Hormone Replacement Therapy: Yes, No, Maybe

Beautiful Bones without Hormones: The All-New Natural Diet and Exercise Program to Reduce the Risk of Osteoporosis and Keep Your Bones Healthy and Strong
by Leon Root, M.D.

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Before going on about osteoporosis in general, I would like to pause to take a look at the effects of hormone replacement therapy on bone health. Hormone replacement therapy provides women with the female hormones, especially estrogen, that decrease dramatically after menopause. When the hormone estrogen is given alone, it is usually referred to as estrogen replacement therapy (ERT). When estrogen is combined with progesterone (the hormone that prepares the uterus for pregnancy each month) it is generally called hormone replacement therapy (HRT). When a woman reaches perimenopause, the transition period leading up to menopause, her hormone levels start to fluctuate, often causing uncomfortable symptoms like hot flashes, mood swings, and interrupted sleeping patterns. Once her hormone levels have fallen dramatically and her periods have stopped for a year, she is considered to be in menopause.

One thing we have known for a while now is that HRT does help prevent bone loss in postmenopausal women. After menopause, when the level of natural estrogen in a woman's body has dropped significantly, her bone loss often accelerates dramatically, to as high as 7% per year, and continues at this rate for the next three to five years. One surefire way to deal with this problem is to replace the estrogen her body was losing with supplemental hormones (HRT). For many years this was the only FDA-approved drug treatment for preventing and treating osteoporosis. Then, in July 2000, when the preliminary results of the federally funded Women's Health Initiative (WHI) study questioned the safety of HRT because of a slight increase in the risk of breast cancer, all bets were off, at least for many of the women taking hormone supplements. In this study, 16,000 randomly selected women, ages fifty to seventy-nine, from all over the U.S., agreed to take part in a long-term effort to learn more about what women can do to stay healthy longer. The study was scheduled to be completed in 2005. The factors to be examined were diet, exercise, calcium supplements, and HRT. The press release in July 2000, which reported a slight increase in the risk of breast cancer, heart attack, and stroke in women on HRT, referred to only the hormone therapy part of the study. The rest of the study is continuing and the results have not yet been announced as of February 2004.

Here's how this particular part of the WHI study worked: Thousands of the participating women were randomly given Prempro, a specific conjugated estrogen and progesterone combination, which at the time was the most widely used hormone treatment, while the others were given a placebo (a sugar pill). Neither the participants nor the doctors conducting the test knew which women in the study were receiving the hormone and which were receiving the placebo.

The hypothesis for this part of the study was that women taking Prempro would show a decrease in coronary heart disease. The researchers also looked at the effect of HRT on breast cancer, stroke, venous thrombosis (blood clotting), colon cancer, and bone fractures.

This study was different from most drug studies because it was designed to help researchers learn about the long-term effects of HRT. Most drug studies look only at the short-term effects of a drug on a particular disease. In other words, the WHI study was designed to try to find out if HRT would help women stay "heart healthy" longer. The minute it became clear that the answer was no, the study would be stopped. The investigators had also agreed that if a significant increase in breast cancer or any of the other secondary diseases they were looking at showed up, the study would be stopped.

After a five-year follow up, the evidence indicated that in 10,000 healthy postmenopausal women who took Prempro for a year, there would be eight more cases of breast cancer (0.08%) than in the similar group not taking Prempro. Looking at the data in this way for the other outcomes, the 10,000 women taking Prempro would have eight extra strokes, eighteen extra pulmonary emboli (blood clots), and seven extra coronary events (heart attacks). However, these same women would have six fewer cases of colon cancer and five fewer bone fractures. There were no differences between the two groups in deaths from any cause. The breakdown would look like this:

Does This Mean That Hormones are Bad?

Not necessarily. Whether or not to take HRT is a highly personal decision based on the medical history and personal philosophy of each and every postmenopausal woman. It is definitely a question that every postmenopausal woman should discuss with her doctor, then weigh the pros and cons and come to her own decision. After the findings of the WHI study, HRT is being prescribed with much more caution these days, but this does not mean that it is absolutely wrong for every woman in every case. What this study showed is that the two products in Prempro should not be given to women to prevent heart disease, stroke, blood clots, or breast cancer. It doesn't mean that they are bad drugs or that they cause these diseases, it simply means that this particular combination of hormones, over time, may (according to this study) increase the chances of developing breast cancer, stroke, blood clots, or heart attack. Another study by the National Cancer Institute published in the Journal of the American Medical Association in July 2002 showed that women who take estrogen alone, without progestin, were at a high risk of developing ovarian cancer. This study found that taking estrogen (without progestin) for ten years increased the risk of ovarian cancer by 60%. Women who took estrogen alone for twenty years would triple their risk of developing ovarian cancer. On the other hand, some preliminary studies indicated that HRT may be helpful in preventing Alzheimer's disease, though very recently this finding has been disputed. The Nurses' Health Study, an observational study in which tens of thousands of nurses reported on their health and hormone use findings, contradicted some of the findings of the WHI study. The nurses study found that hormone users had a 30% reduction in heart attacks, and that HRT may have a positive effect on macular degeneration, which is an age-related loss of vision. The reason for this discrepancy is still unclear.

