6LARC – NICE GuidelinesContraceptive 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
8However Current LARC Usage is Low7 %7. Schering Data on File, 2006, WOMEN AGED 16 TO 44
9Accidental Pregnancy in First Year of Typical Use8 % of accidental pregnancy* Norplant and Norplant 2: Data is from USA where Implanon is not available8 Trussell J. Contraceptive efficacy. In: Hatcher RA, Trussell J, Stewart R. Contraceptive Technology, ed 18. NY: Ardent Media, 2004
11UK Medical Eligibility Criteria UKMEC1 No contraindicationUKMEC2 Benefits usually outweigh risksUKMEC3 Risks usually outweigh benefitsUKMEC4 Contraindicated
12Sterilisation ‘Permanent’ but no longer the most effective Can be reversed but no guaranteeLifelong failure rate 5/1000 (i.e.10 times failure of vasectomy)Requires invasive procedure
13Types of Combined Contraception 20, 30 or 35 micrograms of ethinyloestradiolDifferent progestogens21 day and every day formulationsFixed dose or phasicCombined patch – Evra4 or 12 week withdrawal - SeasonaleContinuous pillCombined Ring – Nuvaring
14Hormonal contraception Combined oestrogen and progestogenCombined pill (COC)Evra transdermal patchNuva-Ring vaginal ring
15Combined methods Advantages Disadvantages Suppress ovulation High efficacyGive predictable ‘periods’DisadvantagesIncreased risk of thrombosis?? Increased risk of breast cancer(Increased risk of hepatocellular cancer)
16Constituents of COCs Oestrogens Ethinyloestradiol Mestranol ProgestogensNorethisteroneLevonorgestrelDesogestrelGestodeneNorgestimateDrospirenoneCyproteroneThe Combined Pill contains two hormones, oestrogen and progestogen. In practice, the type of oestrogen is now always ethinyloestradiol, but the type of progestogen may vary. The most commonly used progestogens nowadays are norethisterone, levonorgestrel and, more recently, desogestrel, gestodene, norgestimate and drospirenone.
20Revised information from MCA May 99 Third generation pills can be prescribed first-lineVTE risk in data sheets: 15 per 100,000 - second generation 25 per 100,000 - third generationIn 1998, following an appeal to the Medicines Commisson, the Department of Health announced an end to the 1995 restrictions on prescribing third generation pills, stating that ‘The absolute risk of VTE in women taking third generation COCs is very small and is much less than the risk in pregnancy’ and ‘provided women are fully informed of these very small risks and do not have medical contraindications, it should be a matter of clinical judgement and personal choice which type of oral contraceptive should be prescribed.’ (MCA 1999).Since 1998, the data sheets of gestodene and desogestrel-containing pills in the UK carry a new wording, stating that these types of pill carry a risk of VTE of ‘about 25 per 100,000 women per year’, while for second generation pills, the risk is ‘about 15 per 100,000 women per year.’. This low risk for second generation pills seems unlikely: there has, after all, not been any change in their formulation. It seems more likely that the risk of VTE with all combined pills is around 30 to 40 per 100,000 women per year (i.e. the figure which has been quoted since the studies of low dose pills in the 1980s, the higher figure from the 1995 studies and consistent with the latest data).
21Breast cancer re-analysis 1996 - results No effect of duration of useNo dose responseCancers in pill users less advancedCausal association unlikely? acceleration of tumour growth? surveillance biasThis excess risk declines progressively after cessation of use, disappearing altogether after 10 years.There was no effect of duration of use, nor was there any effect of pill dose. Breast cancers diagnosed in pill users were clinically less advanced than those in never-users, and were less likely to have spread beyond the breast. This would suggest that mortality from breast cancer might actually be reduced in pill users. The authors state that the lack of both a duration of use and a dose-response effect makes a causal association unlikely. There are two plausible explanations for these results, either or both of which may play a part.Firstly, it is possible that the pill accelerates the growth of tumours which were already present, thus making them clinically obvious earlier. A second possibility is that of surveillance bias i.e. that women who take the pill are more 'breast aware' and are also more likely to be seeing doctors and nurses regularly, allowing the opportunity for advice and examinations. This would explain the earlier diagnosis in pill users compared with never-users, who may be less exposed to medical contact.
