Choosing the best COC and POP

Jill Zelin

21/7 ED

21/7

triphasic

QlairaPOP

levonelle

Evra NuvaRing

ulipristalDepo-Provera

Nexplanon

IUS Cu IUDs

Essure

Filshie clip

non-latexcondoms

PasanteUnique

Mates SkynAvanti Ultima

Latexcondom Femidon

Silicone diaphragm

FemCap

Persona

NFP

Spermicide

% 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

www.fsrh.org

BENEFITS Contraceptive efficacy Ovarian cancer Endometrial cancer Colorectal cancer Menstrual problems Ectopic pregnancy Ovarian cysts Benign breast disease PID

Key Benefits and Risks

Key Benefits and Risks

RISKS Venous disease Arterial disease Breast cancer Cervical cancer

norgestimategestodene desogestrel levonorgestrel norethisteronedrospirenone

30mcg

20mcg

Prog-only

More oestrogenic by function Less oestrogenic by function

cyproterone

35mcg

MarvelonMarvelon

MercilonMercilon

CerazetteCerazette

Femodene/Femodene/KatyaKatya

FemodetteFemodetteSunyaSunya

MicrogynonMicrogynon

Loestrin 20Loestrin 20

CilestCilest

Loestrin 30Loestrin 30

More oestrogenic

by DOSE

Noriday/Noriday/MicronorMicronor

FemulenFemulenNorgestonNorgeston

DianetteDianette

YasminYasmin

COC progestogen ladder

YazYaz

NoriminNoriminBrevinor/OvysmenBrevinor/Ovysmen

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

CHC containing ethinylestradiol plus 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

VTE per 100,000 women/yr

1% mortality

VTE per 100,000 women/yr

Dinger JC et al. Contraception 2007; 75: 344

EURAS: effect of time on VTE risk

Dinger JC et al. Contraception 2007; 75: 344

0 50 100 150

4th/5th year

3rd Year

2nd year

1st 3/12

incidence of VTE per 100,000 WY

EURAS

Dinger JC et al. Contraception 2007; 75: 344

BMI ≥30 3X VTE risk vs. normal weight

Arterial Thromboembolism

MI very small increase in risk in healthy users

vs. non users Ischemic stroke

increased X2 in healthy users vs. non users

Lancet 1996; 347: 1713-27

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

Marchbanks PA et al. NEJM 2002; 346: 2025-32

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]

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?

Milne RL et al. Cancer Epidemiol Biomarkers Prev 2005; 14: 350-6

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

Narod SA et al. NEJM 1998; 339: 424-8Whittemore AS et al. Br J Cancer 2004; 91: 1911-15

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

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

Cervical cancer

Cervical cancer

COC use Smoking HPV

Moreno et al. Lancet 2002; 359: 1085-192

Risk of Cx cancer in women with Cx HPVCOC users vs. never users

Use of COCs OR (95% CI)

<5 years 0.73 (0.52 to 1.03)

5-9 years 2.82 (1.46 to 5.42)

³10 years 4.03 (2.09 to 8.02)

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

The pill is pretty safeBUT

SOME WOMEN ARE DANGEROUS!

Practical Prescribing

Who never? Who maybe?

special advice/monitoring

Assessment

History

Assessment

Examination Blood pressure BMI (weight (kg/m2)/height(m)

UKMEC Eligibility

UKMEC 1: no restriction

UKMEC 2:

UKMEC 3:

UKMEC 4: unacceptable risk

UKMEC 2009

Because:

No associated risks

Benefits > risks

Risks > benefits

Risks >>> benefits

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

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

‘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

Bridging

Breast enlargement / tenderness

Bloating

Weight gain (water retention)

Nausea

Non-infective vaginal discharge

Some headaches

Chloasma

Photosensitivity

Oestrogenic Progestogenic

Acne

Greasy hair

Hirsutism

Weight gain (increased appetite)

Depression

Loss of libido

Vaginal dryness

Oestrogenic and Progestogenic effects

norgestimategestodene desogestrel levonorgestrel norethisteronedrospirenone

30mcg

20mcg

Prog-only

More oestrogenic by function Less oestrogenic by function

cyproterone

35mcg

MarvelonMarvelon

MercilonMercilon

CerazetteCerazette

Femodene/Femodene/KatyaKatya

FemodetteFemodetteSunyaSunya

MicrogynonMicrogynon

Loestrin 20Loestrin 20

CilestCilest

Loestrin 30Loestrin 30

More oestrogenic

by DOSE

Noriday/Noriday/MicronorMicronor

FemulenFemulenNorgestonNorgeston

DianetteDianette

YasminYasmin

COC progestogen ladder

YazYaz

NoriminNoriminBrevinor/OvysmenBrevinor/Ovysmen

Drug interactions

Antibiotics No concerns unless enzyme-inducing

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

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

Progestogen-only pills currently available in the UK

Brand name Type ofprogestogen

Dose (µg)

Cerazette® Desogestrel 75

Noriday® Norethisterone 350

Micronor® Norethisterone 350

Norgeston® Levonorgestrel 30

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!!