Oral contraceptives--induced hypertension--nine years later.

Nine years have gone by since oral contraceptive hypertension was first recognized as a clinical entity. In that time it has become apparent that what at first was thought to be a rare disorder is extremely common. Indeed, overt hypertension develops, in time, in about 5 per cent of Pill users. Increases in blood pressure, albeit within the normal range, are still more common. Pill hypertension may develop gradually. It is sometimes quite severe, and it is characteristically reversible within a few months after therapy is stopped. Oral contraceptives produce changes in the renin-angiotensin-aldosterone system, particularly a consistent marked increase in the plasma renin substrate concentration which may be associated with increases in plasma renin activity and aldosterone excretion. The estrogenic component of contraceptive pills appears to be the more important factor in producing abnormalities in the renin system. The mechanisms for the hypertensive response are not entirely clear since normotensive women using the pill may exhibit similar or even more marked changes in the renin axis. The pressor response could have both volume and vasoconstrictor components mediated by the sodium-retaining effects of the estrogen in the presence of a relatively, if not an absolutely, higher plasma renin activity, with the latter being held abnormal by the high plasma renin-substrate levels. A failure of the kidneys to fully suppress renal renin secretion could thus be an important predisposing factor. Our in vitro experiments support the idea that the increased substrate is involved in pathogenesis because they indicate that in normal subjects plasma renin substrate is not present in "excess". Thus, a doubling of the physiologic levels of substrate by oral contraceptives leads to an almost twofold increase in the capacity for angiotensin production as indicated by studies of the initial reaction velocity. These observations define certain guidelines for applying oral contraceptive therapy. At least one base-line blood pressure measurement should be obtained, and blood pressure and weight should be followed a two- or three-month intervals during treatment. Furthermore, oral contraceptive therapy may be contraindicated in women with a history of hypertension, renal disease, toxemia, or fluid retention. Others in whom oral contraceptives are relatively contraindicated include those with a positive family history of hypertension, younger women in whom a longer term commitment is likely, and groups, such as blacks, especially prone to hypertensive phenomena.