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Acute and Chronic Effects of Hormone Replacement Therapy on the Cardiovascular System in Healthy Postmenopausal Women

Faculty of Physical Education and Health (L.D.K., S.G.T., J.M.G.), Department of Obstetrics and Gynecology (H.M.S.), Cardiac Prevention Centre and Women’s Cardiovascular Health, St. Michael’s Hospital (B.L.A.), University of Toronto, Toronto, Ontario M5S 2W6, Canada; and Department of Obstetrics and Gynecology, Columbia University Medical School (N.J.M.), New York, New York 10032

Address all correspondence and requests for reprints to: Dr. Jack M. Goodman, Ph.D., Faculty of Physical Education and Health, University of Toronto, 55 Harbord Street, Toronto, Ontario M5S 2W6, Canada. E-mail: jack.goodman{at}utoronto.ca.

Previous studies have shown that conjugated estrogens and continuous medroxyprogesterone increases heart disease risk in healthy women. Little is known about the effects of the natural ovarian hormones estradiol and progesterone on cardiovascular function at rest and exercise. The purpose of this study was to investigate the short- and longer-term effects of a cyclic format of hormone replacement therapy (HRT) (1 mg estradiol daily with cyclic micronized progesterone, 200 mg for 10 d/month) on cardiovascular function at rest and during exercise in healthy, postmenopausal women. A double-blind, cross-over study was conducted in 31 patients. Peak oxygen uptake and ventilatory threshold in addition to submaximal cardiac output were determined. Peripheral measures of resting and peak ischemic blood flows were also determined. Measurements were made at baseline, after 4 h of estrogen/placebo exposure, and subsequently after 1, 2, and 3 months. The sequence of data collection was repeated after 6-wk washout. Oral estradiol with cyclic micronized progesterone increases peak ischemic peripheral blood flow chronically but fails to improve exercise tolerance and peak oxygen uptake. Similarly, submaximal central cardiovascular function is unaffected by HRT. This suggests that estradiol has a beneficial effect on peripheral blood flow, but this benefit offers little advantage in terms of peak exercise performance after 3 months of HRT.

This work was supported by the Heart and Stroke Foundation of Ontario Grant NA3367.

Abbreviations: avO2 diff, Arteriovenous oxygen difference; BF, blood flow; CAD, coronary artery disease; ERT, estrogen replacement therapy; G, vascular conductance; HRT, hormone replacement therapy; MAP, mean arterial pressure; MP, micronized progesterone; Q, cardiac output; SV, stroke volume; VCO₂, ventilatory equivalent for carbon dioxide; VO₂, oxygen uptake; VO₂peak, peak oxygen consumption; VT, ventilatory threshold.

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