~ ... ~ ~.. -"" -." ~ ~ -.- - -- ~'"

1.0 ... II ~ . ... - .,.. .. - ...,.. - ~ -- ~~-.. 1,0 ~ ~.. 0,01.. ..-gc:~ ... . ,. "* ~. C81*-'.... ~ ~ ~ -~~ --- ~- ~~~ ~ 1'1111',,- ~ ~TY1I8 JI: :.: C~-:-.::.:--:--:: - ~ 18~. .. .. .~. ..-~ .. d-*-, .,..~ II"-1.3.5C1Ot--".3.1 ~._. . .. .. ~ ~ C,.,..,o... "'** ~ ~ 272.39. ""

.--~~.

Aa.

- ~.I..I-.:.t. ~~...~ - PE=£ST x.-~.:::--.::.. a"'" ~ IS ~~~ It 1'.1""".17.0ttF...fft.20',".3~. 17.J~::;r13 (17w-(.1- . hIS an..~ --- - CJI,.W), - a ~- ~ - --- '- ~

)tI6I:8H.ZI L IIDtP 0 Lapo~Je9 :>8Z 1

~

o~

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li-

Sl3IQe:t(a&eW4&sa6JOu/IOlpeJ&sa )

if!_l~~Yd

a~~.Z/L &fOIP OL~.Z/~ 1161) OL I~ 38~ L IL 9PO~9 38~ L

I-rPREFEST'.

(estradiol/norgestimate )tablets

PH1SIC!M'S pacKAGE ItSERT

~:..-:=::

---

~

Each ta~t 'or oral adminrstration ConClins 1.0 mg 'mdiG In« 1.0 mg 'stradl~ arwJ 0.09 mo of natges-timate, ~ ~. folowtnQ inaave IngtecienCS: CrOIC.-nlibi sdR, ii,K:f«;'-"..,-" ~~-~, magne,unstearate, ~ Oxide red. n IKtott n.-~~.CL"-A PMARMACG.OGY

Endogenous eS1rogMS are &atgely r.~bI. tor U\8 de'ittoC)ment and maintenarcl of lit 'tmaJe reproduc-8ivt system n S8C-*y sexual dIar~~.

~~ --~-q ill vi'"" ~~ of "~-~: w..~-".-li, ~ Is ItI8~ -~~ '--118\ ..u~ " is ~." ~ ~- OlIn Is m."'1It-~5, ,Itrone and 1ICIi-d, at h recept« 1eYIt. The Pfim'Y source fA ~ II normally c,ding ~ women Is lit ovIItan foIide,whCh _rIt8S 70 ~ 500 n«ruv.""nI of .--8i1G daly, ~-'.v ~ ... pbISI of ... ~. Aft8f~~, mOst iI-,.,..-aJS --~, .. ~-~ by ~nw.~ ~ .. - -~-.., ...~ br'" awn-

II ~x. to _one by ~ al1Ues. Thus, A~-ti - '" Mtltt ~Ced b1ft, a"P~ti s~ce, arethe most Ibundant drcutatino ntrooens i\ postmenopausal wom..Estrogens ICt ~ birano k» ~ rIC8ptor1 ~ -.-M--.r..-'- Mssun. To date, two n1rogenr~ ria" been ~. Th8I8 v., i1 ~~~- trUfft ~ " tiaue.Cj(~tino es1rogens ~ate t\e pft~ secretion of the gon~. kltlinlzing hormone (lH) and 'ot-lide stimulating hOf'~e (FSH). hough a ntgatlVt 'Mdback ~m. EStJQgens act k) ,,~. the elevatedIeYets of II8te ~. seen W1 poS'~aI women.

-.~ II a ~ of 19.~ ~ .., ~ to ..-u~ n ~~~~-:ii fK~.lImIar10 ~ ~ '" ~ 'Q"~-" ~~-~-.; . .. .. ~ k) --+. ii':~~~.. ~-.. ~ '"II1rogerWc effects by decrtllino It. ,.,mber of ~ar IItrIdioI r8CepD'I and ~ epfthIIilf Dt'4A Iyn-u.s6s k1 ~trt8 ... .~ -.:--=-~~

..~.

