CONTRACE

E EF

CT OF D STOST !.

DE T ON I

SP E

DOS

J. Frlck, l G. Bartsch,

2

GEST E ENESIS . V S

and W.-H.

E

ION

E

Welskel

I 2 Department of Urology, S a l z b u r g G e n e r a l H o s p i t a l and U r o l o g i c a l D e p a r t m e n t , U n l v e r s i t y of Innsbruck, stria

S

T

Depot m e d r o progesterone acetate ( ) w a s tested for s u p p r e s s i v e effect~ spa t o g e n e s l s in 29 n. A s n l s t e r e d as a nthly i n j e c t i o n of I00 or 150 rag; in addition, t e s t o s t e r o n e s given either in subde al s u s t a i n e d r e l e a s e i m p l a n t s of t e s t o s t e r o n e p r o p l o n a t e (TP), or as a m o n t h l y injection of I00 or 250 mg t e s t o s t e r o n e e n a n t h a t e (TE). S p e r m p r o d u c t i o n was r e d u c e d in 28/29 subjects. In most instances, production s s e v e r e l y inhibited, a s i leafed e i t h e r b y s p e r m c o u n t s below i lilon/ or by t e s t l c u l a r b i o p s y s h o w i n g s p e r m a t o g e n l c arrest. c h a n g e s w e r e r e p o r t e d or o b s e r v e d in the size, consistency, or senS l t l v i t y of breasts, t e s t iJ c l e s or prostate. Some s u b j e c t s r e p o r t e d slight i n i t i a l d e c r e a s e s in libido, but r e t u r n e d to n o r m a l after the flrs t f e w w e e k s of t rear n£. Met ol ic par eters w e r e m e a s u r e d in some subjects, and s h o w e d no s i g n i f i c a n t changes. T r a n s i e n t w e i g h t gain o c c u r r e d in a few subjects.

Accepted

J

1977

for

publication

.15

.6

~ebruary

18,

1977

9

CONTRACE

ION

I

CTION

Depot medro progesterone acetate ( A) h a s be d e l y u s e d as a p r o g e s t l n for fe ie c o n t r a c e p t i o n (1,2,3,4). In u r o l o g y , t h e co po d has been utilized therapy for prostate care 0 , h ernephro prostatoveslcuiltls ....d h e t o s p e r ~ l a (5). l y rain 1 s i d e ...e.f f e c t s h e b e e n d e t e c t e d in t r e a t m e n t of l a r s e n u ers of people (6,7,8). R e p o r t s of i n h i b i t i o n o f s p e production by rats ( 9 ) d n (i0) s u g g e s t e d the p o s s i b i l i t y of u s i n g t h e co ound for male contraception. Accordingly, the current studies re be n, u s co ation wlth a tes st e r o n e p r e p a r a t ion, the i a t t e r d e s i ed to co e n s a t e f o r a n y s y s t e m l c testosteron~e d e c r e a s e (9) p as il as to e n h a n c e the i n d u c e d s u p p r e s s i o n of s p e r togenesls (i0,ii).

DS e s u b j e c t s w e r e 29 u r o l o g i c a l p a t i e n t s . There re 16 n with p r o s ta t e s i c u l i t i s, he t os p e i a o r s u b - f e r t i ~ i ty p r o b l e m s (2 4 42 y e a r s old) a n d 13 m e n w i t h b e n ! prostat~ ~ .......-....t ..r o p h y (BPH) (6382 y e a r s old). e regl ns, d u r a t i o n s of ........ a~e d i s t r i butl s of s jeers are presented T a b l e °~ A f o r i n t r ....s c u l a r i n j e c t i o n the b u t t o ~ ~ s p u r c h a s e d as Depo Provera R from Far talla, M i l a n , i n a c o n c e n t r ~ t l o n of 5 0 rag/ / oule. T e s t o s t e r o n e p r o p l o n a t e c a p s u l e s for s d e al i lantatlon u n d e r the r i g h t ilia were a ~ift of the Population Council, rk. e capsules, of Silastlc r e 2 c ~ in l e n g t h ~ t h 2.4 outer

from Scherl N York.

AG,

Berlln,

or as D e l a t e s t

IR f r o m E . R .

