Often more prominent at the outset and largely due to oestrogen, these include: nausea and, rarely, vomiting; breast discomfort, fluid retention, headache (including increase in migraine), lethargy, abdominal discomfort, vaginal discharge or dryness. Depression may occur but most depression in pill users is not due to the contraceptive.
The above account gives rise to guidelines for use:
Absolute contraindications include:
• A personal history of thromboembolic venous, arterial or cardiac disease or severe or multiple risk factors for these
• Transient cerebral ischaemic attacks without headache
• Infective hepatitis, until 3 months after liver function tests have become normal, and other liver disease including disturbances of hepatic excretion, e.g. cholestatic jaundice, Dubin-Johnson and Rotor syndromes
• Migraine, if there is a typical aura, focal features, or if it is severe and lasts > 72 hours despite treatment, or is treated with an ergot derivative (use with caution is acceptable if there is no aura, focal features, or if it is controlled with a 5HTX receptor agonist)
• Carcinoma of the breast or of the genital tract, past or present
• Other conditions including: systemic lupus erythematosus, porphyria, following evacuation of a hydatidiform mole (until urine and plasma gonadotrophin concentrations are normal), undiagnosed vaginal bleeding.
Relative contraindications or uses with caution, include:
• Family history of venous thromboembolism, arterial disease or a known prothrombotic condition, e.g. factor V Leiden (pretreatment coagulation investigation is advised).
• Diabetes mellitus which may be precipitated or become more difficult to control (avoid if there are diabetic complications).
• Hypertension (avoid if blood pressure exceeds 160/100)
• Smoking > 40 cigarettes per day (15 cigarettes/day enhances the risks of circulatory disease (x 3), and constitutes an absolute contraindication for women over 35 years.
• Obesity (avoid if body mass index exceeds 39 kg/m2)
• Long-term immobility, e.g. due to leg plaster, confinement to bed
The increase in risk with increased duration of use is due to increasing age. The approaching menopause presents an obvious problem. Because cyclic bleeding will continue to occur under the influence of the drugs even after the natural menopause, the only way of deciding whether contraception can be permanently abandoned is by abandoning it (and using another technique) for 3 months annually to see if natural menstruation is resumed; or stop the combined pill for one month and measure LH/FSH concentration in the blood, which indicates the state of pituitary function.
Benefits additional to contraception
Side-effects are commonly assumed always to be unpleasant aspects of drug action, but they can sometimes also be pleasant.
The oestrogen-progestogen pill is associated with reduced risk of functional ovarian cysts and cancer, of endometrial cancer and of benign breast disease; there is a reduced risk of uterine fibroids and they bleed less; menses are regular and blood loss is not excessive; menses are accompanied by less premenstrual tension and dysmenorrhoea. When oestrogen is combined with the antiandrogen cyproterone acetate as the progestogenic agent 'Dianette', the combined pill is useful treatment for acne in young women.
• Pregnancy carries risk.
• Serious adverse effects of the combined pill are rare and 'several times a rare event is still a rare event'.14
• Precise figures on risk with current low-dose formulations are not available. The major studies, involving, e.g. 23 000 women, used higher dose formulations and cannot be repeatedly replicated (cost, logistics) to keep up with developments.
• Overall mortality amongst users (having low risk factors) is either unaffected or only slightly increased.
14 Guillebaud J1989 The pill. Oxford University Press. A general reference for all practical aspects of use.
Formulations of oestrogen-progestogen combination
Oestrogen: ethinylestradiol or mestranol Progestogen
• 2nd generation: norethisterone, levonorgestrel
• 3rd generation: desogestrel, gestodene, norgestimate
Combined oral contraceptives are defined as 2nd or 3rd generation by the progestogen component (1st generation progestogens are obsolete). Those containing a fixed amount of an oestrogen and a progestogen in each active tablet are termed 'mono-phasic'. Other pills employ variable ratios between oestrogen and progestogen, in 2 (biphasic) or 3 (triphasic) periods within the menstrual cycle. The dose of progestogen is low at the beginning and higher at the end, the oestrogen remaining either constant or rising slightly in mid-cycle. The objective is to achieve effective contraception with minimal distortion of natural hormonal rhythms. The advantages claimed for these techniques are diminished adverse metabolic changes, e.g. blood lipids, and a particularly reliable monthly bleeding pattern without loss of contraceptive efficacy. Preparations include BiNovum, TriNovum, Logynon.
It is now appreciated that the earlier preparations had much more oestrogen than was necessary for efficacy. It seems probable that 20 micrograms is about the limit below which serious loss of efficacy can be expected. Indeed in patients whose hepatic enzymes are likely to be induced, e.g. those taking antiepileptic or some antirheumatic drugs, it is advisable to use a preparation containing 50 micrograms or more of oestrogen to avoid loss of efficacy due to increased oestrogen metabolism (elimination of breakthrough bleeding is a guide to adequacy of dose).
Choice of oestrogen-progestogen combination
There is a wide choice of formulations:
• Low oestrogen (20 micrograms) plus low progestogen, e.g. Loestrin 20, Mercilon, Femodette
• Low oestrogen plus high progestogen, e.g. Ovran 30, Eugynon 30
• High oestrogen (50 micrograms) plus low or high progestogen, e.g. Ovran, Norinyl-1.
In general, users should be prescribed the lowest total hormone dose that suits them (good cycle control and minimal side-effects) and should make a start with the first preparation given above, recognising that compliance is particularly important with the 20 microgram dose.
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