New Met H Ods of Horm on a L Con Tracepti On

ANCC Contact Hours 2. 0 / 2. 0

New Meth o ds of Hormon a l Cont raceptio n

Patricia Aikins Murphy, CNM, DrPH, FA C N M

ont raceptio n is one of the most Several new hormonal contraceptive f i c u l ty rem em bering to take daily pre- wi de s pre ad health care inter- vent ive medi c a ti on s . methods have recently been approved C ven ti ons for wom en of repro- A nati onal su rvey of wom en and duc tive age .O f the 60.1 milli o n Ame ric a n by the Food and Drug Administration. obs t etric i a n - gy n e col o gists indicates that wom en of ch i l d be a ring age (ages 15 to Most new methods combine the high wome n want cont raceptive meth o ds that 4 4 ) , 64% use con tracepti on . Am on g simplify their lives . 6 This artic le discusses those who are sex u a lly active and con- efficacy of oral contraceptives with s everal new con traceptive met h ods that si d ered at risk for unintend ed pregna n c y , longer-term delivery methods that elim- ha ve recent l y been approved by the Food 93% use con tracepti on .1 Non et h el e s s , and Drug Ad m i n i s tra ti on (FDA ) . Ma ny inate the need to take a pill each day. 47% of pregnancies that occur annua l ly comb ine the high eff i c a cy associ a t ed wit h in the Un i ted States are uninten ded at New methods also offer reversibility and oral cont raceptives with long er-t erm de- the time of conc eption ; of th e s e , 49% end li very meth o ds that eli m i n a t e the need to resumption of fertility if desired. This ar- in indu ced aborti on .1 Si x ty-six percen t remem b er to take a pill each day, yet of- of bi rths among 15- to 19-ye a r- o l d ticle discusses these new methods and fer reversi bi l i t y and resu m p tio n of fertil - wome n and 39% of bir ths among 20- to reviews the literature on efficacy and it y if des i r ed. These new produc ts reta i n 24 - ye a r -old wome n are unintend ed. 1, 2 de s i red traits of a ny good con traceptive One of the most ef fective met h od s side effects. m et h od ,i n clud i n g excelle nt eff i c a cy and of con tracepti on is oral con traceptive s . s a fety, few nu i s a n ce side ef fect s , ease of In ad d i ti on to being ef fective , t h ey have an excell ent safety us e , and reversi bi l i t y. profi l e . However, comp l i a n c e with daily pill taking remains a probl em for many wom en . F i f ty percent of oral con tracep- ■ Contraceptive Vaginal Ring tive users self - r eport missing one or more pills per cycl e ;2 2 % Con traceptive va ginal ri n gs have been stu d i ed for nearly 4 miss two or more pills . 3 In a stud y that ele ctroni c a l ly recorded deca des . The y are some what smalle r than a diaph ra gm ;h ow- the time and date that an oral cont raceptive pill was remo ved ever, th e y do not need to cover the cervix to be eff ective. The s e f rom a con t a i n er, 30% to 50% of su bj ects missed three or rin g s release cont raceptive steroid hormo nes directl y into the mo re pills per cycle . 4 va gi n a , whe re they pass throu g h the vag inal ep i t h el ium and This is not solely an issue affecting young wom en . Th e i n to the circ u l a ti on . This del ivery sys tem el i m i n a tes (1) the well - k n own Phys i c i a n s’ Health Stu dy, wh i ch eva lu a ted the ne ed to take a daily pill, (2) the gas t roin te s t inal disturb a n ce s c a rd i ovascular pro tective ef fects of d a i ly aspirin versu s that oft en occur with oral adm i n i s t rati on , and (3) the hepa ti c pl a cebo, was preceded by a run-in perio d to ident ify comp l i - f i rst-pass ef fect . Bi oava i l a bi l i ty is gre a ter than with an ora l ant pill takers . O f the 33,223 middl e - a ged male phys i c i a n s cont raceptive, whi c h allo ws a lower hormo ne dose to be used who were eli gi b le to partic i p a te , onl y two- t h i r ds (22,071) re- wit h o u t reducing eff i c ac y . The cont ro ll ed release also avoid s mem b ered to take at least two- t h i r ds of th e ir daily pills dur - the daily fluc tua ti o ns of ho rmo ne levels associ a t ed with oral ing an 18-week peri od .5 The take - h ome message from this con traceptive pill s .7 Con traceptive ri n gs are inten ded to re- stu d y is that most peopl e , even older, well educ a t ed ,m i d dl e - main in place du ring interco u rs e , but may be rem oved for cla s s , and presu m a b ly health-conscious indivi du a l s ,h ave dif- brie f period s . 8 w w w. tn p j. co m The Nu rse Pra cti ti o n er • Feb ru a ry 2003 1 1 New Met h ods of Ho rmonal Co n tra cepti o n

