August 2008 Contraception Update. Contraceptive efficacy Pearl Index Life Table Analysis Perfect use Typical use.

August 2008August 2008

ContraceptionContraceptionUpdateUpdate

Contraceptive efficacyContraceptive efficacy

Pearl IndexPearl Index

Life Table AnalysisLife Table Analysis

Perfect use Perfect use

Typical useTypical use

Current use of contraception by Current use of contraception by age, 2005/6age, 2005/6

ONS, 2007ONS, 2007

www.ffprhc.org.uk

www.fsrh.org.uk

LARC – NICE GuidelinesLARC – NICE Guidelines

Contraceptive service providers should be aware that: all currently available LARC methods (intrauterine devices [IUDs], the intrauterine system [IUS],injectable contraceptives and implants) are more cost effective than the combined oral contraceptive pill even at 1 year of use– IUDs, the IUS and implants are more cost effective than the injectable contraceptives– increasing the uptake of LARC methods will reduce the numbers of unintended pregnancies

77

LARC includes:LARC includes:

Copper IUDCopper IUD

Progestogen-only IUSProgestogen-only IUS

Progestogen-only injectableProgestogen-only injectable

Progestogen-only subdermal implantProgestogen-only subdermal implant

Combined vaginal ringsCombined vaginal rings

88

However Current LARC Usage However Current LARC Usage is Lowis Low77

0

5

10

15

20

25

30

None The Pill MaleCondom

FemaleSterilisation

Vasectomy Injectables IUD Implants IUS

7. Schering Data on File, 2006, WOMEN AGED 16 TO 44

%

99

Accidental Pregnancy in First Year Accidental Pregnancy in First Year of Typical Useof Typical Use88

0

5

10

15

20

cap

diaph

ragm

cond

om POPCOC

Depo

IUD

IUS

Impla

nt *

steril

isatio

n

Perfect use

Typical use

8 Trussell J. Contraceptive efficacy. In: Hatcher RA, Trussell J, Stewart R. Contraceptive Technology, ed 18. NY: Ardent Media, 2004

% o

f acc

iden

tal

preg

nanc

y

* Norplant and Norplant 2: Data is from USA where Implanon is not available

1010

Discontinuation Rates of Discontinuation Rates of Contraceptive MethodsContraceptive Methods11

0

20

40

60

80

100

120

continuingYear 5Year 4Year 3Year 2Year 1

% D

isco

ntin

uatio

n

UK Medical Eligibility CriteriaUK Medical Eligibility Criteria

UKMEC1 No contraindicationUKMEC1 No contraindication

UKMEC2 Benefits usually outweigh risksUKMEC2 Benefits usually outweigh risks

UKMEC3 Risks usually outweigh benefitsUKMEC3 Risks usually outweigh benefits

UKMEC4 ContraindicatedUKMEC4 Contraindicated

SterilisationSterilisation

‘‘Permanent’ but no longer the most Permanent’ but no longer the most effectiveeffective

Can be reversed but no guaranteeCan be reversed but no guarantee

Lifelong failure rate 5/1000 (i.e.10 times Lifelong failure rate 5/1000 (i.e.10 times failure of vasectomy)failure of vasectomy)

Requires invasive procedureRequires invasive procedure

Types of Combined Types of Combined ContraceptionContraception

20, 30 or 35 micrograms of 20, 30 or 35 micrograms of ethinyloestradiolethinyloestradiol

Different progestogensDifferent progestogens

21 day and every day formulations21 day and every day formulations

Fixed dose or phasic Fixed dose or phasic

Combined patch – EvraCombined patch – Evra

4 or 12 week withdrawal - Seasonale4 or 12 week withdrawal - Seasonale

Continuous pillContinuous pill

Combined Ring – NuvaringCombined Ring – Nuvaring

Hormonal contraceptionHormonal contraception

Combined oestrogen and Combined oestrogen and progestogenprogestogen

–Combined pill (COC)Combined pill (COC)

