- 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
3 T+ z* `, @2 }GONADOTROPIN
; [( K; `3 z* t0 m) }4 o$ W' `+ vRICHARD C. KLUGO* AND JOSEPH C. CERNY" `- H8 z$ @3 r6 ?
From the Division of Urology, Henry Ford Hospital, Detroit, Michigan
$ K( F9 E3 B8 j, M3 j! A+ }ABSTRACT
5 T: `+ r5 u5 N9 P2 Z% `& bFive patients were treated with gonadotropin and topical testosterone for micropenis associated
* J; e3 V9 g* H% g. J8 Gwith hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonado-0 |) b0 |6 d @
tropin weekly for 3 weeks, with a 6-week interval followed by 10 per cent topical testosterone* {1 E* u+ z0 y4 V
cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent
) x% C$ ^% ^1 O6 efor both modes of therapy. Average penile growth response with gonadotropin was 14.3 per cent9 K; G( x9 r1 V- T: @2 D& n
increase in length and 5.0 per cent increase of girth. Topical testosterone produced an average
# e4 a% y* @2 fincrease of 60 per cent in penile length and 52. 9 per cent in girth. The greatest growth response9 Z- M Q4 ], ?
occurred in prepuberal male subjects with a minimal response in postpuberal male subjects. This* I( y/ \4 O' j) v4 Q" B
study suggests that 10 per cent topical testosterone cream twice daily will produce effective penile7 r3 W. Y& x+ y' p6 V* J4 P
growth. The response appears to be greater in younger children, which is consistent with previ-
" g. v- Z; T9 ^ously published studies of age-related 5 reductase activity.
v4 J9 o! h* r/ `0 LChildren with microphallus regardless of its etiology will
% `9 v _% n0 a* @6 N4 n! n' Drequire augmentation or consideration for alteration of exter-( Q6 f9 p2 M& }6 [; \
nal genitalia. In many instances urethroplasty for hypo-9 F4 E' e2 e3 ?. w S" I3 `
spadias is easier with previous stimulation of phallic growth.. }. ?) y- m2 O( i9 T" q1 ~2 l1 s
The use of testosterone administered parenterally or topically! w2 z; O* a2 ]4 q% O& [; g* \
has produced effective phallic growth. 1- 3 The mechanism of {' H8 Z! |* K& N
response has been considered as local or systemic. With this8 I; y+ B7 t6 s, l# a
in mind we studied 5 children with microphallus for response2 x( T/ b8 @# C: j4 U) A& T
to gonadotropin and to topical testosterone independently." _; k, r8 h' n9 `, b% `
MATERIALS AND METHODS
/ A' i2 X7 Y2 hFive 46 XY male subjects between 3 and 17 years old were
8 ^' J/ L8 y& a& ?* l$ [6 oevaluated for serum testosterone levels and hypothalamic
# j) \5 k7 Y( o1 x' J0 {function. Of these 5 boys 2 were considered to have Kallmann's
7 t6 l" b$ f# ~" O& Rsyndrome, 1 Prader-Willi syndrome and 2 idiopathic hypotha-: ^% U9 P* `8 U; I8 A; D" P
lamic deficiency. After evaluation of response to luteinizing! [8 [5 x1 V2 c5 l5 ?, X6 X- e
hormone-releasing hormone these patients were treated with% [* }$ a1 |( [5 @
1,000 units of gonadotropin weekly for 3 weeks. Six weeks
2 |# w r s2 B" T2 p# q jafter completion of gonadotropin therapy 10 per cent topical2 X7 m- L0 |! j/ B# e/ m3 S m0 I
testosterone was applied to the phallus twice daily for 3 weeks.