St udies of cont raceptive rin g s containing onl y proges ti n s Irregular ble eding or spot t ing in the first cycle was signi f i c a n t l y demon s t rat ed high rat es of brea k t h ro u g h ble eding and/or in- less among cont raceptive ring users than among oral cont ra- cons i s t ent sup pres s i o n of ovul a ti o n (although eff ects on thick- ceptive users (1.9% vs .3 8 . 8 % ) . In sub s e que nt cycl e s ,a pproxi - ening of cervical mucus may afford con traceptive ben ef i t ma t ely 10% of oral cont raceptive users exp erien c ed irregu l a r des p i t e ovul a ti on ) . 8 Combi n a ti o n cont raceptive rin g s (an es- ble eding or spot ti n g , a rat e not statis ti c a l ly different from the trogen plus a proges t in) provid e bett er mens t rual cycle con- som e what lower rat e among cont raceptive ring users; by the trol . This type of cont raceptive ring is left in the vag ina for 3 sixth cycl e , the ra tes were iden ti c a l . Com p l i a n ce was high in wee k s , t h en rem oved for 1 week to all ow wi t h d rawal bl eed- both grou p s : 92% of cont raceptive ring users were fully com- i n g. A con traceptive ring containing 3-keto - de s oge s trel and pliant with use recomm en d a ti on s ; 75% of oral cont raceptive eth i n yl estradiol (NuvaRi n g , Or ga n o n) recent l y received FDA us e rs did not miss pills . ap proval . The con traceptive ring is sof t ,f l ex i bl e , and tra n s p a ren t . Possible Side Effects It is 4 mm thick and 54 mm wi de (com p a red with the com- Device - s p ecific proble ms with the cont raceptive ring includ e m on ly pre s c ri bed 60- to 80-mm width of con traceptive di- sp ont a n e ous exp u l s i o n (usua l ly associ a t ed with laxity of th e a ph ra gm s ) . The devic e releases 120 mcg of etono ges t rel and va ginal wall ) , forei gn body sen s a ti on s , and reports of coi t a l 15 mcg of eth i n yl estradiol daily. problem s ; these were reported infrequen t l y. Vag inal discom- fort, vagi n i ti s , and discha r g e were also reported infrequen t l y Study Results by stu dy parti c i p a n t s . Ot h er side ef fects com m on ly assoc i- A ph a rm aco k i n etic stu dy9 com p a ring the newly approved a ted with horm onal con tracepti on (ac n e , breast ten dern e s s , cont raceptive ring with an oral cont raceptive containing 150 h e ad ach e , and nausea) were similar bet ween the con tracep- mcg des o ges t rel and 30 mcg of eth i n yl estradiol demon s t rat ed tive ring and oral con traceptive groups and all were infre- that maximum hormo ne serum conc ent rati o ns were rea che d que nt (< 5% of subj e cts ) . 7 ap proxi m a t ely 1 week after insertio n of the cont raceptive rin g , Twenty - o ne wome n (1.8%) with an initial normal Pap a n - with con cen tra ti ons dec reasing over ti m e . In con tra s t , ora l ic olaou (Pap) test had an abno rmal cytol o gy at the end of th e cont raceptives res ult in a daily peak and trou g h of ho rmon e stu d y (usua l ly 1 year later) . This low rat e sug gests that use of l evel s . With the con traceptive ri n g, m a x i mum serum hor- the con traceptive ring does not increase the risk for cervi c a l mo ne conc ent rati o ns were onl y 30% to 40% of the maximum a bn orm a l i ti e s .10 A previous stu dy by the same group eva lu- with oral ad m i n i s tra ti on . Af ter taking differen ces in daily at ed the cervic a l - va g inal epi t h el i um dur ing 20 cycles using a dos a g e into accou n t , the auth o rs of the stud y conc lud ed that proto t ype cont raceptive rin g .The y conc lud ed that there were s ys temic ex po su re to the proge s tin was similar for the con- no adverse cytol o gic or bacterio l o gic cha n g es associ a t ed wit h traceptive ring and oral con traceptive , wh ereas sys temic ex- cont raceptive ring use.11 In a stud y of the eff ects of the cont ra- po su re to et h i nyl estradiol with the con traceptive ring was ceptive ring on vag inal flora, use of the ring for 21, 2 8 ,4 2 , or onl y 50% of the oral cont raceptive. 9 56 days was not associ a t ed with any increase in inflammatory In a 1-yea r ,mul ti c ent er stud y—the largest stud y to date— cells or pathogenic bacteria , whe n comp a r ed with baseli n e . 12 1,145 wome n used the cont raceptive ring for over 12,000 men- s trual cycl e s .10 O n ly six pregnancies occ u rred , giving the ■ Transdermal Contraceptive Patch cont raceptive ring a Pea r l Ind ex* of 0 . 6 5 .O f the six pregna n - Tran s d ermal syst ems for medi c a ti o n deli very have appl i c a ti on s c i e s ,t h ree appear to have occ u rred after ex ten ded ri n g - f ree in the preventi o n of mo ti o n sickness and nicot ine wit h d r awa l period s , sug ges t ing that inappropria t e use of the devic e may and in meno pausal hormo ne repl a ceme nt therap y. Tran s d er- h ave led to some of the uninten ded pregn a n c i e s .1 0 Irreg u l a r mal deli very of suf f i c i e nt amounts of cont raceptive steroids for bl eeding (pri m a ri ly spo t ting in this stu dy) occ u rred infre- eff ective cont raceptio n had not been demon s t rat ed until the quen t l y (2.6% to 6.4% of a ll cycl e s ) ; bre a k t h ro u gh bl eed i n g develo pme nt of an eth i n yl estradiol and norelge s t romin tran s - was reported in 1% of c ycl e s . The inve s ti ga tors reported no dermal cont raceptive patch (Ortho Evra,O rt h o - Mc N eil Phar- cli n i c a l ly rele vant cha n g es in blo od chem i s t ri e s ,h em a to l ogy, ma ceutic a l ) , whi c h was recent l y approved by the FDA. blo od pres su re , or body weigh t . This beig e cont raceptive patch is abou t the size of a match- Ano t h e r stud y comp a r ed users of the cont raceptive rin g book , with a surf a ce area of 20 cm2.Dur ing a 24-hour period , (121 wome n) with users of oral cont raceptives (126 women ) the tran s d ermal cont raceptive patch releases 20 mcg of eth i n yl in terms of m en s trual cycle con trol and side ef fect s .7 Wi t h- es t radiol and 150 mcg of no relge s t romin into the user’ s blo od- dr awal ble eding (dur ing the rin g - f r ee or pill- f r ee weeks) oc- s tre a m . ( Norel ge s tromin is the pri m a ry active met a bo l i te of c u rred in vi rtu a lly all cycles in both gro u p s , and the mean nor ge s ti m a te , the proges t in in several oral cont raceptive pills ) . dura ti o n of wit h d r awal ble eding was comp a ra b le (4 to 6 days) . Ea r ly dosing studies found that the 20 cm2 pa t ch deli vered op-