Squibb a

Sons,

P!as a FSH were dete d b y a pol t e~e t e iflcat l o n o f the th of oslg i a coilab a t o r s (13) ° B a r e's meth (14) s used for assay of plas testostero (T) ~ a Co t a's th (15) s f o r d l h y d r o t es t os t o n e ( T). Pla s es t d io 1 (E2) c centrati s w e determl ace dl to e tec l q u e of Ho iss e t a_~i. (16). e deter ti of plas 1 els s d by the of ist a J a n s s o n (17). Blo sa les oups ilI-V were itored for tabollc para te : d ect a total billin, t ol t b se m E tam 1 cetlc ira a se, s e r glut ic p £c i r a am se, a l II phos tase, a¢ phosphatase~ blo urea nl ogen, choleste I, t r l g l erides, ealc ~ t in, t ~: trliodothyron ej a cortisol. Se n a lyses were p d as usly report (i8). s t l c ies, p r o s t a t e a breasts were e ~i d at each vlsi~. S nta o co nts i o pore y re c d e d .....

650

$

l! 1 9 7 7

L. 15

.6

Table I. g ns, durations of trea nt, ,I age distr%bution of subjects r e c e l v g depot dr yprogesterone acetate ( d testos terone propionate (TP) or ....testosterone (TE). All ec£1 s wet e tr scu far, A I l p I t s wet e sub d e 1. Group I N

er of

S

jeers

Age S. ) 1

1

2

26 30

26 .... 39 II

63 -

74

35

III

68 I 2 4 - 42 "

71-

32,42

V

1977

L. 15

.6

~urati trea

en !00 imj e ct ion s ( ~ce~ 5...we . inter i); 6 capsules pl ted at e of first iection i00 ~ jetted m th ly; 4 ¢aps u les pl ted at t of f irst jecti .

6

:

100 I00 I00 250

] 100150

1 ~

nth jec

s

nth iy

je

s

of nt s

wks

I0,26

s

6-20

s

6-26

s

8

S

16

s

1

C

TRACE

I

Re su It Group

l ....

o in~ections

of !00

D

~5

eek

interval)

lus

6 TP

A z o o s p e r m i a d i d n o t o c c u r in e i t h e r s u b j e c t w i t h i n 6 w e e k s a f t e r the f i r s t i n j e c t i o n (Fig. I). A t I0 w e e k s a f t e r t h e f i r s t i n j e c t l o n (5 w e e k s a f t e r t h e s e c o n d ) , one s ject's sperm counts had decreased f er, f r o m the 6 - w e e k v a l u e of l0 m i l ! i o n / m l to I ~ i l l i o n / m l . e o~er subject was not a i l a b l e f o r f u r t h e r foil up. e e f f e c t s on s p e r m m o t i l i t y w e r e n o t c o n s i s t e n t in e i t h e r s jeer. Blood s dr n w e e k l y f o r 6 w e e k s to d e t e r ne e pias levels of , F S H , T, T a E2 (Fig. I). , FSH a T levels decreas w i t h i n one w e e k a f t e r the f i r s t i n j e c t i o n . In s o m e c a s e s , they s s eq ue n t I y ros e, t h o u g h r e in i ng b e I p r e t r e a t me n t v a l u e s .....the s e c o i n j e c t i o n at 5 w e e k s d i d not p r e v e n t the te e n c y to r i s e . DHT fluctuated d u r i n g the 5 w e e k s f o i l i n g the f i r s t i n j e c t i , and second i n j e c t i o n h a d no a p p a n t e f f e c t . E2 s h ed l i t t l e d l s c e r n i b l e c ge after either injection, e r e w e r e no c h a n g e s s u b s e q u e n t tO e i t h e r i n j e c t i o n in l i b i d o sexual act ity, or in the size, c o n s i s t e n c y or se it i t y of b r e a s t s testicles or p r o s t a t e . Body weight was unchanged ~ t a b o l l c para ters w e r e n o t m o n i t o r e d .... Gr6up

II.

n

ly i n j e c t i o n S 2-3).

of I00

plus 4 T P

sules

_( D i e

.....

