9 Extended-Cycle OC Trial: Summary 91-day extended-cycle OC regimen is as effective a contraceptive as 28-day OC (>99% with perfect use); typical use efficacy lower than class labelingProduces 4 cycles per year compared with 13 with 28-day cycle OCBreakthrough bleeding comparable to 28- day cycle OC, especially by 3rd and 4th 91- day cycle
10 Lybrel 90 g levonorgestrel 20 g ethinyl estradiol Take 1 pill every dayNo pill free intervalPackage insert
11 Efficacy comparable to standard OCPs LybrelEfficacy comparable to standard OCPs
12 Lybrel Month 6 48% no bleeding Month 12 59% no bleeding 20% spotting (no protection)Package insert
14 Recently Approved 24-Day Oral Contraceptive Regimens Loestrin® 24 Fe (norethindrone acetate 1 mg/EE 20 mcg)YAZ® (drospirenone 3 mg/EE 20 mcg)Each has a dosing regimen of 24 active days of hormones followed by 4 hormone-free daysTwo 24-day active pill regimens have recently been approved.These formulations reduce the traditional 7-day pill-free week.Loestrin® [package insert]. Rockaway, NJ: Warner Chilcott Company, Inc.; February Available at: YAZ® [package insert]. Montville, NJ; Berlex Inc.; December Available at:
15 Loestrin 24 Fe Efficacy Norethindrone acetate 1 mg/EE 20 g Comparative study of 24/4 vs 21/7 of same combination24/4 21/7Pearl IndexNakasima ST, Archer DF, Ellman H. Contraception 2007; 75(1):16
16 YAZ Efficacy Drospiranone 3 mg/EE 20 g Non-comparative study 11 pregnancies in 11,140 cyclesPearl index: 1.29- Comparable to other OCsBachmann et al. Contraception 2004; 70:190
17 The Newest Implantable: A Single Rod Etonogestrel subdermal implant 68 mgImplanon is a 3 year progestin-only subdermal implant containing etonogestrel- the active metabolite of desogestrel. It is inserted between the biceps and triceps in the non-dominant arm. It should be inserted or removed only by those clinicians who have received proper training.
18 Design of ENG Rod 40 mm 2 mm Core: 40% Ethylene vinyl acetate (EVA) 60% Etonogestrel (68 mg)Implanon is 40 mm in length and 2 mm in diameter. It is composed of a solid core of Evatane with the crystals of etonogestrel imbedded within the core. Surrounding the core is a thin layer of evatane (0.06mm thick) that controls the rate which etonogestrel is released.Rate-controlling membrane: (0.06 mm)100% EVA6
19 ENG Rod Pharmacokinetics 400300Etonogestrel (pg/ml)200100Inhibits ovulation(90 pg/ml)Serum levels of etenogestrel necessary to inhibit ovulation are achieved within 24 hours of insertion and are maintained well above the minimum level of 90 pg/ml throughout the 3 years of use.12330120210360Days After InsertionDavies GC, et al. Contraception. 1993;47:251–261.
20 Contraceptive Efficacy of ENG Rod Women 2362Cycles 73,429Pregnancies 0Pearl Index (95% CI)Glasier A. Contraception. 2002;65:29–37.
21 Implant Insertion and Removal Time (Minutes)* ENG RodLNG ImplantNMeanSDMin-max6701.10.90.03–5.066184.108.40.206–18.0InsertionNMeanSDMin-max6332.62.00.2–20.013710.28.21.3–50.0During the clinical trials a head to head study was done comparing the insertion and removal times of Implanon with Norplant. All clinicians involved were proficient and experienced with the removal and insertion techniques for both subdermal systems. As the data shows, Implanon was about 4 times faster to insert and about 5 times faster to remove.Removal*Insertion time = time needed for incision (if any) and placement; removal time = time needed for anesthesia, incision, and removal.Mascarenhas L. Eur J Contracept Reprod Health Care. 2000;5(suppl 2):29–34.
22 Bone Mineral Density and ENG Rod Head-to-head study of ENG rod with non-medicated IUD (copper)No differences in BMD changes between 2 groupsAuthors concluded that although ENG rod is a progestin-only method, no bone loss occurs during useBecause some progestin-only methods cause a decrease in bone over time, a BMD study was done during the clinical trials which compared Implanon with a non- medicated copper IUD. During and at the conclusion of the study, no differences in BMD was noted between the two groups and it was concluded that Implanon has no detrimental effect on bone density. This is primarily due to the fact that although ovulation is effectively inhibited, endogenous estrogen production by the ovaries is not significantly affected.Beerthuizen R, et al. Hum Reprod. 2000;15:118–122.
