Consultant in Sexual and Reproductive Healthcare Contraception Update 2018 Dr Caroline Marfleet Consultant in Sexual and Reproductive Healthcare

Contraception in 2018 Sub-dermal implants IUDs Injectables IUS Combined hormonal contraception Contraception in 2018 Male and female sterilisation Progestogen-only pills Female barrier methods Natural FP/withdrawal/LAM Male barrier methods Emergency contraception

Women are all different! No one method will suit all women

Minimal medical interference Choosing a method of contraception Safe Effective Reliable Easy to use Few side effects What’s important to women when deciding on a method of contraception? Easy to remember Easy access No effect on future fertility Minimal medical interference Minimal effect on periods

At the initial visit: A full sexual, reproductive and medical history need to be taken including: Present and past use of contraception History of migraine & risk factors for cardiovascular disease eg smoking; previous VTE; hyperlipidaemia Any personal medical history Drug use (prescription, non-prescription & herbal) Family history – VTE; stroke; arterial disease; breast cancer; diabetes; other BP should be documented Height, weight & BMI should be documented

2018 – 3 methods of delivery of combined hormonal contraception

WHICH CHC? Types of OCPs – combined and progestogen-only Ethinyl oestradiol and progestogens Oestradiol valerate /hemihydrate(body-identical oestrogen) and progestogen Routes of administration -pill.patch, ring Risks and benefits to individuals Side effects relating to oestrogens/progestogens Which pill and managing side effects

COC Progestogen ladder Cyproterone Drospirenone Gestodene Desogestrel Norgestimate Levonorgestrel Norethisterone 35 mcg EE Dianette Cilest Brevinor 30 mcg EE Yasmin Femodene Marvelon Mic 30 Loestrin 30 20 mcg EE Eloine (Yaz) Femodette Mercilon Loestrin 20 POP Cerazette Norgeston Micronor

Androgenicity series Norethisterone Levonorgestrel Gestodene Desogestrel Drospirenone Cyproterone acetate

Choice of COCP by progestogen More oestrogen dominant Less oestrogen dominant Drospirenone Norgestimate Gestodene Desogestrel Levonorgestrel group Norethisterone group

Which COC? Oestrogen dominant COCs Cilest Marvelon Femodene Dianette Yasmin Progestogen dominant COCs Microgynon 30 Loestrin 30

Side effects Oestrogenic Progestogenic Nausea Bloating Weight gain (water retention) Vaginal discharge (no infection) Breast enlargement/tenderness Some headaches Chloasma Photosensitivity Acne Greasy hair Hirsutism Weight gain (increased appetite) Depression Loss of libido Vaginal dryness

Risks and Benefits Potential harms & benefits of CHC in non smokers FSRH Guidance 2012 CHC Potential harms & benefits of CHC in non smokers RR with CHC use in non smokers RISKS Coronary artery disease ? V small inc risk (obesity, other risk factors) Ischaemic stroke 2 fold inc risk (migraine) VTE 3 fold inc risk with LNG, NET; 5 fold inc risk with DSG and GSD Breast cancer Any inc risk likely to be small and to vary with age. No inc risk above background 10 yrs after stopping Cervical cancer Small inc after 5 yrs and 2 fold inc after 10 yrs BENEFITS Ovarian cancer Halving of risk lasting for > 15 yrs Endometrial cancer

Risk of VTE per 200,000 wy (absolute risk) European Pharmacovigilance working party 2011 (MHRA) International working party Berlin 2009 (FSRH) Women not using COC 5-10 40-50 Women using COCs with LNG or NET 20 Women using COCs with DSG or GSD 40 90-100 Pregnant women 60 290

COCs and risk of VTE BMI and smoking are significant risk factors Smoking doubles the risk BMI 30-35 doubles the risk BMI > 35 has a 4-6 fold increased risk BMI 30-34= UKMEC 2 BMI > 35 = UKMEC 3 Smoking age < 25 yrs UKMEC 2 Smoking age > 35 yrs UKMEC 3 (<15/day) or UKMEC 4 (> 15 day)

Migraine and thrombotic stroke risk Age 20 2/100,000 Age 20+COC + migraine 10/100,000 Age 20+COC + migraine + cigarettes 60/100,000 Age 40 20/100,000 Age 40+ migraine 56/100,000 100/100,000

