Managing menopause: hormone therapy & other options.

Remember July 2002? Some think of it as the summer that changed women's health care forever. That's when researchers abruptly halted part of the Women's Health Initiative (WHI), a major federally funded clinical study to assess the effect of long-term use of hormone therapy (HT). Early results indicated that postmenopausal women using a combination estrogen/progestin medication called Prempro faced a slightly increased risk of breast cancer, heart disease, stroke and blood clots, results that were deemed too risky to ethically allow women to continue on the drug. (1)

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Almost overnight, it seemed, women were ditching their hormone therapy like a bad stock. (2) Doctors around the country counseled patients to stop taking hormones, and even the U.S. Food and Drug Administration (FDA) jumped into the fray, requiring that a so-called "black box," the agency's strongest warning label, be added to all estrogen products warning women of the potential risks. (3)

What a difference two years can make.

When investigators announced in March 2004 that they were ending the other major part of the WHI study early--the one involving the estrogen-only product, Premarin--because results showed participants had a slightly increased risk of stroke, the world took the news relatively calmly, with little of the hysteria and media frenzy that ensued in 2002.

Back then, Joan Flynn, 66, of Hilton Head, SC, who had been taking Premarin for nearly 20 years, quit cold turkey, even though the study's findings were for Prempro, an entirely different medication.

But after trying non-hormonal options such as black cohosh and vitamin E and enduring three months of hot flash misery, she returned to Premarin, albeit at a lower dose. Even after the March announcement, she had no intention of changing her mind.

"Every day you hear or read about something that will cause 'something,'" she says. "But while I'm living, I need to be comfortable."

It's an attitude more and more women have taken as the fallout from the 2002 WHI study settles and new research and thinking emerges. Even 50 percent of female ob-gyns surveyed by the American College of Obstetricians and Gynecologists in December 2003 said they used hormone therapy to treat their own menopausal symptoms. (4)

And when researchers surveyed 377 women who regularly used hormone therapy for at least one year before July 1, 2002 and tried to stop taking it between July 2002 and March 2003, they found that about one in four resumed hormone therapy, most because of troublesome symptoms such as hot flashes. (5)

It may be now that women are realizing they shouldn't have thrown the baby out with the bathwater, says Carol Landau, PhD, a clinical professor of psychiatry and human behavior at Brown Medical School in Providence, RI, whose clinical practice focuses on menopausal women. Just as the original findings of the WHI were oversimplified, she says, so, too, was the message of what women should do about them.

"I think the message here is that hormone therapy is still appropriate for recently menopausal women with significant symptoms," says JoAnn E. Manson, MD, DrPH, the Elizabeth F. Brigham Professor of Women's Health at Harvard Medical School, Boston, MA.

The key is tailoring hormone therapy to an individual woman's needs. And, with more than 20 varieties of hormone therapy on the market today, ranging from creams and gels, to patches, rings and pills, that's easier to do than ever before.

Questions About the WHI

Here's the reality behind the WHI: Basically, in 2002 the WHI found that women taking the hormone therapy Prempro, composed of progestin (a synthetic progestogen known as medroxyprogesterone acetate or MPA) and conjugated equine estrogen, had a 26 percent increased risk of invasive breast cancer, a 29 percent increased risk of heart attack, a 41 percent higher rate of stroke and more than a 100 percent increase in blood clots in the lung. (6) Later results also found women taking Prempro had twice the risk of dementia compared to those not using any hormones. (7)

That sounds scary. But when examined in terms of individual risk, the results paint a far less frightening picture. Of 10,000 women taking HT, over the course of one year 23 additional women would develop dementia, eight more would have blood clots in the lung, strokes, or breast cancer, and seven more would have heart attacks or other coronary events, than women not taking Prempro. But don't forget the study's good news: Over the course of a year, those 10,000 women taking Prempro would have five fewer hip fractures and six fewer incidences of colon cancer.

Since July 2002, researchers and health care professionals have raised significant questions about the WHI. For instance, many experts note that with an average participant age of 63, the women in the study started taking hormone therapy 10 to 15 years later than most women do, a delay that could have significantly affected the outcome, says Phillip Sarrel, MD, emeritus professor of obstetrics/gynecology and psychiatry at Yale Medical School in New Haven, CT.