Es~ reach.. its peak serum Concentrltion {C..J It 8W'QxWnltety 7 hours In postmenoplUSai wom,n~ PffJEST (Table 1). Norvesdml1e .. w.,""-t ~~; .. prinwy active mItJboIt8. 11-d8~91"'" , C- It lPIM'O8nately 2 ~.,..,.. (T-. 1). ~ co-ldfNni$tration ~PR.EfEST wilt a ~ fit "'88. OM C- vUS b A~- ~ and IStrooe d. .. meased by 14'- and 2-'-.rlSpecUYtty. and ttIe c... for 17-dtIC~..tlmate was decreased by 16%. The AUt values for these ana.,- -- not ~*"Y .ffected by food.

", TI'8 fi~~ of exogenous estr098R8 Is slmAar to ,,~t of IndogefQIS tSt'O9f"S. EsttOQtns n ~e'V des.

tributed k1 the body and 11'1 generaity kK.-d ., Nghef concenU'ation. ~ ~ ... ~ t.-oe1 organs.Es&roo- ckaMIt ~ .. I*M)d e.vety bound ~ .. ~ I*tfino ~ (SHBG) ~ ~. 11-~,.-.~~~. '" ~ dVI ~ of j"~~~.AI". does not birMI ~ $.-G. but to ~Ier\n ~eina. The ~~. ~ of 17-deac1t)11.v.~-p.T..tt. approximately 99%.

~~EJG96I~ ---~-.. ... m~1d ~ '" ... maIV* IS iI-.1ogi.-"" --~Ii. ~W1Q estrogense. i1 a ~ ~m .- me'-* ~-~~~--I. n.. if(l8""-' .. .. mainly ., '"kYlf'. EstrIdIoIIs caw8f1ed revenibCy ~ ~ n boU\ can be ~v&.18d to estriol. ~ is ~ maiO( U(1-n.-y ~. Es1r"-1i Il1O und8VO ..Wr tiPIUc ~tIOn vta da.. n ~~ ~~ ~'" w.. ~ secrItion of ~- ~ - '" , ... h~~ .. '" .- ~ by r.aor~.~ posUI~~ ~en. a ..':'~. ~ .- III cWQM~ --+-. exist .. date ~~. -.e-daIy estr1WM date, wtMch I«YII .. a ~utdn9 ~ f« lie bma~ of more Idtve estrogens.Nargestimate II txt8tIlvely metabolized by ...t.,ass mld\lntlntl ., b gutrotntesN b'Kt and/or UVtr.--~7_'1 ~ ICM m8t**" II 17-d1Ket~*gest nate.

&crwIM

Es1radof. tS1rone. n ~ Ire IXcrettd it ... urN along wfth O'~ n dIte ~ Noroestimate mltabdltes Ire tlmtnitld II '" 00nt n feces. The half .lft (1",) of I$~ Ind 17 -deacetyt.

norglstimatlln postrnenopiuSli women receiving PRE FEST Is approxImately 16 ~ 37 hour1. reSD8CtivIlv.

OrVf*,WacIMI . -k1 ¥ftro ... " wtvo ~ have shOwn t'it estr.-,s are me~ ~ by eytGCi".~1'8 P4SO W(CYP~). Ti~if ~ ~ ~. 01 CYPW may affect A--viil' ~ metIboIIm. ~ ofCYPJAA ~ as St JoIv1's Wort pt~S ~icum ptttcntum). ~tJMaI. ~l"'. andrifamoen may reduce .ma ~tIons 01 estrovlf\S, ~ ~ i1 I !lUelSe In I1erapeuticen,cts ana/or changes in Che uterine ~ profje. Inhi~or. of CVP3A4 sud\ -II erythromycin. d..ithromyc-., ketoconazt*. Itraconazole. nD\aW and grlpefNit juice may InCt'8Ise piasma concenntions ofiSt.-. -4 and may ,.. ~ - .fttt1s.

