HRT: Quality of Life?

By Christine Haran

Few women's health studies have created as many shock waves as the Women's Health Initiative (WHI), which found that hormone therapy offered more risks than benefits to postmenopausal women who still had their uteruses. Since those results were published in July 2002, many women have stopped taking hormone therapy. This April, researchers published a study examining hormone therapy's impact on quality of life in WHI participants.

Combination hormone therapy, consisting of estrogen and progestin, has been prescribed for decades to quell the symptoms of menopause, prevent heart disease and osteoporosis, and "slow the aging process," thereby helping women no longer producing estrogen stay healthy and feel youthful. This recommendation was based on patients' accounts of their improved health and studies that observed women who were taking hormones and those were not. It is now known that the lower rates of disease and higher quality of life in the women in these studies who took hormones was more likely due to their better overall health than the effects of the hormones. These women tended to be, for example, thinner and to have better access to healthcare. The WHI was the first clinical trial to follow women who were randomly selected to receive either estrogen alone, or in combination with progestin, or an inactive substance.

Jennifer Hayes, PhD, director for the Center for Women's Health at Baylor College of Medicine in Houston, led the study examining health-related quality of life among women in the WHI study. Dr. Hayes and her colleagues' results were published in the May 8th issue of The New England Journal of Medicine. To the surprise of many women and doctors, including the researchers themselves, they found that estrogen plus protestin did not have a clinically meaningful effect on health-related quality of life. Below, Dr. Hayes discusses these controversial findings.

Why did you decide to examine quality of life in the Women's Health Initiative?
This quality of life study was planned from the beginning of the WHI as part of our effort to understand the effects of long-term hormone use on 16,608 women between the ages of 50 and 79. Except for one part of the study looking at women who had had hysterectomies and were taking estrogen alone, the WHI was terminated early. The overall health risks outweighed the health benefits in the women taking estrogen plus progestin, compared to the women in that group who were on placebo. So the next question was, "How did these women fare in terms of quality of life?" That data had been collected when they went into the study. Data were gathered one year later on everyone and, after three years, on 1,511 of the participants.

How did you determine what measures you would use to assess quality of life?
The WHI was a study of long-term hormone therapy use on postmenopausal women. It was not a study on the effects of hormones on perimenopausal women, or women who are undergoing the more symptomatic, transition phase of menopause. Instead, we were interested in how hormone therapy affects overall physical and emotional mental/social health.

We picked the most commonly used measure of quality of life in the world. This measure has eight subscales: general health; physical functioning, emotional or mental health; role limitations due to physical problems; role limitations due to emotional problems; bodily pain; social functioning; energy and fatigue. In addition, we used a depression measure, a sleep disturbance measure, a cognitive impairment and dementia measure, and a question about satisfaction with sex.

What did your study find?
The effects on health-related quality of life were just very, very small. Out of the 13 separate measures that we looked at, there was a significant effect in only one. We had 574 women between the ages of 50 and 54 who reported moderate-to-severe hot flashes when they came into the study. In that group, we found a 5 percent improvement in sleep.

Other studies have found that hormone therapy is effective for hot flashes, so do you think hormone therapy is still appropriate for some women?
I talk to women for whom hormone therapy has made all the difference in their quality of life during that phase where their hot flashes are most bothersome. But I don't know that there is a "safe period" to take it. We found that the rate of stroke, heart attack and blood clots occurred in the first two years. Breast cancer takes longer to develop. The risks are small, and they may be worth it for some women. We think it is important for women to be able to use this information when they are working with their healthcare providers in order to make a good decision for themselves.

How long do menopausal symptoms usually last?
The average woman will have symptoms for one to four or five years. Seventy-five percent of women will have hot flashes during the year that she has her last menstrual cycle. But five years later, only 30 percent of women will still be having hot flashes, and 20 years later only 10 percent will.

Some women may report better sleep or other symptom changes that we were not able to pick up in this study because perimenopausal women who were very symptomatic was primarily not our purpose. But we did have more than 2,000 women who reported moderate-to-severe hot flashes, night sweats or other menopausal symptoms when they came into the study, and it didn't seem to make a difference

What are some of the other options for hot flashes and other symptoms?
There is no other really good approved pharmacologic treatment or drug for hot flashes. There are a few other drugs that have a side effect of helping with hot flashes, but they are drugs that you would take for different conditions like high blood pressure or anxiety and depression. The best advice is behavioral, which no one wants to hear because it's easier to take a pill. But women who exercise have fewer hot flashes. Women who don't smoke have fewer problems with hot flashes. And caffeine, alcohol and hot foods or drinks can all trigger hot flashes.

There are some promising alternative medicines for hot flashes. Some women say that soy helps them, but the data are quite mixed. There are some new studies about black cohosh and one about deep breathing techniques. A friend of mine who had hot flashes in her sleep keeps a little cooler filled with ice packs beside her bed. Wearing layered clothing made of natural fibers helps. It's back to kind of trying to remember what our grandmothers did.

Other menopausal symptoms are widely varied, but sometimes include ******* and memory problems. There are some good alternatives for ******* dryness and the thinning of ******* tissue that makes intercourse painful. Topical estrogen in the form of ******* creams, tablets and a silicone ring with timed-released estrogen—it is inserted and lasts three months—have been found to be effective but are not absorbed into the blood stream, making it less likely that they would cause the problems seen in orally administered estrogen. ******* lubricants are also an option.

As for memory problems, the best advice I know is to keep mentally active. Several studies have found that people who challenge themselves are less likely to develop dementia, though these are observational studies so they aren't definitive. Moderate alcohol intake, getting plenty of sleep and exercising have also been associated with better memory.

I think the important thing to remember is that what really affects our quality of life is disease and disability. So we should do what we can to prevent diseases that occur in women more frequently after menopause because that will improve quality of life.

Do you think the fact that the WHI evaluated only one formulation of hormone therapy was a limitation?
This formulation, Prempro, was used because 85 percent of women who were taking estrogen with a progestin were taking it when the study was started. Now there are some other options, including patches and estrogens and progestins from other sources, from plant-based estrogens and progesterones. The problem is we don't have any data on those other formulations or routes of administration. So until we do, the US Food and Drug Administration has cautioned that they all should be treated the same. All combination hormones must have a black box warning in their physician labeling that highlights the increased health risks.

What were other study limitations?
When you do a clinical trial, you recruit volunteers who are willing to go in the placebo group or in the hormone group, and not know which group they are in. We know from other studies that about 20 percent of women seek medical treatment for menopause. I find it unlikely that we had many of those women in our study because they are not going to risk being in the placebo group. That's the real critical limitation of our study, but I don't know any way around that.