L/ s5 E- q, QSerum testosterone, luteinizing hormone and follicle-stimulat-7 z5 t% j3 }6 ^$ q# e4 H
ing hormone were monitored before, during and after comple-
( F- i6 P7 q% O& I4 ?( ?% Ition of each phase of therapy. Penile stretch length was- G' }( [6 g+ V/ a
obtained by measuring from the symphysis pubis to the tip of
4 P% Q2 r* R7 S1 l. X% rthe glans. Penile circumferential (girth) measurements were
" f$ Z/ ?& G% M8 p7 ~obtained using an orthopedic digital measuring device (see
: T- G* s, P% n, I7 @" o' c/ |figure).
1 h$ M! ?; R' {3 Q2 tRESULTS
6 b- s7 A1 z9 C. KSerum testosterone increased moderately to levels between M/ D$ U, v& l6 Q+ b3 |1 y9 k
50 and 86 ng./dl. with gonadotropin stimulation. Serum testos-; D) z% p% i7 C& n2 d( {
terone levels with topical testosterone remained near pre-/ u( P( [" D& D/ z+ g) ~' u, i
treatment levels (35 ng./dl.) or were elevated to similar levels
& E2 {, e) t2 q; i3 h `developed after gonadotropin therapy (96 ng./dl.). Higher' m' f5 b# `& w/ U5 y% J
serum levels were noted in older patients (12 and 17 years old),
7 ?) V6 q$ l3 v% e9 f8 vwhile lower levels persisted in younger patients (4, 8, and 10
6 z; g* ?8 g# `years old) (see table). Despite absence of profound alterations
: G) M' S/ P& B7 Cof serum testosterone the topical therapy provided a greater
% l$ O( A) A# s/ Q jAccepted for publication July 1, 1977. ·/ Y% Z {# B# k' l9 f) q
Read at annual meeting of American Urological Association,
! U/ {! j- M" {' Q6 c" TChicago, Illinois, April 24-28, 1977.4 q1 U! u( e' r# z) d! q ?
* Requests for reprints: Division of Urology, Henry Ford Hospital,
+ c) E+ ?2 l6 S7 H2799 W. Grand Blvd., Detroit, Michigan 48202./ E2 B; U( o, ^" \6 k3 M
improvement in phallic growth compared to gonadotropin. _- Z0 @, ]' @$ `* a; ]# b N
Average phallic growth with gonadotropin was 14.3 per cent
' ]# s, F& i" C( V6 mincrease in length and 5.0 per cent increase of girth. Topical3 H& h# z, q9 s/ m
testosterone produced a 60.0 per cent increase of phallic length
3 V% p& g1 {$ J% N$ d/ _' g% u9 Eand 52.9 per cent increase of girth (circumference). The7 L5 t1 @& v: |( S$ F5 u7 X1 U
response to topical testosterone was greatest in children be-
q" ?/ [9 I1 o2 ~6 btween 4 and 8 years old, with a gradual decrease to age 17" ] |& B4 s8 L* [! S7 C/ Y
years (see table).
6 {2 F: D" G# ^! ^9 zDISCUSSION* K* v( E/ H9 T: ^- b' H2 m
Topical testosterone has been used effectively by other
1 e3 h' H! n U( }clinicians but its mode of action remains controversial. Im-
( B o0 r, g, x4 B tmergut and associates reported an excellent growth response
) u7 H$ T; z! Wto topical testosterone with low levels of serum testosterone,
2 Y+ Q$ n" }# D. _$ v( H; Q1 [suggesting a local effect.1 Others have obtained growth re-$ _$ I' q d/ ~
sponse with high. levels of serum testosterone after topical
% `2 a6 s: I4 ^/ Oadministration, suggesting a systemic response. 3 The use of
! x" I4 y" H7 O6 ggonadotropin to obtain levels of serum testosterone compara-5 K8 K" t" {. E2 h
ble to levels obtained with topical testosterone would seem to& t7 A3 `1 a- D. {! A+ J3 f2 j
provide a means to compare the relative effectiveness of) P" c' y* C7 c, h6 c
topical testosterone to systemic testosterone effect. It cer-/ |7 W* J8 {' V- A
tainly has been established that gonadotropin as well as par-
" [( E9 g0 ]9 S R1 |9 v7 `enteral testosterone administration will produce genital: t* ]1 [+ U( \7 Y h: ^2 G
growth. Our report shows that the growth of the phallus was
& o2 T% J4 v2 B' isignificantly greater with topical applications than with go-
* a5 Q w0 B: P- snadotropin, particularly in children less than 10 years old.