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timal serum conc ent rati o ns of cont racep- C o n t r a c e p t i v e v a g i n a l Ano t h e r series comp a r ed 812 cont raceptive steroids and demon s t rat ed ovul a ti o n tive patch users with 605 wome n using a rings release contracep- sup pre s s i on ,m en s trual cycle cont rol , ef- tri phasic oral con traceptive con t a i n i n g fects on circu l a t ing estradiol and lutein i z - tive steroid hormones di- le vonor ge s t erel. The proba bi l i t y of preg- ing hormon e , and a side ef fect prof i l e rectly into the vagina, where they pass nancy was 0.6% in the con traceptive similar to that seen in wome n taking an pa t ch group and 1.2% in the oral cont ra- eth i n yl estradi o l / n or ge s ti m a t e oral con- through the vaginal epithelium and into ceptive grou p . The overal l Pea r l Ind ex for traceptive pill. 13 the circulation. This delivery system the con traceptive patch was 1.24, with a The con traceptive patch has three met h od - f a i lu r e index of 0. 9 9 ; the overal l eliminates (1) the need to take a daily la yers: an outer layer,whi c h provid es sup - and meth od - f a i lu r e Pea r l indices for the port and prot ectio n for the middle layer; pill, (2) the gastrointestinal disturbances oral cont raceptive pill were 2.18 and 1.25, a middle layer, whi c h contains the active res p ectively.22 that often occur with oral administra- i n gred i en t s ; and an inner layer, wh i ch prot ects the adh e s i ve and is remo ved jus t tion, and (3) the hepatic first-pass ef- Possible Side Effects before app l i c a ti on . The con traceptive fect. Bioavailability is greater than with The side eff ect profile for the cont racep- p a tch is de s i gn ed to be placed on cl e a n , tive patch is similar to that of oral con- d ry skin on the but tock , a b dom en , u p- an oral contraceptive, which allows a traceptive s , with the ad d i ti on of per outer arm , or upper torso (but not lower hormone dose to be used with- app l i c a ti o n site rea ction s . 23 Rot a t ing the the brea s t s ) . It is first appl i e d after a men- a pp l i c a ti on site each time it is ch a n ged out reducing efficacy. s trual peri od , and the user fo ll ows a he lps reduc e skin rea ction s . Any skin ir- s ch edule of a pp lying a new patch each ri t a ti on gen era lly disappe a rs ra p i dly af- week for 3 week s , foll o wed by a patch- f r ee ,7 - d ay interval . ter the con traceptive patch is rem oved . P h o to toxic and pho t oall er g ic rea ctio ns (to ultravio l e t A and ultravio l e t B ex- Study Results posu r es) are not associ a t ed with cont raceptive patch use.24 Serum levels of cont raceptive hormo nes remain stea dy duri n g The cont raceptive patch does not norma l ly deta ch from the 7 days of us e , eli m i n a t ing the hormo nal peaks and trou gh s the skin—this has occu r red in less than 2% of app l i c a ti on s — as s oc i a t ed with oral cont raceptives . 14,15 These stea dy state levels even under con d i ti ons of physical exerti on and va ri a ble hu- ha ve the same eff ect on cervical mucus and end ome trium as mi d i t y.If this happen s ,h owever,the cont raceptive patch should the peak-and-trough levels associated with oral contracep- be rep l aced with a new on e , wh i ch should then be worn for tives . 16 Ph a rm a cok i n e tic studies have demon s t rat ed that serum the rema i n d er of the wee k .O i l s ,c re a m s , or cos m e tics should le vels remain stable even under vari e d cond i ti o ns of he a t , hu- not be appl i e d around or on the area of pa t ch placemen t . mi d i t y, and exerci s e . 17,18 In add i ti on , the pha rm a cok i n e tics are In unbl i n ded studies that com p a red the con traceptive similar at each of the recommended application sites.19 The p a tch with a tri phasic oral con traceptive containing lev- cont raceptive patch deli vers eth i n yl estradiol and norelge s t ro- on or ge s trel ,2 0 , 2 2 con traceptive patch users had more bre a s t min within a defi n e d referenc e ran g e throu g h 2 full days be- tend erness than oral cont raceptive users; most other side ef- yond the recomm en d ed 7 days of wea r .17 Thus , it is not neces s a r y fects were reported equa l ly betw een grou p s . Ana l yses sug ges t to cha n g e the patch at the exa ct same hour each week . that breast discom fort is reported su b s t a n ti a lly more of ten In a trial of 1,672 wom en who wore the con traceptive by cont raceptive patch users than oral cont raceptive users in p a tch for ei t h er six cycles (1,171 wom en) or 13 cycles (501 the first one or two cycles of trea tm e nt (15% to 19% in con- women ) , the proba bi l i t y of pregnancy throu g h six cycles was traceptive patch users, comp a r ed with 3% to 4% in oral con- 0. 4 % ; th ro u g h 13 cycle s , it was 0.7%, for an overal l Pea r l In- traceptive users in cycle one ) . By the third cycl e ,h owever, onl y dex of 0 . 7 1 . The met h od - f a i lu re ra te (as oppo s ed to a user- 2% to 3% of cont raceptive patch users complain of breast dis- f a i lu re ra te) was calculated to be 0.4%, or a met h od - f a i lu re comf ort, a rat e not signi f i c a n t l y different from the absenc e of Pea r l Ind ex of 0. 5 9 . 20 complaint in the oral con traceptive gro u p.2 0 , 2 2 Com p l i a n ce Ef f i c a cy of the cont raceptive patch is similar to that of oral with the con traceptive patch has been shown to be con s i s- cont raceptives . 21,22 One stud y comp a r ed outcomes among 861 tent l y bett er than with oral cont raceptives . 25 , 2 6 con traceptive patch users with those of 656 users of an ora l con traceptive containing a low dose of et h i nyl estradiol (20 A Caveat mcg) and de s oge s trel . The overa ll prob a bi l i ty of pregn a n c y One caveat with the use of the cont raceptive patch :E f fective- was calculated throu g h 13 cycles as 0.5% in cont raceptive patch ness ma y be reduc ed in wome n with grea t er body wei gh t .O f us e rs, comp a r ed with 0.3% for oral cont raceptive users. 21 15 pregnancies that occu r red among 3,300 users of the con- w w w. tn p j. co m The Nu rse Pra cti ti o n er • Feb ru a ry 2003 1 3 New Met h ods of Ho rmonal Co n tra cepti o n

traceptive patch , on e - t h i rd occ u rred in Transdermal delivery of was high: No pregnancies occu r red in the wome n weig hing 90 kg (198 pounds) or i n j ect a ble con traceptive group in more sufficient amounts of con- m ore , a group repre s en ting on ly 3% of than 8,000 cycles of us e ; one occu r red in the stu dy pop u l a ti on .2 7 Re a s ons for this traceptive steroids for ef- the oral cont raceptive comp a ri s o n grou p . ar e uncle a r , but may be rela t ed to poorer fective contraception had not been The 1-year Pea r l Ind ex for injecta b le con- ab s o rptio n in the pres en c e of mo re sub - traceptive users was 0; for oral con tra- cut a n e ous fat or differenc es in drug cle a r - demonstrated until the development of ceptive users , it was 0.4. Previ o u s a n ce , c i rc u l a ting levels of h orm on e s , or an ethinyl estradiol and norelgestromin i n tern a ti onal trials have had firs t - ye a r time to re ach ste ady state in heavi er f a i lu re ra tes of 0% to 0.2% for mon t h ly 2 8 transdermal contraceptive patch (Ortho 31 wom en . Un fortu n a tely, c a l c u l a ti on of MPA / E 2C injection s an d , in the World weig ht grou p - s p ecific rate s , whi c h wou l d Evra, Ortho-McNeil Pharmaceutical), Health Organ i z a ti o n’s mul ti c ent er stud - all o w a qua n ti f i c a ti o n of an y pot ent ial in- ies invo lving 12,000 wom en and more which was recently approved by the cre a s e d risk of fa i lu re , is not pos s i b le from than 100,000 wom a n - m on t h s , on ly 5 the num e rat or-on l y data current l y avai l - FDA. Effectiveness may be reduced in pregnancies were reported (< 0.1%).29 abl e . More publi s h e d data are needed to women with greater body weight. P h a rm aco k i n etic studies dem on- cla r ify this obs e rvati on . st rat e that the MPA serum conc ent rati o n peaks within a week of ad m i n i s tra ti on ■ Injectable Contraceptive and remains above the level needed for conti n uous sup pres - Inj e cta b le cont raceptio n off ers users eff i c ac y , reversi bi l i t y, an d si o n of ovar ian functio n throu gh o u t the recomm en d ed dos - conveni en c e wit h o u t the need to take a pill every day. Fam i l y ing interva l .E s tradiol cypi on a t e levels peak approxi m a t ely 2 planning clinicians world wid e are familiar with a 3-month con- da ys after injectio n and retur n to baseline by 14 days; the mag- traceptive injectio ns formul a ti o n containing 150 mg ofmed r ox- ni tu d e of the peak is similar to the preovul a t ory estradiol pea k yprogesterone acetate (Depo-Provera, DMPA);this product se en in a normal mens t rual cycle . 32 has been avai l a b le for deca des . Clinicians are also undou b tedly Con traceptive ef fects reverse rel a tively ra p i dly after the familiar with some pot ent ial disadvan t a g es of this met h od ,i n- in j e ctio ns are disconti nu ed . In one stud y, retur n of ovul a ti on , cluding mens t rual cha n g es (partic u l a r ly ameno rrhea) and de- as measur ed by a rise in serum proges t erone levels , occu r red la yed retur n to fertil i t y.29 as early as 63 days after the final injection . 33 Within 12 mont h s