–Evra transdermal patchEvra transdermal patch

–Nuva-Ring vaginal ringNuva-Ring vaginal ring

Combined methodsCombined methods

AdvantagesAdvantages– Suppress ovulationSuppress ovulation– High efficacyHigh efficacy– Give predictable ‘periods’Give predictable ‘periods’

DisadvantagesDisadvantages– Increased risk of thrombosisIncreased risk of thrombosis– ?? Increased risk of breast cancer?? Increased risk of breast cancer– (Increased risk of hepatocellular cancer)(Increased risk of hepatocellular cancer)

Constituents of COCsConstituents of COCs

OestrogensOestrogens

EthinyloestradiolEthinyloestradiol

MestranolMestranol

ProgestogensProgestogens

NorethisteroneNorethisterone

LevonorgestrelLevonorgestrel

DesogestrelDesogestrel

GestodeneGestodene

NorgestimateNorgestimate

DrospirenoneDrospirenone

CyproteroneCyproterone

Limitations on Dose ReductionLimitations on Dose Reduction

Loss of efficacyLoss of efficacy

Loss of cycle control (depends on both Loss of cycle control (depends on both oestrogen and progestin)oestrogen and progestin)

Wide range of blood levels via oral routeWide range of blood levels via oral route

Revised information from MCA Revised information from MCA May 99May 99

Third generation pills can be prescribed first-lineThird generation pills can be prescribed first-line

VTE risk in data sheets:VTE risk in data sheets:

15 per 100,000 - second generation15 per 100,000 - second generation

25 per 100,000 - third generation25 per 100,000 - third generation

Breast cancer re-analysis Breast cancer re-analysis 1996 - results1996 - results

No effect of duration of useNo effect of duration of use

No dose responseNo dose response

Cancers in pill users less advancedCancers in pill users less advanced

Causal association unlikelyCausal association unlikely

? acceleration of tumour growth? acceleration of tumour growth

? surveillance bias? surveillance bias

Cervical cancer risk factorsCervical cancer risk factors

Human PapillomavirusHuman Papillomavirus

SmokingSmoking

Oral contraceptives ?Oral contraceptives ?

Benefits of the COC (1)Benefits of the COC (1)

Very effective, non-intercourse related contraceptionVery effective, non-intercourse related contraception

Reduction in menstrual disordersReduction in menstrual disorders

functional ovarian cysts x 92%functional ovarian cysts x 92%

menorrhagia, irregular bleeding x 50%menorrhagia, irregular bleeding x 50%

dysmenorrhoea x 40%dysmenorrhoea x 40%

PMSPMS

Iron deficiency anaemia x 50%Iron deficiency anaemia x 50%

PID x 50%PID x 50%

Ectopic pregnancy x 90%Ectopic pregnancy x 90%

Benefits of the COC (2)Benefits of the COC (2)

Fibroids x 30%Fibroids x 30%

Benign breast disease x 50 - 75%Benign breast disease x 50 - 75%

Symptomatic relief / treatment of endometriosisSymptomatic relief / treatment of endometriosis

? ? Duodenal ulcer Duodenal ulcer

Rheumatoid arthritis x 50%Rheumatoid arthritis x 50%

Endometrial cancer x 50%Endometrial cancer x 50%

Ovarian cancer x 40%Ovarian cancer x 40%

Colorectal cancer x 20%Colorectal cancer x 20%

Conception due to missed Conception due to missed COCsCOCs

'only' occurs if this leads to lengthening of 'only' occurs if this leads to lengthening of the pill - free intervalthe pill - free interval

NB - at either endNB - at either end

Missed pills – WHO Advice for Missed pills – WHO Advice for COCS COCS

Just keep goingJust keep going

AlsoAlso if pill missed is in week 3 omit pill-free if pill missed is in week 3 omit pill-free intervalinterval

AlsoAlso backup or abstinence for 7 days if following backup or abstinence for 7 days if following number of pills missednumber of pills missed

- - Two for twentyTwo for twenty

- Three for thirty- Three for thirty

Lamotrigine (Lamictal) and the pillLamotrigine (Lamictal) and the pill

Not an enzyme inducerNot an enzyme inducer

Interaction reduces levels of both agentsInteraction reduces levels of both agents

No evidence of reduced efficacy for COCNo evidence of reduced efficacy for COC

No evidence on POPNo evidence on POP

Why take a break ?Why take a break ?

