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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