1. Oral contraceptive prescribing

2. clinical pharmacology
mechanism of action
ADME
interactions
adverse reactions
benefits and harms

3. what are they around since late 1950’s social revolution
progestogen /oestrogen
variety of components and doses
changes over time in both

4. components oestrogen progestogen ethinyoestradiol mestranol
norethisterone
norgestrel
Levonorgestrel
medroxyprogesterone
ethynodiol diacetate
gestodene
desogestrel

5. doses monophasic biphasic triphasic oestrogen - up to 50g/day
progestogen - up to 1mg/day
biphasic
oestrogen: constant
progestogen: eg 11 g
triphasic
oestrogen 30/40/30
progestogen 50/75/125

6. clinical pharmacology
mechanism of action
inhibit secretion of FSH, LH - inhibit ovulation
additional actions on endometrium tubal motility, cervical mucosa

7. clinical pharmacology
absorption
well absorbed orally
distribution
bound to plasma proteins
albumin, SBG, others

8. metabolism Oestrogens Progestogens 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

9. excretion urinary remember the bile duct STO HV PV CBD
About % of estrogen removed
in the first pass through the liver
HMW conjugates are excreted in bile

10. interactions (1) antibiotics
impaired absorption (effect on gut enzymes) reduced bacterial sulfatase leading to reduced entero-hepatic recycling
enzyme induction -> increased clearance, lower plasma estrogen concentrations (eg rifampicin, griseofulvin, anticonvulsants, St John’s Wort)

11. interactions (2) anticonvulsants
Older drugs are enzyme inducers -> 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

12. adverse reactions estrogen excess late cycle breakthrough bleeding
menorrhagia/dysmenorrhoea
nausea/vomiting
fluid retention
breast tenderness

13. adverse reactions progestogen excess amenorrhoea acne/oily skin
weight gain
mood changes
depressed libido
breast tenderness

14. 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

15. big picture risks endometrial cancer ovarian cancer breast cancer
progestogen is protective
ovarian cancer
protective
breast cancer
jury out /data unconvincing
cervical cancer
confounded

16. 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

17. risk of nonfatal VTE

18. other issues compliance gastro. missing pills
alternative forms of hormonal contraception

19. balance sheet benefits harms effective contraception
other health benefits
long-term health and social impact
harms
immediate adverse effects
risk of failure
long-term health effects

20. other uses morning after pill
EE 100mcg + norgestrel 1mg within 72 hours, 2 doses
Failure rate of about 1%