22Cervical cancer risk factors Human PapillomavirusSmokingOral contraceptives ?There has, for many years, been a suggestion of an association between the COC and an increased risk of cervical cancer. However, because the most important risk factor is known to be sexually acquired infection with high risk human papillomavirus (HPV) types, it has always been difficult to separate the possible effects of the COC from those of sexual behaviour.
23Benefits of the COC (1)Very effective, non-intercourse related contraceptionReduction in menstrual disorders¯ functional ovarian cysts x 92%¯ menorrhagia, irregular bleeding x 50%¯ dysmenorrhoea x 40%¯ PMS¯ Iron deficiency anaemia x 50%¯ PID x 50%¯ Ectopic pregnancy x 90%The Pill has many health benefits. Firstly, it is an extremely effective reversible method of contraception.The Pill has a major impact on almost all menstrual disorders. It has been estimated that at least 8% of women on the Pill are taking it for no other reason apart from relief from menstrual problems like dysmenorrhoea and PMS. The reduction in iron deficiency anaemia seen with the Pill is due mainly to the decrease in menorrhagia.Several large studies have shown that the Pill gives a ten fold reduction in the incidence of symptomatic functional ovarian cysts requiring hospitalisation.Similarly, the need for surgery for benign breast disease is reduced by 50-75% in Pill users.The Pill has been shown to reduce the incidence of PID by 50% overall, and by 70% in women who have used it for more than a year.
24Benefits of the COC (2) ¯ Fibroids x 30% ¯ Benign breast disease x %Symptomatic relief / treatment of endometriosis? ¯ Duodenal ulcer¯ Rheumatoid arthritis x 50%¯ Endometrial cancer x 50%¯ Ovarian cancer x 40%¯ Colorectal cancer x 20%The Oxford / FPA study has shown that the risk of fibroids decreases by about 17% with every five years of Pill use, so by ten years, the risk is reduced by 30%. Endometriosis can be a very distressing condition, and not all women tolerate the side effects of Danazol. The Pill is not as effective, but it can certainly reduce the symptoms quite considerably.The RCGP study showed a 50% reduction in the incidence of rheumatoid arthritis in Pill users, and also a reduction in the incidence of duodenal ulcers. The rheumatoid arthritis benefit has in fact now been confirmed by other studies.Pill users have a 50% reduction in the risk of developing endometrial cancer. There is a reduced risk even after only one year of use, by a factor of 20%. At least four years of use are necessary to achieve the 50% reduction, and this appears to persist for 15 years after stopping the pill. This is an important factor, since endometrial cancer is a disease of older women, who are very unlikely to be current or very recent pill users.Similarly, studies have shown a 40% reduction in the risk of developing ovarian cancer after three years of pill taking and about 60% after seven years. As for endometrial cancer, the effect appears to persist for 15 years after cessation of pill. A meta-analysis in 2001 has also shown a 20% reduction in the risk of colorectal cancer in ever users of the pill, with a 50% reduction in recent users.
25Conception due to missed COCs 'only' occurs if this leads to lengthening of the pill - free intervalNB - at either endProlonging the pill -free week is actually the most likely way a woman can become pregnant while taking the pill. Oestrodiol levels rise appreciably during the seven days off the pill. If, for any reason, the woman has a break of more than seven days, ovulation might occur.It is important to remember that this can mean missed pills at the end of a packet as well as being late in starting the new one. Women may not mention this as they will have been falsely reassured by a withdrawal bleed.However, it has also been shown that after 7 days of pill taking, ovarian activity is suppressed. Therefore missing pills in the middle of a packet is unlikely to place the woman at risk.
