day devices

CONTRACEF’TION INlRADTERINE COWl'RACEI-TIONWI!tH G3PPERANDWITH LEVOIKIFGES'IRFI,: ARANDGMIZEDSlUDYOFlHE!Ku ~~~A~ANDLEvONOFGES'IREL~~~~~/DAYDEVICES

1Centerfor BiomedicalResearch The PopulationCouncil New York,New York 10011,USA 2Departamento de Ginecologia y Obstetricia Hospital"Dr.FranciscoMoscosoPuello" SantoDaningo,DcminicanRepublic 3 Centrode Pequisas e Controledas DoencasMaterno-Mantis De Campinas-Cemicanp Campinas,Sao Paula,Brazil 4 Consultorio de Planificacion Familiar Santiago,Chile 5Department of Cbstetrics& Gynecology Ain ShamsUniversity Cairo,Egypt 6Faculdade de Medicina Maternidade Climerode Oliveira Universidade Federalda Bahia Salvador, Bahia,Brazil WSTRACI! Firstyear resultsof a randomized stu% of 1509 usersof the Copper T38OAg with a silvercore or of an IUD releasing20 mcg day of levonorgestrelare reported. The cumulative grosspregnanq ratefor each device was 0.3 per 100 at one year,with more than 490 wcxnen havingone year of use with each device. The levonorgestrel-releasing device was associatedwith significantlyfewer bleeding days and significantly increased hemoglobin levelswhen ccmparedwith pre-admissionvalues or the one year valuesobservedamorrg usersof the lCu38OAg. 'Itxminations attributable to amenorrhea were significantly more frequentamong users of the levonorgestrel -releasingdevice. 'IheTCu 38OAgwas associated with increasedfrequencyand severity of dysmenorrheacompared with pr~ac%nisaionlevels or with the steroid-releasing device. Hemoglobin levelswere sanewhatreduoedamongusersof the Ku 380Agdevice. I&minations attributableto pain were,however,not significantly differentty device. Continuation ratesat the end of the firstyear were not significantly differentty device. Submitted Accepted

NOVEMBER

for publication for publication

September 27, 1984 October 15, 1984

1984VOL.30NO.S

443

CONTRACEPTION

IN!l.BCJXJcTION The firstIUDswith copperwire wound on plastic platformswere smaller but not markedlymore effectivethanplasticonly devices. A majoradvancein effectiveness was firstconfirmeda decade ago when canparative study the Copper T, model'IQ 380A,in a largerandomized with the CopperT200,was foundto have a gross cunulativepfegnancy rate of only 1 per 100 at one year (1). This sighificanti~~e~~ anti-fertility effectwas attributed to two designchanges. of copper,positioned on the crossbarof the T, broughtcoppercloserto the fundusand simultaneously tothetubal lumina. Second, e area of the wire on the verticalstem as increasedto about302 , bringing the totalcoppersurfaceto 3802 . Severalstudieshave since confirmedlow annual pregnancy rates among users of the lCu380devices(2-8). Developnental effortshave centeredon extendingthe durationof effectiveactionof the 380 devBecause copper wire with a silvercoremaintainsits integrity glr prolongedresidence buterp, as observedin studiesof the Nova T and the TCu2OOAg in Scandinavia(9),the Tcu 38OAgdeviceused in the presentstuc@incorporates this feature. Reports encouraging developnent of progesterone- and levonorgestrel-releasing IUDs were firstpresenteda decadeago. IUDs releasingprogesterone (10,ll)or levonorgestrel (12) were associated with diminished menstrualbloodloss. As anemiais endemic in develop ing countries, this featureof steroid intrauterinecontraceptionis estimatesof effectiveness potentially of great importance.Preliminary shred thesesteroiddevicesto be canparable to the standard devices then available. A progesterone-releasing devicequicklyreachedthe stageof regulatory approval and marketing.Aslower pathwas required for the ~yntheticsteroid,levonorgestrel. Finnishresearchers undertodcfurthersafety studies and developin the volme of menstrual ment (9,13). Their studiesshmed reductions flow andlow terminationrates frcmbleeding,pain and infection. These advantages,ascribed to the levonorgestrel releasedlzythe IDD,warrantedlargerscaletrials,as did a twoyear Pearlpregnancy index of 0.4 per 100 (9). D.N. Robertsonand J. Braun developed a productionmodel of a levonorgestrel-releasing devicefor the Population Council. This report concernsa large scale,randomized stuc& of that device and of the copper-releasing TC!u380Ag. It focuseson the ccmparative effectiveness and canparative advantages and disadvantaoes of the two devices. METHODS

