Hormone therapy is all in the timing
After years of frightening findings on hormone therapy, new research suggests that there is a “window of opportunity” near menopause during which estrogen therapy may actually reduce heart disease risk -- not raise it, as starting hormones a decade or so later seems to do.
This makes good biological sense.
“Estrogen slows the early stages of arterial disease,” said Dr. Jacques Rossouw, project officer for the Women’s Health Initiative, a study of 27,000 women age 50 to 79 run by the National Heart, Lung and Blood Institute and published in a series of articles beginning in 2002.
But starting hormones later, say in a woman’s mid-60s, when arteries inevitably become more clogged with plaque, may be dangerous.
“We know now from trials and angiographic studies [of blood vessel walls] that women who already have arterial disease, if you give them hormones, you do them no good and may increase the risk” of heart disease, he said.
“We have come full circle on this,” said Dr. Hunter Champion, a cardiologist at the Johns Hopkins School of Medicine. “It’s not one size fits all” with hormone therapy.
It’s increasingly clear that “a woman’s age, or more specifically, the time since menopause, is an important factor in terms of heart outcomes on hormone therapy,” said Dr. JoAnn Manson, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital.
The idea that starting hormones early can be beneficial was bolstered by two new studies, one published in the Feb. 13 issue of the Archives of Internal Medicine and the other published in the January issue of the Journal of Women’s Health. Two more studies -- one called KEEPS by the Kronos Longevity Research Institute and the other, ELITE (Early versus Late Intervention with Estradiol) sponsored by the National Institute on Aging -- are enrolling women close to the age of menopause to further explore the issue.
In the Feb. 13 study, researchers focused on the youngest women (age 50 to 59) in the part of the Women’s Health Initiative involving women with hysterectomies who took estrogen alone, without progestin, the hormone needed to protect the uterus in women who still have one. Even in the original analysis of this group in 2004, these women had no increased cardiac risk. The new study went further, showing a clear benefit in these women.
In this group, there was a 45% lower rate of cardiac bypass surgery or angioplasty (a technique for opening clogged arteries) in those on estrogen versus those on placebo, and a 34% lower rate of fatal or nonfatal heart attack, bypass or angioplasty.
(For the record, it was in the other part of the 2002 Women’s Health Initiative -- on nearly 17,000 women age 50 to 79 taking both estrogen and progestin -- that researchers found the hormone therapy linked to a modest increase in heart disease, as well as breast cancer, stroke and blood clots. That study panicked millions of women into giving up their hormones, even though the increased cardiac risk was principally in the first year of combined hormone use, and the risk tapered off with time.)
The other recent study involved a different group of women, those participating in the Nurses’ Health Study. This study showed that women who started taking hormones within four years of menopause had a 30% lower risk of heart disease than women who never used hormones. This was true whether a woman took estrogen alone or with progestin, said Manson, an author on both studies.
“It all relates to the underlying stage of atherosclerosis,” said Manson. Estrogen slows development of atherosclerosis in several ways. It decreases “bad” (LDL) cholesterol and raises “good” (HDL). It makes blood vessels more elastic, allowing them to dilate better, which increases blood flow. But in older women who already have plaques on artery walls, estrogen can increase the likelihood of blood clots or plaque ruptures that can trigger heart attacks and strokes.
Estrogen also assists in the secretion of nitric oxide from the cells that line arteries, said Dr. Alan Altman, a menopause specialist in private practice in Brookline, Mass. Nitric oxide helps dilate arteries. But when there is a lot of plaque, as there is in older women, the plaque blocks the access of estrogen to its receptors on artery walls, thus reducing the output of nitric oxide and making it harder for vessels to dilate.
In addition, estrogen stimulates production of a protein called MMP9, an enzyme that breaks down tissue, including plaque on artery walls, said Dr. Howard N. Hodis, chairman of cardiology at the USC Keck School of Medicine. That means that “estrogen may facilitate the rupture” of plaques in older women.
Of course, defining exactly when menopause occurs and thus when to start taking hormones, is “very tricky,” said Dr. Rowan Chlebowski, a medical oncologist at LABioMed, a nonprofit research institute at Harbor-UCLA Medical Center.
The time around menopause, called peri-menopause, can last four or five years. It is only when a woman has not had a period for a year -- which can only be determined retrospectively -- that she is defined as menopausal.
Another unresolved issue is how long to continue taking estrogen if you do start within a few years of menopause. Should it become a lifetime treatment?
Some people shudder at the mere idea that a woman might be wedded to her estrogen until death do them part. The mainstream party line is still that a woman should start estrogen at menopause not for its heart benefits, but to combat symptoms like hot flashes, and that she should stay on it for a short time.
And so it goes. The studies pile up. The data get refined. The nuances get clearer. Some questions get answered, but we’re still stuck with an ever-growing mass of new ones.