In the y o u e r men, 4 Of the 6 s u b j e c t s e ited a z o o s p e r m i a b e e e n 6 a n d 12 w e e k s a f t e r t r e a t m e n t b e g a n ( b l e if). All of e 5 older n sh ed d i s r u p t i of s p e r t o g e n e s i s in t e s t i c u l a r b i o p s i e s perfor d a f t e r 6-7 w e e k s of t r e a t m e n t . Figs .....2 a 3 p r e s e n t th~ t es t icu far h is t o l o g y f or a re pr es e n t a t e s j ec t. values sh ed l i t t l e a n g e a n d no a p p a r e n t p a t t e r n ( b l e II). Plas T d e c r e a s e d s l i g h t l y in 7 s j e e r s , i n c r e a s e d s l i g h t l y in 2 s jeers, a re ined u h a n g e d in 2 s u b j e c t s . No changes occurred in the size, c o n s i s t e n c y or s e it i t y of e h r e e s t s ~ t e s t i c l e s or prostate. E i g h t of t h e II m e n t i o n e d a d e c r e a s e in libido, but o n l y d g the f i r s t 3 w e e of t r e a t nt. ey a l s o e x p e r i e n c e d ight gain, up to 2 b u t this too d i s a p p e a r e d w i t h i n a f w e e k s . . . . tah o l l o p a r a m e t e r s w e r e no~ m o n i t o r e d . Gr

p III

nth _ ble I

ectlons

of

I00

In I of the 2 y o u n g e r s u b j e c t s , 20 m i l l l o n / m l d e s p i t e r e g u l a r t r e a t

652

nt

~

d I

e sperm count (Fig. 4).

.I

did t drop bel e other younger

E 1977

L. 15

. 6

m! O.S'

Oe3i

1

2

3

4

5

6 w

1

2

34

56

in m W ~ IL.H in I

/ml

26 yrs St.S, 30 y r s

R,H.

A

12 9 6 3

2 I

:2

3

4

5

6

o

eks

1

E2 in ~ / ~ 1

2

~/"

30

:3 4

5

6 w

o~~ ....

3~.

~ - 30

10

ie i i

2

3

4

S

6

~

before

~fter3w

~e

" ....

~

~

in ~ t

Sl.S.

ks 1%

Swe li|ily

~ S . -..........-...

Fig. I E f f e c t of capsules i

J

E 1977

I

i n j e c t i o n s (A) of I00 (5-week Inte t e d at e tl of the ffirst I n ~ e c t i o n °

.15

.6

al) and 6 TP

6

NTRACE

ION

ble I I Effect of nthly injections of I00 M m o n t h s (12 w e e k s ) c o ination with implantation capsules at the tlme of the flrst in~ection.

S pe r m C o u n t s I i o n /ml ......:~ , .

.

.

.

.

:::~:,:: ~ 17 •........~.... ........................... ! ............0

39 33 23 -_-_ 20

S

.

.

Sperm

t i i i ty

%

.

Ti

...............................37 ..

ks 8

Pla s t e s t os m t e r o n e ...... ;,looi., a f t e r s t a r t of t r e a t ~it 12wkS 6wks i 0 0 39 : ...Z: . "'

!

17

~ 15

17

28

45

0o39:.0 25

9 10

]

0 6

6 53

3 42

0 30

0,2 2 0,27 0 , 1 4 0,

0

I 4

40

0

14

0 ..5..9 0,50

0

[ 17

28

.

.

i

FOR

f o r 3: of 4 TP

0 38 ............... .........

.

.

.

.

I "7

6.91 8,2

8,5

9,2

7. 6 4,2

9,8 9,8!

6.8

12.3 18.0 14 0

0.28 0,33 8 , 0 i0. ii,0 ~..~..........~ ........ =. =:~............ P la s t e s t osPla s terone 0 i = T£ a f e r st treat

5 SUBJECTS :

.

....

~es tlcu far ~!e-trea en I wide t u l e s w i t h a l l ...s. = a g e s of s p e togenesls, !nterstlt I tissue and L dig cei!s no i.

of trea en. ed ge cell depleC~ . Disorganlza=ion a depopula=ion o =he seml I t ....u l e ep i t h e i£ . S ome ge = e i is necro=i=. L e y d £g c e [ is a t phlc,

654

1

39

e55

0~34

°54

i0~ 2

6.9

7

10,2

8, 4,4

J

1977

0

5

9.

L IS

-

-

-

8,2

.6

CE

'

°'::i

N

o, i

|

i # ~¸ " ~ # o

~i~¸,~

b f.