AND

MATERIALS

Devices The CopperT,model 'ICu38OAg,hasapolyethylene,l%hapedplafform whoseverticaland horizontal dimensions are 36 and 32 mn, respctively.

444

NOVEMBER

1984VOL.30NO.5

CONTRACEPTION

'Iwocoppersleeves,waged on the crossba, provideapproximately 70 MI? of copper surfacein additionto 310 A of copperwire surfaceon the verticalstem of the T. 'Ihewire of 0.25zundiameterweighs about 175 ng, of which 84 percent@ weightis copper,and the remainderis silver in a corewith a diameterof 0.095mm. Polyethylenethreads are tied through a3 mmpolyethyleneballatthe bottanof the T. The Xu 380% deviceswere manufactured ty &t&umpu Cy, Finland. 'Ihelevonorgestrel device (LNg20) is designedto release20 mcg of steroid daily for 2000 to 2300 days. Steroidis carriedin a covered, hanogeneous rod OR the verticalstem of the polyet&lene platform also used for the Nova T IUD (13). The rod is a mixtureof 50 percent,& weight,of steroidand medicalgrade elastaner,silicone rubber (Daw Corning MDX4-4092). Ihe levonorgestreldeviceswere manufactured ty LeirasPharmaceuticals, Finland. Time Period This reportcoversone year of experienceof the first 1509 wcmen, enrolled in stuC& between September 1981 and 31December1982. Ihe cut-offdate of this reportis 31 March1984. Data were analyzed in July 1984. Candidates and Contraindications Candidates were porouswomen,18-38years old, regularlyexposed to the risk of pregnanq and neitherpregnantnor breast-feeding. Historiesof ectopicpregnancy,cardio-vascular problems, copper allergy, persistentabnormal genital bleeding or cancerof any kindwere contraindications, as was PID or salpingitissince the last pregnancy. Current clinical evidence of any of theseconditions or of jaundice, diabetes,mentalillness,anemia,pathologicalgalactorrheaor severe hirsutismruleda candidateineligible for participation. Informed consent was required. Participantsagreed to random assignment.Use of a contraceptive otherthan the assigned~IUDwas consideredas a termination fran the stu&. Handanization Handomizationof devicesbalancedin blocks of 50. Individually sterilized devicespeckedwith insertertubeswere placedinsideopaque, nunberedenvelopesinaccordancewith the randcmallocationand assfxnbled in ascending sequence. Wanen were assigned stu& nunbers,in sequenceof insertion, receivSng-the devicecontainedin the corresponding nunberedenvelope. lhe‘stu% was singleblind. Wanen did not know whichdevicehad been inserted. Visitsand Hxaminations Insertionswereperformedwithin 7days of the onset of nenstruation. F&visits were scheduledat the end of months1, 3, 6 and 12; breastand pelvicexaminations were performedat 6-monthintervals.

