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

Hum Reprod. 2004 Oct;19(10):2411-4. doi: 10.1093/humrep/deh396. Epub 2004 Jul 29.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Flow Velocity / drug effects
  • Blood Pressure / drug effects
  • Carotid Artery, Internal / diagnostic imaging
  • Carotid Artery, Internal / drug effects
  • Carotid Artery, Internal / physiology
  • Cerebrovascular Circulation / drug effects*
  • Double-Blind Method
  • Drug Combinations
  • Dydrogesterone / administration & dosage
  • Dydrogesterone / adverse effects*
  • Dydrogesterone / therapeutic use
  • Estradiol / administration & dosage
  • Estradiol / adverse effects*
  • Estradiol / therapeutic use
  • Estrogen Replacement Therapy / adverse effects*
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Middle Aged
  • Middle Cerebral Artery / diagnostic imaging
  • Middle Cerebral Artery / physiology
  • Norethindrone / administration & dosage
  • Norethindrone / adverse effects*
  • Norethindrone / therapeutic use
  • Pulse
  • Ultrasonography
  • Vasomotor System / drug effects*

Substances

  • Drug Combinations
  • Estradiol
  • Dydrogesterone
  • Norethindrone