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HEALTH SENSE

Hormone drug problems force women to mull alternatives

 

By Judith Forman, Globe Columnist, 7/16/2002

 

OK, now what?

 

Last week, a small group of experts set up to monitor emerging results from the massive Women's Health Initiative, a landmark study on hormone-replacement therapy, dropped a bombshell.

 

To the surprise of millions of us on hormone therapy - 38 percent of all postmenopausal ladies in America - and to many of the researchers in the study as well, the monitoring committee concluded that a popular hormone combination, Prempro, which contains estrogen and a synthetic progesterone, causes more harm than good.

 

Only 5.2 years into the eight-year study, the committee called an abrupt halt to the part of the study involving roughly 16,000 women on Prempro because the data showed that Prempro tended to modestly raise the risk of breast cancer, heart disease, stroke and blood clots, though it reduces the risk of hip fractures and colon cancer. The committee did not stop the arm of the study involving roughly 11,000 women taking estrogen alone.

 

The announcement left millions of women, including this one, scrambling for alternatives to HRT's uncontested ability to combat symptoms of menopause like hot flashes and vaginal dryness, and to accomplish the other things that HRT used to be prescribed for - long-term protection of bones and hearts.

 

Luckily, there are many alternatives - such as different combinations of hormones that may be safer than Prempro; herbal remedies like black cohosh; learning to love tofu, or at least soy protein powder; or finally getting really serious about diet and exercise to protect against osteoporosis and heart disease (the main reasons many women have stayed on HRT for years).

 

The first thing to remember is that the increases in risk in the WHI study were small. For every 10,000 women taking Prempro, there would be an extra seven cases of cardiovascular disease, eight strokes, eight blood clots in the lungs and eight cases of invasive breast cancer. This means that for any individual woman, the risk of harm is really quite small. Some doctors even question whether these increases are really statistically significant.

 

Secondly, it's only combination hormone therapy that appears worrisome. Since estrogen alone has not (yet) been shown to carry the same risks, it may be the progestin that is the bad actor in the combined regimens. (Progestin, an anti-estrogen, has to be taken with estrogen by women who still have a uterus because, if taken alone, estrogen can increase the risk of uterine cancer.) Moreover, the study did not even look at all possible progestins in combination with estrogen. It focused only on Prempro ( Premarin, an estrogen, and Provera, a progestin), even though there are dozens of other estrogens and progestins available.

 

''We've known that the Provera part of Prempro has been a problem for half a decade,'' said Dr. Alan Altman, an assistant professor at Harvard Medical School and a menopause specialist in private practice in Brookline.

 

''Provera is too potent,'' he said. He believes Prometrium, a form of micronized progesterone, may be safer than Provera. Another option is Femhrt, a pill that combines an estrogen (ethinyl estradiol) with norethindrone acetate, a different progestin. Still other options are Prefest and Activella. Estratest, a combination of estrogen and testosterone, may also help some women.

 

These decisions get tricky. For instance, estrogen patches (as opposed to pills) may be better for some women. Adding progesterone further complicates things. In terms of cardiac effects, for instance, estrogen increases HDL, the good cholesterol, but it also increases triglycerides, an undesirable effect, noted Dr. Richard Karas, director of preventive cardiology at New England Medical Center. Provera blunts both this good and bad effect; Prometrium does, too, but to a lesser extent. Go figure.

 

Another option is to cut back to a lower dose of estrogen and to cut back on or change progestins accordingly. There are several ways to do this. For instance, you can take 100 milligrams of Prometrium every day along with low-dose estrogen. Or, you can take half of a 5-milligram pill of Aygestin (another progestin) for 10 days every three or four months. This should bring on a period, which is the point. If the lining of the uterus has been building up for several months on estrogen alone, it must be shed every few months to reduce the risk of uterine cancer.

 

If you do decide to toss out your hormone pills or patches entirely, taper off slowly. If quitting leaves you with vaginal dryness, you can try a tiny pill called Vagifem that, once inserted, sticks to the vaginal wall, or a little device like a diaphragm called Estring.