~ ~ a ~ ~1fiWI"'24) fnwn a ~.. ~-~ II 36~ ,...~~-~ MJloiii~.catId I\ac ... ..., Ita" ~ ~ .. UW'O '" ~ -- it(II~ pi-. ~ lie 'igIiI may be lower ~ 12-18"- . ~ed .,. ~~ 6.~ - .-ri6 *". n. 8\R .~ -.. ..-s may decr.ase

by 4% and '" IInP ..~ti MAl... IMII may ~ by 11% ~ .. t*IdG - --vi*r.ate pf\IStas tontpared . ~ IdmtNs1ered alone. The ~ r"e~. of these ob~~ Is ~.

s,edll Pop.eiaon.R.c. ... bod)' ..,...,The Ifttds of race ... body ~ on .. -~MtJcs of ~ ragesliRatt. n .. ~~-~were ev8uItld In 164 MIIfIy POI8~-~ ~ , (100 CaucUInI. 61 a. 2 8ICkI. - 1 AIi8\).No signifICant pharm~netic dfff~ wu 0b8erYtd b8;-~... 1M C21_~ n ... ttlpar-= POtt.menopausal women. No significant di"-ence due to body w~t W18 ob18rv8d k\ W<WMn In the 60 to 80 kgweight r,nge. ~ with body Might hif* a.., 80 kg. :-~. hid ~""teIy .0% IoWIf peak..,... ... of 17 -;1e8:8tjW- M,,-,'.at8. 30% lower AlK: v ,. 17 -deK8tjl.-M~.I.att and ,x)% IGWe(c.. v-.. for ;.~.~ TIlt cIric8 ~ ~ ... ~-N"". iI ~.No --~.aac;; ~~ ... ~-~ M .. ~ ~-~~.

T8It 1. MEAN PHAR~-~.N;TIC PARAMmRS ~ Ett (" t5. MO 17f.r~'FWOWING SINGlE AND MtA.npl£ 00SIffG Of PREfEST

Fvst First 00II ~~ 0018 ~~ PIrIm- ~ 0.. E, E~ E, E, E, t- poIml 27.. 393 49.7 ..2

t.,... h 7 7 7 7U(o-2. h) PQ. ~ 42. 681 .. 77i

E. C- ~ 210 285 ~1 325t... h 6 6 1 6AAx:f)-24 h) pg. ~ 277. 41S3 ~2t .957

EIS '- ngfml 11.1 13.8 1..9 1..5t- h 5 4 6 SAlK;(G-24 h) ng.h/mL 135 180 198 198 .

17d-M* C- ~ NA,J 515 . NA 643

... h NA 2 NA 2M£,f)-2. ~ PD. I\hRl NA 2148 NA 5322~ h NA 37 NA NA

, EJ8~. E, . Estrone. E.S. Estrone WIatt. 17d~. 17..acett1lUQedmatl. ~ tK8CW'-

rICt8d dati we i~~. tor E.- E. - E,5., t- 8 pea 8um ~ - w '- ~ MIne m r8ld\ pe8t ..,... ~- ~ -.tri~.. ~2. h) = ..a ...,

~ ~.. VI. .. ~ ~ 0 eo 2. ItGn *-. t", ~ h8f-if..J NA- - ~ ra !

"'I'~- .::,, -.. ~ ~. ~. -- ~.. ~~.. 12~...bo~-",*, 01118 -- - ~ -- ~-; 21 and 1& ,... . . ~ ~~~~

--- . ~ " ~. n-. ~ d ~ --~ t.~ IIIPEm r.-,~ - R*d ~ two \ 2 - ~ \ 212 tll8e.y ~~ WGn*' bIIwtttI .0"'15,..d._C~_~.¥.,-..;"'..."'--' --. ...~-~ ~.119) ~... 12 ... IWOIn-. ... ~ .. ~ ~ Table 2.

