- 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
# W$ m0 f- I& t7 w+ N# A( wGONADOTROPIN/ q; Q! Z; A: |; t
RICHARD C. KLUGO* AND JOSEPH C. CERNY
: [+ S+ S( _$ xFrom the Division of Urology, Henry Ford Hospital, Detroit, Michigan4 U8 M$ v) I5 c: K6 H5 W% m
ABSTRACT) n2 w: S2 ?4 J; a! {
Five patients were treated with gonadotropin and topical testosterone for micropenis associated
. S0 v0 a) \# y+ e5 P3 o' ewith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-: E$ L+ i% l0 q, U
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone
3 S! L9 A0 K9 |% Ycream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent
, Q! ?' [' U6 \# h6 q; Pfor both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent% O# X; [6 R S* v; _" A p
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average
' m s+ y/ U" @; h6 xincrease of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response( u5 a+ e Z. ^' m' A6 f
occurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This
8 W+ R) S8 @- A; Sstudy suggests that 10 per cent topical testosterone cream twice daily will produce effective penile
/ W5 N& ~3 T. _2 d: v* A# Xgrowth. The response appears to be greater in younger children, which is consistent with previ-
. Q, I6 ~: `; v+ k. Y1 Wously published studies of age-related 5 reductase activity.5 r! ]0 [3 j% t: [ b6 D
Children with microphallus regardless of its etiology will( p4 W8 q8 a6 S+ o
require augmentation or consideration for alteration of exter-
8 ^& C6 G" b" w/ Inal genitalia. In many instances urethroplasty for hypo-
" c) q" a1 W) h& a( Gspadias is easier with previous stimulation of phallic growth.
/ x8 C$ E& R% E2 R% \& i- @The use of testosterone administered parenterally or topically5 a m6 `! Q, R& V7 m% W3 D
has produced effective phallic growth. 1- 3 The mechanism of N7 G8 O F* b$ R
response has been considered as local or systemic. With this
/ J% q. Y: S3 g( F. zin mind we studied 5 children with microphallus for response
0 L; q! y# W& I/ [" q5 r2 x, k1 _to gonadotropin and to topical testosterone independently.& k( k& C; m( a' @
MATERIALS AND METHODS
! |( ^ V7 o* CFive 46 XY male subjects between 3 and 17 years old were
/ I4 U3 ~) ?/ s. \( sevaluated for serum testosterone levels and hypothalamic# w ]+ E7 w+ K6 Q
function. Of these 5 boys 2 were considered to have Kallmann's
, y+ j0 Z( {( t9 q$ l Y% lsyndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-- @8 k) b6 {# G4 Y* \$ G$ Q! p4 q! }
lamic deficiency. After evaluation of response to luteinizing
! G$ A( Z, h8 l- Dhormone-releasing hormone these patients were treated with
6 W! K0 P" u3 x# q- C7 l1,000 units of gonadotropin weekly for 3 weeks. Six weeks
1 F% o# I# x, ?! f; J8 V+ ?after completion of gonadotropin therapy 10 per cent topical) E1 [* n! b# |% w; S
testosterone was applied to the phallus twice daily for 3 weeks.2 r- L' P8 p' v0 `' z( D9 o1 [
Serum testosterone, luteinizing hormone and follicle-stimulat-
& t: [5 k+ l' y4 f% Jing hormone were monitored before, during and after comple-
$ [5 a2 D6 K+ mtion of each phase of therapy. Penile stretch length was
" j9 ?$ |/ n8 I3 B, Mobtained by measuring from the symphysis pubis to the tip of
' C6 J5 D R7 Tthe glans. Penile circumferential (girth) measurements were
- [. m' d5 |! S& V/ Q: I4 f9 O5 _obtained using an orthopedic digital measuring device (see
6 D1 J, K7 [" B" I5 Ofigure).
! @# Z7 J' i/ y5 `: WRESULTS
/ M3 ^5 |1 S0 z6 e1 }& T1 v5 G fSerum testosterone increased moderately to levels between
v# P7 v# e' m" E50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-; c! {6 @: C/ o+ S2 u
terone levels with topical testosterone remained near pre-) ^' L: N% _2 o6 D" D
treatment levels (35 ng./dl.) or were elevated to similar levels
1 m6 j5 G1 e" v: c& kdeveloped after gonadotropin therapy (96 ng./dl.). Higher
( Q. {' ^3 e- \/ {! Xserum levels were noted in older patients (12 and 17 years old),9 z% X, E8 n8 T8 N8 }
while lower levels persisted in younger patients (4, 8, and 10/ q/ }1 [! B0 l1 T6 ]& i2 g
years old) (see table). Despite absence of profound alterations
2 ?0 B- L% i* B! I+ Y1 mof serum testosterone the topical therapy provided a greater
% t- \6 J$ K. O1 d- nAccepted for publication July 1, 1977. ·5 d5 @% _+ _- j# Y( C
Read at annual meeting of American Urological Association,
4 e! p: V8 q1 q$ ]Chicago, Illinois, April 24-28, 1977.