A second injecta b le cont raceptive, avai l a b le in the Uni t ed of di s c onti n uing injection s , 82% of us e rs of the MPA/ E 2C in- St a t es since 2000, has a formul a ti o n of med r oxy proges t erone je cta b le cont raceptive who wanted to become pregnant were acet a te (MPA ) , 25 mg, and estradiol cyp i on a te (E2C ) , 5 mg ab le to suc ces s f u l ly conc eive, whi c h is similar to the 12-mont h (Lu n e lle Mont h l y Cont raceptive Inj e cti on ,P h a rm ac i a , Inc . ) . rat es of forme r oral cont raceptive users and wome n who had This formu l a ti on has been ava i l a ble in other co u n tries for a not been using a cont raceptive. 31 num b er of yea rs .

The MPA / E2C inject a ble con traceptive , wh en ad m i n i s- Possible Side Efects tered mont h l y,in h i b its gona dot ropin secr etio n and sup pres s e s Ble eding epi s o des in users of the MPA/ E 2C injecta b le cont ra- fo llicular matu ra ti on and ovu l a ti on . Be s i des being a high ly ceptive tend to occur predi ct a b ly, ap proxi m a t ely 22 days (± 3 ef f i c i ent con traceptive , the estradiol cyp i on a te com pon en t da ys) after each injectio n in the U. S .s tu dy.34 The averag e leng t h a ll ows a regular mon t h ly bl eeding pattern that is familiar to of ble eding epi s o des was 6 days (comp a r ed with 5 days in the wome n not using hormo nal cont raception , as well as to users oral con traceptive com p a ri s on gro u p ) . Pred i ct a ble bl eed i n g of oral cont raceptives . The injecta b le cont raceptive is adm i n - pa t t erns were correla t ed to receiving repeat injectio ns at regu - i s tered intra mu s c u l a rly within 5 days of the on s et of a nor- la r ly spaced interval s . Brea k t h ro u g h ble eding was slight l y less mal peri od or of a firs t - tri m e s ter aborti on . Po s tp a rtum use comm o n among the MPA/ E 2C injecta b le cont raceptive grou p ca l ls for injectio ns no earli e r than 4 weeks pos tp a r tum if th e than the oral cont raceptive group (6.1% of cy cles vs. 8.0% of woman is not brea s t - f eedi n g , or 6 weeks pos tp a r tum if she is cy cle s , res p ectively) , but ameno rrhea or missed perio ds were l act a ti n g.In j ecti ons are given every 28 to 30 days , within a sl i gh t l y more comm o n (14.6% vs .3 . 3 % , res p ectively) . 34 10 - d a y win d ow (23 to 33 days) . 30 Non et h el e s s ,m en s trual disturb a n c es are among the most comm on l y reported side eff ects associ a t ed with the mont h l y

Study Results MPA / E 2C injecta b le cont raceptive. Irregular ble eding (defi n e d In the Uni t ed States , a mul ti s i t e stud y comp a r ed users of th e as a ran g e of le ngths of ble edi n g - f r ee intervals) was more com- in j e cta b le cont raceptive (782 wome n) with users of a triph a - mon among MPA/E2C injectable contraceptive users than sic oral con traceptive (321 wom en ) . Con traceptive ef f i c ac y among oral contraceptive users in the first 3 months of use

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(39.4% among injectable contraceptive I n j e c t a b l e c o n t r a c e p t i o n pelvic inflammatory disease (PID) due to us e rs vs. 30.7% among oral cont raceptive a unique de s i gn flaw: a mu l ti f i l a m en t offers users efficacy, re- us e rs) and after nearly 1 year ofuse (30.4% s tring covered with a pro tective sheath. vs. 16.9% res p ectively) . 30 In interna ti on a l ve r s i b i l i t y , and convenience Whe n the string was cut at inserti on ,t h e stu d i e s , 57% of MPA / E 2C injecta b le con- without the need to take a pill every day. end of the sheath was comp romi s ed , pro- traceptive users reported vari a ti o ns from viding a portal that allo wed pathogens to th e ir regular ble eding pattern dur ing the The MPA/E2C injectable contraceptive, en ter the en dom etrial cavi ty pro tected first 3 months of use, a proportion that when administered monthly, inhibits go- f rom cervical mucus defense sys tem s .3 5 dr ops to 30% by the end of the first yea r . Cur rent IUDs have a monof i l a m e nt tail, nadotropin secretion and suppresses fol- Although these bleeding variations are whi c h does not pose this same ris k . more common among MPA/E2C in- licular maturation and ovulation. A cop- A copper IUD and a proges t erone - je cta b le cont raceptive users than among releasing IUD have been avai l a b le in the per IUD and a progesterone-releasing oral cont raceptive users, these rat es are far Uni t ed States for a num b er of yea rs . The lo wer than those reported among DMPA IUD have been available in the United copper IUD (Pa ra G a rd T380A, O rt h o - in j e cta b le cont raceptive users (91% wit h States for a number of years. In late 2000, McN eil Pharma ceutical) is approved for ble eding vari a ti o ns in the first 3 mont h s ; up to 10 ye a rs of u s e ; the proge s teron e - 92% during the first year of use).31 For the FDA approved a levonorgestrel-re- releasing IUD (Proges t a s e rt, Alza Corp) , wome n who des i r e the conveni en c e of in - leasing IUD (Mirena, Berlex Laborato- for 12 months of u s e . In late 2000, t h e je ctio ns over the need to take a pill every FD A approved a levonor ge s t rel- r ele a s i n g ries) for 5 years of use. day, the appropriate comparison is with IUD (Mir ena , Berle x Laborat ories) for 5 an o t h e r injecta b le meth od . ye a rs of u s e . This devi ce has been ava i l-