°

4

Fig. 2 Pretreat nt t e s t l c u l a r b i o p s y o f 6 3 - y e a r - o l d s u b j e c t II). No al w de t u l e s w i t h a l l s t a g e s o f s p e r togenesls. s t i t £a I t i s sue a n d L e y d l g ce I i s n o r i. ~tx ....Eo s in; p r l m s t ion 2 00X )

.

.

.

.

.

.

(see T a b l e Intergni f£ ca-

,,

~o

Fig 3 Testlcular blopsy of the s s ject as in Fig. 2, at 7 w e s a f t e r o n s e t of t r e a t n t (I00 m E m o n t h l y , 4 T P imp! ts at t i m e o f f l r s t inJ e c t l o n ) , rke d ge ce! 1 d e p l e t l o n .... ters t l t l a l tls sue flbrotlc, L d i g ee lls p a r t ly at ph~c. (Htx-Eosln; primary gnificat i o n 200X. )

J

1977

L. t 5 N O . 6

655

CONTRACE

ION

Sper~

80

counts

mil3. im!

d ~

70

Ko

.

% Moti!ity

35 y r s

~

80

7

|

60

~

50

~

50

40

~

40

30

-

60

~

,30

|

2o

,~ -

2o

4

:|

1

Sperm

2

3

coun{s

4

5

6

7

S

9

mi!!.lm

10 11 !2

~ Moti!ity 6 ~

7Q

Joj.

months

35

yrs

• .... O

I

70 60

50 . b ~ 40 '~

30

i

.

.

.

/r 0/

.

~

20

•

=

~! 50 q 40

B

~

°

30

20

I0

10

i

2

3

4

5

6

7

8

9

!0

IX i2

m0nths

Fig. 4

Effect of s

nthly Inject¢ons

(A)of

I00

and i00

TE in the younger

.1

L. 15

e c t s.

656

E 1977

.6

P T P g / 1 O0 m (

o.sj,

MPA

0,6 ~

nglm!

A i

O.Z 2

4

6

........... i 0 '12

months

2

4

LH m Uim !

F S ff m U / m !

~0 40

50

30

30

40

20

: %

10

~O~wO

T

,/o

20 10

O

8 10 12

6.

~ os °

~

2~.........4..............6...... 8

I0 12 m o ~ s

2

4

8

6

10 12

EZ pqim!

60 40

K.J.

35 y r s

* . . . . . . . . -J.J.

35 y r S

30 20 10 2

4

6

8 i 0 12

months

Flg. Effec:t yo

of s

E 1977

nthly £:njectlons P 8 s ~ects

. ~i5 ~ ~

,~

(~)of as

5

I00 mg in Fig

and

I00

mg

TE

in

e

4).

657

CE':~ TO~N

....

PT

pg!!O0m!

Poll

68 y r s

7r

~4 !

N

2

i

6

$ i0 12 14 i6 18 20 22 24

6

8

S

tH mU/m| 6 4

2

2

4

l0 12 !4 i6 18 20 22 24 w

FSH mU/m! 15 12 9

6 3 ~

2

4

6

8 1O 12 14 16 18 20 22 ~

S

2

4

6

S 1O 12 14 16 18 20

:s

Pg/m! 40

30 20

10

Fig. Eft ct of representat

658

n e

iy £njectlo o!der s jeer.

(&)

o~

6

100

...a .n d

I 0 0 ...m.g

1977

in

L. 15

a

.6

,

,

N

¸

ble III. Ser emlst data for a 6 8 - y e a r - o l d s J e c t t r e a t e d w £ t h I00 a I00 TE n t h 1 7 (sa s ject as £n . 6) o V a l u e s are g i v e n r direct a n d total b i l i r in, th I turb£dity3 se Siut Ic o ioacetlc t r a n s ~nase, set glut py v l c iron8 inase, alkallne phosphatasep acid phosphatase, blood urea nltrogen~ oleste 1 e trlglycerl s, calcl xln, th y........ (effect e t h y r o x l n ratlo t E ) j and rtiso I, respect ely

....

I

% %

|

%

O.IS

3 M~ 1-15 1-15

S

m! ml

i

il

t 1t

i

~ ~

%

lm

IL

. IS

. 6

rag%

= %__ e

~

1

~

!

I

W 1

1

° °

t7

tO

! I ~

t I

3

~

,S ~ S it

1977

I I!

|

LS

I ilo!

