B,- D' u1 _) t: v: x# V0 B
example of penile girth computed easily and accurately.
4 A, X: T7 I6 [7 s: `1 I2 n, }conversion of testosterone to dihydrotestosterone. It is in this
6 h' N1 ~' Z7 V' V- F+ @% S3 _7 colder group that others have noted high levels of serum9 ]; X1 B% h2 {7 W
testosterone with topical application. It would also appear/ ?; \( p' N2 @. \! @" I$ u
that phallic response during puberty is related directly to the
, ~$ {" b5 q | f6 G6 ^serum testosterone level. There also is other evidence of local% D/ k/ T* g) L5 F1 ]0 L
response to testosterone with hair growth and with spermato-% {( s0 A3 b+ V/ i
genesis. 5• 60 P T+ C: r, p1 n- u: ^& k# s$ L
Administration of larger doses of gonadotropin or systemic2 i4 s! Q. o$ h" D) J
testosterone, as well as topical applications that produce- s! G+ s# p; N* g8 S6 f. p
higher levels of serum testosterone (150 to 900 ng./dl.), will1 M( p3 J, v5 j* s, |
also produce phallic growth but risks accelerated skeletal/ q" c A# r" f" x+ e
maturation even after stopping treatment. It would appear
( h7 S5 b' b# A, g ^+ S% d2 p; gthat this may be avoided by topical applications of testosterone
2 w8 G% ~5 F: j, Mand monitoring of serum testosterone. Even with this control
1 K5 H5 ?5 b/ Othe duration of our therapy did not exceed 3 weeks at any
{- R! Z6 _& Rtime. It is apparent that the prepuberal male subject may/ v' x' X" o$ d2 U, E3 O3 `+ O1 b
suffer accelerated bone growth with testosterone levels near
; Y3 d2 v( x* z. o200 ng./dl. When skeletal maturation is complete the level of: O) j8 p! c* }" ?9 W, O" T
serum testosterone can be maintained in the 700 to 1,300 ng./9 P6 P& F/ {8 C% {
dl. range to stimulate phallic growth and secondary sexual6 a; V: |" O: x: k+ y
changes. Therefore, after skeletal maturation parenteral tes-
) Y( p0 l" b4 U0 a! q8 ^tosterone may be used to advantage. Before skeletal matura-: e( G, U" H- ]- o; U; m
tion care must be taken to avoid maintaining levels of serum2 ^2 z/ T" e& f& j+ F
testosterone more than 100 ng./dl. Low-dose gonadotropin0 A( j2 c! `7 v0 S( Z
depends upon intrinsic testicular activity and may require& H' F7 y! K! d9 Y8 d
prolonged administration for any response.
$ l* k$ U9 \3 m2 }: MAlternately, topical testosterone does not depend upon tes-
) I8 ~) d H D9 b+ zticular function and may provide a more constant level of* E2 I% ]. | z& b }( W
REFERENCES
, [6 `, i# F7 j1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
# Q% @; p( x: K4 N) jR.: The local application of testosterone cream to the prepub-3 x6 V5 a' M; q, H6 t4 s! e5 T
ertal phallus. J. Urol., 105: 905, 1971.. k {- q- [# b6 v# Q' D1 `" {# O7 z
2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone$ `% P1 g- Y1 Y/ S; W4 A
treatment for micropenis during early childhood. J. Pediat.,
! L& W+ k4 H- z3 `- g2 H83: 247, 1973.) ^7 H2 U6 r' _; o6 z- q
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-5 S: G& {; i1 \. y5 A9 }! I* q+ l
one therapy for penile growth. Urology, 6: 708, 1975.! M. r* ^1 e L% u, R6 k
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone
, c H- |+ Y6 uto 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
) U2 q1 y8 t4 u2 ]5 ]- _. pskin slices of man. J. Clin. Invest., 48: 371, 1969./ y) w8 i3 L( ^" q, }: M' O6 D& d2 U
5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth
9 _0 T a/ J7 p2 I3 E; O rby topical application of androgens. J.A.M.A., 191: 521, 1965.
& m4 Q9 V Q$ P6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
6 z2 d/ Z& L( l! T' nandrogenic effect of interstitial cell tumor of the testis. J./ z- j: V3 r+ ~# H% j8 b
Urol., 104: 774, 1970.
! J- m5 G* b. Q/ q7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-7 _8 E2 |' j& M9 ], E+ a, e
tion in the male genitalia from birth to maturity. J. Urol., 48: |
|