" { E3 ~# p4 x+ p* Requests for reprints: Division of Urology, Henry Ford Hospital,! i1 E M; t! \( I' Q
2799 W. Grand Blvd., Detroit, Michigan 48202." j9 C" L) R. H" b" x
improvement in phallic growth compared to gonadotropin.' X$ ?2 J! P% L- L4 s& d; H6 n
Average phallic growth with gonadotropin was 14.3 per cent
/ Y+ A' }$ L7 B( jincrease in length and 5.0 per cent increase of girth. Topical+ Y+ u* j; p7 g, x2 Y; v, N3 g) u; o
testosterone produced a 60.0 per cent increase of phallic length
: M9 j- t5 {9 _and 52.9 per cent increase of girth (circumference). The, B, D, k& G, M2 ~! j8 T
response to topical testosterone was greatest in children be-
i9 V, i1 h- u" m- v# m; d3 ?( H/ Ltween 4 and 8 years old, with a gradual decrease to age 17 ]" C2 x) p; D: B0 |
years (see table).
* R$ f+ S0 @+ }3 WDISCUSSION. b3 j8 s, x1 N v
Topical testosterone has been used effectively by other
) y2 Z) E4 S ]( J% t& H5 Gclinicians but its mode of action remains controversial. Im-
5 i T) \- }' |6 ?0 Zmergut and associates reported an excellent growth response8 B. w8 J" f* a
to topical testosterone with low levels of serum testosterone,& R" A/ l5 Y! M$ t8 O2 U; F
suggesting a local effect.1 Others have obtained growth re-6 h- l1 n5 U9 H! h* m2 A' y
sponse with high. levels of serum testosterone after topical2 C9 [' n0 P$ j: y b z8 e1 @& Z
administration, suggesting a systemic response. 3 The use of! j) t( }5 \3 t, m( Q
gonadotropin to obtain levels of serum testosterone compara-. S6 p. M3 v D5 E$ j- U
ble to levels obtained with topical testosterone would seem to
. u1 x4 U3 ?% D( ^% P. cprovide a means to compare the relative effectiveness of
5 x0 G. i: V4 Y5 u) [0 Rtopical testosterone to systemic testosterone effect. It cer-1 `* V2 I7 e1 x/ g& X# f) g8 w) r
tainly has been established that gonadotropin as well as par-
, ?3 p% h6 I: m7 K2 j; T0 ]7 _# Oenteral testosterone administration will produce genital
! P0 p+ g1 z9 @& G* Z* Y0 v0 b7 ]. xgrowth. Our report shows that the growth of the phallus was3 R! ?; h" H0 X& ?# {6 [. C4 A4 i
significantly greater with topical applications than with go-
$ o# M: \. Q8 G8 m+ m b! X! Q vnadotropin, particularly in children less than 10 years old.
! @( Q6 M& r: q/ T/ i! H) o4 vThe levels of serum testosterone remained similar or lower
) N M- ?4 {# f8 a" @0 hthan with gonadotropin during therapy, suggesting that topi-
, p. m G2 E: G4 H9 p7 l9 B+ j x* rcal application produces genital growth by its local effect as" x: X0 w+ P+ O; G! s
well as its systemic effect.7 x$ q4 u, S6 M6 n$ q
Review of our patients and their growth response related to" w% ~4 G p- m# h, Q$ W
age shows a greater growth response at an earlier age. This is# y) \* Z9 c$ J& P
consistent with the findings of Wilson and Walker, who. U; |0 U1 _4 f' o2 N2 g; Z
reported an increased conversion of testosterone to dihydrotes-
" q5 A% g3 E) M+ M2 w/ `) mtosterone in the foreskin of neonates and infants.4 This activ-1 a2 h8 y5 g" o0 R/ b% ?