8 !7

U

1

]

1

6

CONTRACE

,)eet e m o n t h s to motillty treatments" a it re severe i w a y as sh

I

ted sere o l i g o z o o s p e r m l a (d to l O , O 0 0 / m l ) f r o m 2 1/2 5 I/2 nths (3 m o n t h s a f t e r the last i n j e c t i o n ) . Sperm s d e p r e s s e d in one s u b j e c t d u r i n g a ~ d i e d l a t e l y f o i l Ing the o t h e r s u b j e c t h a d i sperm ~ i l l t y b e f o r e treat n, ined I . e g o l d e r s u b j e c t s In thls gr p a l l sh ed i b i t i o n of sper togenesls dur g DM treat nt, in the sa n pr i o u s l y in F i g s . 2-3.

Plas a FSH va es in the 2 unger s jeers d e c r e a s e d w i t h in =he f i r s t w e e k (Fig. 5 ) , en sh d so rec cry durl treat nt, except for in o s ~ect. T I e!s f l u c t u a t e d d ing e period of ections. E 2 increased a then declined d ing t r e a t nt .... d e c l i n e d sl ly, and at a b o u t the s a m e g n l t u d e , in the 2 s ~ects; h ever, in one s u b j e c t this o c c u r r e d d e s p i t e the c o n t i a t i o n of i n j e c ~ i o n s ~ w h e r e a s in the o t h e r it o c c u r r e d a f t e r ~he c e s s a t l of in~ec~ion8 .

e plas hot p a t t e r n s for the 5 o ~ e r n w e r e s i m i l a r to each other3 and representat e data are present in Fig. 6~ P!as , FSH a T declined durl t h e co se of the i n j e c t i o n s , cress E2 i n c r e a s e d . No d a t a a r e a i l a b l e for i els. No of e 7 s jeers in e gr p had a es in l i b i d o or s e x u a l act e size, c o iste y or s e n s i t i t y of e breasts ~ testicles or prostate, e tabollc pard ters f o r the g r o u p sh ed n o p r o n o u n c e d t r e n d s d ing t r e a t m e n t . In T le l l l , r e p r e s e n ~~, a t ! 6 e d a t a a r e p r e s e n t e d for e s u b j e c t of F 6. ( e n tho ~iis S pretreat n t S G P T and S G O T v a l u e s w e r e s l i g h t l y el ated~ no adverse changes occurred durl treat nt.) M e t a b o l i c pars ters a l s o re ined nor 1 for all subjects after treatment s discontl ed. ere w e r e n o = h a n g e s in 5 y w e i g h t . Group

.

th !y i

ec tions

of I00

D

a

25 0

..............

the 3/4 unger s ..1cots in &s p who were obse ed r more t h a n 6 w e e k s , o l ~ g o z o o s p e r m i a (I0 .... l l l o n / m ! less) h a d o c rred within 4 6 wee a f t e r o n s e t of t r e a t nt (Fig ....7). E x t r e oligozoosp (I i i l o n / m l or less) w a s a t t a i n e d b y lO-14 w e e k s , a pc= .... sisted 2 of e 3 d e s p i t e long inte Is l o l l g an jectlon. t i l i ~ y w a s less c sistently 4epressed. In e 3 older n~ t e s t l cuiar biopsies i to e a t m e n t a n d at 6-7 eks a f t e r i n l t l a t i o n of eat t r ealed sper t o g e n i c a r r e s t at the tl of the s e c o 51opsy~ e sa y as p v l o u s l y &n FiNs ....2-3.

J

1977

L-. IS

. 6

CONTRACE

S p e r m ceu 60 ¸ +50 ........."~ 0+

+++

I

militm! W.A+ 42 y ~ 8.0, 37 yrs ........ P.W. 30 yrs .....................6,14. 24 yrs .

.

.

.

.

.

.

.

.

3 ,IL+++ !

1:0 t

+.

3

6

9

13 15 18

26 weeks

Sperm motility % 60 ~" 50 . 0

:

"+

~

30

d

~.

Sp

20 1+0

j

3

6

9

1315

Fig.

Effe of yo get s

J

1977

nthly Injecelons 3ecCs-

L+ 15 N O . 6

18

s

26 weeks

7

~)+ of 100

and 250

in the

661

NTRACE

N

P T prJ!iO0 ml

LH

/ 0.6

t

o.s

""

"

,

mUlml

-

15 -

0.4

....... • W.A. B.O.