NOVEMBER

1984 VOL. 30 NO. 5

445

CONTRACEPTION

The first 100 acceptors at each clinic maintained daily menstrual records. All participants were asked, either at the one year visit or upon earlier termination, to characterize their menstrual experience subsequent to acceptance. Subject Characteristics Seven-hundred-and-fifty-five wanen received the LNg 20 device and 754 coded on the admission forms the Copper T 380Ag. Of 20 characteristics there were no statistically significant differences in distribution between users of either device. Table I Characteristics at Adnission Percentage Distribution

18-24 25-29 30-38 Bean (SE) Parity

Desires additional children

Nunber in Study

1 2 3+ Mean (SE) Yes No Uncertain

LNg 41.7 34.3 24.0 26.0 (0.2) 26.7 35.7 37.7 2.44 (.05) 34.7 57.9 7.4 755

380 40.8 36.1 23.1 26.0 (0.2) 28.6 36.2 35.1 2.32 (.05) 36.2 54.6 9.2

P>.O5

P>.O5

P>.O5

754

&an age at acoeptance was 26.0 for wanen with each device. Bore than 40 percent of participants were under age 25 (Table I). Mean parity of LNg 20 device recipients was 2.4, not significantly different fran the 2.3 mean parity of the Copper T 380Ag users. A majority in each group said, at a&i&on, they wished to have no additional children (Table I). On average, the last pregnancy of the acceptors had ended about 2 years before enrollment in this St@. The last pregnancy had ended in spontaneous or induced abortion for 13 percent of the acceptors and in de1 ivery for the remainder. Ohe-fourth of the wanen enrolled had previously used IUDs; nine to ten percent reported having pelvic inflammatory disease (PID) prior to their most recent pregnancy. Mean duration of menstrual flow before a&.ssion was 4.1 dqs. Smewhat wer 80 percent of the wcmen were menstruating at insertion (Table II).

446

NOVEMBER 1984 VOL 30 NO. 5

CONTRACEPTION

lkbleII MenstrualCharacteristics at Adnission Means (SD.) W 20 ms sinceonsetof lastmenses 3.2 (2.0) Usualdurationofflow (days) 4.1 (1.1) Rxcentages Menstruating atadnission Has frequentdysmenorrhea Has severedysmenorrhea Ekperiencesintemenstrual bleedingor spotting

Icu 3aOAg 3.4 (2.1) 4.1 (1.2) 80.4

84.4 15.1 3.8 4.5

19.1 5.6 4.5

Analyses Both multipledecrement(net)and single decrenent (gross) event rates for the firstsegmentof use are reported.By the cut-offdate, 31 March1984,more than one year had elapsedsincethe last insertion. One year results are presented. Maq participntsreturhedtothe clinicfor the one year visit in ordinalmonth13, just after the conthe end of the clusion of the year. Becausethisvisit is functionally year (14)and coincideswith an increased monthlyremovalrate,data are presentedbelm as of the conclusionofordinalnxmth13. InsertionEaseand Pain F@siciahs recordedwhetherinsertion was easy or difficult. At least aa percent of insertionswith either device were "easy". Nsvertheless, a significantly higherpercentageof insertions of the L&Q 20 device were recordedas difficult(TableIII). F@siciansascribed ahigher percentage the difficulty to theinsertertube. Corxxmitantly of wanen receivingthe L&Q 20 device (15.9%)feltmoderateor severe pain at insertion than was the casewith the TCu 36OAg device (9.3%) (TableIII). Table III Insertion olaracteristics percentages !Icu380Ag WI

X2

Insertion (Physician's judgment) EW Difficult

88.7 11.3

97.0

38.8 45.3 14.3 1.6

44.2 46.6 a.2 1.1

3.0

35.8 PLO01

Pain at insertion (Wanan'sstatement) NorIf?

Mild Moderate Severe

NOVEMBER 1984 VOL. 30 NO. 5

15.87 P<.Ol

447

CONTRACEPTION

Therewere 5 insertionfailureswith the L&Q 20 device,all at a single clinic. NO insertionfailureswere recordedfor the 'Ku 38OAg. A singlefundalperforation was recordedafterinsertion of the L&g were recordedafterinsertion of the 20 device; no fundalperforations Tcu 38OAg. Pregnancy Fourwanenbecamepregnantin the firstyear while usingstuc$ devices. 'Iwo had used the LNg 20 deviceand the othertwo the 'Ku 380Ag. Net and grosscumulativerateswere both 0.3 per 100 for each device year (TablesIV and V). Gne of the 2 pregnancies with the LNg 20 followed an unnoticed 20 was carriedto term expulsion. The second pregnancy with the L&$-J A normal,healthytie childwas born. After with the deviceiD_. confirmationof the pregnancieswith the copperdeviceiD&, neither of the two warm returnedto the clinic. Outcanesare unknown. Table