Plus, the North American Menopause Society, in its most recent statement on the WHI released in September 2003, cautions that the effects of hormone therapy on the risk for breast cancer and osteoporotic fractures on perimenopausal women--the ones most likely to need hormone therapy for symptom relief--have not been established. (8)

All of which leaves the ball, so to speak, squarely in the court of individual women. "What I think happened is that women were getting this very strong message for the past 10 years to take hormone therapy long-term to prevent heart disease and other chronic health conditions," says Dr. Landau, "and then they got this other message, to stop immediately. Finally, they've had enough."

To try and help women understand their choices, she and Michele G. Cyr, MD, internist and Associate Dean for Women in Medicine at Brown Medical School, wrote, The New Truth About Menopause (St. Martin's Press, 2003). As they point out in their book: Even though the WHI study was stopped and it is probably wise to take the smallest dose of hormone therapy for the shortest amount of time, "that's an individual decision. While there were very small increases in risk in WHI, certainly enough to stop the study and certainly enough to make you think, they weren't enough to make you say 'never,'" says Dr. Landau.

Stopping Hormone Therapy

Still, for some women, the only answer to the hormone therapy question is to stop taking it. Before quitting, however, talk to your health care professional. Many women just went "cold turkey" after the 2002 WHI report, notes Dr. Landau, causing unnecessary discomfort that might have been reduced had they gradually tapered off the medication.

Unfortunately, no one really knows the best way to discontinue hormone therapy. In fact, a study published in the December 2003 issue of the journal Obstetrics and Gynecology found that women who abruptly stopped taking hormone therapy experienced fewer withdrawal symptoms than those who tapered off. (5) That could be because the women didn't taper off slowly enough, the authors suggest.

The researchers also found that women who had undergone a hysterectomy and who started hormone therapy for menopausal symptoms and had used hormones for more than 10 years were most likely to-return to hormones once they stopped than other women. Plus, women who reported troublesome symptoms after stopping were nearly nine times more likely to resume using hormone therapy than women without such symptoms. (5)

The good news, though, is that the study found just one-third of women who stopped using hormone therapy--either abruptly or gradually--experienced severe symptoms. (5)

Evaluating Your Own Risk

Whether you stop hormone therapy or continue it, you need to consider your own health risks and where you are in the menopausal process. "Women who are recently menopausal have a very low baseline risk of heart disease," says Dr. Manson. "Even the 20 to 30 percent increase in the risk of heart disease the WHI study found translates into a very small risk for the individual woman."

And while the research is pretty clear about the fact that starting hormone therapy 10 to 20 years after menopause is not advisable, especially for the purpose of preventing chronic disease, Dr. Manson says, "there are very few women in that age group who experience the primary symptom that drives most women to hormone therapy in the first place: hot flashes. As far as its use for moderate to severe hot flashes, I think it still has a role in clinical practice for short-term treatment and is the most effective treatment out there."

Indeed, the WHI study found that 77 percent of the 2,000 women in the study who complained of hot flashes said their flashes diminished while on Prempro. (9) Of course, keep in mind that women with severe hot flashes were not included in the study to begin with, since they would have known immediately whether they were taking the drug or a placebo. The results of the medication's effectiveness in reducing hot flashes have not been released yet.

And while there are other options for hot flashes (see page 6), none are as effective as hormone therapy and none are FDA-approved for the purpose.

Exploring the Options

When the WHI results on Prempro were announced in 2002, none of Dr. Sarrel's patients stopped taking the drug. That's because he's only ever prescribed natural progesterone, such as Prometrium, and the form of estrogen called estradiol, for his patients.

According to Dr. Sarrel, the estrogen used in Prempro bears little resemblance to the estrogen produced by a woman's body, and it contains MPA, one of the strongest progestins available. MPA, he says, interferes with estrogen's action on various tissues throughout the body and actually negates or even reverses some of estrogen's beneficial effects.

Indeed, it is looking possible that the culprit in the Prempro trials may be MPA, in conjunction with estrogen, since the estrogen-only arm found no increase in breast cancer or heart disease, notes Dr. Manson.

