Choosing the best COC and POP Jill Zelin

POP 21/7 ED Qlaira Persona 21/7 triphasic Evra NuvaRing NFP levonelle Silicone diaphragm Spermicide Depo-Provera ulipristal Nexplanon FemCap Pasante Unique Latex condom non-latex condoms IUS Femidon Cu IUDs Mates Skyn Avanti Ultima Essure Filshie clip

DFFP course: COCs Ovulation inhibited by effects on LH and FSH MacGregor EA

% of women experiencing an unintended pregnancy during the first year of use Trussell J. In: Hatcher et al. (eds) Contraceptive Technology (20th Edition). New York, Ardent Media 2011

DFFP course: COCs www.fsrh.org MacGregor EA

Key Benefits and Risks BENEFITS Contraceptive efficacy Ovarian cancer DFFP course: COCs Key Benefits and Risks BENEFITS Contraceptive efficacy Ovarian cancer Endometrial cancer Colorectal cancer Menstrual problems Ectopic pregnancy Ovarian cysts Benign breast disease PID MacGregor EA

Key Benefits and Risks RISKS BENEFITS Venous disease DFFP course: COCs Key Benefits and Risks RISKS Venous disease Arterial disease Breast cancer Cervical cancer BENEFITS Contraceptive efficacy Ovarian cancer Endometrial cancer Colorectal cancer Menstrual problems Ectopic pregnancy Ovarian cysts Benign breast disease PID MacGregor EA

DFFP course: COCs Also leads on the slide of benefits of COC which = side effects of not ie. remember - not being on the pill has side-effects MacGregor EA

COC progestogen ladder DFFP course: COCs COC progestogen ladder cyproterone drospirenone gestodene desogestrel norgestimate levonorgestrel norethisterone More oestrogenic by DOSE Dianette 35mcg Cilest Norimin Brevinor/Ovysmen 30mcg Yasmin Femodene/ Katya Marvelon Microgynon Loestrin 30 20mcg Yaz Femodette Sunya Mercilon Loestrin 20 Prog-only Femulen Cerazette Norgeston Noriday/ Micronor More oestrogenic by function Less oestrogenic by function MacGregor EA

Risk of venous thromboembolism (VTE) associated with non-use, combined hormonal contraception (CHC) use over the course of 1 year Risk of VTE per 10,000 healthy women Non contraceptive users and not pregnant 2 CHC containing ethinylestradiol plus levonorgestrel, norgestimate or Norethisterone 5-7 CHC containing etonogestrel (ring) and norelgestromin (patch) 6-12 gestodene, desogestrel, drospirenone 9-12 (adapted from http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news /2013/11/news_detail_001969.jsp&mid=WC0b01ac058004d5c1)

Pharmacokinetics & dynamics Based on data from various sources, no direct comparative data

DFFP course: COCs VTE per 100,000 women/yr 1% mortality MacGregor EA

VTE per 100,000 women/yr Dinger JC et al. Contraception 2007; 75: 344 DFFP course: COCs VTE per 100,000 women/yr Dinger JC et al. Contraception 2007; 75: 344 MacGregor EA

EURAS: effect of time on VTE risk DFFP course: COCs EURAS: effect of time on VTE risk Obesity is biggest risk Risk for all COCs is around 90/100,000 Baseline was 44/100,000 (higher than usual 5/100,000!) BMI>30 on COC was 230/100,000 Pregnant 290/100,000 Once no safer than preg, no longer have grounds to prescribe COCs Dinger JC et al. Contraception 2007; 75: 344 MacGregor EA

BMI ≥30 EURAS 3X VTE risk vs. normal weight DFFP course: COCs EURAS BMI ≥30 3X VTE risk vs. normal weight Obesity is biggest risk Risk for all COCs is around 90/100,000 Baseline was 44/100,000 (higher than usual 5/100,000!) BMI>30 on COC was 230/100,000 Pregnant 290/100,000 Once no safer than preg, no longer have grounds to prescribe COCs Dinger JC et al. Contraception 2007; 75: 344 MacGregor EA

Arterial Thromboembolism DFFP course: COCs Arterial Thromboembolism MI very small increase in risk in healthy users vs. non users Ischemic stroke increased X2 in healthy users vs. non users MacGregor EA

Collaborative Group on Hormonal Factors & Ca Breast 1996 DFFP course: COCs Collaborative Group on Hormonal Factors & Ca Breast 1996 Meta-analysis of 54 studies from 26 countries 53,297 women with Ca Breast 100,239 women without Ca Breast Current COC users:RR=1.24[1.15-1.33] i.e. 24% increased risk Lancet 1996; 347: 1713-27 MacGregor EA