26Missed pills – WHO Advice for COCS Just keep goingAlso if pill missed is in week 3 omit pill-free intervalAlso backup or abstinence for 7 days if following number of pills missed- Two for twenty- Three for thirtyIt is important to teach each woman the basics of how to take COCs and to reinforce this information at check visits. The actions necessary in the case of missed tablets and the other factors that may reduce contraceptive effectiveness also need careful explanation. This verbal information should be backed up with appropriate written information
27Lamotrigine (Lamictal) and the pill Not an enzyme inducerInteraction reduces levels of both agentsNo evidence of reduced efficacy for COCNo evidence on POP
28Why take a break ? History Tricycling 25/3 may give better ovarian suppressionContinuous
29EVRA: Simple administration schedule 20 mcg ethinyloestradiol and 150 mcg norelgestrominApply weekly for 3 weeksApply same day-of-the-week1 week patch-freeSundaySundaySundaySundaySundayPatch # 1Patch # 2Patch # 3Patch-freeStart next cycle28-day cycle28-day cycleRef: Evra SmPC
30EVRA Continuously Delivers EE Within Reference Ranges 150Evra125Cilest100EE serum concentration (pg/mL)75Patch removed5025123456789101112DaysAdapted from Abrams Fertility and Sterility 2002
31Dosing Reserve Results for ethinyl estradiol 10080Patch changed on schedulePatch removal delayed60EE serum concentration (pg/mL)Patch removed 3 days late402024681012141618DaysRef: Abrams et al Fertility and Sterility 2002,
32Evra – is a patch really better ? Less variability in levels, but not a lower doseEffects on SHBG similar or greater? Relevance of enzyme-inducers, antibiotics, etc? Thrombosis risk
33New Delivery System: 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
34Progestogen-only methods AdvantagesGreater safetyVariable efficacy (from extremely low to better than COC)Some measure of loss of cycle control (varies with route, type and dose)
38Emergency Contraception ProductsLevonelle One StepAny copper IUD, including GyneFixIndicationsUnprotected sexPotential barrier failuresPotential pill failure2 missed pills in first week4 missed pills in mid-packetPotential IUD failureIncreased risk of ectopic in failuresAwareness of risk may not translate into action
39Levonelle One Step 1500 micrograms levonorgestrel Within 72 hours Efficacy< 24 hours 95 %24-48 hours 85 %49-72 hours 58 %
41Depo-Provera 150 mg medroxyprogesterone acetate IM Every 12 weeks Failure rate approx 0.5%High incidence of amenorrhoeaLong-term use associated with reduced bone density which recovers with addback or discontinuation
42Fertility awareness Depends on abstinence Requires high degree of motivationFailure rates high especially in new usersBased on a number of false premises about fertility, therefore relatively high method failure rate as well as high user failure
43IUD (Copper devices) Gold standard Copper T 380 Not user-dependant Good efficacy (failure rate 1% or less p.a.)Requires insertion and removalSome increased risk of infection in first 60 days especially when cervix colonisedPeriods may be heavier, longer, more painful
47Mirena Good contraception Control of menorrhagia May help dysmenorrhoeaEffective endometrial protectionSome systemic absorptionIrregular bleeding may persistInsertion not always easy
48Implanon Subdermal Etonogestrel Menstrual irregularity common Failure rate far below that of sterilisation
49The design of Implanon® Progestogen only contraceptive CoreRate-controlling membrane (0.06 mm)2 mm40 mmCore: 40% EVA60% etonogestrelMembrane: 100% EVA
50Implanon® Mode of action Ovulation inhibition : primary effect Effect on cervical mucus: secondary effectCore message - Mechanisms of action of Implanon®. It primarily acts by inhibiting ovulation but in the third year the effect on the cervical mucous is an important secondary effect.For further information refer to pages of the Contraception supplement published in December 1998.