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Use of cardiovascular age for assessing risks and benefits of menopausal hormone therapy

Santen, Richard J. MD

doi: 10.1097/GME.0000000000000847
Personal Perspective

The Women's Health Initiative studies and others have suggested that menopausal hormone therapy may enhance the risk of new cardiovascular (CV) events in older women and diminish the development of coronary atherosclerosis in younger women. The underlying mechanisms to explain these findings are encapsulated in the term “Timing Hypothesis.” Extensive pathophysiologic studies have provided mechanistic evidence for the dichotomous effects of estrogen on coronary artery vasculature. Early in the atherosclerotic disease process, estrogen exerts protective effects on the endothelium and retards plaque formation. Late in the process, estrogen causes plaque erosion or rupture with subsequent thrombosis and acute coronary events. Analysis of the Timing Hypothesis in women examined in the Women's Health Initiative primarily used chronologic age to assess divergent effects of estrogen. The complexity of the data underlying coronary pathophysiology has resulted in controversy whether MHT can be used in older women or those with prior CV disease. In a debate of this issue at a recent International Menopause Society meeting, the concept of using CV age rather than chronologic age was discussed as a practical method of resolving this issue and facilitating therapeutic decisions in older women. This “Personal Perspective” will review the concepts underlying CV age, describe how it is determined, provide support for its utility, and propose future studies using this parameter.

Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Virginia Health Sciences System, Charlottesville, VA.

Address correspondence to: Richard J. Santen, MD, University of Virginia Health Sciences System, PO Box 801416, 450 Ray S Hunt Drive, Rm 2313, Charlottesville, VA 22908-1416. E-mail:

Received 15 November, 2016

Revised 22 December, 2016

Accepted 22 December, 2016

Funding/support: None.

Financial disclosure/conflicts of interest: R.J.S. serves on the advisory boards for Sermonix Pharmaceuticals and Pfizer.

© 2017 by The North American Menopause Society.