IV

Net Cumulative Termination Ratesper 100 AfterOne Year Visit- FirstSegment LNg 20 Rate (S.E.) Reason 0.3 (0.2) Pregnancy 6.1 (0.9) Expulsion * 10.0 (1.1) Menstrual/Pain 4.0 (0.7) Othermedical 2.3 (0.6) Planningpregnancy 2.6 (0.6) Otherpersonal Total

Termination Continuation

Numbers TotalTerminations Lost to Follcw-up Cmpleted Year Number of Acceptors Wanan-Years of Use

25.3 (1.7) 74.7 (1.7):

174(23.0%) 90(11.9%) 491(65.0%) 755 640

X1.1380 Ag Rate (S.E.) 0.3 (0.2) 5.5 (0.9) * 6.8 (1.0) 4.8 (0.8) 2.4 (0.6) 1.9 (0.5) 21.8 (1.6) 78.2 (1.6)

150 (19.9%) 99 (13.1%) 505 (70.0%) 754 645

"P < .05 Cut-off31 March1984 Expulsion Wet expulsionratesreached5.5 to 6.1 per 100 at one year (Table Differences in expulsionrates-between deviceswere 1.2 per 100 or m. less at 4 of the 6 participating clinics. In the remaining clinics,one had sanewhatmorefavorableexperience with the LNg 20 devicewhile the

NOVEMBER 1984VOL.30NO.S

CONTRACEPTION

otherhad a lowerexpulsionratewith the Cop~xrT 380Ag. Wanen under age 25 experienced expulsionat the rate of 7 to 8 per 100 while those aged 30 and over had abut half that rate. Decreasedexpulsionratesty age were observedwith both devices. TableV GrossTermination Pates,StandardErrors& Events at the End of 1 Year ty Device R&S?3

Reasonfor Termination

w

380

Pregnancy 0.3 0.3 6.4 5.8 Expulsion Menstrual/Pain 11.1 * 7.5 4.4 5.2 OtherMedical 2.8 2.9 PlanningPregnancy 3.0 2.2 OtherPersonal DetailedReasons Menstrual/Pain Amenorrhea OtherMenstrual Pain OtherMedical PID "Hormonal" changes OtherMedical

Events

Standard Errors W 380

W

0.2 1.0 1.6 0.9 0.7 0.7

0.2 0.9 1.1 0.9 0.7 0.6

2 43 69 27 15 18

2 39 47 33 16 13

0 28 19 8 5 20

1.0

-

314 56 2.5

0.0 4.2 3.4

K-

0.8

32 22 15

1.6 0.7 2.3

1.3 0.8 3.3

0.5 0.4 0.6

0.4 0.4 0.7

10 4 13

***

380

*p<.o5 ***p<.oo1 Menstrualpatternsandpain The two lTJDs evokedmarkedly differentmenstrual patterns (Table VI). A large majority (77.1 percent)of wanen usingthe LNg 20 IUD reporteddecreased menstrualflw and 58.9 percent reported decreased days of menstrualbleedingafter insertion. Concomitantly,half (52.2 percent)reportedthe lengthof the menstrualcycleincreased.In cc* flow trast, a majorityof 'Ku 380Agusersreportedincreasedmenstrual and half (49.8percent)reportedincreased daysof bleeding. Cycle length was not greatlyaffectedamcngusersof the ICu38OAg. For the menstrualflow,dqsof bleedingandlengthof cyclevariables, theprobabilitiesthat thesedivergentreportsare attributable to chancewere less than one in one million. For all menstrualvariablesin Table VI the probabilities were less than one in 10,000 (P<.OOOl).

