Hormones and your heart

What a woman should know that could save her life

Fourteen years past menopause, 56-year-old Anne Harrow has never felt healthier. Her weight and blood pressure are normal, her cholesterol profile is on target with recommended levels and her bones are strong. She has only flickering memories of the hot flashes that tormented her when she unexpectedly entered menopause at the tender age of 42.

"I feel fine," Anne says. "So I was shocked recently when my doctor told me, 'You've gone long enough without estrogen; for your heart's sake, it's time to begin hormone replacement.'"

Anne is not alone. Many women are surprised to learn that after menopause their risk of heart disease soars--and that their doctors consider estrogen the preventive prescription of choice.

The question is, can hormone-replacement therapy (HRT) benefit every woman's heart and health? And, more important, can it benefit your heart?

Despite the widespread concern over America's rising breast-cancer rate, heart disease is actually the number-one killer of American women. Though it typically strikes 10 years later in women than in men, by age 60 women face the same risk as men. And since a woman's risk rises as her estrogen level dwindles, it stands to reason that replacing lost estrogen could diminish her risk.

In fact, the incidence of coronary disease and cardiovascular death in postmenopausal women who take estrogen is about half that of women who have never used it. This, according to the Nurses' Health Study, a 10-year examination of nearly 50,000 women (New England Journal of Medicine, September 12, 1991).

"Several studies indicate that oral estrogen replacement both lowers harmful LDL cholesterol and raises protective HDL cholesterol up to 15 percent in each case," says Baylor College of Medicine's Antonio M. Gotto Jr., M.D., D.Phil., a past president of the American Heart Association.

"To appreciate the significance of these numbers," explains Dr. Gotto, "consider that for about every 2percent increase in HDL, there's a 3to 5 percent decrease in heart-diseaserisk in women."

When a progestin, a synthetic form of progesterone, is added to the estrogen, which it commonly is, the HDL-boosting benefit of taking estrogen is depressed somewhat. But according to the recently completed Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, combining estrogen with a progestin still has cardioprotective effects (Journal of the American Medical Association, January 18, 1995).

Research also suggests that estrogen, in the low doses commonly given today, may improve blood flow to the heart muscle, prevent the constriction (closing) of blood vessels often seen with cardiovascular disease and inhibit the rise in blood-clotting factors that occurs with age.

"These nonlipid benefits may actually prove to be the greatest advantage of HRT," says Roger Blumenthal, M.D., of Johns Hopkins Hospital.

Despite the logic of the connection between HRT and heart health and the very encouraging research that supports it, caution is in order.

"We know that estrogen does significantly change risk factors for heart disease for the better. But we still do not know whether estrogen can actually cause a reduced incidence of coronary-artery disease," says Marianne Legato, M.D., associate professor of clinical medicine, Columbia University College of Physicians and Surgeons. In the Nurses' Health Study, for example, it's unclear whether the lower incidence of heart disease in the women taking hormones was a direct result of HRT or due to other factors, like a healthy overall lifestyle.

Unfortunately, too, taking estrogen is not without risk. "Everyplace you turn in a woman's body there are estrogen receptors. They're in her heart, her bones, her arteries and brain, not just in her reproductive organs and breasts," notes Cleveland Clinic Foundation cardiologist (and former NIH director) Bernadine Healy, M.D. "This confirms that estrogen plays a complex role beyond reproduction. It's a role not yet fully understood and one that may have some effects that are not all positive, such as the risk for breast cancer.

"The decision to start hormone-replacement therapy is a big one," she adds. "It should be treated with the same deliberation as if you were considering surgery."

For some women, estrogen might prove to be lifesaving. A postmenopausal woman with existing heart disease, for example, may be an excellent candidate for HRT, most cardiologists would agree. Beyond this prescription, however, the recommendations get blurry.

Following the lead of the National Cholesterol Education Program, many doctors suggest that women age 55 and over with elevated LDL cholesterol consider HRT to counter their increased heart-disease risk. Some experts may go so far as to say every woman above age 55 should at least consider it. But, of the distinguished panel of heart specialists we consulted, most took a more conservative approach. It's possible, they note, that postmenopausal women who opt for HRT to preserve strong bones or ease menopausal symptoms might reap a heart-health bonus, even if they have no coronary risk factors. But at this point there's not enough evidence to justify estrogen replacement for the purpose of preventing heart disease in risk-free women. "If a woman has no risk factors for heart disease other than age (over 55), there's no reason for her to take hormones," says HRT researcher Elizabeth Barrett-Connor, M.D., one of the principal investigators for the PEPI Trial.

Clearly, the decision to take or not to take hormones for your heart largely hinges on coronary risk. "The more risk factors you have, the greater the strength of the rationale for taking estrogen," notes Dr. Blumenthal.

Poor cholesterol profile, high blood pressure, smoking (even one cigarette a day), diabetes, waist-hip ratio greater than 0.80 (divide waist measurement by your hip measurement), abnormal EKG, sedentary lifestyle or a family history of heart disease are all significant risk factors. "And a woman who enters menopause early (either naturally or surgically) starts on the track to early heart disease," William Castelli, M.D., director of the famed Framingham heart study, adds.