ity gradually decreases with age until puberty when it ap-8 e0 V' B' x, ~
proaches the same level of activity as peripheral skin. It may
2 f9 m4 [: y0 M8 R5 r! uwell be that absorption of testosterone is less when applied at
: u+ r4 p6 A- w* Z# Qan earlier age as suggested by lower serum levels in children
- c% q) H2 p. e; ^less than 10 years old. This fact may be explained by the
) x9 P# ~# t! d: J# v; a! p0 kgreater ability of phallic skin to convert testosterone to dihy-. N! A- k8 ?4 j4 L# o% G5 H+ ^" U
drotestosterone at this age. Conversely, serum levels in older5 ?3 b' I- o' O8 S
patients were higher, possibly because of decreased local3 x$ f6 u( C* B% o5 g
667- v5 H0 W' ?( R! q' x% J$ a. {* x
668 KLUGO AND CERNY" p5 O) C# B9 e
Pt. Age
% s+ ~9 q6 V3 a3 q' j& Z(yrs.)+ l. W/ O% T5 j3 X8 ]
Serum Testosterone Phallus (cm.) Change Length% j% O# ^0 e* C3 D
(ng./dl.) Girth x Length (%)
" S3 Q+ `: R8 A7 \4& B2 ]# a8 w' s, }
84 \/ u1 c8 r- c6 T" p3 b1 u4 m
10
0 N7 i( l" d+ X } a# Y2 C5 _12
' b8 z' ]' o3 l2 q$ n! ~' O17; B1 r" ^8 y" J% S( u$ Q, ]
Gonadotropin
5 k' d6 N; S: S$ a% X. _& }71.6 2.0 X 3 16.6& h! \" l p6 Z! G! _
50.4 4.0 X 5.0 20.0) w! E( V2 L( k( j( u
22.0 4.5 X 4.0 25.0" Y& z2 O4 H, }& c) a$ _; ]
84.6 4.0 X 4.5 11.1
0 o5 W6 q3 v9 V# z9 R: {85.9 4.5 X 5.5 9.0
8 i' O. j6 G+ G0 h8 IAv. 14.38 J& R4 U7 Y6 P2 x$ w$ |
44 a& ~- b: u4 H* x: o
8% W; Z/ y5 }- q3 {4 _. y0 E
104 s* ~. P% r- p8 X
129 ~' D+ r' r2 M% Y* c: U0 y
17, f& Q8 w* M3 W, V7 L; `
Topical testosterone+ _. Y' Y# w$ X% _% T5 L5 L2 ~
34.6 4.5 X 6.5 85- a J- W* x0 _1 R) I8 c
38.8 6.0 X 8.5 70& }! Q% E2 t7 q: P8 D/ j# N- s
40.0 6.0 X 6.5 62.5
' P2 q- v: l5 I93.6 6.0 X 7.0 55.5
) F$ M4 ^8 ]' U0 |0 Z0 H95.0 6.5 X 7.0 27.2, j# k$ J+ H$ Z9 p, \
Av. 60.0
" m, K8 K) o% q" B# {! j7 Q+ @available testosterone. Again, emphasis should be placed on* v. z: d" t. f$ O" g( \* m$ n7 ~, s
early therapy when lower levels of testosterone appear to
9 J! R. m3 X1 @+ o5 ~ z) }2 _provide the best responses. The earlier therapy is instituted
. h6 f7 H! i( e, V! h9 B: c1 G3 v3 ^ Bthe more likely there will be an excellent response with low) @4 t9 L7 ]6 X L5 J6 ?
serum levels. Response occurs throughout adolescence as
7 D% |' T4 P4 h" b& ~& \# {noted in nomograms of phallic growth. 7 The actual response
2 z1 Y0 [6 R0 X* Lto a given serum level of testosterone is much greater at birth
) H8 O- b- Q' n# @: z2 Tand gradually decreases as boys reach puberty. This is most
$ ^8 ?/ i8 J; d) P; A, P' Olikely related to the conversion of testosterone to dihydrotes-
5 [2 Z" C2 R$ {3 u/ s6 b; \tosterone and correlates well with the studies of testosterone$ h2 l. }' c+ Z' {+ E. k
conversion in foreskin at various ages.3 B: m- ]0 Y5 `- X+ u" ]
The question arises regarding early treatment as to whether
5 I% e$ h4 x H' U# Ione might sacrifice ultimate potential growth as with acceler-
! e: u- v5 t4 cated bone growth. The situation appears quite the reverse6 u2 C% R9 B' f4 t
with phallic response. If the early growth period is not used6 Y6 V9 O- }: W' M1 Z
when 5a reductase activity is greatest then potential growth( i% ~7 J* _; D' \, n% z
may be lost. We have not observed any regression of growth
2 m% R. L% k* R4 @# Hattained with topical or gonadotropin therapy. It may well' A. g5 s, j* T1 C* M/ ^3 @
be that some patients will show little or no response to any
4 G5 `( ]6 K1 F. ~+ _form of therapy. This would suggest a defect in the ability to E! {' \$ l5 m2 S' B' B
convert testosterone to dihydrotestosterone and indicate that
7 A `' f0 [0 m) H$ k! n7 m* B4 v7 Jphallic and peripheral skin, and subcutaneous tissue should
7 Z* B5 P# A8 ube compared for 5a reductase activity.& i* K7 f9 K: R
A, loop enlarges to measure penile girth in millimeters. B,
/ X; M2 z$ `" h( \" Y0 s/ nexample of penile girth computed easily and accurately.
