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FOR MANY WOMEN, STOPPING HORMONE REPL ACEMENT THER APY HRT MAY INVOLVE SIGNIFICANT MEDICAL RISK, RECENT RESE ARCH HA S FOUND. " We hope the main reason for women to discontinue [hormone replacement therapy] is that they don't need it anymore. However, due to the fear of using HRT, many women ... annually or biannually try to manage without HRT." TOMI MIKKOLA, MD, ASSOCIATE PROFESSOR OF OBSTETRICS AND GYNECOLOGY AT HELSINKI UNIVERSITY HOSPITAL Assessing the Risk of Ending Hormone Replacement Therapy H R T C A N R E L I E V E menopause symptoms such as vag ina l dr yness, hot f lashes and difficulty sleeping. However, many women stop treatment to avoid increasing their risk of conditions including uterine cancer, breast cancer and deep vein thrombosis. That decision may involve dangers of its own. A recent Finnish study observed more than 332,000 women age 40 and older who had discontinued HRT between 1994 and 2009. It found significantly higher risk for cardiovascular death within the first year following HRT cessation, as well as increased likelihood of death due to stroke in the first year post-treatment. Both cardiovascular and stroke death risk decreased after one year. Women who discontinued HRT before age 60 were at even higher risk for cardiac mortality. The observational study cannot demonstrate clear cause and e„ect, says Tomi Mikkola, MD, Associate Professor of Obstetrics and Gynecology at Helsinki University Hospital and lead author of the study, published in The Journal of Clinical Endocrinology & Metabolism. There are several possibilities, however. "Estrogen has rapid vasodilatory e„ects in the coronary and carotid arteries mediated by va sodi lator y a gents, such a s nitric oxide a nd prostacyclin," Dr. Mikkola says. "Estrogen also inhibits the release of endothelin-1, the most potent vasoconstrictor. Therefore, estrogen withdrawal, as in discontinuation of HRT, may result in arterial constriction. This could endanger adequate coronary circulation, for example in women with unstable angina. These changes may result in potentially fatal myocardial infarction. Furthermore, women with vasomotor hot flashes also frequently report palpitations or arrhythmias. Since HRT prevents vasomotor hot flashes and palpitations, HRT withdrawal could predispose some women to fatal arrhythmias." RETHINKING THE APPROACH According to Dr. Mikkola, the research has additional implications for women who cease HRT, restart treatment because of recurring menopause symptoms, then stop it again due to fear of side e„ects. A broad spectrum of research supports careful use of HRT, he adds. "Several observational studies, randomized controlled trials and meta-analyses indicate that when initiated close to menopause, HRT reduces mortality," he says. Howard N. Hodis, MD, Harry J. Bauer and Dorothy Bauer Rawlins Professor of Cardiology, Professor of Medicine and Preventive Medicine, Molecular Pharmacology and Toxicology, and Director of the Atherosclerosis Research Unit at the Keck School of Medicine at the University of Southern California, is troubled by what he sees as irrational fear of HRT. "The pain and su„ering many women endure because they are scared or their doctor is scared need to stop ...," Dr. Hodis says. "These drugs are safe. The risks are no greater than any other drugs we use." ■ The Peril of Quitting: BY MELISSA MOORE SPECIAL CLINICAL SECTION: WOMEN'S HEALTH 2 0