HistoryHistory

TricyclingTricycling

25/3 may give better ovarian suppression25/3 may give better ovarian suppression

Continuous Continuous

EVRAEVRA: : Simple administration schedule

– 20 mcg ethinyloestradiol and 150 mcg norelgestromin

– Apply weekly for 3 weeks– Apply same day-of-the-week– 1 week patch-free

SundaySunday SundaySunday SundaySunday SundaySunday

Patch # 1 Patch # 2 Patch # 3

28-day cycle

Patch-freePatch-free

SundaySunday

Start next cycleStart next cycle

28-day cycle28-day cycle

Ref: Evra SmPC

EVRA Continuously Delivers EVRA Continuously Delivers EEEEWithin Reference Ranges Within Reference Ranges

0 1 2 3 4 5 6 7 8 9 10 11 12

Days

150

125

100

75

EE

se

rum

co

nce

ntr

atio

n

(pg/

mL)

50

25

0

Patch removed

Evra

Cilest

Adapted from Abrams Fertility and Sterility 2002

Dosing Reserve Dosing Reserve Results for ethinyl estradiolResults for ethinyl estradiol100

60

EE

se

rum

co

nce

ntr

atio

n

(pg/

mL)

40

20

00 2 4 86 10 12 14 16 18

80

Days

Patch changed on schedule

Patch removal delayed

Patch removed 3 days late

Ref: Abrams et al Fertility and Sterility 2002,

Evra – is a patch really better ?Evra – is a patch really better ?

Less variability in levels, but not a lower Less variability in levels, but not a lower dosedose

Effects on SHBG similar or greaterEffects on SHBG similar or greater

? Relevance of enzyme-inducers, ? Relevance of enzyme-inducers, antibiotics, etcantibiotics, etc

? Thrombosis risk? Thrombosis risk

New Delivery System:New Delivery System:Vaginal RingVaginal Ring

Progestin: Etonogestrel: 120 Progestin: Etonogestrel: 120 µµg/dayg/day

Estrogen: Ethinyl estradiol: 15 Estrogen: Ethinyl estradiol: 15 µµg/dayg/day

Worn for three out of four weeksWorn for three out of four weeks

Self insertion & removalSelf insertion & removal

Pregnancy rate 0.65 per 100 woman–yearsPregnancy rate 0.65 per 100 woman–years

Roumen FJ, et al. Hum Reprod. 2001;16(3):469-475.

Progestogen-only methodsProgestogen-only methods

AdvantagesAdvantages– Greater safetyGreater safety

Variable efficacy (from extremely low to Variable efficacy (from extremely low to better than COC)better than COC)

Some measure of loss of cycle control Some measure of loss of cycle control (varies with route, type and dose)(varies with route, type and dose)

Routes availableRoutes available

Progestogen-only pill (POP)Progestogen-only pill (POP)

Emergency contraception (Levonelle)Emergency contraception (Levonelle)

Injectable (Depo-Provera)Injectable (Depo-Provera)

Intrauterine (Mirena)Intrauterine (Mirena)

Implant (Implanon)Implant (Implanon)

Desogestrel POP (Cerazette)Desogestrel POP (Cerazette)

75 micrograms Desogestrel75 micrograms Desogestrel

Suppresses ovulationSuppresses ovulation

Lower failure rateLower failure rate

Different rules for missed pills Different rules for missed pills

Emergency ContraceptionEmergency ContraceptionProductsProducts– Levonelle One StepLevonelle One Step– Any copper IUD, including GyneFixAny copper IUD, including GyneFix

IndicationsIndications– Unprotected sexUnprotected sex– Potential barrier failuresPotential barrier failures– Potential pill failurePotential pill failure