NOVEMBER

1984VOL.30 NO.5

449

CONTRACEPTION

Table

VI

Menstrual Experience During IUD Use (Compared to Cwn PreInsertion Experience) Percentage Reporting Status ky Device Characteristic Device Increase No Chanoe Decrease 13.3 Menstrual 9.6 77.1 32.5 Flm 59.7 7.7 ms of Bleeding

611.8

x2

P <.OOOl

359.8

<.OOOl

21.8 49.8

19.5 42.5

58.9

52.2 15.4

20.3* 62.3*

17.5 22.2

195.1

COO01

Intermenstr ual Bleeding/Spotting

22.6 21.3

68.5 77.8

8.9 0.8

44.9

<.OOOl

Qsmenor rheaFrequency

21.4 36.5

58.8 56.8

19.8 6.7

63.5

COO01

D+anenorrhea Severity

13.6 27.1

68.8 68.5

17.5 4.4

75.0

<.OOOl

LN9 380

Length of Cycle

*Includes <5 wunen stating Respondents: L&k320 616 380@ 609

7.7

change was variable.

Increased frequency and increased severity of dysmenorrhea following insertion were reported ty significantly larger percentages Of wanen (Table VI). using the TCu 38OAg than b users of the L&g 20 device Decreased frequency and decreased severity of asnenorrhea were more frequently reported ky users of the steroid-releasing device. The major ity using each device, however, reported no change in either frequency or severity of &smenorrhea. Perceptions of menstrual patterns reported at the end of the first year were substantiated ky diaries maintained throughout the year ly the first 100 acceptors at each clinic. After the initial month, 50 to 62 percent of LEg 20 IUD users recorded no bleeding ws whatever in ary selected month (3O_aarYinterval). In contrast, 15.6 was the highest percentage of Copper T 380 users who reported no bleeding days in any month during the first year (Table VII). Frcanthe second month of use through the twelfth, the average ntnnber of bleeding days experienced ky users of the copper device ranged nartrend in the rowly between 3.8 and 4.3 days. There was no perceptible monthly averages. In contrast users of the L&Q20 device experienced on the average, far fewer days of bleeding each month. !Ihe mean declined fran 2.2 days per wanan in month 2 to an average of 1.3 ws of bleeding per month in the tenth through 12th month. For all months after the the differences between devices in the associated average nwnber first, of days of bleeding was significant at P<.OOl.

450

NOVEMBER 1984 VOL. 30 NO. 5

CONTRACEPTION

Deriod Dqsfrall Admission 1 - 30 ;: 1;; 91 - 120 121 - 150 151 - 180 181 - 210 211 -240 241 - 270 271 - 300 301 - 330 331 - 360 * P < .05

TableVII MenstrualDiaryAnalysis Darcentage of Wanen with Characteristic in Specified3O-DayIntervalsfran Mnission @ Device No Bleeding No Bleeding >8Days or Spotting of Bleeding LNFI 380 LNg 380 LN9 380 19.5 21.7 4.9 7.6 3.1 * 9.4 4.4 3.1 2.2 4.9 4.6 6.8 4.6 8.9 5.5 5.5 2.9 * 8.8 2.3 4.6 1.6 4.8 0.0 2.9 **PC.01 *** P<,OOl

Recordsfor 215 LNg usersand 226 TCu 380Agusersin days l-30 Recordsfor 120 LNg usersand 139 'Ku 38OiQusersin days 331-360 Spottingdayswere as, or slightlymore,frequentthan bleedingdays among wanen usingtheLNg 20 IUD. Beginningwith monththree (day61) themonthlymean numberof bleedingand spottingdayswas significantly smaller for usersof the LN~ devicethan for usersof the 38OAgto the end of the year (TableVII). Over the firstyear hemoglobinlevelsof wanen using the steroid device rose slightly,0.26g/dl,but statistically significantly. Wanen with the 380&gexperienced a mall, 0.36g/dl,but statistically significant decline. On average however,wanen usingeitherdevicewho had initialhemoglobin levelsbelow12 g/dl were measuredas having higher hemoglobinvalues after1 year of use. Conversely, wanenusingeither devicewho had initial hemoglobinmeasurementsat 14g/dl or above, tended to have sanewhat lcwermeasurements at one year (TableVIII). This regression to mean values is frequentlyobserved in repetitive measurenent processes.