Si de ef fects among MPA / E2C inject a ble con traceptive ab le in Eur ope for more than a deca de. us e rs are similar to those exp erien c ed by users of oral cont raceptives . Breast tend erne s s , weig ht cha n ge , and acne were fre- Study Results qu en t ly reported. However, th e y were not major rea s o ns for The levonor ge s t rel- r eleasing IUD consists of a small T-s h a p ed d i s con ti nuing the MPA / E2C injecti on s , being cited by on ly fr ame with a res e rvoir that releases 20 mcg of le vonor ge s t rel 1 . 8 % , 5 . 7 % , and 1.9% of wom en , re s pectively, as the re a s on da i l y. This pot ent proges t in is found in many oral cont racep- for stopping tre a tm en t . Wei ght ch a n ges were noted amon g tive s . The devi ce has a tail that com bines po ly u rethane and us e rs of the MPA/ E 2C injecta b le cont raceptive, but not among ir on oxi de . The iron adds col o r to the threa ds and makes them the com p a ra tors taking oral con traceptive s . The med i a n ea s i e r to see after insertion . The levonor ge s t rel- r eleasing IUD wei ght ch a n ge over the 15-month stu dy was 5 po u n d s .3 0 has a newly de s i gn ed , on e - h a n ded inserter sys tem , wh i ch is Wom en wei ghing 150 pounds or less at stu dy en try ga i n ed di s c a r ded after use. This IUD should be inserted within 7 days s om ewhat less (2 to 4 pounds) than wom en wei ghing over of a mens t rual peri od ;u n l i ke the copper IUD,it is not exp ected 150 pounds (3 to 8 pou n d s ) . No cli n i c a l ly significant cha n ge s to act as emer g ency cont raceptio n and thus should not be in- in blo od pres su r e or clinical laborat ory tests were associ a t ed se rted later in the mens t rual cycle for that purpos e . The lev- with the use of the MPA/ E 2C injecta b le cont raceptive. onor ge s t rel- r eleasing IUD is approved for 5 yea r s of us e . One drawba ck to the use of this highl y eff ective meth o d The levon or ge s trel - releasing IUD is high ly ef fective at of cont raceptio n is the need to make mont h l y appoin tm en t s prevent ing pregna n c y . Its prim a r y mechanisms of actio n are with a clinician for repeat injection s . A subc ut a n e ous formu- t h i ckening of cervical mu c u s , i n h i bi ti on of s perm moti l i ty l a ti on , wh i ch could be sel f - ad m i n i s tered mu ch as insulin is, and functi on , and altera ti on of the en dom etriu m ,3 6 , 3 7 and it has been develo ped and is current l y underg oing clinical tria l s . has failu re ra tes of 0.1% du ring the first year and 0.7% cu- mul a t ive over 5 yea rs . 38 , 3 9 These rat es are comp a ra b le to those ■ Intrauterine Contraceptive Device of s teri l i z a ti on ,4 0 but with the ad ded ben efit of revers i bi l i ty. The first intrau terine cont raceptive devic es (IUDs) were de- The risk of ectopic pregnancy is also ext reme ly low: The rat e velo ped in the early 1900s, prio r to the avai l a bi l i t y of an ti b i- of 0.2 to 0.6 per 1,000 woma n - ye a r s is lower than other IUDs ot ics and easily acces s i b le pain reli e vers, and their use qui ck l y and lower than the backg round rat e among all wome n in the became associ a t ed with serious infectio ns and patie nt discom- Uni t ed States . 39 , 4 1 fort . A resu r g en ce of i n terest in IUDs tri ggered the devel op- Ovul a ti o n may be inhibit ed in some women ,a l t h o u g h this me nt in the 1960s of se veral plastic device s , as well as a devic e is rar e after the first year of us e . 42 As levonor ge s t rel is rele a s e d wra pped with a thin copper wire . One all - p l a s tic devi ce in t o the uterine cavit y,it is absorbed throu g h the end ome trium (D a l k on shield) came to be associ a t ed with significant risk of in t o the syst emic circu l a ti on . Aft er the first few weeks of us e , w w w. tn p j. co m The Nu rse Pra cti ti o n er • Feb ru a ry 2003 1 5 New Met h ods of Ho rmonal Co n tra cepti o n

Comparing the New Hormonal Contraceptives

Ho rm o n e s Do s a g e and Adm i n i s t ra t i o n

Co n t r a c e p t i ve ring 3- ke t o - d e s o g e s t r e l , Releases 120 mcg/day of etonogestrel and 15 mcg/day of (NuvaRing, Organon; et h i n yl estradiol et h i n yl estradiol over 3 weeks htt p : / / w w w. n u v a r i n g . c o m ) • Ea c h ring is effe c t i ve for 3 weeks. The ring is inserted into the vagina and remains in place continuously for 3 weeks. It is then removed for 1 week, followed by insertion of a new ring at the end of the week. • Timing of the first insertion depends on whether the woman never took a hormonal contraception, is being sw i t c hed from another hormonal contraceptive, just had an ab o r tion, or recently gave birth. See prescribing information for details.

Transdermal contraceptive Et h i n yl estradiol, Releases 150 mcg/day of norelgestromin and 20 mcg/day of pa t c h (Ortho Evra, norelgestromin et h i n yl estradiol Or tho-McNeil • Ea c h patch is effe c t i ve for 1 week. A new patch is applied Ph a r m a c e u t i c a l ; once a week for 3 weeks, followed by 1 week without a htt p : / / w w w . orth o e v r a . c o m ) pa t c h. At the end of the patch-free week, a new patch is applied to start the cycle agai n . • The patch should be applied to clean, dry, intact skin on the bu tt o c k, abdomen, upper outer arm, or upper torso (not on the breast, however). • The patch should be applied on the same day each week. Timing of the first patch application depends on whether the woman never used a hormonal contraception, is being sw i t c hed from another hormonal contraceptive, just had an ab o r tion, or recently gave birth. See prescribing information for details.

Injectable contraceptive Me d r ox y p r o g e s t e r o n e 0.5 mL administered by intramuscular injection into the del- (Lunelle Monthly acetate, estradiol toid, gluteus maximus, or anterior thigh Co n t r a c e p t i ve Injection, cy p i o n a t e • Aqueous suspension must be shaken just before use to en- Pharmacia, Inc; sure a uniform suspension of 25 mg of medroxy p r o g e s - ht tp:// www.lunelle. com) terone acetate and 5 mg of estradiol cypionate. • Ea c h injection is effe c t i ve for 1 month. Timing of the first injection depends on whether the woman never used a hormonal contraception, is being switched from another hormonal contraceptive, just had an abortion, or recently gave birth. See prescribing information for details.

