Effect of a gonadotropin releasing hormone analog on cerebral hemodynamics in premenopausal women

Abstract

Background Impaired reactivity of cerebral blood vessels is associated with increased risk of stroke. Female sex hormones have vasoactive effects in a number of vascular beds but their effects upon the cerebral circulation are not well understood. Ultrasound techniques allow us to examine the ability of intracranial vessels to dilate in response to a pharmacological stimulus (the carbonic anhydrase inhibitor acetazolamide). We studied intracranial hemodynamics in a group of premenopausal women before and after induction of a temporary hypoestrogenic state.Methods We examined middle cerebral artery mean flow velocity, common and internal carotid artery pulsatility index and cerebrovascular reactivity to acetazolamide (CVR) in a group of women undergoing treatment for menstrual disorders. Volunteers underwent ultrasound examination during the follicular phase of the menstrual cycle and after completing treatment with gonadotropin releasing hormone (GnRH, goserelin 3.6 mg) administered subcutaneously every 28 days for 12 weeks. The study was conducted in a prospective, single-blind fashion and analyzed using parametric comparisons of means to examine change in intracranial hemodynamic parameters between pre- and postmenopausal states.Results Twelve premenopausal women aged 37.2 ± 7 years and without overt vascular disease completed the protocol. GnRH reduced serum estrogen concentration (215.6 ± 122 pg/ml vs. 82.4 ± 12 pg/ml, p = 0.0047) but this was not associated with a change in CVR (145 ± 19% and 146 ± 14% for follicular and post-GnRH studies, respectively (p = 0.6). No significant changes in blood pressure, internal carotid or middle cerebral artery pulsatility or mean flow velocity were observed between time points.Conclusion Neither resting cerebral hemodynamics nor reactivity of cerebral resistance vessels to a potent vasodilatory stimulus changed when the circulating concentration of estradiol was artificially decreased using a GnRH agonist. Induction of a hypoestrogenic state does not appear to influence cerebral vasodilatory capacity in the short term.