~ z. - . M . ~_~.18 -- ~~ M8TI MnI ,. - ~-~~ " ~ ., ~ -~ .. MY)

lit

21 \1.0 . \0.9~. a 3.3 2t U~. 21 11 Z3 0..~12 21 \.1 2' 0.7

ThlIIKU ~.,. ~ d -i'-~'" ~ .. - -- ~~.--~-~. ~-~~ ~A_~_A_~_~" - ~.I.I:-_IIB-. . .. , ..""- ~ -- - &.. ~. -- ~r - -- -.. .., - .8..' 12"'-'~~* ~ ~ ~ ..~~. -.. .. ;-.,-.. . ... -.D:-:-_"'~ I,.;"".-. .~_X-'III-I-I._-',""'~"";"'-~~' 12 "M3.-.,..::::: :.=--~-_.:_.:..: 42 ._,..- .",CI.CI.'." ~-i-:::.~~~ -- .. . ~ - ~ ~ .. .. -.II for ..-ndOft ... ~ ... ..- ~

~3.

I - ~ -=;':'-:- ,.=.r ~ -:.=' ~I. ~ -~ . MAl..- ~ .-.118 --~ .. .-1UYI ~ 7 ~ MfM ~, . aI.-.- . - .. - ..

2$.161.2

5.1

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.22.1

7.21!.'

~I ("-32)0.0

-.,191

-- - - ::--::~-:--::: ;;;- ~ - ..aT... ..-"-'. - ;-~. - 12'--~. '- ~ -*1-....,...~ .. =c:-:~:::E . ..::-It8AlNYfWUII& AmI II ~ .. ~,,-TO,..

~-= ~,""_~- HI.", 285 242-- _. ;;~ 2S6 (17"1 'lD ~

¥';;'-;-"-'", 1G (71", 227 (1~s-. :-.~ .. C2It.I 0 ..~ : 2 ~."t 0 "....".~ .. c~~..:!: .. . ~ 0 ~

" - 12 ~.;.~ ~ ~ -., -..w:---::'..t ~... . ~.:J: 1. ---~~ ~ ~... PWfST. No'" ~'-"'- 01..-"""'. -.. ~f-. . ... 80"'::'.'.""TN tfIecU d ~T. ne no. . ,~~..., ~ c.w , II.12.~'" ~ ,-*' we --" f.,. ,.

1: -.eta... ~ :"-,...r 0.. TIR88 ~~~ .. ~ .. - . It . ... -- ~ -- 12). ~ - TrIll ,

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5552..41 . ' -~ ., ~ 51

31 31 to ., ,.0"0 0 0 0"".0

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~. ,.. '::':W_8 ~A ..., - ~ ~ -. ~ ~. ... ~ . ~ - 16.- ~-- ~ -; -- ~~~ . ~ &3 ... ~ . . 79; 83.ft ~ I.W 88:k. 5.ft ~~ .- .. '* n ~ ~ .. .. ~ 0.825 nil ... ~ ~ ,.. 2.5 IRI n-*o..

~ ~~_ii~::; ",,~-~~ .II.II~~ ~ - ~ ~~ ~ ..~ -, ~ ~ pq ~-~ ~- m.. .. am

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. ~ ...~~:c_- ~~~.._~::-"-~..~~c .~ ~ ~.~ ~_OIJ-.

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. ~ ~~ ~_.. --~-~ ... ~ - ~~~~.;Fcw ... ~ ~ it .. -.. - ~ ~ ... ,. 1 0.- , -- . Iw ~~ ~-. 7 -- am-., ~-., ~Pfs. -, -- ~~C8-~~~..~,.1o.-~ "_'--c8~~_5' ~.11W ~~ ~ .. fI ... ~ . at --- '*- - 19 ~ 10,(XM) ,..., Thlre .. 1M) iISi...~ ~ '" ~ it - ~ ..~. cs- - ~~ ...