Intrauterine system Levo n o r g e s t r e l Releases 20 mcg/day of levon o r g e s t r e l (Mirena, Berlex Laboratories; • Eff e c t i ve for 5 years htt p : / / w w w. m i r e n a - u s . c o m ) • In s e r ted into the uterine cavity within 7 days of the onset of menstruation or immediately after a first trimester aborti o n .

Oral contraceptive pill Drospirenone, ethinyl Daily oral hormonal contraceptive pill (Y asmin, Berlex Laboratories; es t r a d i o l • 21 active pills, each containing 3 mg of drospirenone and htt p : / / w w w . yasmin-us.com) 30 mcg of ethinyl estradiol, plus 7 inert pills • The first pill of the first cycle is taken on either the first day of the menstrual period or the first Sunday after the onset of the menstrual period; all subsequent 28-day regimens should begin on the same day of the week as the first pill of the first regimen, regardless of whether the next menstrual period has occurred or is still in progress.

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Co n t ra i n d i c a t i o n s Possible Side Effects (not inclusive)

Thrombophlebitis or thromboembolic disorders, history of DVT or Vaginitis, headaches, leukorrhea, weight gai n , thromboembolic disorder, cerebral vascular or coronary artery dis- nausea, acne, breast tenderness device-related ease, valvular heart disease with complications, diabetes with vascu- events (foreign body sensation, coital problems, lar involvement, severe hyp e r tension, headaches with focal device expulsion), ar ter ial throm b o e m b o l i s m , neurologic symptoms, major surgery with immobilization, breast can- deep vein thrombosis ce r , endometrial cancer or other estrogen-dependent neoplasia, undiagnosed abnormal genital bleeding, jaundice from pregnancy or use of other hormonal contraceptives, liver disease or tumors, pregnancy, older than age 35 and a heavy smoker (15 or more cigar e t tes a day), hyp e rs e n s i t i vity to any component of the product

Thrombophlebitis or thromboembolic disorders, history of DVT or Breast tenderness (tenderness may occur more thromboembolic disorder, cerebral vascular or coronary artery dis- frequently in users compared to those taking oral ease, valvular heart disease with complications, diabetes with vascu- hormonal contraceptives), headache, application lar involvement, severe hyp e r tension, headaches with focal site reactions, nausea, menstrual cramps, neurologic symptoms, major surgery with immobilization, breast bloating, irregular bleeding episodes, menstrual ca n c e r , endometrial cancer or other estrogen-dependent neoplasia, disturbances, ar ter ial throm b o e m b o l i s m , de e p undiagnosed abnormal genital bleeding, jaundice from pregnancy or vein throm b o s i s use of other hormonal contraceptives, liver disease or tumors, pregna n c y , older than age 35 and a heavy smoker (15 or more cigar e tt e s a day), hyp e rs e n s i t i vity to any component of the product

Pre g n a n c y , thrombophlebitis or thromboembolic disorders, history Acne, headache, nausea, weight cha n g e s of DVT or thromboembolic disorder, cerebral vascular or coronary (increase or decrease), menstrual disturbances, ar tery disease, undiagnosed abnormal genital bleeding, liver dys- breast tenderness, ar ter ial throm b o e m b o l i s m , function or disease (hepatic adenoma or carcinoma), jaundice from deep vein thrombosis pregnancy or use of other hormonal contraceptives, endometrial cancer or other estrogen-dependent neoplasia, hyp e rs e n s i t i vity to an y component of the product, older than age 35 and a heavy sm o k er (15 or more cigar e t tes a day), severe hyp e r tension, diabetes with vascular involvement, headaches with focal neurologic symptoms, valvular heart disease with complications

Pre g n a n c y , congenital or acquired uterine abnormalities, acute PID Acne, nausea, nervousness, decreased libido, or history of PID, postpartum endometriosis or infected abortion in altered menstrual patterns, lower abdominal pain, the past 3 months, uterine or cervical cancer, unresolved, abnormal asymptomatic and symptomatic ovarian follicular Pap smear, genital bleeding of unknown etiology, untreated acute cy s t s cervicitis or vaginitis, acute liver disease or tumor, multiple sexual pa rt n e r s, increased susceptibility to infection, genital actinomyc o s i s , breast cancer, history or risk of ectopic pregnancy

Renal insuffi c i e n c y , hepatic dysfunction, adrenal insuffi c i e n c y , throm- Breast tenderness, nausea, irregular bleeding, bophlebitis or thromboembolic disorders, history of DVT or throm- migraine, menstrual cramps and bloating, acne, boembolic disorder, cerebral vascular or coronary artery disease, theoretically hyp e r k alemia, ar teri a l breast cancer, endometrial cancer or other estrogen-dependent neo- th ro m b o e m b o l i s m , deep vein throm b o s i s plasia, undiagnosed abnormal genital bleeding, jaundice from pregnancy or use of other hormonal contraceptives, liver disease or tu m o r s, pregnancy, older than age 35 and a heavy smoker (15 or more cigar e t tes a day)

Compiled by Anne Woods, RN, CRNP, APRN,BC, MSN Source: Facts and Comparisons 2002, Product Information *Side effects in bold indicate a serious condition w w w. tn p j. co m The Nu rse Pra cti ti o n er • Feb ru a ry 2003 1 7 New Met h ods of Ho rmonal Co n tra cepti o n