In general, Dr. Legato prescribes HRT only for postmenopausal women with two or more coronary risk factors. And, given estrogen's well-established ability to improve blood lipids, her first consideration in evaluating risk is a woman's cholesterol profile. "If a woman came to me with very low HDLs as well as a family history of heart disease, I would consider using estrogen," says Dr. Legato. "Certainly, if a woman has low HDLs and two other risk factors for coronary-artery disease, she is a good candidate for estrogen." Dr. Castelli agrees that evaluating heart risk starts with cholesterol numbers.

"The top three lipid risk factors that would indicate the need for estrogen are low HDLs, high LDLs and high triglycerides," Dr. Castelli explains. "If I know what those numbers are, I can tell you where you're headed with heart disease. If total cholesterol is over 150, I look at the ratio of total cholesterol to HDL. If the ratio (total cholesterol divided by HDL) is 4.0 or higher, it means you don't have enough of the good HDL cholesterol to balance out the nasty LDL cholesterol and you're in trouble."

A woman with a ratio over 4.0 and triglycerides of 150 or higher is in double jeopardy, Dr. Castelli notes. But before recommending hormone replacement, Dr. Castelli prescribes lifestyle changes.

"Lifestyle changes, if comprehensive enough, may be preferable to estrogen for heart protection. They not only reduce your risk of heart disease but protect against cancer, as well. Estrogen lowers that heart-disease risk but may promote some types of cancer," explains Prevention advisor Dean Ornish, M.D., president and director of the Preventive Medicine Research Institute. In Dr. Ornish's now famous Lifestyle Heart Trial, patients following an ultra-low-fat (10 percent calories from fat), high-fiber diet combined with moderate aerobic exercise, emotional support and stress management actually experienced a reversal of heart disease. (See Prevention, February 1994.)

One interesting finding from Dr. Ornish's study was that the small number of women subjects averaged more heart benefits than the men, though both groups had the same degree of lifestyle change.

"Three-quarters of all women with bad blood lipids make it to safe numbers with diet and exercise," Dr. Castelli maintains. "If the numbers don't improve with these lifestyle changes after a three-month trial period, I would continue with the lifestyle approach but probably convince a woman that she needs to be on estrogen, too.

"Some women taking estrogen may experience a rise in triglycerides. But I wouldn't worry about that," says Dr. Castelli. "It appears that the elevation is in the type of triglycerides that doesn't harm your heart."

Even when HRT does not have an effect on a specific risk factor--blood pressure, family history or diabetes--that risk factor should be counted as a possible reason to take HRT, because HRT will work in other ways to lower the danger to your heart, Dr. Blumenthal explains.

"We consider HRT first-line medical treatment for postmenopausal women of any age at risk for heart disease," Dr. Blumenthal says. Dr. Healy concurs: "Because estrogen does more than influence lipids, the cardiovascular benefit will be broader than from cholesterol-lowering drugs alone," she explains. For a woman who is already taking a cholesterol-lowering drug when she reaches menopause, her physician may consider decreasing the dose or possibly replacing the medication with HRT. However, it remains unclear--although likely--whether there is any benefit to adding HRT to a current drug-treatment regimen.

To maximize the benefits, it's best to choose estrogen pills over the patch. Since estrogen from the patch bypasses the liver, and it's these trips through the liver that may largely account for its immediate impact on HDL, the patch appears to have less effect on blood cholesterol levels.

Still, if you decide to use the patch, you shouldn't think you're totally missing out on estrogen's cardiovascular protection, says Dr. Healy. "The estrogen is still circulating through the bloodstream. While studies remain to be done, it seems likely there is a benefit, even if the effect is not as immediate or powerful as with oral doses."

Remember, too, it's never too late to start taking hormones--even if you're over 60--several of our experts agreed. Of course, there are many other considerations and risks to weigh when deciding on HRT. (See also "Heart and Womb Protection" on page 74 and "Breast Cancer Versus Heart Disease" on page 76.)

A qualified primary-care physician or gynecologist ought to be able to help you assess the pros and cons of HRT. But if you have any risk factors for heart disease, do not hesitate to see a cardiologist.

While a physician can provide useful information, ultimately the decision belongs to you alone. "If you decide to begin HRT," Dr. Healy says, "make sure it's not because 'My doctor made me do it.' Make sure it's because 'I made this decision as a woman taking control of my life and my future health, knowing the benefits, knowing the risks, and monitoring new information as it comes along.' " Indeed, with several important studies now in progress, says Dr. Healy, "Women should stay tuned."