Non contraceptive health benefits of oral contraceptives Endometriosis; dysmenorrhoea and ovulatory pain Menorrhagia; Fe deficiency anaemia; fibroids Endometrial and ovarian cancer; colon cancer Acne; hirsutism; symptoms of PCOS Functional ovarian cysts; PID; benign breast disease; rheumatoid arthritis PMS RCGP study - women in the UK who have ever used the oral contraceptive pill are less likely to die from any cause, including all cancers and heart disease, compared with never users FSRH Guidance 2012 CHC

Reasons to stop immediately Serious neurological effects (prolonged headache, getting worse) Partial or complete loss of vision Sudden disturbance of hearing or other perceptual disorders Dysphasia 1st epileptic seizure or weakness, motor disturbance or numbness affecting one side or part of body Sudden chest pain Sudden breathlessness Haemoptysis Severe pain in one calf Hepatitis, jaundice, enlarged liver Severe depression BP > 100/160 Detection of a risk factor (UKMEC) FSRH Guidance 2012 CHC

Yasmin Monophasic COC with 30 mcg EE + Drospirenone 3 mg It acts as an anti-androgen & is therefore an alternative to Dianette for women with moderate acne or PCOS It has diuretic properties due to antimineralocortocoid activity It offers a useful oestrogen dominant pill for control of minor side effects such as bloating and cyclical breast enlargement EURAS and Ingenix studies – no difference in VTE risk compared with 2nd generation OCs

Yasmin GPRD (UK) + Pharmetrics (US) Both showed a 2-3 fold increase of VTE BUT – GPRD – low numbers, data missing (obesity), case mix not reflecting clinical practice Pharmetrics – incomplete data on obesity, unrelaible data on duration of exposure to Ocs Evidence for increased risk is inconclusive and absolute risk of VTE when using low dose OCs is small

Dianette An anti-androgen plus oestrogen combination Licensed for acne/hirsutism – not for contraception Data on the risk of VTE with Dianette is conflicting and has been quoted as being higher than in users of conventional COCs but other case controlled studies have shown no difference in risk Duration of pill use does not appear to affect VTE risk Mainly used for women with PCO-type symptoms – acne, hirsutism PCOS – obesity, insulin resistance, dyslipidaemia, hypertension Alternatives are an oestrogen dominant pill such as Yasmin or Marvelon

Qlaira COC containing estradiol valerate (E2V) and dienogest (DNG) E2V Estradiol (E2 = natural oestrogen) DNG offers good suppression of endometrial proliferation The first and only COC to deliver E2 The first product in the UK to contain DNG

Regimen 26/2 Maintain stable E2 levels, optimise cycle control, inhibit ovulation The first 2 pills of the Qlaira pack deliver E2 only and no progestogen, this promotes endometrial proliferation, stabilising the endometrium. The endometrium is stabilised before the addition of the progestogen on day 3 of the cycle. The use of DNG ensures suppression of endometrial proliferation and secretory transformation, maturing the endometrium; its stepwise increase further stabilises the endometrium. A progressive oestrogen step-down with two oestrogen-only days at the end of the cycle avoids a rapid decline in oestrogen levels. In the majority of women, the lack of hormones during the placebo days leads to shedding of the endometrium and a withdrawal bleed. (Note that the withdrawal bleed does not necessarily occur during the placebo day; it usually starts during the intake of the last tablets of a pack and may not have finished before the first pills of a new pack are taken). The net result of the Qlaira regimen is a stable endometrium and a good bleeding profile. oestrogen dominant increasing progestogenic activity oestrogen only

Summary - Qlaira Clinical studies of E2V/DNG demonstrate Relatively stable oestrogen levels throughout the menstrual cycle Effective inhibition of ovulation Effective contraception Good bleeding profile – shorter, lighter bleeding and fewer bleeding/spotting days compared with monophasic EE/LNG An absence of all bleeding or spotting occurred in 15.4% of cycles No discontinuations due to bleeding disorders

Zoely 24 active pills/ 4 placebo pills – no PFI 1.5 mg estradiol (as hemi hydrate) + Nomegestrol acetate 2.5 mg (NOMAC) NOMAC has a strong affinity for progesterone receptor, strong antigonadotrophic activity, mild antiandrogenic activity Shorter/lighter WTB, higher incidence of absent WTB Acne improvement Efficacy comparable to COC (Yasmin ethinylestradiol, drospirenone) Faculty of SRH Statement from CEU May 2013

Nuvaring – vaginal ring A flexible transparent ring of ethylene vinyl acetate with an outer diameter of 54 mm and cross-sectional diameter of 4 mm One size for all! Combined hormonal contraceptive vaginal ring containing 2.7 mg ethinylestradiol and 11.7 mg etonorgestrel It has the lowest oestrogen content of any combined hormonal contraceptive FSRH Guidance 2012 CHC

