Combined hormonal contraception

of 45/45
University of Warwick MSc course 2007 Combined hormonal contraceptio n
  • date post

    27-Jun-2015
  • Category

    Documents

  • view

    527
  • download

    4

Embed Size (px)

Transcript of Combined hormonal contraception

  • 1. Combined hormonal contraception

2. Types

  • Oral (COC pill)
  • Transdermal
  • Vaginal ring
  • Injectable

3. History of COC

  • 1950Synthesis of norethisterone
  • 1956First human trials reported
  • 1961COC available in UK
  • 1963Synthesis of norgestrel

4. Composition of COCs

  • Ethinylestradiol 20 35 mcg
  • Progestogen

5. Constituents of COCs

  • Oestrogens
  • Ethinylestradiol
  • Mestranol
  • Progestogens
  • Norethisterone
  • Levonorgestrel
  • Norgestimate
  • Desogestrel
  • Gestodene
  • Drosperinone

6. Formulations

  • Monophasic
  • Phasic (biphasic, triphasic)
  • Everyday (ED)
  • Seasonale (four packets in a row)
  • Lybrel (continuous)

7. Pill use by age GB 2004/5 8. Failure ( first year unintended pregnancy % rates) 0.05 3 Lunelle 0.3 8 NuvaRing 0.3 8 Evra 0.3 8 COC/POP Perfect use Typical use Method 9. Mechanism of action

  • Inhibition of ovulation through suppression of the hypothalamic-pituitary-ovarian axis
  • Endometrial suppression
  • Thickening of cervical mucus

10. 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

11. Risks/benefits

  • Risks apply to a minority
  • Benefits apply to all

12. What women worry about

  • Infertility
  • Cancer

13. Expressing risk

  • Relative risk can be misleading and anxiety provoking for women
  • Use absolute risk

14. Annual deaths per million 15. Risks of VTE per 100,000 per year 16. 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

17. 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

18. Risk factors for arterial disease

  • Smoking, esp. > 15 cigs/day
  • Hypertension
  • Diabetes
  • Android obesity
  • FH arterial/venous thrombosis
  • Age
  • Hyperlipidaemia
  • Migraine

19. 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

20. 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.

21. 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

22. 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

23. 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

24. 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

25. Diabetes and COC

  • WHO4 if:
    • retinopathy
    • nephropathy
    • neuropathy
    • duration of diabetes > 20 years

26. Contraindications

  • Cardiovascular
  • Hepatic
  • Other

27. Cardiovascular disease

  • Hypertension: > 160/100
  • Ischaemic heart disease
  • Stroke
  • Valvular heart disease complicated by pulmonary hypertension, atrial fibrillation or infective endocarditis

28. Liver disease

  • Viral hepatitis: active
  • Cirrhosis
  • Benign tumours (adenoma)
  • Malignant tumours (hepatoma)
  • Acute hepatic porphyrias
  • Gallbladder disease: symptomatic or medically treated

29. Other contraindications

  • Pregnancy
  • Genital tract bleeding
  • Oestrogen-dependent tumours

30. COC and migraine

  • The following are WHO4:
  • Loss of part of visual field
  • Unilateral weakness/parasthesiae
  • Speech disturbance
  • Status migrainosus
  • The following are safe: blurred vision, photophobia, phonophobia and flashing lights affecting whole visual field

31. 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

32. Starting routines after pregnancy

  • Start the day after the 2 ndvisit/expulsion for medical abortion or the day after a surgical procedure (earliest recorded ovulation day 16)
  • Start in the 4 thweek after delivery (clotting factors still raised for up to 3 weeks; earliest recorded ovulation day 30)

33. 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

34. 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

35. Side effects: progestogen excess

  • dry vagina
  • sustained weight gain (increased appetite)
  • depression
  • loss of sexual drive
  • lassitude
  • acne/hirsutism
  • Change to more oestrogenic pill e.g. Ovysmen/Brevinor or to a less progestogenic pill e.g. Femodene or Marvelon

36. 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

37. 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

38. 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

39. Extended use

  • Tricycling/continuous use
  • Fewer withdrawal bleeds
  • Ovulation better suppressed
  • Fewer missed pills
  • Treatment for dysmenorrhoea and menorrhagia
  • Good for military

40. Evra 1

  • A flesh-coloured combined transdermal patch
  • ethinylestradiol 20g/norelgestromin 150g
  • 4.5 x 4.5 cm
  • patches last 7 days
  • worn for 3 weeks out of four
  • Launched in UK in 2003

41. 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

42. 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

43. NuvaRing1

  • A combined vaginal ring
  • made of ethylene vinylacetate
  • ethinylestradiol 15g/etonogestrel 120g
  • 5.4cm diameter
  • worn for 3 weeks out of 4
  • almost all have regular withdrawal bleeds

44. NuvaRing2

  • 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

45. Lunelle

  • A combined monthly injectable
  • medroxyprogesterone acetate 25mg/ estradiol cypionate 5mg
  • similar efficacy to COC
  • most have regular withdrawal bleeds