Cholesterol-Related Compound Can Block Estrogen From Helping To Prevent Heart Disease

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A molecule related to cholesterol can block the hormone estrogenfrom performing functions in blood vessels that keep them healthy andprotected against heart disease, according to a study published Sundayonline in the October issue of the journal Nature Medicine, the Wall Street Journal reports.

For the study, David Mangelsdorf and colleagues at the University of Texas-Southwestern Medical Centeridentified the molecule 27-hydroxycholesterol, or 27HC, which is aby-product created as the body processes cholesterol. The researchersfound in experiments in mice that 27HC and estrogen target the samereceptors in blood vessels. According to the findings, estrogenattaches to the receptors when it is present in normal amounts and 27HCis low, which triggers functions that protect the heart. When estrogenlevels decrease -- as is typical during menopause -- 27HC can reach thereceptors before the estrogen and interrupt its ability to protect theheart, the researchers found.

Application to Women's Health Initiative Findings, Reaction

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According to the Journal, the findings could help explain why hormone replacement therapy failed to prevent heart disease in some participants of the NIH-sponsored Women's Health Initiative study (Winslow, Wall Street Journal, 9/17).

NIHresearchers in July 2002 ended the WHI study on combination HRT threeyears early because they determined that the treatment might increasethe risk for heart disease, invasive breast cancer and other healthproblems. A later WHI analysis, published in the April 4 issue of the Journal of the American Medical Association, found that HRT use among women in their 50s does not increase their risk for heart attack (Kaiser Daily Women's Health Policy Report, 7/24).

Women in the WHI started on estrogen at an average of 13 years after the onset of menopause, the Journalreports. Mangelsdorf said his findings indicate that during thatperiod, 27HC had taken over the estrogen receptors, prompting processesthat increased the risk of heart disease. "Estrogen is a protector,it's not therapeutic," Mangelsdorf said, adding, "You can't give it tocure something that's started."

Donald McDonell of Duke University's School of Medicine,who was not involved in the study, said the report "brings a newperspective" to the findings of the WHI study and a "very plausible(scenario) that has been tested out in the best (animal) models we haveavailable." It is also consistent with recent closer examination ofthat study, he added.

JoAnn Manson, a principal investigatorof WHI, said Mangelsdorf's study provides "intriguing" insight intoresults of WHI. Manson said she questioned a finding from the WHI studyin which women with high cholesterol tended to have worse outcomes onHRT than those with low cholesterol. Since high levels of 27HC reflecthigh levels of cholesterol in the blood, the new study supports thatresult, she said. "Their overall finding ties together very nicely withthe clinical-trial results," Manson, who is chief of preventivemedicine at Brigham and Women's Hospital, said, adding, "This could help fit pieces of the puzzle together" (Wall Street Journal, 9/17).

Reprinted with permission from kaisernetwork.org. You can view theentire Kaiser DailyWomen's Health Policy Report, search the archives, and sign up for emaildelivery at kaisernetwork.org/email. The Kaiser Daily Women's Health Policy Report is published for kaisernetwork.org, afree service of The Henry J. Kaiser Family Foundation.

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