23 Etonogestrel/Ethinyl Estradiol Vaginal Ring The etonogestrel/EE ring is a flexible, soft, transparent ring with an outer diameter of 54 mm and a cross section of 4 mmThe etonogestrel/EE vaginal ring is a new, highly effective contraceptive method recently approved by the FDA
24 Etonogestrel/Ethinyl Estradiol Vaginal Ring Progestin: Etonogestrel: 120 µg/dayEstrogen: Ethinyl estradiol: 15 µg/dayWorn for three out of four weeksSelf insertion & removalPregnancy rate 0.65 per 100 woman–yearsThis ring releases 120 µg of the progestin etonogestrel, formerly 3-keto-desogestrel, and 15 µg of the estrogen ethinyl estradiol per dayIt can be easily inserted and removed by the woman herself, and is intended to be used for one cycle consisting of 3 weeks of continuous ring use and a 1 week ring-free periodA total of six pregnancies were reported during treatment, giving it a Pearl Index of 0.65Roumen FJ, et al. Hum Reprod. 2001;16(3):Suggested Core Slide
25 Vaginal RingPatient ManagementPatient inserts ring and it is supposed to remain in the vagina for 3 weeksRing is removed during the fourth week, menstrual period should beginIf ring is removed or slips out of place for > 3 hrs, back-up contraception is necessary for 7 daysThe ring must be kept in place for three consecutive weeksRemove the ring three weeks after insertion on the same day of the week as it was inserted, and at about the same timeYour menstrual period will usually start two to three days after the ring is removed and may not have finished before the next ring is inserted. To continue to be protected from pregnancy, you must insert the ring one week after the last one was removed, even if your menstrual bleeding has not stoppedIt should be noted that the ring can be expelled from the vagina while removing a tampon, moving the bowels, straining, or with severe constipationIf the ring slips out and it has been out less than three hours, you should still be protected from pregnancy. The ring should be re-inserted as soon as possible. If it has been out of the vagina for more than three hours, you may not be protected from pregnancy. You must use an additional method of birth control, such as male condoms or spermicide, until the ring has been in place for seven days in a row
26 Summary Good cycle control Vaginal RingSummaryGood cycle controlIrregular bleeding was rare (2.6% - 6.4% of evaluable cycles)Withdrawal bleeding occurred (97.9% % of evaluable cycles)Compliance with the regimen was met in 90.8% of cyclesThis study demonstrated that the ring is an effective method of contraception with good cycle control. It is easy to use, well-tolerated and well- accepted by usersThe ring has a good bleeding profile. Irregular bleeding occurred in only 2.6% – 6.4% of the cycles. The irregular bleeding that occurred consisted mainly of spotting only; breakthrough bleeding was reported in only 0.4% – 1.1% of the cyclesCompliance to the regimen was high (90.8%)Roumen FJ, et al. Hum Reprod. 2001;16(3):Suggested Core Slide
27 Application of the Transdermal Patch on Abdomen Contraceptive PatchApplication of the Transdermal Patch on AbdomenThe patch (ORTHO EVRA™) is beige in color, very thin, and pliableThe patch can be applied to the buttocks, upper outer arm, lower abdomen (shown), or upper torso (not the breasts)No makeup, creams, lotions, powders, or other topical products should be applied to the skin area where the patch is or will be appliedThe patch is comprised of three layers – a backing layer, a middle layer, and a release liner – this is referred to as a matrix systemIn this system, the hormones are actually in the middle layer with the adhesiveSuggested Core Slide
28 Equivalence of Sites: EE Results Contraceptive PatchEquivalence of Sites: EE Results10075AbdomenArmEE Serum Concentration (pg/mL)50ButtockTorsoA pharmacokinetics study was conducted to determine the therapeutic equivalence of the patch on four different application sitesThe absorption of norelgestromin (NGMN), 17-deacetylnorgestimate and ethinyl estradiol (EE) was determined to be therapeutically equivalent for application on the abdomen, arm, buttock, and torso2512345678910DaysSkee D, et al. Clin Pharm Ther. 2000;67:159.Suggested Core Slide
29 NGMN and EE Levels Patch vs OC* Contraceptive PatchNGMN and EE Levels Patch vs OC*150Patch EE2.1Patch NGMN1251.8EENGMN1001.5EE Serum Concentration (pg/mL)Reference Range75NGMN Serum Concentration (ng/mL)1.2Patch Removed50.9Delivers constant levels of NGMN and EE compared to the peaks and troughs of OCsDelivers NGMN 150 μg/day and EE 20 μg/day to the systemic circulationFollowing application, the patch delivers steady-state levels of norelgestromin and EE throughout the wear periodThe reference range was established based on the systemic exposure of norgestimate and EE in subjects taking ORTHO-CYCLENThis illustration shows patch data overlaid with data from oral dosing. One can see the peaks and troughs associated with oral administration versus steady-state delivery25.6.3123456789101112DaysAbrams L, et al. Contraception. 2001;64:*Noncomparative dataSuggested Core Slide