But before you switch to a different type of progestogen (the class of medications that includes natural progesterone as well as synthetic progestin), it's important to realize that other types may have the same risks. Same with estradiol, says Dr. Manson, who says some studies suggest similar increased risks of heart disease and breast cancer with 17-beta estradiol, the type found in most estradiol therapy preparations. In general, she says, lower doses of any hormone therapy should be safer in terms of health risks, even though no studies yet prove that.

It's important that women don't ignore their symptoms and be aware that they still have hormonal options in the post-WHI world, suggests Dr. Landau. "If you're having bad hot flashes and you've tried other things, like black cohosh and vitamin E, and you're still having hot flashes, my view is there is no need to suffer or 'tough it out,'" she says. Plus, cautions Dr. Landau, untreated hot flashes can lead to depression due to lack of sleep.

Thus, she and other experts recommend that women who feel they still need hormone therapy for symptom relief talk to their health care professionals about starting on the lowest possible dose, then gradually increasing it until they're comfortable.

They might also consider using transdermal hormonal options, such patches or gels, instead of taking oral hormones, says Dr. Manson. Because transdermal estrogens are metabolized by the liver in much lower concentrations than estrogens taken orally, estrogens from transdermal formulations are less likely to increase clotting factors, triglycerides and inflammatory markers such as CRP, all of which can play a role in heart disease and stroke. Plus, notes Dr. Sarrel, today's transdermal options provide exceptionally accurate delivery of hormones.

For problems with vaginal dryness and sexual dysfunction, which can interfere with intimate relationships, consider a topical estrogen formulation, such as an estrogen ring or estrogen cream, suggests Dr. Manson. These formulations work locally on the areas to which they are applied and only small amounts are absorbed by the body as compared with oral formulations. "So, there is strong reason to believe that you will not have the same risks that you would have with oral or patch estrogens," she says.

New Hormone Therapy Available

Beginning in mid-2004, women will have a brand-new option. EstroGel, approved by the FDA in February 2004, is a clear, odorless, fast-drying gel that's applied once a day on one arm from the shoulder to the wrist. It is approved for hot flashes and night sweats, and for vulvar and vaginal atrophy. (10) EstroGel has been used for more than 25 years in Europe, according to Dr. Sarrel. It should be available throughout the U.S. by this summer.

Other hormone therapy options, oral and non-oral alike, likely will appear in the next few years.

Resources

American Menopause Foundation

350 Fifth Avenue, Suite 2822

New York, NY 10118

212-714-2398

http://www.americanmenopause.org

Offers support, information and resources on menopause-related issues.

Hormone Foundation

4350 East West Highway, Suite 500

Bethesda, MD 20814-4410

1-800-467-6663

http://www.hormone.org

Provides information and resources on hormone-related disorders.

Landau, C. and Cyr, MG.

The New Truth About Menopause

New York: St. Martin's Press, 2003

National Institutes of Health

Postmenopausal Hormone Therapy Information

http://www.nih.gov/PHTindex.htm

Provides details on WHI and resources and links to hormone therapy, women's health and menopause information.

North American Menopause Society

5900 Landerbrook Drive, Suite 195

Mayfield Heights, OH 44124

440-442-7550

http://www.menopause.org

Offers consumer and professional information on menopause-related topics and research.

Women's Health Initiative Home Page

National Heart, Lung and Blood Institute

http://www.nhlbi.nih.gov/whi

Provides information on the WHI study and menopause and women's health.

RELATED ARTICLE: NWHRC Menopausal Hormone Therapy Survey Reveals Concerns, Interest in Options

In the Fall of 2003, the National Women's Health Resource Center conducted an online survey to learn more about women's views on menopausal hormone therapy. Six hundred and forty-eight visitors completed the survey, and about 60 percent had experienced either natural or surgical menopause. Among the results:

* Nearly 70 percent of respondents said they were very or somewhat confused about the safety of menopausal hormone therapy.

* One out of five (22 percent) said they stopped taking hormone therapy after news reports questioning its safety were published, and only 20 percent of those women said they discussed their decision with their health care professional.

* Eight percent of those who stopped hormone therapy said they were considering taking it again, while 15 percent said they were investigating alternative options.

* More than 70 percent of women said that they would consider an alternative natural hormone therapy if it was approved by the FDA. (11)