This multi-part series explores the background behind the establishment of the Women’s Health Initiative (WHI) and the major findings for women’s health on the benefits of various interventions. Part I addresses the WHI’s background and describes findings on low fat diets. This section looks at what we’ve learned from the WHI about menopause hormone therapy and calcium/vitamin D.
Want incontinence, gall bladder surgery and cognitive decline? Then start taking hormones!
Although most women have heard the big news from the WHI’s hormone therapy (HT) trials, not as much attention has been paid to the effect of hormones on other important health issues for older women. The big news – that hormones taken after menopause don’t help prevent heart attacks, but they do increase the risk of strokes and breast cancer – reached most women very quickly after the National Institutes of Health (NIH) announced that it was ending both hormone therapy trials early. Neither estrogen alone (for women who had had a hysterectomy) nor estrogen-plus-progestin (for women who still had their uterus) helped prevent heart disease, and both clearly increased the risk of strokes and blood clots. Estrogen plus progestin also increased the risk of breast cancer. These risks were significant enough to outweigh the reduced fracture risk seen in women on HT. The risk of stroke, blood clots and breast cancer are serious, but uncommon; but many women rightly wonder about HT’s impact on other, more common conditions experienced by older women. With one big exception, the news isn’t good.
Colon cancer: Let’s start with the good news first. Both estrogen and estrogen-plus-progestin reduced women’s risk of developing colon cancer. This is important, as colon cancer is one of three most common cancers in women. There’s no way to get this benefit, however, without also being exposed to HT’s risks, so — at least for now — no one is recommending women use menopause hormone therapy to reduce their risk of developing colon cancer. Luckily, colon cancer screening actually not only identifies disease, but also reduces the risk of developing the cancer. Even though it’s unpleasant, the screening is an effective step women can take to reduce their chance of developing colon cancer.
Gall bladder disease: Although it wasn’t widely known before the WHI trials, it’s been clear for some time that HT users are much more likely to be treated for gall bladder disease than are other postmenopausal women who don’t take HT. In some studies, HT users were as much as six times more likely to be treated for gall bladder disease! The WHI trials found that gall bladder disease was increased by about 60 percent among women taking hormones.
Incontinence: Here’s a real shocker. Before the WHI results were released, most gynecologists believed that HT could help keep women’s incontinence from worsening, and maybe even reverse it. The belief seems to be based on extrapolations from the good effects that estrogen cream has on vaginal tissue, among women who complain about painful intercourse after menopause. The bladder and urethra are right next to the vagina, so the thinking was that maybe estrogen would help that tissue too. Now we know HT actually makes incontinence worse in women who already have it, and it makes it more likely to develop in women who don’t. Gynecologists seem to be getting the word not to recommend HT to women with urinary incontinence, but they have yet to develop any guidelines for when to suggest that women on HT consider stopping the drugs. So, take matters into your own hands. If you’ve chosen to take HT for your own good reasons, and you find yourself experiencing incontinence, go off the hormones, at least for a while, and see if your condition improves.
Cognitive Decline: Now here’s some really bad news. In the days when almost every gynecologist prescribed HT to almost every postmenopausal woman, many women were told that it looked like hormones would prevent Alzheimer’s disease. Who wouldn’t want to take a pill to prevent Alzheimer’s? Luckily for us, as the WHI was being designed, researchers persuaded the NIH to allow them to include a very detailed study of the mental acuity of over 3,000 women. When the results were unveiled and the researchers were able to compare women on HT with those on placebo pills, it became clear that hormones made things worse. While there weren’t enough cases of Alzheimer’s disease in the group to see a difference, the researchers evaluated women for a milder condition (cognitive decline) and found that, again, hormones made things worse.
This study was only conducted in women who were at least 65 years old when they began taking hormones. So, the results are very useful to counteract the old advice that all women should consider taking hormones as replacement therapy, but they don’t tell us anything about the effects of menopause hormone therapy on the brains of women in their 40s, 50s and early 60s. This lack of information has left the door open for the people who believe that taking HT early — before women are fully postmenopausal — could be beneficial for the brain as well as the heart.