plasma levels plateau at 150 to 200 mcg/mL; this level is lower 2 1 - d ay active pill regi m en (Cycl e s s a , O r ga n on ) . An o t h er than that found with oral cont raceptives , proges ti n - on l y oral tri phasic prep a ra ti on also contains 25 mcg of et h i nyl estra- cont raceptives , or proges t in implants (combi n e d oral cont ra- di o l , but it has 0.180 mg/0.215 mg/0.250 mg of nor ge s ti m a t e ceptives produce serum concentrations 50 times higher for (O r tho Tri- C ycle n Lo, Ort h o - Mc N eil Pharma ceutic a l ) . New sh o rt period s ) . 43 , 4 4 The newly approved IUD releases abou t 20 gene ric versi o ns of ma n y approved oral cont raceptive prod- mcg of le vonor ge s t rel daily, whi c h is conc ent rat ed in the en- uc ts are also avai l a bl e . dometrium. Daily intrauterine release of 50 mcg of lev- One new oral con traceptive (Ya s m i n , Berl ex Labora to- onorgestrel is generally needed to completely suppress ries) repres e nts a cha n g e from cont raceptive hormo nes long ovul a ti on . 44 Retur n to fertil i t y after use of the levonor ge s t rel- ava i l a ble in the Un i ted State s . This produ ct contains a new releasing IUD is rap i d ; 80% of wome n disconti n uing the de- proge s ti n ,d ro s p i ren on e ,p lus eth i n yl estrad i o l .D ro s p i renon e vic e to conc eive, suc ces s f u l ly do so within 1 yea r . This rat e is is an analog of s p i ron o l acton e , with pha rm a co l ogic proper- similar to users of copper IUDs and barrie r meth od s . 45 ties similar to natur al proges t erone . It has proges t ogenic properti e s ,a n ti m i n eral o cortic oid and antia n d r ogenic activit y, but Possible Side Efects few estrogenic or gluc ocortic oid propertie s . 50 , 5 1 Because proge s tin is del ivered direct ly to the uterine cavi ty, with the con s equ ent profound su ppre s s i on of the en- Study Results dom etriu m , most users wi ll ex peri en ce altered men s tru a l This new formu l a ti on is high ly ef fective , with a Pe a rl In dex ble eding patterns . Irregular spot t ing or ble eding may increa s e of < 0.5. St udies also indicate it provid es good mens t rual cy- du ring the first few months of u s e ; by 3 to 6 months of u s e , cle cont rol and has infreque nt side eff ects . Its clinical profi l e , the nu m ber of bl eeding or spo t ting days dec reases sign i f i- t h erefore , is gen era lly similar to all curren t ly ava i l a bl e , low - ca n t l y,with an approxi m a t e 90% reduc tio n in mens t rual blo od dose oral cont raceptives . 52 - 5 4 l o s s . Approx i m a tely 20% of u s ers wi ll become amen orrh ei c Some laborat ory studies have sug ges t ed that the antim i n - af t er 12 mont h s . 46 This ameno rrhea is pri m a ri ly due to loca l eral o cortic oid activit y of dro s p i r eno ne could cou n t eract the su ppre s s i on of the en dom etriu m , not to anovu l a ti on , a fact s od ium- and flu i d - retaining ef fects of et h i nyl estrad i o l , re- that needs to be stre s s ed to po ten tial users of the lev- ducing fluid retenti o n and/or premen s t rual symp toms in sus - on or ge s trel - releasing IUD. Men s trual irreg u l a ri ties are the cepti ble wom en .5 2 , 5 5 , 5 6 In some stu d i e s , s m a ll tem pora ry prim a r y rea s o n wome n discon ti nue the meth od ; in one tria l dec reases in avera ge wei ght have been reported , as was an in In d i a , d i s con ti nu a ti on was twi ce as high for users of t h e overa ll loss of s od ium and water. Overa ll , h owever, t h e l evonor ge s t rel - releasing IUD than for users of copper IUDs d ro s p i ren on e - containing oral con traceptive has perform ed (14% vs .7 % ) .47 si m i l a r ly to other oral cont raceptives and has not been asso- Lower abdominal pain is another side ef fect assoc i a ted c i a ted with ei t h er net wei ght gain or wei ght loss over with the use of the levon or ge s trel - releasing IUD, with ap- ti m e .5 3 , 5 4 , 5 7 , 5 8 Thu s , the clinical import a n ce of i n i tial wei gh t proxi m a t ely 10% of us e rs reporting it within the first 3 mont h s cha n g es is unproved. Ind eed ,s ome res e a r che rs have sug ges t ed of us e . 39 As with other proges ti n - on l y meth o ds of cont racep- that sod ium and fluid reten ti on with current low - dose con- tion , both asymp toma t ic and symp toma t ic ovar ian foll i c u l a r traceptive formul a ti o ns using any proges t in is at best negli g i- c ysts may devel op in approx i m a tely 8% to 12% of u s ers .4 6 bl e ,5 9 and it is unclear wh a t , i f a ny, i m p act may derive from These do not requ i re tre a tm ent or rem oval of the devi ce , the new formul a ti on . me rely moni t oring until their event ual spont a n e ous res o l u- Po s s i ble ben efits of this new proge s tin on prem en s tru a l tio n after 2 to 3 mont h s . s ym ptoms have been su gge s ted but incom p l etely assessed . The risk of PID is also low. In a 3-year stu dy in Eu rope , One stud y54 found small but statis ti c a l ly significant improve- the risk of PID was 0.5 for levonor ge s t rel- r eleasing IUD users, me nts in subj e ctive feeli n g s of wa t er retenti on , in c re a s e d ap- as comp a r ed with 2.0 for copper IUD users. 48 As with all IUDs, peti te , and nega tivi ty among wom en taking the new risk of i n fecti on is mainly assoc i a ted with inserti on and oc- formul a ti on , but there was no cont rol grou p ; thu s , a placebo cu r s within the first 2 to 3 weeks after insertion . 49 Aft er that, ef fect or a gen eral oral con traceptive ef fect cannot be ru l ed the risk of in f ectio n is prim a ri l y associ a t ed with the woma n ’s o ut . An o t h er stu dy57 found that the dro s p i ren on e - con t a i n- risk of sex u a l ly tran s m i t t ed infection s . ing oral cont raceptive was not associ a t ed with any cha n g e in premen s t rual symp toms . One group of in ves ti ga t ors60 eval u- ■ Oral Contraceptive a ted this dru g’s ef fects on severe prem en s trual syndrom e Several new oral cont raceptives have recent l y been approved. ( prem en s trual dys ph oric disorder, or PMDD). Use of t h e One new tri phasic prep a ra ti on contains 25 mcg of et h i nyl dro s p i r en on e - containing oral con traceptive caused a stati s- e s tradiol and 100 mcg/125 mcg/150 mcg of de s oge s trel in a ti c a lly significant improvem ent in on ly one of four sym p- w w w. tn p j. co m The Nu rse Pra cti ti o n er • Feb ru a ry 2003 1 9 New Met h ods of Ho rmonal Co n tra cepti o n