, e- ~' M; P7 u0 _) w' \The levels of serum testosterone remained similar or lower, r+ U1 f5 C" K* n
than with gonadotropin during therapy, suggesting that topi-
( f1 X3 ?/ B) {. v/ |+ b2 Kcal application produces genital growth by its local effect as
% K0 p: O7 t& Jwell as its systemic effect.' N; H2 |' @ E( m
Review of our patients and their growth response related to
/ \6 Z- ?: j8 N* w7 i1 n( [age shows a greater growth response at an earlier age. This is
f; _8 R3 ?3 gconsistent with the findings of Wilson and Walker, who1 G2 _2 W, w+ c" e' _
reported an increased conversion of testosterone to dihydrotes-0 c) c( o H" p+ Y0 S9 e
tosterone in the foreskin of neonates and infants.4 This activ-
8 q1 d& ]7 }3 {/ f2 [ity gradually decreases with age until puberty when it ap-* Q) F/ t) C. A5 s0 ?/ r3 @- y
proaches the same level of activity as peripheral skin. It may3 v' L# p( H3 E) s2 U$ y* i0 t
well be that absorption of testosterone is less when applied at) i3 X% S. e5 V8 x$ m- \" J
an earlier age as suggested by lower serum levels in children
( \9 b, J# c4 Z% T5 E- S, qless than 10 years old. This fact may be explained by the1 Z1 | N0 `7 E' G' n( `
greater ability of phallic skin to convert testosterone to dihy-6 u4 b% U5 L$ |$ h
drotestosterone at this age. Conversely, serum levels in older9 R0 e5 B) ?0 x; g8 A& e& @( L
patients were higher, possibly because of decreased local; @' p" w, p1 ]9 r6 a! d& S
667
' [9 @8 f4 }8 e" {7 l" X7 j- p668 KLUGO AND CERNY
% d, N! g, [6 |Pt. Age& o1 b) L' m* V: j) e& l5 ~
(yrs.)
4 O0 |" x' @# b/ n7 aSerum Testosterone Phallus (cm.) Change Length
) X2 B2 u8 v5 ?( _" K8 s(ng./dl.) Girth x Length (%)0 P/ t9 J( ?6 M& g
4& K) _* R; y+ r2 U% a Y7 u
8* ^) n" R; s3 ^! j. h! t' c
10
) O' X3 L' p1 `6 u2 l4 `, i12
! ]5 L4 o6 b- o0 w17
# [! O+ c: a+ R# U) E, HGonadotropin1 q* i- |( n. X% Q3 W( c
71.6 2.0 X 3 16.6
7 @* D5 Z7 Q# |# A! L, s1 |! j50.4 4.0 X 5.0 20.01 p E4 v9 \7 b( _( Y# m
22.0 4.5 X 4.0 25.03 A5 R6 Q) d6 u- R5 a# E
84.6 4.0 X 4.5 11.19 r# ~7 y. w- D! a4 h, x# r! W! F
85.9 4.5 X 5.5 9.0
( p% Q: o1 j" { VAv. 14.3
3 }- J+ j0 L4 a5 T4
1 a H0 r3 O- Q2 ?80 z$ e# n2 F' I' j+ W4 l9 r! H
10* B8 d' X6 x: C* p0 G7 o% ^
12
B# X# m7 i( z2 L, \17
0 C" L* o7 z# w: V3 E" Y9 yTopical testosterone$ Y# }. O+ u* Y# _ |
34.6 4.5 X 6.5 850 E$ Z1 O4 v( L; T
38.8 6.0 X 8.5 70
: j3 Q" t4 q& l6 }$ J, l6 a40.0 6.0 X 6.5 62.5( F! F0 I1 M+ k$ E& l
93.6 6.0 X 7.0 55.5% e9 ~; z) g2 Q4 N8 Z: c( h+ g
95.0 6.5 X 7.0 27.2( ?8 K4 ]$ {; |$ y
Av. 60.0
& @ K1 ~: I1 b) _" F( q% \available testosterone. Again, emphasis should be placed on
0 r H- X& x- j7 u( J: A. Xearly therapy when lower levels of testosterone appear to+ B% U' n% v3 u+ y/ z
provide the best responses. The earlier therapy is instituted5 d: F+ R2 }' N! @9 t3 T% Y: D5 p
the more likely there will be an excellent response with low