............ - P . W .

" ................. +

B.H.

42 y r s 37 y r s

30yrs 24 y r s

91!-

03 ~ ~ O. 2 ~

./

3

6

9

O

13!5

18

26

/

....

weeks

6

9

1315

18

6

9

1~=15 i8

26

F S H m U/m i

15 E Z pglm I

12

I

"

""

.

.

.

.

.

~

30

3 I-

1o 3

6

9

1315

18

26

3

weeks Fig.

8

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In t h e y o u n g e r s Jeers, plas FSH and T decreased initially, en sh ed a t l e a s t p a r t i a l r e c ery in so s .~ects (Fig. S). e inte al be een s typlcally ionger an 4 wee . E2 sh ed n o s i g n l f i c a n t a i t e r a t l o . I els are not ailabie for this g r o . In the older subjects3 blo s ples were obtained at 2 w e e k s a f t e r t h e ...s.e c o pa of Jectlo , rath than after a 4 eek inte al. At at t , a n d F S H h a d d e c r e a s e d b y 20-507.. ~ ....s I00-400% higher a T s increased by 25-i0 . Plas E2 els were un anged for 2 s jects~ a re i n c r e a s e d 1007o f o r t h e i r d .... In t h i s e n t i r e g r o u p , t h e r e w e r e n o a n g e s in l i b i d o o r se i act ity, or i n e s e, s e it ity c o n s i s t e n c y of the b r e a s t s , t e s t i c l e s or p r o s t a t e , tabolic pard ters were hanged, iEht gain occurred. Gr

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e of e 2 subjects attained s ere ollgoz sperm , a the o er azoosper~ia, within 8-12 wee after e begi g of treat t Ea en inta ed his respect e state f 2 n t h s (Fig. 9). e ollgozoospermic s ject e depression in spe count conti ed a t l e a s t 18 w e e k s a f t e r e last D injection, a!th gh sperm motii~ ity had tee ered fully durl e sa time peri In the a z o o s p e r talc s u b ~ e c t ~ the r erse s true; spe togenesis rec ered before t i i ity s res tored. Plas , FSH a T decreased during e flrst e of treat t I0) FSH fluctuated d ing treat nt~ but d T b e g a n to r i s e before the decline .... I els, i c h o c c u r r e d p r i o r to the C es s a t i of i n~ e c t i s. E 2 s c need dot Ing e inJ e c t l o n p e r i . In st instances, hor~o 1 rebou s were o~se ed l o l l g e e of the reel , though plas co entratlo to O. 9 /ml were as ed ...8. w e e after e last (Fig.

Except for a t n s l e n t , s l i E h t d e c r e a s e i n lib o in o n e s jeet~ e re a es l i b i d o o r se I act ity, o r in e size, consistency or se it ity of the breasts, testicles or prostate, ere were no a n g e s in tabollc pa te or y t. Dis

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n t y e i g h t o f t h e 29 s u b j e c t s per need a pronou ed d r o p i n sperm pr uction d i treat nt. e g s jeer, a significan= decil in sperm c might h e been detect i f obse ai s h been c =i ed beyo 6 weeks after e f S t t n J e = t i o n (one week after the seco jet=ion) s= s jet=s, s rm ¢o ts dropped Co bel 1 milli /mi, o r b i o p s y s h sper togenic arrest. Beta e of r i a t l o n s in t r t nt a se a t i o n , it is i oss ie to dr co lus i s about effect e n e s s .... a t 18, e er a re far nthly reel n of 100-150 will cons lstently pr e a i n t a i n e i t h e r azoos rmia or s ere ollgozoosper than I m~illon/ml) w l d s t l c r e d u c t i o n in s p e r m m o t i l i t y . H er~ t h e s e