 

These products, sold by prescription, supply low doses of estrogen directly to the vagina without seeping out to the rest of the body. But precisely because of that, warns the North American Menopause Society, these approaches will not help with hot flashes. Another option is to use a vaginal estrogen cream, but this will get absorbed into the rest of the body - with all the pros and cons that that means.

 

A nonhormonal, over-the-counter remedy for vaginal dryness is to use Astroglide, a lubricant, during sex.

 

For women who want to get off hormones but are concerned about osteoporosis, one approach is to use bisphosphonate drugs such as Actonel and Fosamax, 1,200 milligrams a day of calcium and 600 to 800 International Units of vitamin D. Evista, a ''designer'' estrogen, can also help protect bones, though it causes hot flashes.

 

For women who dump their hormones but worry about heart disease, the statin drugs, which can lower both cholesterol and the risk of heart attack, may be a good choice. (Obviously, for both osteoporosis and heart-disease prevention, exercise is also key.) For nondrug solutions to menopausal problems, the best bet is undoubtedly soy.

 

Soybeans are legumes that are rich in plant estrogens (also known as phytoestrogens). The most important ones are genistein and daidzen, which are also known as isoflavones. But a warning: Like the estrogens that humans make in their bodies or buy by prescription, phytoestrogens may drive cell proliferation, which means soy could spur cancer growth, particularly breast cancer, which is often driven by estrogen.

 

Though soy is a popular way to combat hot flashes, studies suggest it's only somewhat better than placebo. A reasonable dose is 50 grams of soy protein a day, which you can get either from protein concentrate, a cup of tofu, a quarter of a cup of soy beans or a glass and a half of soy milk.

 

If you prefer supplements, you can take one pill containing 25 milligrams of soy isoflavones twice a day, said Dr. Machelle Seibel, medical director of Inverness Medical Inc. in Waltham, which makes SoyCare products. Soy can also help lower cholesterol and can slow down the rate of bone loss at menopause, he added. (Flax seed oil also may help but appears less potent than soy.) Other remedies for hot flashes are the SSRI antidepressant drugs such as Effexor, Paxil, Zoloft, Prozac and the like, or a blood pressure medication called Catapres, said Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital.

 

Vitamin E at 400 to 800 International Units a day also may help, but its effects are minimal: It probably would eliminate only one hot flash a day, said Dr. Nananda Col, a menopause specialist also at Brigham and Women's Hospital.

 

Among the herbals, black cohosh is probably the best for combating hot flashes, and some women swear by it. But, if you take a black cohosh product like Remifemin, don't take it for more than six months because there's little reliable longer-term data.

 

Another option for hot flashes is red clover, which comes in products such as Promensil. ''It seems to help some people,'' said gynecologist Altman, ''but there are no definitive studies to say it's better than placebo.''

 

Forget Dong Quai, a favorite among some herbalists. A Kaiser Permanente study several years ago showed it to be no better than placebo.

 

Oil of evening primrose seems to help some women, though the evidence is scanty. The oil is a prostaglandin, which means it could in theory cause pain and uterine contractions.

 

Ginseng is another question mark. It seems to help some women when herbalists prescribe it as a part of a mixture with other herbs, but isn't effective alone in head-to-head comparisons with placebo, Altman noted.

 

And skip the wild yams. For one thing, said Col of Brigham and Women's, they can cause serious liver toxicity. Moreover, as Altman put it, ''wild yam cream is utterly useless because there's no progesterone in Mexican yams.''

 

Because hormone-replacement therapy had been prescribed for so many short- and long-term menopausal problems, replacing it with a hodgepodge of other remedies will mean a lot of individual experimentation as women, and their doctors, sort through the options.

 

But look at it this way. The new results that are now creating such chaos for so many women stem from precisely the kind of rigorous research that women have (rightly) been clamoring for for years.

 

We asked for it. We paid for it. We got it. Now we have to live with it. That's science.

 

Judy Foreman's column appears every other week in Health-Science. Her past columns are available on Boston.com and www.myhealthsense.com. Her e-mail address is foreman@globe.com.

 

 

This story ran on page C1 of the Boston Globe on 7/16/2002.

? Copyright 2002 Globe Newspaper Company.