30 Contraceptive PatchComparative Randomized, Controlled Trial Data: Efficacy (pregnancies per 100 woman-years)Pearl IndicesCycles(n)Pregnancies(n)OverallPearl*MethodPearl**Patch524051.240.99Data published in JAMA demonstrate the efficacy data are reported as the Pearl IndicesComparing the total Overall Pearl to the Method Pearl, one can infer that there were few patch failures associated with poor user complianceA contraceptive with high compliance would be associated with an overall failure rate (method plus user failure) that is very similar to the method failure alone, as seen with the transdermal patchIn the patch group, 4 method-failure pregnancies and 1 user-failure pregnancy occurred among 811 women treated for 5240 cyclesIn the OC group, comprised of a triphasic LNG, 4 method-failure and 3 user-failure pregnancies occurred among 605 women treated for 4167 cyclesWhile the numerical differences in Pearl Indices are not statistically significant, this demonstrates that the transdermal contraceptive system is a highly effective method of contraceptionAdditional evidence that better compliance contributed to the low probability of pregnancy with the patch is seen from analysis of 6-cycle data, a treatment duration all participants were to complete. After 6 cycles, the overall probability of pregnancy with the patch was half that of the OC (0.6% vs 1.2%) while the method failure probability of pregnancy was nearly the same (0.4% vs 0.6%)OC416772.181.25*User failure plus method failure**Failure when taken as directedAudet M, et al. JAMA. 2001;285:Suggested Core Slide
31 Mean Proportion of Participants’ Cycles With Perfect Compliance Contraceptive PatchMean Proportion of Participants’ Cycles With Perfect ComplianceNTotal Cycles% of CyclesPatch811514188.2*OC605413477.7An important finding in a randomized, controlled trial was that use of the transdermal contraceptive system resulted in statistically better compliance than with the OC comparatorImproved compliance may be due to the simple weekly dosing scheduleThis is important because while OCs have failure rates in clinical trials around 1%, Trussell, et al., estimate that actual use failure rates can be as high as 7% with OCsSince incorrect and inconsistent use of contraception can lead to higher pregnancy rates – it is hoped that the improved compliance profile of the patch will result in improved “actual use” efficacy in broad usagePerfect compliance was defined as 21 consecutive days of drug-taking during a 28-day cycleFor the transdermal system, each patch had to be worn for exactly 7 days, for three consecutive weeks*(p<.001)Audet M, et al. JAMA. 2001;285:Suggested Core Slide
32 Compliance by Age Group Contraceptive PatchCompliance by Age Group% Compliant CyclesP<0.001P<0.001P<0.001P<0.008P<0.006P<0.005Usage of the patch resulted in increased compliance across all age groupsCompliance rates were similar for all age groups using the patch, whereas the rates varied among the age groups for OCsTherefore, the increased compliance seen with the patch is a potential benefit to a wide range of womenAge (years)Archer D, et al. Fertil Steril. 2001;76:S20. Abstract O-50.Suggested Core Slide
33 Distribution of Pregnancies by Baseline Body Weight Deciles (n=3319 subjects) Decile Weight Pregnancies Range (kg) Total1 <52 1<55 2<58 0<60 0<63 2<66 0<69 1<74 0<80 210 80 785 – 90 1> 90 5While patch is highly efficacious for the vast majority of women, the patch may be less efficacious in women >198 lbs.This phenomenon was also seen with Norplant but no data is available for other hormonal methods. The NIH is currently funding a study to look at the impact of weight on contraceptive efficacy.5 pregnancies among the 83 subjects with body weight 90 kg (198 lbs) (3% of study population)10 pregnancies among the subjects with body weight 198 lbs. were uniformly distributed90 kg (threshold) supported by statistical analysesZieman et al., Fertil Steril 2001; vol. 76:S19(abst O-48)
34 Comparative Data: Most Common Adverse Events Contraceptive PatchComparative Data: Most Common Adverse EventsPatch (N=812)OC (N=605)OverallTreatment LimitingBreast discomfort19%1.0%6%0.2%Headache22%1.5%0.3%Application site reaction20%2.6%NANausea1.8%18%0.8%Abdominal pain8%Dysmenorrhea13%10%Overall, the patch is well-tolerated with mild, transient side effects similar to OCsThere were no unexpected adverse events in either treatment groupWith the exception of mild-to-moderate application site reactions, the types of adverse events were similar between the patch and OC. More patients experienced slight breast discomfort on the patch vs. OCs, but only in the first two cyclesFor the patch and OC, approximately 2% of participants reported a serious adverse event – these events were generally similar between treatment groupsAudet M, et al. JAMA. 2001;285:Suggested Core Slide