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U n f o r t u n a t e l y , t h e r e is no c u r r e n t w o r k l d e f i n i t i o n of t i l l t y , s h o r t of a z o o s p e r m i a . H e v e r , it w Id n o t be u easot ~ l e to c r e a s e the . n i t.u d e. an .d'i or. f r.e q u e n c y of d o s a g e , if n e c e s s a ~ - , g to a c h l e a z o o s p e r m l a , b e c a u s e the p r e s e n t t r e a t m e n t s e t incurred cha es in m e t a b o l i c para ters, b r e a s t s , t e s t i c l e s , prostate. O t h e r st ies are currently u er . . . . . u s i n g a n i n i t i a l i-gr dose, to a t te t t o red uce e s era l - m o n t h int e a I r e q u i r e d to i ibl t sper toge sis. ta f r o m t h e s e s t u d i e s are r e p ted in the co anion a r t i c l e (I~). e were a f reports of i n i t i a l d e c r e a s e s in libido. Since the d e c r e a s e s d ~ not p e r s i s t , t h e r e y not h e b e e n a d r u g e f f e c t .... H er, w i t h one e x c e p t i o n , the r e p o r t s ca fro~ s jeers h i s er I i lants, ther t h a n i n j e c t i o n s , for t e s t o s t e r o n e r e p l a c e nt. T h e n t h ly de I of a p p r o x r e l y 4 8- 72 T b y the plant ~y be i n s u f f i c i e n t to intain nor i i ido, ile e I 0 0 or 250 del ered by e injection method y s p o r t l l b i d o b e t t e r .... en t h o u g h e T I els p r e s e n t b y t h e d of the nth are similar f o r the o types of r e p l a c e nt the p y (both b e i pretreat nt c o n trol lues). It is a l s o p o s s i b l e at ere is n o physlol'oglcal b a s i s for a Ii5 o deficit, e lack of a e in b r e a s t s , t e s t i c l e s a prostate, a a l s o in se n volu ~ suggests a£ ere s sufficient testosterone for Inten ce o f le aracterlstics. In s i m i l a r st les in s Angeles, I ido w a s u ffect d e s p i t e the s h a r p r e d u c t l o n in T I els (20). e v a r i a t i o n s in t r e a t nt a se a t ! o n , p l u s the into leteness ...of . data on 1 ....Is, p r e c l u d e f l r ~ s ~ a t e nts a b o u t chani~m Qf a c t i o n . It is n o t c l e a r ether sper togenic sup esslon by d e n d s on g o n a d o t r o p i n a /or T d e p r e s s l o n , e i t h e r for its I n l t i a t i or f ~ r its intenence. In ese s tudles, , and T usually declined foil e inlt t l o n of £ r e a t m e n t , e n o f t e n te ed to r i s e d e s p i t e ~e c ti ti of t r e a t nt -- S O tl S e n p r i o r to a d e c l i in I els. E2 s usually affected by e treat nt. D a t a on the p r o f i ! e of h o t I response duri the f i r s t 2 w e e k s l o l l inj e c t i o n 8 r e r e p o r t e d in the c p a n l o n a r t i c l e (19). Ac e nt e auth s are I to M i s s G e r d a H ~ I z I a ss Pia D e j a c c o f e e I lent te n ! c a l ass is tahoe. ~ ~Y iS w o r k s u e r t a k e n as r t of the cont~acept~J e d elop nt resear pro a~ sponsored a coordinated by e ter rio i Co ittee for Contraception s e a r c h of e Populatlon Council~ N Y or k e References I. shell, D.R., . P gress report: for c o n t r a c e p t i o n . C o n t e m p erary /G 3 (4): 15 ....17 . (1974). 2. S c I lle, P. C a Asse o, J . R . C o n t r a c e p t e u s e - e l f lea ~t y utillzl Depo era R a d m i n l s t e r e d as a n I n j e c t l o n o n c e cry s nths. C o n t r a c e p t i o n 6 : 3 1 5 - 3 2 7 (1972). 3. Sc P.C. a Asse o~ J.R. C o n t r a c e p t e use-efflca st utilizing dr progesterone a c e t a t e a d m l n l s t ed as a n I n t r a scular in~ectlon once e 90 d s .... F e r t i l S t e r l l 2 4 - 3 3 1 ...3..3 9 (1973).

666

J

E 1977

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4. H o r n s b y , V.P°L. exper£ence Afr d J 49 -714 724 (1972)

in family pl

nlng

C

N

~n Nalrobl.