Ingredients - Nuvaring Every 24 hours the device releases: 15 mcg EE 120 mcg ENG The hormones are absorbed into the rich supply of blood vessels within the vagina and enter the general circulation, avoiding the first-pass metabolism by the liver Each Nuvaring is used for one monthly cycle It stay in the vagina for 3 weeks and is then removed for a 1 week ring-free interval The 7 days without Nuvaring allows for a withdrawal bleed

Nuvaring Low dose Good cycle control No daily pill to remember No daily fluctuations in hormone levels Easy to use No interference with SI Useful if GI absorption problems

Evra - contraceptive patch Daily dose 20mcg EE + 150 mcg Norelgestromin (similar to Cilest) Levels sufficient to inhibit ovulation for at least 7 days Contraindications similar to COCs Efficacy similar to triphasic COC (overall PI 1.24) Probable reduced efficacy in women > 90 Kg BTB more common in 1st 2 cycles than COC Additional contraception advised for women on enzyme inducers Suitable for women with absorption problems, who are forgetful or have difficulty swallowing pills BUT – 60% more exposure to oestrogen

Checklist for BTB with CHC Disease Disorders of pregnancy Default Drugs Diarrhoea and vomiting Disturbances of absorption Diet Duration of use Dose

CEU 2017 Drug interactions and hormonal contraception Additional precautions NO longer required when using non- enzyme inducing antibiotics with CHC All women on enzyme inducing drugs should be advised to use methods unaffected by those drugs – Cu-IUD; IUS; Injectables CHC not recommended in women on Lamotrigine monotherapy (inc risk of seizures) UPA not recommended while using enzyme inducers or within 28 days

Tailored regimens for use of combined hormonal contraception Type of regimen Suggested regimen CHC-free interval Extended use Tricycling 7 days taken after finishing 3rd packet, 3rd ring or 9th patch Shortened hormone-free interval 3 weeks of CHC use 4 days taken after each packet of pills, each ring or 3rd patch Extended with shortened interval Method used continuously until BTB occurs for 3-4 days 4 day interval Extended use with regular interval 7 day interval FSRH Clinical Guidance Combined Hormonal Contraception Oct 2011

UKMEC and CHC 2017 History of VTE or Current VTE (on anticoagulants) = UKMEC 4 Family Hx (1st degree relative <45 = UKMEC 3 Family Hx (1st degree relative >45 = UKMEC 2 Major surgery with prolonged immobilisation= UKMEC 4 Major surgery without prolonged immobilisation= UKMEC 2 Minor surgery without immobilisation =UKMEC 2 Immobility (in a wheelchair) = UKMEC 3

UKMEC and CHC 2017 Varicose veins = UKMEC 1 Superficial venous thrombosis = UKMEC 2 Known thrombotic mutations = UKMEC 4

Breastfeeding and CHC 2017 No differentiation between full and partial breastfeeding <6 weeks postnatal CHC is still UKMEC4 6 weeks to 6 months postnatal CHC is UKMEC2 whether full or partial feeding No evidence of effect on breastfeeding Code: UKWHG07160046 Date of prep: August 2016

Long Acting Reversible Contraception (LARC)

Intrauterine Contraception Jaydess ▼ All long acting methods with many advantages including high efficacy – TT Cu series last 10 yrs; Cu IUDs effective for e.c.; Cu IUDs non-hormonal good for women concerned re hormone effects; Mirena IUS last 5 years and also suitable for menorrhagia and endometrial protection Can truly fit and forget Gynefix TT380S Mirena NovaT380 MultiLoadCu385

Copper IUDs Use IUDs with >300 sqmm Copper Effective: failure rate < 2 in 100 women over 5 years Reversible and no effect on future fertility No systemic effects Reduces risk of ectopic pregnancy Can be fitted in nulliparous women (consider local anaesthesia) Failure rate < 1% when used for post coital contraception TT380 licensed and effective for 10 years Cu IUDs fitted > age 40 may be left until after menopause Is least costly LARC method

Nexplanon Single rod releasing 30-40 mcg etonorgestrel per day Contains 3% barium sulphate >99% inhibition of ovulation Most effective LARC method Lasts 3 years ( no need to change early if high BMI) Not recommended for women on enzyme inducers Does not affect bone density 20% amenorrhoea (but 47% will get bleeding by 2 years) 50% infrequent, frequent or prolonged bleeding Not associated with weight change, mood, libido or headaches May be associated with acne FSRH Guidance 2014 P-O Iimplants

