Oral contraceptives--induced hypertension--nine years later

Abstract

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.

PIP: Overt hypertension, developing in about 5% of Pill users, and increases in blood pressure (but within normal limits) in many more is believed to be the result of changes in the renin-angiotensin-aldosterone system, particularly a consistent and marked increase in the plasma renin substrate concentrations. The mechanisms for the hypertensive response are unclear since normal women may demonstrate marked changes in the renin system. In in vitro testing, in which renin was added in a constant amount to the serum of patients with oral contraceptive-induced hypertension, the capacity to generate angiotensin 2 was found to increase linearly with increases in substrate levels. These responses were maintained as much as 2 or more times that of normal. In normal subjects plasma renin in "excess" is absent, suggesting the possibility of some regulation mechanism. The ef fect of the volume component on angiotensin secretion caused by the estrogens in oral contraceptives could further explain the Pill-induced hypertension. A failure of the kidneys to fully suppress renal renin secretion could thus be an important predisposing factor. These observations provide guidelines for the prescription of oral contraceptives. A baseline blood pressure measurement should be obtained, and blood pressure and weight should be followed at 2- or 3-month intervals during treatment. Oral contraceptive therapy should be contraindicated for individuals with a history of hypertension, renal disease, toxemia, or fluid retention. A positive family history of hypertension, women for whom long-term therapy is indicated, and groups such as blacks, especially prone to hypertensive phenomena, are all relative contraindications for the Pill.