2 missed pills in first week2 missed pills in first week4 missed pills in mid-packet4 missed pills in mid-packet

– Potential IUD failurePotential IUD failure– Increased risk of ectopic in failuresIncreased risk of ectopic in failures

Awareness of risk may not translate into actionAwareness of risk may not translate into action

Levonelle One StepLevonelle One Step

1500 micrograms levonorgestrel1500 micrograms levonorgestrel

Within 72 hoursWithin 72 hours

EfficacyEfficacy– < 24 hours< 24 hours 95 %95 %– 24-48 hours24-48 hours 85 %85 %– 49-72 hours49-72 hours 58 %58 %

Emergency Hormonal Emergency Hormonal Contraception (EHC)Contraception (EHC)

Side effectsSide effects– 23 % nausea23 % nausea– 6 % vomiting6 % vomiting

ContraindicationsContraindications– Established pregnancyEstablished pregnancy

Depo-ProveraDepo-Provera

150 mg medroxyprogesterone acetate 150 mg medroxyprogesterone acetate – IMIM– Every 12 weeksEvery 12 weeks– Failure rate approx 0.5%Failure rate approx 0.5%– High incidence of amenorrhoeaHigh incidence of amenorrhoea– Long-term use associated with reduced bone Long-term use associated with reduced bone

density which recovers with addback or density which recovers with addback or discontinuationdiscontinuation

Fertility awarenessFertility awareness

Depends on abstinenceDepends on abstinence

Requires high degree of motivationRequires high degree of motivation

Failure rates high especially in new usersFailure rates high especially in new users

Based on a number of false premises Based on a number of false premises about fertility, therefore relatively high about fertility, therefore relatively high method failure rate as well as high user method failure rate as well as high user failurefailure

IUD (Copper devices)IUD (Copper devices)

Gold standard Copper T 380Gold standard Copper T 380

Not user-dependantNot user-dependant

Good efficacy (failure rate 1% or less p.a.)Good efficacy (failure rate 1% or less p.a.)

Requires insertion and removalRequires insertion and removal

Some increased risk of infection in first 60 Some increased risk of infection in first 60 days especially when cervix coloniseddays especially when cervix colonised

Periods may be heavier, longer, more Periods may be heavier, longer, more painfulpainful

IntrauterineIntrauterine

Mirena releases 20 mcg levonorgestrel Mirena releases 20 mcg levonorgestrel daily for 5 yearsdaily for 5 years

Failure rate equal to or less than female Failure rate equal to or less than female sterilisationsterilisation

Reduction in menstrual loss a beneficial Reduction in menstrual loss a beneficial side-effectside-effect

MirenaMirena

Good contraceptionGood contraception

Control of Control of menorrhagiamenorrhagia

May help May help dysmenorrhoeadysmenorrhoea

Effective endometrial Effective endometrial protectionprotection

Some systemic Some systemic absorptionabsorption

Irregular bleeding Irregular bleeding may persistmay persist

Insertion not always Insertion not always easyeasy

ImplanonImplanon

SubdermalSubdermal

EtonogestrelEtonogestrel

Menstrual irregularity commonMenstrual irregularity common

Failure rate far below that of sterilisationFailure rate far below that of sterilisation

4949

The design of ImplanonThe design of Implanon®®

Progestogen only contraceptiveProgestogen only contraceptive

Core

Rate-controlling membrane (0.06 mm)

2 mm

40 mm

Core: 40% EVA60% etonogestrel

Membrane: 100% EVA

ImplanonImplanon®®

Mode of actionMode of actionOvulation inhibition : primary effectOvulation inhibition : primary effect

Effect on cervical mucus: secondary Effect on cervical mucus: secondary effect effect

5151

0

1

2

3

4

5

6

7

8

6 12 18 24 30 36 42

Per

cent

age

Amenorrhoea Bleeding irregularities

Adverse experiences Other reasons

Discontinuation rates with Implanon® (n=720)

months

Contraception 1998;58: 99S-107S