-.-~~

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151

131118

~_..~T . "k*' iI -- .. ... . ... -.. 1. T~."'" ~ .,.-.,,-,-. .~-::~~ we lie ~-:-~~'!!-

2. i- 8' =~-~. --- ~~~.. ~ ~~-- ~..,.. lie ~ ..-:-:-:;.~-:-~ - -- ~.. ~ ~~~~.~~

3. ~~--. ~ ~ ., -. ~~ -*tf .. lie ..~o1CIt ~ ~~::~!!!'c~~.c;-.:-. ..., ~ .., . ~.-r... .. -. . -.-~.. ... . ~~~- - ..."'" ~::::;-~.. ~. ~ ~..."- . ' -".;a~ ~... ~~ .ro-~- --. =:--=~ .. ~ 0 ~ - ~ ~~ ~:: ~-!-:: ...,. ;--;..~'-:-;~- - .... ~ 1- ... - ~.. Ctilft.11w-., -- - ~.~ ~ :-_I'_-J'-~

.., be .. wilt ~ cIIt8'y ~. ~ D ~","b of 4OO..8CM) ... .. be . --- ~~ .., ~ ~ ~ _.~~~ ,po..,- ..~ ~ .." ~ . - .. .. - ~ ~~~.; OL~~1. ~"-'-~-.m.~MId1g.--. ~ --1- . ~ . ~ . .. ~~. ~-~..~ ..~~ :-IIP"II'.~ .. ;: ~ '-nUii8"j ..~w « N8Iry - -- oL~... - ...

* ~ -. -~ ~..II.~C ~ ~~ .. . . - - . -. . - .A-

l-I...I... MRS' -* - .. ~ . ~ ~ ~ ~-~_:~ '» - ..~7. "-. ~-~~~ ~~. T-. . . ~Y. .. PMFESI M ...~ - ".0;,-. T-. ~ ...

~ . M ;-~~ rtIk ~ bill ~ it -- . hM -- 8Id ",-og .. -~.--~.., ~ - P,-",.o;,- cs.

~~.. -- =---===- -t. ~~--~.._;.

E-.., ~"'" - '-' ~ will. ---,. ~ _~..a_~... ~.~-- ...tb'" --. -. - ~~ - ~_~.I-=--, 1.. ~. .. VI£). ~ .. - - ~ .. . ~~ ":I:-~-. -- -* "

~~ ~-~~1M ... b ..~::- ~ ""-'-" ~ ~ - --~....~ .. ... . ~~ W'...i*r.L &.-;.-, ~ ~ ., ...

" .. a:.wA ~ ~ --. ~ (Wtt). 8t i"u:-.-s .- ~ ,*~-, '-t --pq ~ "~-.:-a i_'*-.. 01) ~ - .-, -- ~~ ~ ~. " - ,~ .. (37 . ~,. 10.- .-" 118 ~-- .--~ ~._~-~ ;:":---~-~~t".. - ~~~ -~,. ~.. - ,,-,-.8: a ~ " - ~~ .. C21- 21 ~ to.- ,... 181t. n. ..J~ it .. -

- - ..~~ ~L~~ ... '-t -- (na2.763.""" ..7,...) .~.~ ~ ~ ~ ac..-~-j jW" ~ ~iJ!:~- -- ~.. Ea--~.~~~~=~. ~ ~ -.~~ .. ~ O.a25l.,rl.- ~.. ..==-':---:-.. ~

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* . ..~ it . ~ ~ ~.. ~ ~ ~ I. ,... .. ~ I

- .. w=;;-~ 2.7 ,.., b . ~ ~ 6.8 ,.. ~. ~ ~ QI) ... -- ~-~ -- it b aIWA ~ .. .. .. .. it tERS. tEAS I, Ind ~.

l8gI ~ ~ -0.- C5 , ~.. ~-" -- ~".. eM-~ ~ . ~ - .. ~ ~ . . - ~~~~ .-- - it- . m-.~~~~~~-~~-~~-, __8al- ."';"'-_~_~.18-

.. ~ .11 ~-I-,rIIJ.

" .. ~ , ~ ... . 2.~ ... .. ~ Y1t. ~ ~ - =~~-::~ ..'--""'" - , ..~.. .. -.. it- ~ ~~ . -- o oV ....,. TblrW ~ VTE W8S 34 ,. 10,fXrJ WIMn8t-,... ~... .-x;.-.p.-~ W 16,. 10,000

~ TbI m- .. m.- - ;,.; b, ..~.CS-~~~~~~~~~Y.~~.) .