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5. Frick, J., Bartsch, G. and Jakse, G. Radlol noass s of e t h i n y l norgestrienone (R2323)and medro p r o g e s t e r o n e a c e t a t e ( Ai ~ and the i r C I inl ca i app ii cab i ii ty. Uro i s in p re s s. 6. Spellacy, W~N., McLeod, A.G.W., B i, W Co a n d Birk, S.A. e e f f e c t s of dro progeste ne a c e t a t e on c a r b o h y d r a t e tabolism: a s u r e ~ e n t s of g l u se, insulln, a n d growth h o one af er t w e ~ e h " use. Fertli Sterl! (1972). 7. I n, W.H.W. ro oe o l i c dlsease and the s t e r o i d a ! content of oral c o n t r a c e p t es: a report to the Ittee on saf~e !ty Of Drugs @ Br d j 2:203-209 (1970) 8. Lel n, G. po ...medro . p r o g e s t e r o n e a c e t a t e as a contracept e agent: its effect on ight and b l o o d pressure. J Obstet ecol 114:97102 (1972). 9. Terner, C. and c ughlln, J. Effects of sex ho s on ge inal cells of the rat testis: a tionale for the use of p r o g e s t l n end d r o g e n co i n a t i o n s in the cont i of le fertility. J R e p r o d F e r t l l 32 453 ...~64 . (i973). i0.

cLeod, J., in A g e n t s A f f e c t g F e r t i l l t y (C.R. A u s t i n a n d J.S. Per , Editors) Little, Bro , Boston, 1965, p. 9 3 - 1 2 2

ii

en r, G uss, J., Bo"'rs ~ , G., Bor chef, K., Ri ter, E , L ~ d ec ~'...... and c W. Effect of !ong-te testoste ne o e n a n ate a d m l n l s t £1on on le r e p r o d u c t i v e functlon: clinical evaluan[on, set F SH, , ... t...e s t o s t e r e~ and semi I fluid a n a l y s e s in nor i men. A c t a Endocrl i ) 78: 3 7 3 - 3 8 4 (1975).

12. R o h e r t s o n ,

D.N.

Personal

co

£catlon.

13. C roslgnanl, P.G., N ra, R.Mo Hovl d, D . N . d Mishell, D°R., Jr. A thod of solld phase radiol noas say u t i l l z £ po lyp le dl s c s. J C I in ~ d o cr i ~ I M e t S 0: I 5 3-16 0 (i 9 7 O). 14. Bart , A Steele, R,E., sto, N. and ~ i tions In plas testoste ne 1 e s in a It Endocrinolo 9 2 : 2 2 3 ...12 . 8 (1973).

ii, B.V Fluctuaie rats and m i c e

15. Coyotupa, J , r , A . F . 8 n d Ab r C °E. S itaneous ra41oi ass of plas t e s t o s t e r o n e and dlhy testosterone, ai Let t e r s 5: 329- 340 ( i972 ). 16. H o t kiss~ J., At nson, L.E. and obil, E~ T£ course o f set e s t r o g e n and l u t e l n i z l n N ho ne ncentrations during e nst cle o f the esus ey. E n d o c r l n o i o 8 9 : 1 7 7 - 1 8 3 ...(197!). .

J

1977

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6 67

CONTRACE ,. . . . . ~

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17.

E d q v l s t , L -E. a n d J o h a n s s o n , E D.B. Radio and oestradlol h n and bovine peripheral d o c r i n o I (Kbh) 71: 7 1 6 - 7 3 0 ( 1 9 7 2 ).

18.

F r i c k , J. Cont ro i of spe a t o g e n e s is i n m e n b y co ined admlnlstration of p r o g e s t l n a n d a n d r o g e n .... C o n t r a c e p t l o n 8 191-206 (1973)

19.

F r i c k , J., B a r t s c h , G. a n d i s k e , W. The effect of ~onthly depot d r o x y p r o g e s t e r o n e a c e ta t e d t e s to s e r o n e o n h s p e r ~ a to g e n e s is. II H i g h in it la i d o s e .... C o n t r a c ep t i o n 15: 6 6 9 (1977).

20.

66:8

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of oestrone Acta

67

Brenner, P , Mishell, D.R., Jr., Bernstein, G.S. a n d O r t l z , A. S tu d y o f m e d r o x y p r o ge s t e r o n e a c e t a t e a n d t e s t o s t e t o n e e n a n t h a t e as a ie contracept e Contraception 15: 6 7 9 - 6 9 1 ( i 9 7 7 ) .

J

1977

L. 15 NO. 6 ....