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


CONCLUSIONS
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.
Division of Developmental Medicine, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK. gcl203@clinmed.gla.ac.uk
C A L
CA
Bain
M R
MR
Walters
K R
KR
Lees
M A
MA
Lumsden
D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D004338:Drug Combinations; D004394:Dydrogesterone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000502:physiology; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011674:Pulse; D014463:Ultrasonography; D014666:Vasomotor System / Q000187:drug effects*
D004338:Drug Combinations; D004958:Estradiol; D004394:Dydrogesterone; D009640:Norethindrone