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Rethinking Hormone Therapy

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“Would you like hormones with your menopause?”

Once upon a time, taking pills that contain estrogen—or later, estrogen plus progestin—was considered the fountain of youth.

Then it became a poison pill.

Now strong new evidence is triggering another look at whether, for certain women, at certain times in their lives, hormone therapy is (dare we say?) beneficial for long-term health.

“The pendulum had swung from one extreme, where hormone replacement therapy was thought to be beneficial for every woman, to the other, where it was beneficial for no woman,” said Owen Montgomery, MD, chair of the obstetrics and gynecology department at Drexel University College of Medicine.

“Now it’s shifting again.”

When a woman begins hormone therapy, it turns out, is a key factor in determining whether the benefits outweigh the risks—and whether the therapy might even help her live a longer life.

Menopause expert Mache Seibel, MD, a professor of gynecology and obstetrics at the University of Massachusetts, feels so strongly about the difference age makes in the risk/benefit calculation that he named his new book The Estrogen Window.

A NEW ERA IN MENOPAUSE RESEARCH

The modern era of hormone therapy for menopause started in 2002. Until then, many doctors were prescribing oral estrogen (conjugated equine estrogen), often with progestin (a synthetic form of progesterone), to women going through menopause—not only to treat symptoms such as hot flashes but to reduce risk for chronic diseases that rise with menopause, including heart disease and osteoporosis.

Then the Women’s Health Initiative (WHI)—the first relevant randomized placebo-controlled trial, the gold standard of biomedical research—turned those assumptions upside down. Key finding: Women who took estrogen plus progestin were more likely to get breast cancer and slightly more likely to get heart disease, too. A few years later, a second WHI study in women who had hysterectomies and were taking estrogen only reported an increased risk for stroke as well.

The findings were strong enough that both studies were stopped before they were completed—it was considered unethical to give women hormones when it increased their health risks. The risk wasn’t enormous statistically—eight more cases of breast cancer for each 10,000 women, for example. “That’s an increase in risk of less than one-tenth of 1%,” noted Dr. Seibel. “But in a study that is supposed to be preventive, that was unacceptable.”

It should be noted that hormone replacement therapy did decrease fractures—by 23% in the group that received estrogen plus progestin and by 30% to 39% in the estrogen-only group.

Hormone-therapy prescriptions plummeted.

But science marches on. In the original WHI, the women’s average age was in the mid 60s—about 15 years after menopause, on average. A new analysis of the WHI, along with other new studies, finds a very different story in women who start hormone therapy before age 60

  • A 32% reduction in heart disease.
  • A 39% reduction in all-cause death.

Women up to age 60 who took estrogen plus progestin also had less colon cancer, although the risk for breast cancer is still slightly elevated at all age groups for women who took estrogen/progestin for at least five years. While that’s a particular concern for women with a family history of breast cancer, for most women, the breast cancer risk is dwarfed by the cardiovascular benefits.

“The reality is that heart disease is a much larger threat to most women than breast cancer,” said Dr. Montgomery. Statistics back that up—one in every 36 women dies from breast cancer, but one in every three women dies from heart disease. “If the WHI study were repeated with only 50-year-old women taking hormones for 10 years, we would have slightly more cases of breast cancer but, overall, we would have a lot more women alive.”

A new statistical analysis from Yale University School of Medicine makes this fact pretty stark. For women in their 50s who had had hysterectomies, not taking oral hormones that include estrogen may have caused nearly 92,000 women to die before the age of 60 over a 10-year period.

After age 60, the story changes—benefits decline and risks, including cardiovascular risks, increase. In most cases, hormone therapy no longer makes sense. But how can that be? How can the same therapy protect younger women but harm older women?

New studies shed light on that, too.

THE HEART PARADOX EXPLAINED

Estrogen protects women against atherosclerosis, narrowing of the arteries. That’s one reason why fatal heart attacks are more common in men in their 40s than in women…the women are still producing plenty of estrogen.

But estrogen has another cardiovascular effect—it makes blood slightly more likely to clot, so it’s “thicker.”

In the WHI studies, some women in their late 60s and 70s began to take estrogen after many years of no estrogen. During that interim period, some of those older women had already developed narrowing of the arteries around their hearts and brains. So when these older women began to take estrogen, they had thickened blood traveling through narrowed arteries. It’s no wonder that the incidence of heart attacks, strokes and dementia—which often has a cardiovascular component—increased in this population.