NOVEMBER

1984 VOL. 30 NO. 5

451

CONTRACEPTION TableVIII Mean Changesin Hemoglobin ty Valueat Adnissionand Device InitialValue W 20 'ICu380 Ag Signif. N-an SE Mean SE Signif.

14 15 16+ ALL

+0.26

10 11 ::

Change

Q-mw

+3.1 +2.5 +1.1 +0.8 +0.4 -0.6 -1.2 -1.4

?F

8*! 0:2 0.1

NA Yes Yes Yes

8:: 0.2 0.4 0.09

2.0 1.0 -0:4 -K

0.7 0.2 0.2 0.2

NA Yes NC Yes No

Yes Yes NA

-0.9 -1.5 -1.6

::; 0.1 0.6

Yes Yes NA

Yes

-0.36

0.08

Yes

NA meansN < 10, significance was not tested. !Ihecontrasting menstrual experience of the userswas acampaniedQj a significantdifferencebetween devices in the grossremovalrate attributahletobleeding and pain. When analyzedin termsof 3 constituent factors, menorrhea, othermenstrualproblemsand pain,differencesbetweendevicescenteron the problemof amenorrhea. Ihirlq-two wanen had the LNg 20 deviceremovedbecauseof amenorrhea in the first 13 months;no one stoppeduse of the Xu 38OpGfor this reason, (P<.OU usersof the lYJu380Agterminated intrauterine (Table V). Ccnversely, contraceptionbecause of "other menstrual problems" at a marginally higher rate than didusersofthe the LNg 20 device (P>.O5).Terminationsascribable to lowerabdaninalor backpain or to dysmenorrhea were alsomarginallyhigheramongusersof the ICu 380Ag (P>.O5). Rmoval rates attributabletobleeding andpain diminish&significantly for users of the LF.Q20 deviceas age and as parityincreased. Similarbut more modestdiminutions in these removal rates were observed among users of the TCu 380Ag.

[email protected] Inflammatot'y Disease&Other MedicalReasons for Temu.tX&iOn The incidenceof pelvicinflammatory disease(PID)was similarmoq users of the two kindsof devices(TableV). No consistent patternof difference betweendevicesmerged by age,parity,desirefor additional children or b clinic. All cases of PIDwereconsideredtobe terminations. Therewere no significant differences betweendevicesin termination rates ascribed to hormonalchangesor to othermedicdlreasons(Tables IV andvj. When askedto describetheirexperience at the end of the first year or at temination,usersof eitherdevicereportedincreases and decreasesin nervoumess,dizziness,depression,in acne and in Users of the other skin conditions with similar frequencies.

levonorgestrel-releasing device, however, reported headaches and in nausea significantly more frequently than did users of the ‘Ku 380%.

452

increases

in

(P<.Olfor each)

NOVEMBER 1984 VOL. 30 NO. 5

CONTRACEFTION

Continuation At the end of month13, 74.7 per 100 wanencontinuedin the stu& as a useroftheLWg20device. Continuation was 76.2 per 100 amongwanen assignedthe Tcu 38OAg. The continuation rate was sanewhat,but not significantly lowerfor the steroid-releasing devicethan it was for the copper-releasing device (TableIV). Continuation rateswere positively correlated with age and with parity. Wanen who at atmissiondesiredto have additional childrenhad significantly lowercontinuation ratesat one year than did women who had said thq wishedno more children(TableIX). TableIX Gne Year Pregnancyand Continuation Patespar 100 by Age, Parity& Desirefor Additional olildren Continuation

Age 18-24 25-29 30-38

LNg 0.0 0.4 0.6

Pregnancy 380 0.4 0.4 0.0

7% 73.3 84.6

73572 79.6 81.8

Parity1 2 3+

0.0 0.4 0.4

0.5 0.0 0.4

68.1 75.5 78.9

77.1 76.3 81.1

0.0 0.5

::"o

68.0 79.2

72.5 81.5

0.3

0.3

74.7

78.2

Desiresadditional children Yes No All groups

DISCUSSION Both devicesprovedto be highly effective,with gross pegnanq rates of only 0.3 per 100 at1 year. Thesepregnanq ratesare of a magnitudeusuallyassociated with the theoretical effectiveness of oral contraceptives.