6 M1 K6 ^0 W' d Userum levels. Response occurs throughout adolescence as
8 |2 L2 }% @: d, z7 k. e5 \noted in nomograms of phallic growth. 7 The actual response
j( h& X+ w1 W6 r" z& Z+ |/ L0 yto a given serum level of testosterone is much greater at birth' S6 q9 ^* o% ~* K+ [( }6 ]
and gradually decreases as boys reach puberty. This is most" r& g7 L# t( i' }% i4 b
likely related to the conversion of testosterone to dihydrotes-
! m* P% p% Q) D7 R2 J, ntosterone and correlates well with the studies of testosterone! w0 l4 N; v; a, x4 V
conversion in foreskin at various ages.
( U( H5 Y7 ]+ b: f. p/ GThe question arises regarding early treatment as to whether- u+ s2 K( r" p& ~! a, E. r# h
one might sacrifice ultimate potential growth as with acceler-
+ _4 `( J2 G& G2 n' R _ated bone growth. The situation appears quite the reverse* y- p5 j1 p" R4 c" {: _
with phallic response. If the early growth period is not used
) f3 D, {# L# g9 \, Dwhen 5a reductase activity is greatest then potential growth
" F. n# c1 T7 u; b; Ymay be lost. We have not observed any regression of growth7 t4 r; n0 O8 Y* _
attained with topical or gonadotropin therapy. It may well) x- N$ {, H+ n- c* z |/ Z
be that some patients will show little or no response to any
# {# J1 E* o- U. m1 aform of therapy. This would suggest a defect in the ability to
: | h' ?2 \/ P9 R+ y+ h! `0 C7 ]3 }convert testosterone to dihydrotestosterone and indicate that
* y; k+ n( z. V, P. @9 o7 O$ V8 Wphallic and peripheral skin, and subcutaneous tissue should+ r3 O" ?2 G! `, d g
be compared for 5a reductase activity.
- l. C6 y x, F6 _+ }" iA, loop enlarges to measure penile girth in millimeters. B,. E6 G# g1 E; q
example of penile girth computed easily and accurately.+ Q, D9 H l- \9 a: z$ d
conversion of testosterone to dihydrotestosterone. It is in this1 R/ S/ A& w0 `
older group that others have noted high levels of serum
1 {. q' k( p z1 F" h) v3 K8 Itestosterone with topical application. It would also appear) V, R2 V, y, l- R7 \
that phallic response during puberty is related directly to the3 q& a* X9 `. \9 b
serum testosterone level. There also is other evidence of local
3 _* g3 G8 B4 e9 Y# S& P# Aresponse to testosterone with hair growth and with spermato-
- f; ^4 v b3 G3 z* B: @genesis. 5• 6" _8 a( p' @8 }/ _
Administration of larger doses of gonadotropin or systemic
8 C, e! ]$ f6 P5 ~( }+ h; x* Ktestosterone, as well as topical applications that produce
! P5 x. K c6 W+ l' J; khigher levels of serum testosterone (150 to 900 ng./dl.), will
- g* [7 t& r9 m& ?! ~5 `; oalso produce phallic growth but risks accelerated skeletal
! M6 Y, f9 `9 j" v, ?+ D# v3 v9 qmaturation even after stopping treatment. It would appear
$ `; g J1 p: Z0 E( ]) pthat this may be avoided by topical applications of testosterone- [$ {+ M( i7 M3 b% D8 c
and monitoring of serum testosterone. Even with this control7 B+ G* ^3 @6 ^! N: o1 {! W$ ?
