Long Term Effects of Menopausal Hormone Therapy on Cerebral Pulsatility Index

Abstract

Menopausal hormone therapy (MHT) is used for management of menopausal symptoms; however, the long-term effects of MHT on the cardiovascular and cerebrovascular system are controversial. Previous studies have shown that pulsatility index (a measure of the variability of blood velocity in a vessel) of the middle cerebral artery (MCA) decreases during the use of MHT, but increases again within months after suspension of MHT; however, these effects have not been studied long term. PURPOSE: The purpose of this study was to evaluate the long term effects of prior use of MHT on MCA pulsatility index (PI). METHODS: Fifty-four postmenopausal women were evaluated 3 years after cessation of use of MHT or placebo (as part of a 4 year randomized, placebo-controlled clinical trial). Women had received either a placebo (PLA: n=19; age=59±3 y; BMI=28±3 kg/m2) or MHT (MHT: n=35; age=60±3 y; BMI=27±5 kg/m2). MCA velocity (MCAv), mean arterial pressure (MAP), and end-tidal CO2 were continuously measured throughout the study. Baseline measurements were recorded then women underwent a stepped hypercapnic protocol inhaling 2%, 4%, then 6% CO2 at each stage for three minutes. PI was calculated as (systolic MCAv-diastolic MCAv)/mean MCAv. RESULTS: Baseline MAP and MCAv were similar between groups (PLA: MAP=90±2 mmHg; MCAv=60±3 cm/s; MHT: MAP=91±1 mmHg; MCAv=69±3 cm/s; p>0.05 for both). PI was greater in the MHT group compared to the placebo group at baseline (MHT: PI=0.86±0.02 vs. PLA: PI=0.77±0.02; p<0.05), during 2% CO2 (MHT: PI=0.85±0.02 vs. PLA: PI=0.76±0.02; p<0.05), and during 4% CO2 (MHT: PI=0.82±0.02 vs. PLA: PI=0.73±0.02; p<0.05). PI was not different between groups during 6% CO2 (MHT: PI=0.75±0.02; PLA: PI=0.71±0.02; p=0.28). CONCLUSIONS: Cerebral PI was higher in women who had taken MHT compared to women who had not taken MHT. The differences between groups persisted until the CO2 vasodilatory stimulus increased to 6%. Taken together, these results suggest that previous use of MHT alters regulation of the cerebral circulation that has effects at least up to three years after cessation. Supported by NIH grant AG44170, HL118154