Combined hormonal contraception
Transcript of Combined hormonal contraception
![Page 1: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/1.jpg)
University of Warwick MSc course 2007
Combined hormonal
contraception
![Page 2: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/2.jpg)
Types
• Oral (COC pill)
• Transdermal
• Vaginal ring
• Injectable
![Page 3: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/3.jpg)
History of COC
• 1950 Synthesis of norethisterone
• 1956 First human trials reported
• 1961 COC available in UK
• 1963 Synthesis of norgestrel
![Page 4: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/4.jpg)
Composition of COCs
• Ethinylestradiol 20 – 35 mcg
• Progestogen
![Page 5: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/5.jpg)
Constituents of COCs
• Oestrogens
• Ethinylestradiol• Mestranol
• Progestogens
• Norethisterone• Levonorgestrel• Norgestimate• Desogestrel• Gestodene• Drosperinone
![Page 6: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/6.jpg)
Formulations
• Monophasic
• Phasic (biphasic, triphasic)
• Everyday (ED)
• Seasonale (four packets in a row)
• Lybrel (continuous)
![Page 7: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/7.jpg)
ONS Omnibus Survey
Pill use by age GB 2004/5
0
10
20
30
40
50
60
16-17 18-19 20-24 25-29 30-34 35-39 40-44 45-49
%
![Page 8: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/8.jpg)
Trussell 2004
Failure ( first year unintended pregnancy % rates)
Method Typical use Perfect use
COC/POP 8 0.3
Evra 8 0.3
NuvaRing 8 0.3
Lunelle 3 0.05
![Page 9: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/9.jpg)
Mechanism of action
• Inhibition of ovulation through suppression of the hypothalamic-pituitary-ovarian axis
• Endometrial suppression
• Thickening of cervical mucus
![Page 10: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/10.jpg)
Non-contraceptive benefits
• Better cycles: lighter & shorter (less anaemia), regular, less dysmen, less PMS
• Less PID• Fewer ectopics• Less benign breast
disease• Bone sparing
• Fewer functional ovarian cysts
• Less hospitalisation for fibroids
• Less symptomatic endometriosis
• Protection against carcinoma of ovary, endometrium and colon
![Page 11: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/11.jpg)
Risks/benefits
• Risks apply to a minority
• Benefits apply to all
![Page 12: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/12.jpg)
What women worry about
• Infertility
• Cancer
![Page 13: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/13.jpg)
Expressing risk
• Relative risk can be misleading and anxiety provoking for women
• Use absolute risk
![Page 14: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/14.jpg)
Annual deaths per million
0
20
0
40
0
60
0
80
0
10
00
12
00
14
00
16
00
18
00
Childbirth, UK
VTE M30
VTE off COC
COC all causes
Home accidents
RTAs
Scuba diving
Smoking (in next year age 35)
![Page 15: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/15.jpg)
Risks of VTE per 100,000 per year
0 10 20 30 40 50 60 70
Pregnancy
Gestodene/desogestrelCOC
LNG/NE COC
No COC
![Page 16: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/16.jpg)
Co-cyprindiol (Dianette)
• 35mcg EE with 2mg cyproterone acetate
• not licensed as a contraceptive
• indicated for severe acne which has not responded to antibiotics
• RR of VTE compared to LNG COCs is 3.9
![Page 17: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/17.jpg)
Body mass index and COC
• Traditionally, BMI 30-39 regarded as relative contraindication and 40+ absolute contraindication
• WHO-MEC gives a BMI of 30 and over a category 2 (advantages generally outweigh risks), with no upper limit
![Page 18: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/18.jpg)
Risk factors for arterial disease
• Smoking, esp. > 15 cigs/day• Hypertension• Diabetes• Android obesity• FH arterial/venous thrombosis• Age• Hyperlipidaemia• Migraine
![Page 19: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/19.jpg)
Risk factors for VTE
• FH of VTE/genetic predisposition• Acquired e.g. antiphospholipid (Hughes’)
syndrome• Obesity: BMI > 30• Severe varicose veins• Dehydration• Trauma and immobilisation• Age
![Page 20: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/20.jpg)
Thrombophilias
• Factor V Leiden mutation• G20120A mutation• Protein C deficiency• Protein S deficiency• Antithrombin III deficiency
Prevalence of factor V Leiden mutation is 1 in 20; if these individuals take a COC, risk of VTE is increased 35-fold or absolute risk 3 additional cases of VTE per 1000 users per year.