2 L& S8 e8 c9 ^8 O# ?* x: d# {: B0 ^conversion of testosterone to dihydrotestosterone. It is in this
. s _7 G; H8 ?0 ~. R7 [older group that others have noted high levels of serum
4 N" \( h% Z/ x$ |testosterone with topical application. It would also appear; o& e1 P0 i) u' S2 l+ ]
that phallic response during puberty is related directly to the4 q. t6 ?/ N8 m( j# c) Y
serum testosterone level. There also is other evidence of local U0 q/ W" ]' V5 k. A% A
response to testosterone with hair growth and with spermato-
" g0 ]& A: i' Y" ^' Y5 Ggenesis. 5• 6
* c8 E3 X& {" S+ t/ |8 ~( |; oAdministration of larger doses of gonadotropin or systemic; l) M5 G( L# w4 d# S$ D0 H
testosterone, as well as topical applications that produce
# p* V* f3 Y* [higher levels of serum testosterone (150 to 900 ng./dl.), will
- ^* c2 Y; d8 Salso produce phallic growth but risks accelerated skeletal& o& i. [1 ~% f+ [! G
maturation even after stopping treatment. It would appear2 E. T5 ?4 O' c4 ?
that this may be avoided by topical applications of testosterone
2 P$ V) J) ~1 p4 n6 Pand monitoring of serum testosterone. Even with this control5 X9 h. D4 @3 w }4 N3 ?' i
the duration of our therapy did not exceed 3 weeks at any1 u+ g7 q/ h! I, `: ]1 a: a
time. It is apparent that the prepuberal male subject may
0 O% C2 \4 V. U4 A0 wsuffer accelerated bone growth with testosterone levels near; V7 Q3 G( i, K5 I( S8 }0 f* Y0 D
200 ng./dl. When skeletal maturation is complete the level of
) `* j z/ a$ r5 w! [serum testosterone can be maintained in the 700 to 1,300 ng./
9 R, ?- H9 a/ p- J j. \dl. range to stimulate phallic growth and secondary sexual
; F, l; G' h X4 L# ], K3 ?* E3 A% }7 Rchanges. Therefore, after skeletal maturation parenteral tes-
L, ~$ P! c( I3 B: ^8 V4 W* w" Vtosterone may be used to advantage. Before skeletal matura-
d5 A% U* R# x9 w. `5 [tion care must be taken to avoid maintaining levels of serum. R' ]/ k! x7 ~; l; P
testosterone more than 100 ng./dl. Low-dose gonadotropin
! i: ~% C/ z, n( k) A' fdepends upon intrinsic testicular activity and may require0 W# Z1 \: s2 V0 h8 ^* e/ g
prolonged administration for any response." d# }5 k4 ^3 a; O7 n- v u
Alternately, topical testosterone does not depend upon tes-
+ }# a% n( h3 `/ s( ~- ]) s/ Gticular function and may provide a more constant level of) m. G6 H, J& j9 v# {& f ?
REFERENCES0 T( ~6 v' I- S
1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,% o& {+ |- N6 j% _( u- j% \2 o
R.: The local application of testosterone cream to the prepub-
4 w4 |+ `; }2 b# q/ Yertal phallus. J. Urol., 105: 905, 1971.
7 P' D$ q% Y, V. {2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone
/ [* Y0 b6 x5 l1 V2 |8 _. mtreatment for micropenis during early childhood. J. Pediat.,0 h2 @% r& D9 o9 B
83: 247, 1973.; Z' v" v9 w' t6 o& {
3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-3 m7 i1 H5 K+ P0 X/ U; E$ W' R
one therapy for penile growth. Urology, 6: 708, 1975.5 i* h& u1 k0 {" B0 T% i& `0 M5 ~
4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone- ?. M5 y( b" S3 S9 b2 B
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by# W7 e/ h% V+ m* X, O
skin slices of man. J. Clin. Invest., 48: 371, 1969.
, |) l" B r* M, X6 C: k5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth. E; _1 j; r9 Z4 v+ D) g
by topical application of androgens. J.A.M.A., 191: 521, 1965.
9 v1 x+ i/ d0 K% n6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
. i# C1 X2 Q9 }: b9 v9 iandrogenic effect of interstitial cell tumor of the testis. J.
! o/ X7 u3 Q* H( \2 g4 jUrol., 104: 774, 1970.
' `' Y1 S8 x- i! J8 X+ d$ Q1 H7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-
7 h2 p* P4 p4 X3 J3 F' u" y' ^/ `tion in the male genitalia from birth to maturity. J. Urol., 48: |
|