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Subsequent fertility. After stopping the pill, fertility that is normal for the age the woman has now reached is restored, although conception may be delayed for a few months longer in younger and as much as a year in older users than if other methods had been used.

Effect on an existing pregnancy. Although progestogens can masculinise the female fetus, the doses for contraception are so low that risk of harming an undiagnosed pregnancy is extremely low, probably less than 1 in 1000 (the background incidence of birth defects is 1-2%).

Carcinoma of the breast and cervix may be unaffected or very slightly increased in incidence; hepatoma (very rare) is increased. The risk to life seems to be less than that of moderate smoking (10 cigarettes/day). Carcinoma of the ovary and the endometrium are substantially reduced. Total incidence of cancer is unaltered.

Effect on menstruation (it is not true menstruation, see above) is generally to regularise it, and often to diminish blood loss, but amenorrhoea can occur. In some women 'break-through' intermenstrual bleeding occurs, especially at the outset, but this seldom persists for more than a few cycles. Premenstrual tension and dysmenorrhoea are much reduced.

Libido is greatly subject to psychosocial influences, and removal of fear of pregnancy may permit enthusiasm for the first time. It is likely that direct pharmacological effect (reduction) is rare. There is evidence that the normal increase in female-initiated sexual activity at time of ovulation is suppressed.11

Cardiovascular complications. Incidence of venous thromboembolism is increased in pill users. It is lowest in the 20-35 microgram pill and rises progressively with the 50 microgram and 100 microgram preparations; it is not known if there is any difference between doses of 20-35 micrograms. The small increase in hypertension, cerebrovascular event and acute myocardial infarction is principally confined to smokers.

Increased arterial disease also appears to be associated with the type of progestogen in the combined pill. The '3rd generation' pills (see later) appear to carry a higher risk of venous thrombosis,12 but may have a lower risk of arterial thrombosis because their lower androgen activity leads to slightly higher HDL levels than older pills.13 The progestogen-only pill does not significantly affect coagulation.

Major surgery (in patients taking oestrogen-progestogen contraceptives and postmenopausal hormone replacement therapy). Because of the added risk of venous thromboembolism (surgery causes a fall in antithrombin) it has been advised that these oral contraceptives should be withdrawn, if practicable, 4 weeks before all lower limb operations or any major elective surgery (and started again at the first menstruation to occur more than 2 weeks after surgery). But increase in clotting factors may persist for many weeks and there is also the risk of pregnancy to be considered (plainly, alternative contraception should be used). An

11 Adams D B et al 1978 New England Journal of Medicine 299:1145.

12 Estimated to be 30 thromboembolic episodes per 100 000 women taking the pill compared with 15 per 100 000 with 2nd generation pills (the background rate is 8 per 100 000).

13 Spitzer W O et al 1996 Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. British Medical Journal 312: 83-88.

alternative for emergencies is to use low molecular weight heparin (though this may not reverse all the oestrogen effects on coagulation) and other means (mechanical stimulation of venous return) to prevent postoperative thrombosis. A similar problem arises with prolonged immobilisation from other causes.

Hepatic function may be impaired as may drug-metabolising capacity (t]/2 of antipyrine, a general indicator of the drug-metabolising capacity, may increase by 30%). Gallbladder disease is more common, and highly vascular hepatocellular adenomas occur (rare).

Cervical ectropion (erosion) incidence is double (it is a harmless condition).

Crohn's disease is more frequent.

Decreased glucose tolerance occurs, perhaps due to a peripheral effect reducing the action of insulin.

Plasma lipoproteins may be adversely affected; least where the progestogen is desogestrel or low-dose norethisterone.

Plasma proteins. Oestrogens cause an increase in proteins, particularly the globulins that bind hydrocortisone, thyroxine and iron. As a result, the total plasma concentration of the bound substances is increased, though the concentration of free and active substance remains normal. This can be misleading in diagnostic tests, e.g. of thyroid function. This effect on plasma proteins passes off about 6 weeks after cessation of the oestrogen.

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