Postmenopausal hormone replacement therapy in hypertensive women: is it time for a change in attitude?

Abstract

For many years postmenopausal oestrogen replacement therapy was considered to be relatively contraindicated in women with hypertension. This reticence to use oestrogen or other forms of hormone replacement therapy (HRT) appears to stem from the experience with contraceptive dose oestrogen. The higher doses used in the oral contraceptive pill do appear to raise blood pressure among users by about 3-5%, 1 although the blood pressure normally remains within the normal range. Rarely however, some women develop severe hypertension with endorgan damage. Epidemiological evidence suggests that the menopause itself, independent of increasing age, is associated with an elevation of diastolic blood pressure by 2-3 mm Hg and an increase in the year by year rate of rise of systolic blood pressure. 2 Furthermore, it is not possible to extrapolate the effects of high dose contraceptive oestrogen to the physiological doses used in postmenopausal HRT. Why should HRT effect blood pressure?Hypertension is characterised to a varying degree by abnormal vasoconstriction, salt and water retention and impaired endothelial function. Numerous investigators have now documented the vasodilatory effects of 17-␤ oestradiol both in vivo and in vitro. 3,4 This vasodilatory effect appears to effect both the peripheral, uterine and coronary circulations and is sufficient in magnitude to bring about anti-anginal benefits for women with coronary artery disease. 5 The predominant mechanism appears to be restoration of impaired endothelial function, with paradoxical acetyl-choline induced vasoconstriction being restored to a normal vasodilatory pattern. This has been documented in the peripheral circulation utilising forearm blood flow studies and also in female coronary arteries during cardiac catheterisCorrespondence: Dr Guy Lloyd Received and accepted 9 December 1997 ation. 3,4 Aside from increased nitric oxide release, in vitro models provide evidence for more than a single mechanism of action. Investigations using preconstricted rabbit coronary artery segments have demonstrated that even when the endothelium is denuded, vasodilation continues to occur and a calcium antagonist effect has been proposed. 6 Oestradiol also antagonises the effects of endothelin-1, a potent vasoconstrictor 7 substance whose metabolism is deranged in hypertensive patients. Oestradiol, especially in contraceptive doses, exerts a mineralocorticoid effect thus promoting sodium and water retention, however to offset this effect circulating plasma angiotensin-converting enzyme activity has been demonstrated to be lower among users of HRT. 8 Oestrogen therapy has been demonstrated to increase aortic compliance and distensability providing a mechanism by which the course of systolic hypertension, prevalent in post-menopausal women might be influenced. 9 A further mechanism whereby oestrogen could effect blood pressure is through the sympathetic nervous system, an association which is mediated both centrally and at the level of the catecholamine receptor. This modulation of a...