The effect of HRT on cerebral haemodynamics and cerebral vasomotor reactivity in post-menopausal women

Abstract

Background: Cerebral vasomotor reactivity (CVR) is an index of cerebrovascular dilatory capacity which can readily be assessed using trans-cranial Doppler ultrasound. Impaired CVR is associated with elevated risk of stroke. We performed a randomized, double-blind placebo-controlled trial to investigate the effect of two HRT preparations upon CVR. Methods: We examined middle cerebral artery mean flow velocity (MFV), internal carotid artery pulsatility index (PI) and CVR to an i.v. acetazolamide bolus using ultrasound in three groups of post-menopausal women randomized to oral estradiol 1 mg + norethisterone 0.5 mg (group N), estradiol 1 mg + dydrogesterone 5 mg (group D) or placebo (group P). The MFV, PI and CVR were measured before and after 3 months treatment. Results: Thirty-eight post-menopausal women were recruited (N = 12, D = 14, P = 12); mean (SE) age was 56.7 (4) years. Neither HRT preparation affected CVR [% (SE) change from baseline N + 4.2 (11); D + 3.8 (5.5); P + 4.0 (3.8); all comparisons P = NS]. PI was significantly reduced in recipients of dydrogesterone [% (SE) change from baseline D - 5.4% (4.6); N + 12.3 (6.9); P + 11.6 (6.9). P = 0.025]. Middle cerebral artery velocity was significantly increased following dydrogesterone treatment compared with placebo [% (SE) change from baseline D + 6.8 (3.4) N + 3.9 (4.2) P - 4.6% (3.4) P = 0.03 for D versus P]. Conclusion: HRT did not alter CVR. The reduced PI and increased MFV suggest HRT-induced intracranial vasodilatation, which is more apparent in dydrogesterone recipients. Differences may exist between progestogens with regard to changes in intracranial haemodynamics. © European Society of Human Reproduction and Embryology 2004; all rights reserved.