Oral contraceptive prescribing

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Oral contraceptive prescribing
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• clinical pharmacology
• mechanism of action
• ADME
• interactions
• adverse reactions
• benefits and harms

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what are they

• around since late 1950s
• social revolution
• progestogen /oestrogen
• variety of components and doses
• changes over time in both

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components

• oestrogen
• ethinyoestradiol
• mestranol

• progestogen
• norethisterone
• norgestrel
• Levonorgestrel
• medroxyprogesterone
• ethynodiol diacetate
• gestodene
• desogestrel

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doses

• monophasic
• oestrogen - up to 50?g/day
• progestogen - up to 1mg/day
• biphasic
• oestrogen constant
• progestogen eg 11 days _at_50, 10 _at_125 ?g
• triphasic
• oestrogen 30/40/30
• progestogen 50/75/125

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clinical pharmacology

• mechanism of action
• inhibit secretion of FSH, LH - inhibit ovulation
• additional actions on endometrium tubal motility,
  cervical mucosa

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clinical pharmacology

• absorption
• well absorbed orally
• distribution
• bound to plasma proteins
• albumin, SBG, others

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metabolism

• Oestrogens
• first pass clearance
• metabolised in liver, conjugated
• excreted in the bile - (estradiol vs EE)
• enterohepatic circulation
• Progestogens
• depends on which one - natural progestogen
  extensive first pass metabolism

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excretion

• urinary
• remember the bile duct

STO
HV
PV
CBD
About 40-60 of estrogen removed in the first
pass through the liver HMW conjugates are
excreted in bile
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interactions (1)

• antibiotics
• impaired absorption (effect on gut enzymes)
  reduced bacterial sulfatase leading to reduced
  entero-hepatic recycling
• enzyme induction -gt increased clearance, lower
  plasma estrogen concentrations (eg rifampicin,
  griseofulvin, anticonvulsants, St Johns Wort)

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interactions (2)

• anticonvulsants
• Older drugs are enzyme inducers -gt increased
  clearance and reduced concentration and failure
  (phenytoin, phenobarbitone, primidone,
  carbamazepine). No effect of sodium valproate
• Newer drug have variable effects (no change with
  gabapentin, lamotrigine, tiagabine,
  levetiracetam) (induction with topiramate and
  oxcarbazepine)
• try higher dose estrogen pills, double product
  dosing
• valproate less of a problem

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adverse reactions

• estrogen excess
• late cycle breakthrough bleeding
• menorrhagia/dysmenorrhoea
• nausea/vomiting
• fluid retention
• breast tenderness

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adverse reactions

• progestogen excess
• amenorrhoea
• acne/oily skin
• weight gain
• mood changes
• depressed libido
• breast tenderness

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other risks

• thromboembolic disorder
• high dose oestrogen - Inman, dose response
  relationship
• worse with other risk factors (age, smoking)
• ?third generation progestogens
• differentiating effects on VTE and other
  cardiovascular disease

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big picture risks

• endometrial cancer
• progestogen is protective
• ovarian cancer
• protective
• breast cancer
• jury out /data unconvincing
• cervical cancer
• confounded

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other benefits

• reduction in menstrual flow - may lower incidence
  of anemia
• reduction in dysmenorrhoea
• possible reduction in auto-immune thyroid
  disease, rheumatoid arthritis
• some protection against PID

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risk of nonfatal VTE
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other issues

• compliance
• gastro.
• missing pills
• alternative forms of hormonal contraception

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balance sheet

• benefits
• effective contraception
• other health benefits
• long-term health and social impact

• harms
• immediate adverse effects
• risk of failure
• long-term health effects

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other uses

• morning after pill
• EE 100mcg norgestrel 1mg within 72 hours, 2
  doses
• Failure rate of about 1