Women’s CARE Study 2002 Population-based case-control study in US DFFP course: COCs Women’s CARE Study 2002 Population-based case-control study in US 4575 women with Ca breast 4682 controls Current COC users: RR = 1.0 [0.8-1.3] Past COC users: RR = 0.9 [0.8-1.0] Marchbanks PA et al. NEJM 2002; 346: 2025-32 MacGregor EA

Why the differences? Surveillance bias Age of population DFFP course: COCs Why the differences? Surveillance bias Age of population 2002: restricted to women aged 35-64 1996: 9% of women with Ca Breast were <35 years at the time of diagnosis Are young women with BRCA1 and BRCA2 mutations using COCs at increased risk of Ca Breast? MacGregor EA

Three-Nation Study 2005 Population-based case-control study DFFP course: COCs Three-Nation Study 2005 Population-based case-control study Is COC use a risk factor for early Ca Breast in Caucasian carriers and non-carriers of BRCA1 and BRCA2 mutations? Low-dose COCs are NOT associated with increased risk of Ca Breast in BRCA1 or BRCA2 carriers, or in non-carriers Milne RL et al. Cancer Epidemiol Biomarkers Prev 2005; 14: 350-6 MacGregor EA

BRCA and Ovarian Cancer DFFP course: COCs BRCA and Ovarian Cancer BRCA mutations associated with increased risk of Ca ovaries Low-dose COCs may be associated with reduced risk of Ca ovaries in BRCA1&2 carriers Narod SA et al. NEJM 1998; 339: 424-8 Whittemore AS et al. Br J Cancer 2004; 91: 1911-15 MacGregor EA

FHx Ca Breast: Practical Prescribing DFFP course: COCs FHx Ca Breast: Practical Prescribing Can use CHCs (UKMEC 1) Counsel about inherent increased background risk Consider benefits Reduced Ovarian, Endometrial, Colorectal Ca Relief from period-related problems MacGregor EA

Cervical cancer DFFP course: COCs Cervical cancer increased with use of COCs Effect of HPV - main cause of cervical cancer - not usually taken into account. Aim: to assess how use of COCs affected risk of cervical cancer in women with HPV in a multicentric case-control study. Results: long-term use of COCs could be a co-factor that increases risk of cervical cancer by up to 4-fold in women who are positive for cervical HPV DNA. Extra effort should be made to included long-term users of COCs in cervical screening programmes. MacGregor EA

Cervical cancer COC use Smoking HPV DFFP course: COCs Cervical cancer increased with use of COCs Effect of HPV - main cause of cervical cancer - not usually taken into account. Aim: to assess how use of COCs affected risk of cervical cancer in women with HPV in a multicentric case-control study. Results: long-term use of COCs could be a co-factor that increases risk of cervical cancer by up to 4-fold in women who are positive for cervical HPV DNA. Extra effort should be made to included long-term users of COCs in cervical screening programmes. MacGregor EA

Risk of Cx cancer in women with Cx HPV COC users vs. never users DFFP course: COCs Risk of Cx cancer in women with Cx HPV COC users vs. never users Cervical cancer increased with use of COCs Effect of HPV - main cause of cervical cancer - not usually taken into account. Aim: to assess how use of COCs affected risk of cervical cancer in women with HPV in a multicentric case-control study. Results: long-term use of COCs could be a co-factor that increases risk of cervical cancer by up to 4-fold in women who are positive for cervical HPV DNA. Extra effort should be made to included long-term users of COCs in cervical screening programmes. Moreno et al. Lancet 2002; 359: 1085-192 MacGregor EA

Ca Cervix: Practical Prescribing DFFP course: COCs Ca Cervix: Practical Prescribing Women using CHCs should be counselled: Against smoking Use condoms to protect against STIs Take up the Cervical Screening Programme Women with CIN can continue CHCs during treatment MacGregor EA

The pill is pretty safe BUT DFFP course: COCs The pill is pretty safe BUT SOME WOMEN ARE DANGEROUS! MacGregor EA

Practical Prescribing DFFP course: COCs Practical Prescribing Who never? Who maybe? special advice/monitoring MacGregor EA

DFFP course: COCs Assessment History MacGregor EA

Assessment Examination Blood pressure BMI (weight (kg/m2)/height(m) DFFP course: COCs Assessment Examination Blood pressure BMI (weight (kg/m2)/height(m) MacGregor EA

UKMEC Eligibility Because: UKMEC 1: no restriction No associated risks DFFP course: COCs UKMEC Eligibility UKMEC 1: no restriction UKMEC 2: UKMEC 3: UKMEC 4: unacceptable risk Because: No associated risks Benefits > risks Risks > benefits Risks >>> benefits UKMEC 2009 MacGregor EA