the duration of our therapy did not exceed 3 weeks at any
9 f* U7 d: T3 F9 y0 itime. It is apparent that the prepuberal male subject may
6 K6 b# x- V; k' r* ~1 h* bsuffer accelerated bone growth with testosterone levels near
1 G' d ?5 c/ } N( ~' C200 ng./dl. When skeletal maturation is complete the level of
" d; B) h0 q* q/ f# `6 r, t7 Cserum testosterone can be maintained in the 700 to 1,300 ng./
) Y0 m: X" ]/ {# \dl. range to stimulate phallic growth and secondary sexual
; Z, j+ j# P9 q; K9 r9 f' p N1 Xchanges. Therefore, after skeletal maturation parenteral tes-8 c1 P/ \7 I) j! B6 k$ _9 f
tosterone may be used to advantage. Before skeletal matura-
4 d6 o+ @. F3 Qtion care must be taken to avoid maintaining levels of serum
9 X/ v# }2 [, a' h6 {0 R1 D5 qtestosterone more than 100 ng./dl. Low-dose gonadotropin
" B7 ~- Z) r. j. {5 Pdepends upon intrinsic testicular activity and may require5 \+ I: L; Q& \3 A4 f& V; C
prolonged administration for any response.
7 b2 H5 F: ?, S! ^ n& bAlternately, topical testosterone does not depend upon tes-
# g* d( |) a0 Eticular function and may provide a more constant level of
. l! V2 h( L# z2 c3 W. bREFERENCES
. b, Q9 t2 F& D9 Q5 k1. Immergut, M., Boldus, R., Yannone, E., Bunge, R. and Flocks,
) f$ d9 n$ l4 c0 N7 MR.: The local application of testosterone cream to the prepub-, V6 t6 M& w! O% e/ h
ertal phallus. J. Urol., 105: 905, 1971.
; G/ T u$ A$ e# E2. Guthrie, R. D., Smith, D. W. and Graham, C. B.: Testosterone7 F9 U k' I; E, T: |
treatment for micropenis during early childhood. J. Pediat.,
$ U9 Y8 _2 o3 i3 v3 x( p83: 247, 1973.
0 n8 B8 |8 F8 ^$ d; c/ r3. Jacobs, S. C., Kaplan, G. W. and Gittes, R. F.: Topical testoster-
8 k! q: E% W$ K$ f8 M1 `: Yone therapy for penile growth. Urology, 6: 708, 1975.
! s' Z+ a& q* ?2 p% w* `1 X0 s4. Wilson, J. D. and Walker, J. D.: The conversion of testosterone# w* w* r; Z+ n) p5 e8 B: e
to 5 alpha-androstan-17 beta-01-3-one (dihydrotestosterone) by
4 d4 r, E4 r% u& Oskin slices of man. J. Clin. Invest., 48: 371, 1969.
% [! X! ^ F4 X. Y" [1 _- b* _5. Papa, C. M. and Klingman, A. M.: Stimulation of hair growth% E7 f; n- r2 j" U$ S& S6 Y
by topical application of androgens. J.A.M.A., 191: 521, 1965.
+ `- ]; g' |7 \4 ^ ?6. Gittes, R. F., Smith, G., Conn, C. A. and Smith, F.: Local
) Q6 a% L9 q( \) T* h# P! e0 r: aandrogenic effect of interstitial cell tumor of the testis. J.
- u& n/ H# ?! ]# H# q$ qUrol., 104: 774, 1970.9 L0 f2 f: p5 ?2 Q# \
7. Schonfeld, W. A. and Beebe, G. W.: Normal growth and varia-
5 D0 ?: \" e1 L" \; F: ltion in the male genitalia from birth to maturity. J. Urol., 48: |
|