![Page 21: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/21.jpg)
Ischaemic stroke
• Risk of ischaemic stroke for COC users: OR 2.7 (2 meta-analyses with combined total of studies of 28)
• Among women who do not smoke, have no history of migraine, have regular BP checks and who are normotensive increased risk is less
![Page 22: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/22.jpg)
Myocardial infarction
• Risk of MI for COC users: OR 2.0 for 30mcg pills and 0.9 for 20mcg pills (meta-analysis of 23 studies)
• In smokers on COC, OR 9.5 cf non-smokers not on COC
• Women who do not smoke, who have regular BP checks and who do not have hypertension or diabetes are at no increased risk of MI, regardless of their age
![Page 23: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/23.jpg)
Breast cancer
Conflicting data from different studies• Collaborative reanalysis Lancet 1996: relative
risk for current users = 1.24• Marchbanks case-control study NEJM 2002
showed no increased risk in current users aged 35-64 at time of diagnosis
No duration of use effect and no synergy with FH of breast cancer
![Page 24: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/24.jpg)
Cervical cancer
• Increased risk of cervical neoplasia (invasive/in-situ) with duration of COC use > 5 years; RR 2.2 with duration 10+ years (systematic review Lancet 2003)
• COC users can avoid this risk by attending regularly for cervical screening at usual intervals
![Page 25: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/25.jpg)
Diabetes and COC
• WHO4 if:– retinopathy– nephropathy– neuropathy– duration of diabetes > 20 years
![Page 26: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/26.jpg)
Contraindications
• Cardiovascular
• Hepatic
• Other
![Page 27: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/27.jpg)
Cardiovascular disease
• Hypertension: > 160/100
• Ischaemic heart disease
• Stroke
• Valvular heart disease complicated by pulmonary hypertension, atrial fibrillation or infective endocarditis
![Page 28: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/28.jpg)
Liver disease
• Viral hepatitis: active
• Cirrhosis
• Benign tumours (adenoma)
• Malignant tumours (hepatoma)
• Acute hepatic porphyrias
• Gallbladder disease: symptomatic or medically treated
![Page 29: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/29.jpg)
Other contraindications
• Pregnancy
• Genital tract bleeding
• Oestrogen-dependent tumours
![Page 30: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/30.jpg)
COC and migraine
The following are WHO4:• Loss of part of visual field• Unilateral weakness/parasthesiae• Speech disturbance• Status migrainosusThe following are safe: blurred vision,
photophobia, phonophobia and flashing lights affecting whole visual field
![Page 31: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/31.jpg)
Starting routines
• WHO Selected Practice Recommendations: up to day 5 of cycle
• Quickstart: confirm not pregnant, then start any time with extra precautions for 7 days
![Page 32: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/32.jpg)
Starting routines after pregnancy
• Start the day after the 2nd visit/expulsion for medical abortion or the day after a surgical procedure (earliest recorded ovulation day 16)
• Start in the 4th week after delivery (clotting factors still raised for up to 3 weeks; earliest recorded ovulation day 30)
![Page 33: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/33.jpg)
FFP April 2005
Missed pills
• Definition now is 24 hrs late
• If 2 x 20mcg pills or 3 x 30mcg pills are missed:– take a pill a.s.a.p.– addit. precautions for next 7 days– ? EC if missed pills in week 1 – omit PFI if missed pills in week 3
![Page 34: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/34.jpg)
Side effects: oestrogen excess
• nausea• dizziness• cyclical weight gain• bloating• vaginal discharge• breast tenderness
Change to 20mcg pill or to a more progestogenic pill e.g. Loestrin 30 or Norimin
![Page 35: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/35.jpg)
Side effects: progestogen excess
• dry vagina• sustained weight gain (increased appetite)• depression• loss of sexual drive• lassitude• acne/hirsutismChange to more oestrogenic pill e.g.
Ovysmen/Brevinor or to a less progestogenic pill e.g. Femodene or Marvelon
![Page 36: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/36.jpg)
Causes of BTB
• Cervical bleeding:– ectropion– cervicitis– carcinoma cx.
• Chlamydia• Pregnancy:
– miscarriage– trophoblastic disease
• Missed pills• Drug interaction• Vomiting• Severe diarrhoea• Vegetarian diet• Malabsorption e.g.
coeliac disease• Smoking
![Page 37: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/37.jpg)
Enzyme-inducing drugs
• Antiepileptic drugs– carbamazepine– oxcarbazepine– phenytoin– phenobarbital– primidone– topiramate
• Herbal– Hypericum
• Anti-TB drugs– rifampicin– rifabutin
• Antifungal drugs– griseofulvin
• Antiretroviral drugs– see BNF
• CNS stimulants– modafinil
![Page 38: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/38.jpg)
Broad-spectrum antibiotics
• May reduce efficacy of COCs• Impair bacterial flora responsible for
recycling of EE from large bowel• Flora develop antibiotic resistance after
3 weeks• Broad-spectrum penicillins e.g.
amoxicillin; cephalosporins; tetracyclines
![Page 39: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/39.jpg)
Extended use
• Tricycling/continuous use
• Fewer withdrawal bleeds
• Ovulation better suppressed
• Fewer missed pills
• Treatment for dysmenorrhoea and menorrhagia
• Good for military
![Page 40: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/40.jpg)
Evra 1
• A flesh-coloured combined transdermal patch
• ethinylestradiol 20µg/norelgestromin 150µg
• 4.5 x 4.5 cm• patches last 7 days• worn for 3 weeks out of four • Launched in UK in 2003
![Page 41: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/41.jpg)
Evra 2
Compared to COC:• compliance better, especially in teenagers• efficacy as good as COC overall, but not so
good in those > 90kg• BTB more common in cycles 1 & 2• mastalgia more common in cycles 1&2• 3% discontinue because of skin reactions
![Page 42: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/42.jpg)
Patch rules
• Patch detachment in last 24 hrs: no additional precautions needed
• Delayed patch application (patches 2 or 3): up to 48 hr window where no additional precautions needed
![Page 43: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/43.jpg)
NuvaRing 1
• A combined vaginal ring• made of ethylene vinylacetate• ethinylestradiol 15µg/
etonogestrel 120µg• 5.4cm diameter• worn for 3 weeks out of 4• almost all have regular withdrawal
bleeds
![Page 44: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/44.jpg)
NuvaRing 2
• Steady state release level within 3 days of insertion
• Efficacy similar to COC• Incidence of BTB low• Can cause vaginal discharge• Can be removed for 3 hours for sex• Tampon use is OK• Available in US, Canada, Australia and many
European countries including Ireland
![Page 45: Combined hormonal contraception](https://reader034.fdocuments.us/reader034/viewer/2022052412/558e2e1b1a28ab89468b4621/html5/thumbnails/45.jpg)
Lunelle
• A combined monthly injectable• medroxyprogesterone acetate 25mg/
estradiol cypionate 5mg• similar efficacy to COC• most have regular withdrawal bleeds• <5% amenorrhoeic by one year• rapid return of fertility• not yet available in UK