35 IUDs Have low increased risk of infection Are not major or independent cause of PIDDo not increase risk of ectopic pregnancyDo not cause infertility after removedAre NOT abortifacients
36 Levonorgestrel 20 mcg/day Mirena®Releases 20 µg/day of LNG in vitro for the first year and about half that amount by the fifth year of useLong-term reversible methodEarly spotting, anemiaReduction in menstrual blood lossLow systemic levels of LNGSteroid reservoirSteroid reservoir32 mm32 mmResearch conducted since 1970 into several hormonally medicated intrauterine systems led to the development of the levonorgestrel intrauterine system (LNG IUS), which is licensed in 25 countries and was approved for use as a intrauterine contraceptive in the U.S. by the FDA in December, (In other countries, it is also approved for the treatment of menorrhagia.)As shown here, this polyethylene system consists of a T-shaped frame that is 32 mm in diameter. The polyethylene is compounded with barium sulfate, making it radiopaque.A “sleeve” or reservoir on the vertical stem of the T-body contains 52 mg of levonorgestrel dispersed in polydimethylsiloxane. It is covered by a silicone rate-limiting surface membrane.A monofilament, polyethylene thread attached to the end of the vertical stem is provided for purposes of removing the IUS.The LNG IUS releases 20 µg/day of LNG in vitro for the first year and about half that amount by the fifth year of use.Levonorgestrel 20 mcg/dayLevonorgestrel 20 mcg/dayMIRENA® Package Insert.MIRENA® Package Insert.
37 Levonorgestrel IUS: Efficacy Intrauterine SystemLevonorgestrel IUS: EfficacyOverall failure rate 0.1 per 100 womenGross cumulative five-year failure rate is 0.7 per 100 womenSafety and efficacy of LNG IUS was studied in two large clinical trialsIn study sites that had evaluable data and informed consent, 1169 women (18 to 35 years of age at enrollment) used the LNG IUS for up to 5 yearsReported pregnancy rates for one year were less than or equal to 0.2 and the 5-year cumulative rate was approximately Due to limitations of available data, a precise estimate of the pregnancy rate is not possibleNonetheless, the LNG IUS is a highly effective, long-term method of birth controlLuukkainen T, et al. Contraception. 1987;36:Mirena Package Insert.
38 IUD Labeling change for CuT 380A (2005) Use by nulliparous women now allowedHistory of PID no longer a contraindicationWoman must be in a “stable” (rather than “mutually monogamous”) relationship
39 Essure® Soft, flexible micro-insert The Essure procedure is performed by a trained gynecologist and is an alternative to surgical sterilizationEssure is 99.8% effective in preventing pregnancyAnother method of birth control must be used for at least three months after the procedureUterusCervixESSURE® Package Insert.
40 Nestorone / Ethynyl Estradiol Wear for 3 weeks Remove for 1 week Pop Council RingNestorone / Ethynyl EstradiolWear for 3 weeksRemove for 1 weekReinsert (13 cycles)One reason we want to improve successful contraceptive use is because contraception saves lives!As you can see, there are significant morbidity and mortality consequences associated with unintended pregnancy in the United States.This is another reason why all pregnancies should be planned pregnancies.
42 Hormone % Azospermic Asian Caucasian TE 91 60 TE + DMPA 96 59 19NT + DMPA9867Waites, GMH. British Medical Bulletin 1993;49:
43 Effective, Reversible, Safe Contraceptives IUSVaginal RingSpermicideImplantInjectableBarrierDMPAPatchOral Contraceptives3 mos. +1 wk – 1 moDaily or with IntercourseFrequency of UseCombination of estrogen and progestinOne common feature of these newer methods is that they are used for an extended duration and therefore, are not associated with intercourse and do not require daily attentionThe new methods offer a variety of different dosing regimens (weekly, monthly, etc.)Options include methods that deliver combination estrogen and progestin as well as progestin only
44 Comparison of New Contraceptive Methods OverviewComparison of New Contraceptive MethodsMonthly InjectableImplantIUSRingPatchEfficaciousYesOffice visits1 MonthInsertion & removalInsertion & removalPrescriptionEasily reversibleDosing frequency1 month3-5 yrs5 yrsEvery 4 weeksWeeklyUser-controlledNoDiscreetSometimesNew contraceptive options offer women and clinicians flexibility in choosing a method that suits the woman’s needsThere are a variety of characteristics by which contraceptive methods are evaluatedWomen and providers have new options available to them, and these methods are now in the form of new delivery systems. Hopefully with expanded choices, women can find a method that suits their particular lifestyle