Calcium: Too much, not enough, or just right?
Another surprising result from the WHI announced earlier this year was the finding from the “CaD” study that calcium and vitamin D supplements did not significantly reduce women’s risk of bone fractures or colon cancer. In this large, randomized trial, 36,000 women took either a pill containing 1,000 mg of calcium and 400 IU of vitamin D (CaD), or took look-alike placebos, every day for seven years. (Pills for women in the active group contained 500 mg of calcium carbonate and 200 IU of vitamin D3, for a total of 1,000 mg of calcium and 400 IU of vitamin D contained in the study pills they took each day.) The trial was designed to explore the overall benefit of calcium and vitamin D for post-menopausal women on colon cancer and all types of osteoporosis-related fractures. The results were disappointing, because researchers had hoped to confirm earlier studies that suggested dietary or supplemental calcium has a protective effect for women. Although CaD was shown to reduce the number of hip fractures experienced by women who were at least 60 years old when they began the trial, hopes had been much higher.
Women in the CaD trial also participated in the WHI’s other trials as well (HT or dietary modification). Asking women who were already participating in the WHI trials to volunteer for CaD was an easy way to test another important theory about women’s health. The decision to take the easy (and less expensive) approach, however, led to a less than ideal testing environment. Because every woman in the CaD trial had already agreed make lots of changes in their lives in order to participate in the dietary modification and/or the HT trials, researchers decided not to ask women to give up any calcium supplements they were already taking when the trial began. This decision to allow women to continue taking their own supplements was bolstered by government recommendations that all postmenopausal women get at least 1,200 mg of calcium daily.
Women who agreed to participate in CaD were questioned carefully before being given the study pills. It turns out that these healthy volunteers were already getting an average daily dose of 1,150 mg of calcium and 360 mg of vitamin D. This dose is much bigger than womenï¿½s typical daily intake, which research indicates is as low as 400 mg per day. So, it could be that calcium is effective, and the women in the CaD trial were already getting enough calcium to get the protective benefit, regardless of whether they took more or not. For example, women who received the placebo pills (rather than the calcium or vitamin D supplements) experienced less than half the number of hip fractures that was originally predicted by the researchers — possibly because they were already consuming higher-than-average amounts of calcium. It could be that some calcium is good, but more isnï¿½t any better. This rationale does not explain the failure to find any effects on colon cancer rates, however, as the women in this study were diagnosed with colon cancer at the rate expected by the researchers.
Another complicating factor in the CaD study was that a large percentage of women stopped taking the study pills altogether. Women were asked to take their calcium and vitamin D pills twice a day — and those pills were whoppers! Moreover, for the first few years, the pills came in a chewable form that apparently wasn’t too tasty. Researchers found a way to provide the needed dose in pills that could be swallowed (instead of chewed) but even so, by the end of the study, only 76 percent of the women were still taking their pills. Just 59 percent were taking all of their pills. When researchers looked only at women who continued to take all their pills over the entire study period, they saw a statistically significant decrease in hip fractures: four fewer hip fractures for every 10,000 women.
So, if you’re an older woman who wants a safe way to lessen your risk of hip fractures, and you know you can remember to take a pill twice a day, should you take calcium and vitamin D supplements? It’s certainly easier for women in the real world, who have access to reasonably sized pills that can be easily swallowed. But, maybe the decision isn’t as easy as that. Even though CaD is a supplement, not a prescription medicine, it’s not risk-free. In contrast to the four women out of every 10,000 who benefited by preventing a hip fracture, five out of every 10,000 women in the study developed kidney stones as a result of the CaD supplements. It’s likely that the worst experience with a kidney stone isn’t as devastating as the best outcome of a hip fracture. But that’s a decision that can only be made by an informed woman, weighing the risks and benefits for herself.
In short, the WHI has overturned some of the things we thought we knew, and raised interesting and important new questions for study. It provided a lot more information that women can use to become more educated and empowered health advocates on their own behalf. And, if there’s one thing we’ve learned over the years we’ve spent advocating for women’s healthï¿½ information is essential.