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~_.~ -~-=- - --- it T.~ -:- .1. p 1-- - .. .. ~C- :..:.-~ .. .. ~ ~ ~~ taC8. .. .. a...wA , ~ .. -" ~ ~~ IWr -- . 2IIt ~ ~

c..c.- C38 " ~ pw 10,CXXJ ,.." 8"'" ~ S.2,.. ~ ;; ,..i- ~.. . -- ""-. ~ ~. ~ - ;~ ... ~ '-J~ ..- ~ C8D' -- ~, .. 4 .. . ~ ~ - '..-;.. ,.. _."~,.:-::-=-~ - ~ ~ , .. .. . -- ~ .- -- ...~ ~:,,-~~ . ~ ~ ... .. 11M ~ .. - --- (s. ~-~"L--- -=-~-~ ~ ~)~.~ ~ ~ 8I1ICf~ risk ~ C8D' it ~- ~~ ... '-J~.v-- ~ ~ -- . . . ~ ~ - ~~-~~ -

,'. ~ ~.. 51 ~.. -.-d -- ~ - ~ - I. .~~~ ~~.. ~.., 8I;a-~ .. ~ --- ~ ~ ~~7:::-~--

~&.. ~ '" - ~ ~~~ - ~~.. _..~.. ~-.a.t-~ - 5 ,.. « ~ S-.. ~ .. ,.. '~I_I ~ , ..- ,--.~ ~'~J-~ - ~.;-~ ~... ~ ~ ~ -- ~ -~,;. A ~ ~ - - ~ I .. .~ ~ ""'" ...

- - ~ -. ~ ~~~~. ~~. --~ - ~,.., ~ -". ~ eft"'" - , -- - ---:~.:: .. ~

... .I.~.'-" II =-~L- ~~.~-- ~ be ~-~ ~. ~. -"'-.s.

2.

.. ::-~:_J~_IW~~ ~ ~ risk ~ .-=~i--~ -.. --. ... 2. m 12-~ greater_. ~..~. -- _.~~~- ~~. --. -~ ~~~::,.. ~- ~~ ~ -., _I_~__. - ~ - ~ ~

,-, w-I ~-=~::; .. , -. . ~~~ ,.. ~ 15- " 24'- b' ftwe m

.. ~ . - - -.. - ~ ~ . ,... . . ~ . - 15 ~ .. ~. Iw-

.,.~_.:.__d«-. .- ~~ ~ . - ~ -.. -.¥o-)gIIIr; ...~ . ...~-~. ~-~ dig-~ -.. i.~ I-~- ~~ --.'-. ~ ~ ~. ~. ~ ~ ,it.~ I~- II.~~ '-"--~MII:::'-~.- .~ 11M .. - ~ ..~.. ~ it I ~ .-.o"k;..~ - ~ ... J'r-:;-~

~~ - .::::-~-~ 11.'1"11 ~

A 2. ~ ..- ~U- . ~ - ~ ~*~~ -- ~ u.-Y it ~ .~.-~- -; -~ .. ~ ::-~1..11"~

~=;::-::~ ..J:~I~~. -~ -- ;-~-::~::.. ~ ~ ~ - ~ . ~-~~-~ ~ - -- ~ *III ~. ~ - _..~.. ~~ ~.~ c*-~

I.

4.

$ ~--~ ~ ;-.~ ~. ~ OK-~ ---~ .CC--~~ ---~- ~~ ~

".;.., ,...~--~. ~ .. n~ . ~~,Iww.- ;:...~~ --~. ~* ~:; ~ M ~~

,A.'-'-.

