A Textbook of Clinical Pharmacology and Therapeutics

310 REPRODUCTIVE ENDOCRINOLOGY
disease, severe hypertension, migraine with focal
neurological symptoms, severe liver disease, porphyria,
otosclerosis, breast or genital tract carcinoma,
undiagnosed vaginal bleeding and breast-feeding.
• Relative contraindications: uncomplicated migraine,
cholelithiasis, hypertension, dyslipidaemia, diabetes
mellitus, varicose veins, severe depression, long-term
immobilization, sickle-cell disease, inflammatory bowel
disease.
Key points
Combined oral contraceptive (COC) – absolute
contraindications
• pregnancy;
• thrombo-embolism;
• multiple risk factors for arterial disease;
• ischaemic heart disease;
• severe hypertension;
• otosclerosis;
• breast or genital carcinoma;
• undiagnosed vaginal bleeding;
• breast-feeding;
• porphyria.
Drug interactions with the COC
Oestrogens increase clotting factors and reduce the efficacy of
oral anticoagulants. This is not a contraindication to their continued
use in patients to be started on warfarin (in whom pregnancy
is highly undesirable), but it is a reason for increased
frequency of monitoring of the international normalized ratio
(INR).
Antihypertensive therapy may be adversely affected by
oral contraceptives, at least partly because of increased circulating
renin substrate.
Enzyme inducers (e.g. rifampicin, carbamazepine, phenytoin,
nelfinavir, nevirapine, ritonavir, St John’s wort) decrease
the plasma levels of contraceptive oestrogen, thus decreasing
the effectiveness of the combined contraceptive pill. Breakthrough
bleeding and/or unwanted pregnancy have been
described.
Oral contraceptive steroids undergo enterohepatic circulation,
and conjugated steroid in the bile is broken down by bacteria
in the gut to the parent steroid and subsequently reabsorbed.
Broad-spectrum antibiotics (e.g. amoxicillin, tetracycline) alter
colonic bacteria, increase faecal excretion of contraceptive oestrogen
and decrease plasma concentrations, resulting in possible
contraceptive failure. This does not appear to be a problem with
progestogen-only pills.
POST-COITAL CONTRACEPTION
Post-coital contraception (the ‘morning-after’ pill) consists of
1.5 mg levonorgestrel, given as soon as possible, preferably
within 12 hours and no later than 72 hours after unprotected
intercourse. This prevents approximately 84% of expected
pregnancies. If vomiting occurs within three hours of ingestion,
the dose should be repeated. A single dose of mifepristone (a
progesterone antagonist) is highly effective. The
abortion statistics suggest that post-coital contraception is
under-utilized in the UK.
Key point
Post-coital contraception
Levonorgestrel 1.5 g as a single dose as soon as possible,
preferably within 12 hours of, and no later than 72 hours
after, unprotected sexual intercourse.
PROGESTOGEN-ONLY CONTRACEPTIVES
Progestogen-only contraception is available as an oral pill, a
depot injection administered every 12 weeks, a single flexible
rod implanted subdermally into the lower surface of the upper
arm which lasts up to three years and as an intra-uterine device.
The single flexible rod implant releases etonogestrel. The
intra-uterine device (IUD) releases levonorgestrel directly into
the uterine cavity and is licensed for use as a contraceptive and
for the treatment of primary menorrhagia, as well as prevention
of endometrial hypoplasia during oestroegen replacement
therapy. This IUD can be effective for up to five years.
Uses
Progestogen-only contraceptive pills (e.g. norethisterone,
norgestrel) are associated with a high incidence of menstrual
disturbances, but are useful if oestrogen-containing pills are
poorly tolerated or contraindicated (e.g. in women with risk
factors for vascular disease such as older smokers, diabetics or
those with valvular heart disease or migraine) or during
breast-feeding. Contraceptive effectiveness is less than with
the combined pill, as ovulation is suppressed in only approximately
40% of women and the major contraceptive effect is on
the cervical mucus and endometrium. This effect is maximal
three to four hours after ingestion and declines over the next
16–20 hours, so the pill should be taken at the same time each
day, preferably three to four hours before the usual time of
intercourse. Pregnancy rates are of the same order as those
with the intra-uterine contraceptive device or barrier methods
(approximately 1.5–2 per 100 women per year, compared to
0.3 per 100 women per year for the COCs). Progestogen-only
pills are taken continuously throughout the menstrual cycle,
which is convenient for some patients.
Depot progesterone injections are more effective than oral
preparations. A single intramuscular injection of medroxyprogesterone
acetate provides contraception for ten weeks
with a failure rate of 0.25 per 100 women per year. It is mainly
used as a temporary method (e.g. while waiting for vasectomy
to become effective), but is occasionally indicated for long-term
use in women for whom other methods are unacceptable. The
side effects are essentially similar to those of oral progestogenonly
preparations. After two years of treatment up to 40% of
women develop amenorrhoea and infertility, so that pregnancy
is unlikely for 9–12 months after the last injection.