Severalindependent, randunized comparativestudies involvingthe !Ku 380, eitherwith or withouta silvercore,haveshownverylcw pregnancyrates. In multicentered studies,grosspregnancyrateshave been 0.1, 0.3 and 0.9 at1 year and in singleclinicrandanized studiesthe grosspregnamy rateswere 0.0 and 0.5 at one year (7,8,2,5,3). The currentstu* thus is at the medianof thesevalues. In this stu& the LWg 20 device proved as effective as the Xu 380Ag. Insofar as pregnancy is concerned, the selecteddosageof 20 mcg/dayappearsentirelyadequate. !Ihefirstmarketedsteroid-releasing device,the ProgestasertR,is

NOVEMBER

1984VOL.30NO.5

CONTRACEPTION

associatedwith an ectopic pregnancy ratefour to ten timesthat of devicehad a sevencopperDJDs (15). A secondprogesterone-releasing fold risk of ectopic gestation in randomizedtrials with copper IODs (16). A primeconcernin this stug was the incidenceof extrauterine pregnanciesassociatedwith the LNg 20. !Ihepointestimatein this studjwas zero;neitherof the 2 pregnancies with the LNg 20 device reporteddata Of was ectopic. This resultcoupledwith the previously Nillsonpfa. (91, yieldsa pointestimateof 1.1 ectopic pregnancies per 1,000 m-years of LNg 20 use. Thisvalueis similarto the incidenceof ectopicpregnancyobservedwith plasticand copperdevices. TheLNg 2Odevice reduced the numberof bleeding or bleeding and spotting dqs both in ccanparison with the lCu38OAgand with respectto the wcmen'sexperience beforeIUD insertion.One consequencewas that users of the LNg 20 IUD experienced a slightbut significant, increase in hemoglobin.Gn the otherhard,sane wcmen were sufficientlydisturbed& prolongedabsenceof menstruation that they stoppeduse. Dissatisfaction with this featureappearsto be the principal reason that the continuationrates of LNg IUD userswere sanewhat(P>.O5)below thoseof wanenwho used the 380A device. Becauseccmbinedoral contraceptives provideprotection againstPID, sane investigatorshad thought it plausible thata levonorgestrelreleasingIUD wouldprovidea similar protection. The current studj does not support the wpothesis of protection, at leastin ccmparison with the l'Cu380Ag. Therewas no differencebetween devices in the incidenceof PID. Followingthe relatively poor experience IUD insertertube is beingredesigned.

in this stu&, the LNg 20

Overall,the two devicesperformedsimilarly with respect to pregnancy, expulsion,ranovalsfor medicalreasonsand totalcontinuation. !thevery high effectiveness and good continuation rate associatedwith each devicemakeseach usefulfor wcmen seekingintrauterine protection againstpregnancy.!thedeterminationof the effectivelife span of thesedevicesisaprincipalgoal of the continuing stu*.

This stu* was undertaken as part of the contraceptivedevelopnent programof the International Cunmitteefor ContraceptionHesearch of the PopulationCouncil.Financialsupportprovided& the Ford Foundation, the GeorgeJ. HechtFund,the International Development HesearchCentre of Canada,the MellonFoundation, the RockefellerFoundationand the United States Agency for International Development is gratefully acknowledged.TheLNg 2Odevicesusedinthe stug weredonatedbqr Leiras pharmaceuticals.