Absolute contraindications DFFP course: COCs Absolute contraindications < 6 weeks postpartum if breastfeeding Smoker ≥ age 35 ≥15 cigs/day BP systolic >160 or diastolic ≥95 Current or past Hx VTE Known thrombogenic mutations Major surgery with prolonged immobilization Systemic Lupus Erythematosus Current or past Hx IHD/CVA Diabetes > 20yrs OR with “opathies” Complicated valvular heart disease Migraine aura (“focal”) Current breast cancer Liver tumours Liver disease: active hepatitis/severe cirrhosis MacGregor EA

Smokers: Practical Prescribing DFFP course: COCs Smokers: Practical Prescribing CHCs not recommended in smokers >35 years <15 cigs/day UKMEC 3 ≥15 cigs/day UKMEC 4 Healthy, non-smoking women may continue to use CHCs until menopause MacGregor EA

[Insert Lecture Name Here] ‘Quick Start’ Method Start at any time during menstrual cycle Use of back-up barrier contraception for 7 days If following emergency contraception, do urine pregnancy test in 3 weeks Talking Points: Start at any time during menstrual cycle Provider should recommend use of back-up barrier contraception or abstinence for 7 days. If unprotected intercourse occurs days emergency contraception should be considered. If Quick Start method is used with emergency contraception, it is important to obtain a urine pregnancy test in 3 weeks to ensure that the patient was not already pregnant when the implant was inserted. - - - Original content for this slide submitted by Clinical Advisory Committee for New Developments in Contraception: The Single-Rod Implant in July 2007. Original funding received from Organon through an unrestricted educational grant. This slide is available at www.arhp.org/core.

Bridging

Oestrogenic and Progestogenic effects DFFP course: COCs Oestrogenic and Progestogenic effects Oestrogenic Progestogenic Breast enlargement / tenderness Acne Bloating Greasy hair Weight gain (water retention) Hirsutism Nausea Weight gain (increased appetite) Non-infective vaginal discharge *these side effects are much less likely with newer pills containing progestogens other than levonorgestrel and norethisterone Some headaches Depression Chloasma Loss of libido Photosensitivity Vaginal dryness MacGregor EA

COC progestogen ladder DFFP course: COCs COC progestogen ladder cyproterone drospirenone gestodene desogestrel norgestimate levonorgestrel norethisterone More oestrogenic by DOSE Dianette 35mcg Cilest Norimin Brevinor/Ovysmen 30mcg Yasmin Femodene/ Katya Marvelon Microgynon Loestrin 30 20mcg Yaz Femodette Sunya Mercilon Loestrin 20 Prog-only Femulen Cerazette Norgeston Noriday/ Micronor More oestrogenic by function Less oestrogenic by function MacGregor EA

Drug interactions Antibiotics No concerns unless enzyme-inducing DFFP course: COCs Drug interactions Antibiotics No concerns unless enzyme-inducing MacGregor EA

Drug interactions Enzyme-inducing agents Antibiotics Antifungals DFFP course: COCs Drug interactions Enzyme-inducing agents Anti-epileptics Anti-retrovirals St John’s Wort Antibiotics Rifampicin Antifungals Griseofulvin FFPRHC guidance (April 2005) Drug interactions with hormonal contraception MacGregor EA

Enzyme-inducing agents DFFP course: COCs Enzyme-inducing agents CHCs 50 mcg monophasic Norinyl-1 50 mcg mestranol 20 + 20 OR 20 + 30 standard COC (off-licence) 4 day PFI tricycle/continuous If seizures occur in PFI consider tricycling MacGregor EA

DFFP course: COCs MacGregor EA

DFFP course: COCs MacGregor EA

Progestogen-only pills currently available in the UK Brand name Type of progestogen Dose (µg) Cerazette® Desogestrel 75 Noriday® Norethisterone 350 Micronor® Norgeston® Levonorgestrel 30

no longer manufactured POP Femulen® - Etynodiol diacetate 500µg no longer manufactured

UKMEC 3 Current ischaemic heart disease Stroke while taking POP Headaches migraine with aura, at any age starting while taking POP Gestational trophoblastic neoplasia with abnormal hCG Breast cancer in the past (5 years+) Viral hepatitis active/Cirrhosis severe (decompensated)/Liver tumours

UKMEC 4 Breast cancer current or within the last 5 years

Women over 40 Little benefit in using Cerazette – traditional POPs as effective Failure rates for traditional POPs vary are lower for women aged over 40 compared to younger women

POP and weight There is no evidence that the efficacy of progestogen-only pills is reduced in women weighing >70 kg and therefore the licensed use of one pill per day is recommended. But I usually give 2!!