By Steve Schwade with Toby Hanlon

SOURCES: Elizabeth Barrett-Connor, M.D., professor and chair, department of family and preventive medicine, University of California, San Diego, La Jolla; Roger Blumenthal, M.D., assistant professor of medicine, Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Hospital, Baltimore; William Castelli, M.D., medical director, Framingham Heart Study, and Prevention Advisor; Antonio M. Gotto Jr., M.D., D.Phil., professor and chairman, department of medicine, Baylor College of Medicine, chief, Internal Medicine Service, Methodist Hospital, Houston, and past president, American Heart Association; Susan Harlap, M.D., chief, epidemiology service, Memorial Sloan-Kettering Cancer Center, New York; Bernadine Healy, M.D., cardiologist, Cleveland Clinic Foundation, former director of the National Institutes of Health and author of the forthcoming A New Prescription for Women's Health (Viking, August 1995); Marianne Legato, M.D., associate professor of clinical medicine, Columbia University College of Physicians and Surgeons, New York; Dean Ornish, M.D., president and director, Preventive Medicine Research Institute, Sausalito, California, assistant clinical professor of medicine, University of California, San Francisco, and author of Dr. Dean Ornish's Program for Reversing Heart Disease (Random House, 1990) and Eat More, Weigh Less (HarperCollins, 1993).

If you've had a hysterectomy, you can skip this section. If you haven't, be forewarned: Taking your estrogen straight unfortunately can raise your risk of uterine (endometrial) cancer.

Without estrogen replacement, a woman's lifetime risk of endometrial cancer is 1 in 20. With estrogen replacement (i.e., estrogen taken alone, called unopposed estrogen) the risk would increase substantially--perhaps fivefold--according to Susan Harlap, M.D., chief of the epidemiology service at Memorial Sloan-Kettering Cancer Center in New York City.

What happens is this: Taking estro-gen stimulates the cells of the endo-metrium (lining of the uterus) to grow and thicken. If this growth continues excessively--called endometrial hyperplasia--and goes undetected and untreated, this condition can be an early step in the development of cancer.

Taking estrogen with progestin, a synthetic form of progesterone, however, offers protection against estrogen-induced hyperplasia and cancer. Progestin triggers the uterine lining to stop growing and shed. However, progestin's protection comes at a price: The hormone blunts the effect of estrogen on HDL. In the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, though unopposed estrogen raised HDL between 6 and 12 percent, estrogen with progestin raised HDL by only 2 to 4 percent. The type of progestin may make a difference, however. Estrogen combined with micronized progesterone produced a 5 to 9 percent increase in HDL. (Micronized progesterone is not yet widely available.)

The lessened increase in HDL, while important, may not seriously diminish the value of combination therapy. First, combination therapy is every bit as effective as unopposed estrogen when it comes to lowering LDL, each dropping LDL from 10 to 12 percent in PEPI and up to 15 percent in other studies. And second, as Roger Blumenthal, M.D., notes, "the nonlipid effects of estrogen are probably as important as the lipid effects, and these are probably not diminished by the addition of progestin."

Of course, some women just can'thandle the side effects of progestin. Forthese women, estrogen may be givenunopposed, with careful monitoring. Ifthere are signs of endometrial hy-perplasia, a woman can sometimes betreated with short-term progestin. "This is an option we have to leave open for women who cannot tolerate progestin," says Elizabeth Barrett-Connor, M.D.

For monitoring a woman with an intact uterus who chooses to take estrogen alone, "A standard Pap smear is not enough," warns Bernadine Healy, M.D. "These women need an endometrial biopsy once a year. This involves inserting a small catheter and taking a tissue sample, a procedure that can be done in your doctor's office. It's not comfortable, but it's not a major procedure, either."

One more note: Physicians recommend that all women considering HRT have a gynecological exam to rule out existing uterine abnormalities.

Over the remainder of her lifetime, the average 50-year-old woman faces almost a 1 in 2 chance of developing heart disease and a 1 in 10 risk of getting breast cancer. Taking estrogen can change those numbers. Heart-disease risk drops dramatically (by 12 percentage points), while breast-cancer risk nudges up (by 3 percentage points, or 5 in women with a family history) (Annals of Internal Medicine, December 1992).

Still, cold numbers can never be the sole basis for a decision. "Risks and benefits are very personal," says Bernadine Healy, M.D. "If in a woman's particular family she has seen two sisters and her mother die of breast cancer, she may say 'I don't care about whatever numbers you give me, I fear breast cancer; therefore I don't want to take hormones.'

"I don't think we should ever be dogmatic and just give patients statistics, because ultimately it's still that one patient who has her own unique risks, her own concerns, her own family history, her own genetic makeup.

"I personally believe that most women should seriously consider HRT, even if they have a family history of breast cancer. But ultimately a woman must decide for herself. As we develop better diagnostic tools and more precise ways to define risk, these decisions will become easier to make. And it's the doctor's role to make the decision easier for her patients. I believe in empowering women to make those decisions for themselves."

If you do decide on hormone replacement, have a mammogram beforehand to rule out existing disease and continue with careful monitoring (monthly breast self-exam, regular physician exam and annual mammogram) thereafter.

"Some women may want to begin HRT later in life," says Roger Blumenthal, M.D. Because the risk of breast cancer doesn't appear to rise until after 10 to 15 years, taking hormones for a shorter period of time may be a safer alternative.

GRAPH: Why heart protection is a high priority: As women grow older, their risk of heart disease rises dramatically--higher even than breast-cancer risk. (Source: NCI, based on NCHS public use files, 1992)

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