.~~:-:~.~~ w -~ ~ III ~". ~'-'" 10. -- - ~. "'* ~ ~ .., ~ ~~ . a ~~ ~ ~ a ~ ~:::,~.;x ~ ~~~:.,-ptIIii... ~ be --=- bJ e.-~. ~~... -- be. ~ . 0'... C88.n.. ... ~, ,... ... ... ..., . ~~-~~ ~ .. - ~ ~~ ... --~

. "--"'-0.&:. 1-.1a-=a A~~~_~~C8g'b. --- ~ . ...~ ~::~ to.. r-. u.JCo ~-.-; - ~ ~~s..w"p;..-~~~ . -- --" ~ ~ ..::~.. ..,~. ~ po-;;;;..-;... -- .: ~ ~ --.r~-- i"'.. ~ -.:..,. -.. ~~... ~'*'... -. iiI""-"~ - ..~. ~ po - - -. ~ ,~ ",. ~. .. ~ .. ~ -..,. _..-~ " ~-,I.-=-_.~. ~ ~ -- ~ ~ ~~ ~ ~ ~ 11__. ---~ ...,.., De =-c::-::-::~~...~""'-"" ~~ ~ ~~ -~ c~=~-~-~""~~_.~:IEIt-~.. .., be ,.., . ~. : ~ ~ f.- *-by - L~~- ~:~ ~--~ ~ - ... ...~-.. ~ ~.~~_.~~-~~:::~~.~."..I_~_~

'8 .- ~', CM De ~::-::~~ ~ -- bIII-.Ig. - ::"-~-r-~.I-E*IIn ~~... ~ ~ ~~ --- ~ ~ ~ ~..... ... ~ C8' r.-;~ .. .. ..-: - bf ~ .. ~ ~ , ...

T.- TJ -- ~.~. ~ -- ~ "'-~~~."... ; .~ =: ..., .. .. - .~ .., ~ ia.--~ ~~ .. , ,-;:;.4-- ,. n- -- ~ .. """" ~ --it ... ~ -.:.~ .. '- -- ~. . =~~~~ ~~~~k- ,..~~.. ~ C88 - -- -- ~ ~::.c:.~ -- .. 0--. ..... be -, - f8:D. .at . . C8dK . ... ~, ~ c.-. ... - ~

-- -~ .. ~.

I.

a

4.

&

..

7.

ERogens may C8a8 bdCNI d -"ma."".eIibIS. ~IepsY. mqaine or ~a and~ be used .. ~ it ~ ... ... i:or~.

I. P8u.d"""~ ... IdwIIId ~ t8Ieuss ... w. -fti d '" PATfJfT ~ Ieaftet wiU\ patients Q wtIOme.ey po-"'-- ~T.

C. l8J«~j"""ER-~ ~ be 9'Dd by ~ ""-' . '" kJW8st dose b ... ~ KIdI-caticwt. railer f'8fI by -- tUUM-ii .. (8.9.. ~. ~.

o. ..., j Tat "~~:!!:L1. ~ po--'-'~..;w; -.. , ..-v.I;-~~~ MIl. Ind , .., ...;

~ pI8III ~ ~ 1acbs .. W 81MgIn. . .. ~ ..-Nt. IX. x.XI. W-X ~ I-W-X ~ ~ beta.fwOlr';::-r~';:;'~~ ~ 11.-" --~~ XI'"an~ui\ -. ..-~ ~ . IC8wfty; itcrII8Id ~ of ~.1iJ9tr' ~ ;.,' ii'i~ ~ ~ 8Itigen Md dilly.

2. k" ~.., "" (T8G111v8 W --~ ~ ~ ..,... hor.mone levels as ed by P'*n--.nd tP8I». T. levels (by column « by

T ~ .. T J -.Is by rd*ftftV --- . T J .. ~ is deaNIId. r~ '"-.v8ted T8G ~ T. ... tee TJ ~'.:**...S n ~. Pati8la on ~ ~..., may ~ ... dc-.I of ~ tamone.

1. oaw ~ ~ ,., be eIev8d it ..., iXiI~\*i I*dng"" ~ ..t'-"~~ (9llGl1I8Ing -. ia88d ~ ~-- ... .x ~~ ff88.. *-~::-~~; ... .. ~"""" pro-w. ..., be ;.c;.-": (8- -.~, ~ .. .1..~ JpsM, ~~)-

4. m as- to ~ ~~. iXiI :..~-t*R ~ La. ~~ ~a--. ~ .1iiJr.ei'~ 188.