tom groups associ a t ed with PMDD: ap petite , acn e , and food 1996;11(11):2443-8. 12. D avies GC, Feng LX, Newton JR, et al.: E f fects of a com bi n ed con traceptive 6 0 c ravi n gs . Aga i n , wi t h o ut a con trol gro u p, it is not clear if vaginal ring releasing ethinyloestradiol and 3-ketodesogestrel on vaginal flora. the same ef fect would be seen with any oral con traceptive , Contraception 1992;45(5):511-8. 13. Di t tri ch R, Pa rker L, Ro s en JB, et al.: Tra n s dermal con tracepti on : eva lu a ti on rega rdless of proge s ti n ,i f this repre s ents a placebo ef fect , or of t h ree tra n s dermal norel ge s trom i n / et h i nyl estradiol doses in a ra n dom i zed , if it could be a true bene fit rela t ed to the new formul a ti on . multicenter, dose-response study. Am J Obstet Gynecol 2002;186(1):15-20. 14. S h a n gold G, F i s h er AC , Ru bin A :P h a rm acodynamics of the con traceptive patch. Obstet Gynecol 2000;95(4):S36. Risk of Hyperkalemia 15 . Abrams LS, Skee DM, Nat a ra j an J, et al: Mul ti p l e - d ose pha rm a cok i n e tics of a contraceptive patch in healthy wome n partic i p a n t s . Cont raceptio n 2001;64(5):287-94. Because of its anti m i n era l ocortocoid properti e s , t h e 16. Grow DR, Ah m ed S: New con traceptive met h od s . Ob s tet Gy n ecol Clin Nort h dro s p i r enon e - c ontaining oral cont raceptive poses a theoreti- Am 2000;27(4):901-16, vii-viii. 17. Abrams LS, Skee DM, Na t a ra jan J, et al.: P h a rm aco k i n etics of n orel ge s trom i n cal pos s i bi l i t y of in c r easing the risk of hyperka l e mia in some and et h i nyl estradiol del ivered by a con traceptive patch (Ortho Evra / Evra ) women , su ch as those with renal or ad renal insu f f i c i ency or u n der con d i ti ons of h e a t , hu m i d i ty, and exerc i s e . J Clin Pharm aco l 2001;41(12):1301-9. li ver dysf u n c tion . Packa g e labeling advises against using this 18. Zacur HA,Hedon B,Mansour D,et al.:Integrated summary of Ortho Evra/Evra oral cont raceptive in wome n with these cond i ti on s . In add i - con traceptive patch ad h e s i on in va ri ed cl i m a tes and con d i ti on s . Fertil Steri l 2002;77(2 Suppl 2):S32-5. tion , wome n who regu l a r ly take medi c a ti o ns known to affect 19. Abrams LS, Skee DM, Na t a ra jan J, et al.: P h a rm aco k i n etics of a con traceptive se rum pot a s s i um (suc h as NSAIDS, pot a s s i um supp l em en t s , p a tch (Ortho Evra /Evra) containing norel ge s tromin and et h i nyl oe s tradiol at four application sites. Br J Clin Pharmacol 2002;53(2):141-6. and certain antih ypertens i ves) should have pot a s s i um levels 20. Sm a llwood GH, Me ador ML, Lenihan JP,et al.: E f f i c acy and safety of a tra n s- m on i tored , use of this con traceptive should discon ti nu ed if dermal contraceptive system. Obstet Gynecol 2001;98(5 Pt 1):799-805. 21. Helmerhorst FJ, Cronje HS, Hedon B, et al: Comparison of efficacy, cycle con- 61 le vels are ele vat ed. tro l , com p l i a n ce , and safety in users of a con traceptive patch vs . an oral contraceptive. Int J Gynaecol Obstet 2000;70(suppl 1):78. 22. Au det MC, Moreau M, Ko l tun W D, et al: Evalu a ti o n of con traceptive ef f i c ac y ■ Summary and cycle con trol of a tra n s dermal con traceptive patch vs . an oral con tracep- Several new horm onal con traceptive produ cts have becom e tive: A randomized controlled trial. JAMA 2001;286(18):2347-54. 23. Sibai BM, O dlind V, Me ador ML, et al.: A com p a ra tive and poo l ed analysis of avai l a b le in the Uni t ed States dur ing the last few yea rs . Mos t the safety and tolerability of the contraceptive patch (Ortho Evra/Evra). Fertil of fer innova tive del ivery sys tems that redu ce the need to re- Steril 2002;77(2 Suppl):S19-26. 24. Thorne EG,Roach J,Hall N, et al:Lack of phototoxicity and photoallergy with mem b er to take a pill each day while stil l conf erring the high a contraceptive patch [abstract]. J Pharmacol Exp Ther 2000;14:A1341. eff i c a cy of oral cont raceptives . These innovati o ns provid e new 25. Archer DF,Bigrigg A, Smallwood GH, et al.: Assessment of compliance with a weekly contraceptive patch (Ortho Evra/Evra) among North American women. opti ons for wom en of ch i l d be a ring age who de s i re to avoi d Fertil Steril 2002;77(2 suppl 2):S27-31. pregna n c y . 26 . Creasy G, Hal l N, Sh a n g old G: Pa ti ent adh e renc e with the cont raceptive patch dosing sche dule versus oral cont raceptives . Obs t et Gyn e col 2000;95(4;part2 ) : S 6 0 . 27. Zieman M, Guillebaud J, Weisberg G, et al: Integrated summary of contracep- ABOUT THEAUTHOR tive ef f i c acy with the Ortho Evra / Evra tra n s dermal sys tem [abstract ] . 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To earn CE credit, follow these instructions: Wilkins. You’ll also receive an answer sheet with the rationale for 1. Choose one answer for each question and darken box. each correct answer. If you fail the test, you can take the test again 2. Fill in registration information and evaluation on answer form for free. For questions about test results, contact Lippincott (Social Security or nursing license number must be included to Williams & Wilkins, CE Dept., 345 Hudson St., New York, N.Y. 10014; process test). 1-800-933-6525, ext. 332. 3. Mail your answer form (copies accepted) and $12.95 p r o c e s s i n g Provider Information: fee to: Lippincott Williams & Wilkins, 2710 Yorktowne Blvd., This continuing nursing education (CNE) activity for 2.0 contact Brick, NJ 08723. Make checks payable to Lippincott Williams & hours is provided by Lippincott Williams & Wilkins, which is accred- W i l k i n s; if paying by credit card, include number and expiration ited as a provider of continuing education in nursing by the date. Within 4 weeks, you’ll be notified of your test results. American Nurses Credentialing Center’s Commission on 4. New discount procedure: Take 75¢ off the price of each test if sub- Accreditation and by the American Association of Critical-Care mitting two or more tests at a time from any issue. Nurses (AACN 9722; category O). This activity is also provider- 5. Fax-back service: Fax your test (credit card orders only) to 732- approved by the California Board of Registered Nursing, provider 255-2926 and we’ll fax back your CE certificate within 2 business #CEP11749, for 2.0 contact hours. Lippincott Williams & Wilkins is days. Provide a fax number for a location where confidential infor- also an approved provider of CNE in Alabama (#ABNP0114), Florida mation will be safe (home/workplace). Faxes sent to a workplace (#FBN2454), and Iowa (#75)*. All of its home study activities are will be accompanied by a cover letter. We aren’t responsible for classified for Texas nursing continuing-education requirements as faxes not received due to malfunctioning machine on receiving Type 1. Your certificate is valid in all states. end. A CE certificate will be mailed after attempts to fax have *In accordance with Iowa Board of Nursing administrative rules gov- failed. erning grievances, a copy of your evaluation of this CE offering may be 6. Take tests on-line at http://www.n u r s i n g c e n t e r. c o m / p r o d e v / c e _ o n l i n e . a s p submitted to the Iowa Board of Nursing. and have them processed immediately. TEST RESULTS MUST BE The passing score for tests is 70%. If you pass, a certificate for POSTMARKED BY F E B R UA RY 28, 2 0 0 5. earned contact hours will be awarded by Lippincott Williams &

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