454

NOVEMBER

1984VOL.30NO.5

CONTRACEPTION

REFERENCES

1. Tatum,H.J. Canparative experience with newermodelsof the Coppx T in the UnitedStates.m: Analysisof Intrauterine Contraception (F.Hefnawiand S.J. Segal,editors).AmericanElsevierPublishingCo.,Inc..New York,155163,1975. 2. Sivin,I. and Stern,J. Long-Acting, More EffectiveCopparT IUDs: 1970-1975. Studiesin FamilyPlanA sumrary of U.S. experience, ning 10:263-281,1979. 3. Rq, S., Casagrande, J., Cooper,D.L.,and Mishell,D. Canparison of threedifferentmodelsof the CopperT intrauterine contracep tive device.Am. J. Cbstet.Gynecol.134:%8-574r1979. 4. Sivin,I. and Tatum,H. Fouryearsof experience with the Tcu 380A intrauterine contraceptive device.Fertilityand Sterility 36(2):159-163,1981. 5. Diaz,J., Diaz,KM., Pastene,L., Araki,R., and Fat&es, A. Randcmized clinical stu& of the 'Ku 38OAandthe LippesLoop.Cop traception 28(3):221-238,1982. our, A., and Abdullah,S.A. A pros6. Shaaban,M.M.,Sal implants and the Tcu 38OAgIUDin pective stu* of Assiut,Egypt.Studiesin FamilyPlanning14 (6/7):163-169,1983. 7. Sung,S., Qian,L.J.,and Liu, X. Cunperative clinical experience with 3 IUDs: lCu 38OAg, 'ICu 220C and MahuaRing in Tianjin, People'sRepublicof china.Contraception 29(3):229-239,1984. 8. Cole,L.P.,Potts,M., Aranda, C., Behilovic,B., Eln-ar,S., of the Ku 38OAgand the Moreno, J., and Ran&c, L. An evaluation MultiloadCu375.Fertilityand Sterility(In Press)1984. T. mo years 9. Nillson,C.G.,Allonen,H., Diaz,J., and Luukkainen, experiencewith two levonorgestrel releasingintrauterine devices andone copperreleasing intrauterine device: A randanizedccmE;az.; performance stu&. Fertilityand Sterility39(2):187,

.

S., Pizarro,E., and Diethelm,P. Contra10. We, P.J.,Xoetsawang, ceptive bleeding patterns of a progesterone-releasing IUD.a: Analysisof IntrauterineContraception (F. Hefnawi and S.J. Co., Inc., New York, segal, editors). AmericanElsevierPublishing 185-198,1975. J., &xxx, R, Rosado, A., and Maqueo,M. Clin11. Martinez-Manautou, ical experience with intrauterine progesterone releasingsystems. _Ip&~ysfs of Intrauterine Contraception(F.Hefnawi and S.J. , editors). AmericanElsevierPublishing Co., Inc.,NewYork,

NOVEMBER

1984VOL. 30 NO. 5

455

CONTRACEPTION

173-184,1975. 12. El-Mahgoub, S. d-Norgestrel slow releasing T deviceas an intrauterine contraceptive. D: Analysisof Intrauterine Contraception (F.Hefnawiand S.J. &gal, editors).hnericanElsevierPublishing co., Inc.,NewYork,317-324,1975. 13. Nil&on, C.G.,Luukkainen, T., Diaz,J., and Allonen, H. Intrauterinecontraception with levonorgestrel: A cunparative randunized clinicalperformance studj.Lancet1:557,198l. 14. WHO Task Forceon Intrauterine Devicesfor FertilityRegulation: Interval IUD insertionin parouswunen:A randcxnized multicentre comparative trialof the Lipps loop D, 'Ku22OCand the Coppx 7. Contraception 26(1):1-22,1982. 15. Alza Corporation ProgestasertR IntrauterineProgesteroneCbntraCeptiVeSystem:Warnings(latMling),1983(Jan.). 16. World HealthOrganization, SpecialProgranrme of Research Develop ment and ResearchTraininginHunanReaoduction.~:llthAnnual Report,Progresterone releasinglUDS.Geneva,53-55,1982.

456

NOVEMBER

1984 VOL. 30 NO. 5