5. ~~~--~.t. RG.- re..- ~ ;,;:-, ,. 18It.

E. c.-O»:III a 11'1. L-J ":'", - ...~-C ~,..,.

,.

G.

H

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you .. ~ST .-y ~ Pfe*It ~- frOOI iMf".up88, . will ~ ewe 8Wo.-" ... ~ u or ~ Ii .. .' .. be bIa8' .. ~. '1QI n ". .-.~ PIowtIel ~ ... rep*'tf *-It ~ *' ~ cordi-. ~ ~S1~-bI8q ~ ~ « ""*". -18iII ~ - ~ D --- .., --b.- ,ala' d88K:81. .x - ~ a.-opr ' lis im~ w -Ii b) ... aut _die ... ...~ .. ~ ~ C8e PIO*Jef beb'e II8tng l.eRt.

.. ~ - T- PMFEmDo .. take ~i . JaIl 11M ,.. r~ ~.""-"'.~ST CCWIIan I ... -ovn;'.. ~ 11Ia-.iI& ... d8as ... ~ ... 1M IdWs. . ~ . - IBM .\derus. ~ dO not need I ~ - ~ ~ - .. ~.00 no! ,.., taIcW'O Pf£f£ST if JCM':. ~.,.. ca.TenIr""'.'" 88Id c.t8 ~ Eg:-y#= ., ~ '" d..:a ... .. ~

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. '** you , be pregn8nt

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-- -- . """'" .. effects ~ ~T. far - ~ Ilk fa' ~ c.-e prowtder or~~

MIll CIft '8 ~ ~.",~ at. '* ~ ~ ~T?. t- wilt ... ~ c.. ~ ret#8tJ ~ JCMI ~ ClX'*-IIkI'V iII£fESi.. Set JIMI' ~ C8e ~ rigid .., . ,.-. fit .. ... ~ ~ .. Have a ~ -- .. ~-" ,... X-f.-) .., ,.. ~ -- C88 P'otti*r till ~_.. ~---i fA... ~ IN.- ~«. ~ Mwe br..r kImPI oran ~~ ~ ,ou may need t) b8.e ItI«8 *".. If ~ Mft . .. ~. ~...~ . ~ I*od). ~. .. ~-~ « If ~ ..~. '*' .., IIIwe -- cIwIC8S b ~ hI8t A* ,... cn ~ b WIP t)kJwer .".. d8aI b 1lII8IO h8t ~ ~ ...~ 8M ~ .. - ..~. .. .. ~i

MIcIci".as .. iW"a5...~... ,. ~uoM-oi .. .e ~ ~ in p-..I ~ 1e8fteIs. ~not ... Pf*:ff.ST . w-~ ... whidI it .. '* ~. ~ ~ .;we PAEfEST t) -- ~. -- Ifthey haoe lit IBM ~ ,.., heft. . may "-"' I*R. ... PRfFEST BUt " ~ -=-~...T- Ieaftet pro.-.es . v of b..sc ~ .-ma-. 8caIt ~. . "* ... .. .ut...matm, tall. ,... -- cn PfowidIr « ,..macast. bJ ~ .. b ~. ~ Pl&fST ... iswrinel\ b ... -.-s ~ get mcM'e InIIWmatKw1 bv ~ .. d - , 1 -a- 776- 3631 .seted ~ s.

.. .. ~..a - PREFESnPREf£ST ax1tak'8 two sep.- CMIIeU. ~ ~ -- ~ ~ 1.0 nag ~, CfOICarm8IOI8 m-urn, "krw-~ ~, ~ -- ~ 0-. ,ed. n IICIose ~ate. The.. ~(wtite c-*M') ca-.1.0 RIg .--~ 0.09 -0 '-""'" ~"IiIose~. nicrw-~" ~-. ~ "", w ~ ,..,..

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