A recent report gives even more credibility to the age effect. When hormone therapy was initiated in women within six years after menopause, it slowed down narrowing of the coronary arteries. But there was no such benefit when hormone therapy was started more than 10 years after menopause.

PUTTING IT ALL TOGETHER: THE NEW MENOPAUSE CALCULUS

The choice to embark on, or forgo, hormone therapy, is a personal decision that requires a careful assessment of each individual’s potential risks and benefits. A few key facts…

  • Hormone therapy is approved only for the treatment of symptoms of menopause—such as hot flashes, night sweats and vaginal dryness—even with the new evidence, it’s not approved for women without symptoms just for the prevention of heart disease. It hasn’t been studied for that purpose.
  • While hormone therapy is approved for prevention of osteoporosis, there are other therapies that work better, so it is rarely used as a first-line therapy.
  • You don’t need to be suffering from unbearable hot flashes to be eligible for treatment. Painful intercourse caused by changes in vaginal elasticity and lubrication, for example, is a symptom that can be treated with hormone therapy.
  • Unless you’ve had a hysterectomy, hormone therapy is always estrogen plus progestin. If you have a uterus, estrogen taken alone increases the risk for endometrial cancer.
  • Early menopause? In almost all cases, you need hormone therapy. Both Dr. Montgomery and Dr. Seibel agree that the data are clear that women who have gone through menopause before the age of 40 should absolutely be on hormone therapy to replace the hormones that they have lost prematurely. Therapy should last at least until the age of normal physiologic menopause (about age 51). Women who have been through premature menopause are at a much higher risk for cardiovascular disease and dementia if they do not take hormone therapy.
  • Women with certain conditions—including vaginal bleeding that is not explained, a sensitivity or allergy to estrogen, liver disease, an estrogen-fueled cancer or an increased risk of clotting—should avoid oral hormone therapy.
  • If oral hormone therapy is not appropriate, other forms of estrogen may be—vaginal creams to treat vaginal dryness, for example, or patches (transdermal estrogen) to treat night sweats. “Women at increased risk of blood clotting may be able to take transdermal estrogen,” said Dr. Seibel. “It bypasses the liver and works well on vaginal symptoms, too.” Women with estrogen-positive breast cancer, whether survivors or patients under current treatment, can safely use vaginal estrogen, he added.
  • If you don’t want to go down the hormone therapy route—the choice is always yours—there are many nondrug approaches that help relieve symptoms, including supplements, self-hypnosis and more.

BEYOND ONE SIZE FITS ALL

While each woman has a unique set of risks and benefits, the new evidence makes it easier to figure out who may want to consider hormone therapy—and who shouldn’t.

Should a 72-year-old woman with no menopause symptoms consider hormones? “No!” replied Dr. Montgomery. “But it’s a very different answer when we talk about a 52-year-old woman who is suffering with symptoms that affect her quality of life. For her, it just doesn’t make sense to not take a medication for which there are convincing data that it will help keep her alive in the next decade while relieving her symptoms and improving her quality of life.”

Even if you do decide to get hormone therapy, a prudent approach is to start with the lowest dose that works—for the shortest duration. The current guidelines call for women who still have their uteruses who get hormone therapy to do so only up to five years and then reevaluate whether it’s appropriate to continue for up to another five years. However, said Dr. Seibel, “New data is rapidly supporting that the estrogen window is widening. Stay tuned.”

Dr. Montgomery recommended that women who do take hormone therapy revisit the decision every year. “Try drug holidays to see if you are still symptomatic. Menopause symptoms tend to last from one to 10 years, with four years the average—but about 10% of women are still symptomatic in their 70s. It’s very individual.”

Hormone therapy is not a one-size-fits-all treatment. There is no doubt that there are risks involved, as there are with nearly every drug or supplement, but the benefit-to-harm ratio for you depends on your unique set of circumstances. It’s a decision that every woman needs to make eventually—and now you have the latest information to discuss with your health-care provider as you figure out what’s best for you.

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Source:

s: Mache Seibel, MD, professor of gynecology and obstetrics, University of Massachusetts Medical School, Worcester, and author of The Estrogen Window. Drmache.com


Owen Montgomery, MD, chair, obstetrics and gynecology department, Drexel University College of Medicine, Philadelphia.


Study titled “The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women aged 50 to 59 years” by researchers at Yale University Medical School, New Haven, Connecticut, published in American Journal of Public Health.


Study titled “Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol” by researchers at University of California, Los Angeles, Stanford University, California, published in The New England Journal of Medicine.

Date: July 11, 2016 Publication: Health Insider