Management of women taking anticoagulants or anti platelet medications who request IUC or SDI Insertion of IUC and SDI in women using Warfarin is unlikely to be associated with a risk of significant bleeding From clinical experience, DOAC use with these procedures carries a low bleeding risk FSRH CEU Guidance March 2017

Assessment of women with bleeding risks What anticoagulant is she taking and why? Is she highly anticoagulated? Expected duration of therapy? Previous bleeding problems with procedures? (e.g. dental work) Other medical conditions or medications that may increase the risk of bleeding further (e.g. dual anti platelet therapy, liver disease) Result and date of most recent INR if on Warfarin Is she postnatal/breastfeeding? Increased risk of perforation in 1st 36 weeks postnatal and if breast feeding Previous difficult/failed IUC insertions FSRH CEU Guidance March 2017

Management of women with bleeding risks IUC and SDI insertions should be performed by clinicians with the relevant LOC and who are specialist contraceptive providers Women who are anticoagulated can have their SDI or IUC fitted within the GP or C&SH clinic Ideally, procedure should take place within office hours Patients using LMWHs should have their device fitted to coincide with the lowest anticoagulant effect Avoid fitting IUC or SDI in the first 2 weeks of Apixaban use Women who have a target INR > 3.5 or who are on higher than standard doses of LMWH should have their IUC fitted in a hospital setting but could have an SDI fitted in the community If LMWH taken in evening, fit device in afternoon FSRH CEU Guidance March 2017

Injectables Depoprovera Sayana-Press Medroxyprogesterone acetate 150 mg/ml every 13 weeks by deep i.m. injection If necessary, can be given from 10 weeks CEU guidance states it can be given up to 7 days late without need for additional precautions Cost: £6.01 Annual cost: £26.11 Medroxyprogesterone acetate 104 mg in 0.65 ml suspension every 13 weeks s.c. into upper thigh or lower abdomen Can be given up to 7 days early or late without need for additional precautions Cost: £6.90 Annual cost: £27.68 FSRH CEU New Product Review 2013 FSRH Clinical Guidance Progestogen-only Injectables March 2015

UKMEC Injectables History of VTE = UKMEC 2 Current VTE (on anticoagulants) = UKMEC 2 Family Hx of VTE (any age) = UKMEC 1 Major surgery with prolonged immobilisation = UKMEC 2 Major surgery without prolonged immobilisation or immobility = UKMEC 1 Known thrombotic mutations = UKMEC 2

4 unique aspects! Cannot be speedily reversed Can cause delayed return of (but no loss of) fertility Can truly cause weight gain (mean of 3 kg in 2 years) Excellent choice for women on EIDs so no change in usual injection frequency during EID use Essential counselling points: The liver’s clearance of the progestogen equated to total hepatic blood flow so good choice for women on EIDs since they will not increase this 100% clearance FSRH CEU Guidance Progestogen-only Injectables Nov 2008

MHRA Guidance 2004 Women < 18 yrs – DMPA may be used as 1st line contraception after all options have been discussed and are considered unsuitable or unacceptable A re-evaluation of the risks and benefits of treatment should be carried out every 2 years in those who wish to continue use Women with considerable life style and/or medical risk factors for osteoporosis should consider other methods of contraception

Quick starting contraception!!! Criteria for excluding pregnancy: No SI since last menses Is correctly and consistently using a reliable method Is within 7 days of onset of menses Is within 4 weeks postpartum and not breast feeding Is fully or nearly fully breast feeding, amenorrhoeic and < 6 months postpartum

What drug interactions are relevant to e.c.use? Women using EIDs should be advised that the efficacy of UPA-ec and LNG-ec could be reduced Women using EIDs should be offered a Cu-IUD Women using EIDs can be offered 3 mg LNG-ec but the efficacy is not known. A double dose of UPA-ec is not recommended The efficacy of UPA-ec could be reduced if progestogens are taken in 5 days after UPA-ec The efficacy of UPA-ec could be reduced if progestogens in 7 days prior to UPA-ec

Contraception following UPA e. c Contraception following UPA e.c. CEU advises that women should not start a hormonal method for 5 days after UPA UPA= day 0 Methods (day UPA + 5) Requirement for additional contraception UPA then wait at least 5 days CHC (except Qlaira) 7 days Qlaira 9 days POP (traditional and DSG) 2 days POI or Implant

Intrauterine methods injectables implants pills Vaginal rings patches 2018 - different routes, new hormones, more choice Vaginal rings patches barriers Natural methods Surgical methods