What is clear, though, is that there are some positives to hormone therapy. It can relieve the symptoms of menopause, it can keep a woman's skin looking younger, and it helps lower the risk of colon cancer, bone fractures, and perhaps even macular degeneration. But another study of 140,584 women, presented in April 2003 by Dr. Elizabeth Barrett-Connor of the University of California at San Diego, found that when postmenopausal women stopped taking estrogen, they rapidly lost their protection against hip fracture.

Then, on June 25, 2003, a follow-up report on the WHI study was published, and this concluded that compared with women not on hormones, those who take estrogen and progestin tend to develop breast tumors that are harder to spot, and because these tumors are therefore discovered at a more advanced stage, they are harder to cure. In this follow-up study of the 8,506 women on hormones, 199 developed invasive breast cancers, compared with 150 cases in the 8,102 women taking placebos. All of the women in the study had yearly mammograms. Of those using hormones, 25.4% had cancers that had begun to spread to other parts of the body, while this was the case with only 16% of the women taking the placebo. What's more, after one year of treatment, 9.4% of the women in the hormone group had abnormal mammograms, compared with 5.4% in the placebo-taking group.

A second, alarming report found that the combination of estrogen and progestin increased the risk of breast cancer even when the progestin was given in a sequential manner - that is, only on certain days of the month, instead of every day as with Prempro. It had been thought that sequential progestin might be safer than taking it every day, but that no longer appears to be the case. This second report, based on a study directed by Dr. Christopher Li of the Fred Hutchinson Cancer Research Center in Seattle, corroborated the previous finding that women who took estrogen alone had no increased risk of breast cancer, even if they took it for twenty-five years. The problem, though, is that estrogen dramatically increases the risk of uterine cancer, so only women who have had hysterectomies are advised to take unopposed estrogen.

It appears to me that the dangers of HRT have increasingly begun to outweigh the benefits. As I suggested before, what it really comes down to is this: Each woman should talk with a doctor who knows her complete medical history, and together they should decide whether HRT is right for her. Many doctors who formerly advocated the use of HRT now recommend it only for women with very severe symptoms of menopause, such as nearly unbearable hot flashes, and then for only a short period of time. For our purposes here, however, I'm going to talk about how to prevent and treat osteoporosis without hormone therapy, since there is so much controversy about the long-term safety of the hormone medications currently available on the market.

Let's Bone Up On Bones

Our skeletons are made up of two types of bone tissue: trabecular bone and cortical bone.

Trabecular bone makes up the interior of the bones of the vertebra, and some is also found in the ends of long bones. It looks like a honeycomb consisting of a system of struts and arches. It is often called "spongy" or "cancellous" bone because of its latticelike structure. Trabecular bone is filled with bone marrow. It accounts for about 20% of the bone in our body, and has a high metabolic rate.

Cortical bone surrounds the trabecular bone and accounts for the remaining 80% of the bone in our bodies. It is solid, dense, and strong, and gives the long bones in our hips, legs, and forearms their strength. It forms the outer layer of the long bones and has a slow metabolic rate so it is broken down and replaced (remodeled) much more slowly than trabecular bone.

If you were to look at a cross section of healthy, dense bone, it would look a little like a latticework, or perhaps Swiss cheese, with lots of solid cheese and a few holes. If you were to look at a cross section of the bone of someone with osteopenia or osteoporosis, it would also look like Swiss cheese, but with lots of holes and very little cheese. From the outside both bones would probably appear to be healthy, but if you were able to see what was going on inside the trabecular part of the second bone, you'd be able to tell right away that the bone is thin, brittle, and weak.

Bone mass and bone density are closely related. When bone mass decreases, bone strength decreases, and fractures are likely to happen with even the slightest amount of external force. Sometimes simply bending over to pick up the newspaper, or even coughing, can cause a fracture.

Why Do Bones Break Down?

The remodeling process I've been talking about requires the action of two types of bone cells, osteoblasts (bone builders) and osteoclasts (bone removers). As I've mentioned above, during childhood, the activity of the osteoblasts, the builders, outdoes that of the osteoclasts, the removers, so that young bones can grow in size, weight, density, and strength. Between the ages of twenty-five and thirty our bones have reached their maximum density, and the rapid rate of growth begins to slow down and eventually reverse. Resorption (bone loss) slowly begins to overtake formation, and the gradual process of bone thinning begins. I'll explain more about this in Chapter 5, "The Calcium Revolution," but do remember that one of the best ways to ensure long-term bone health is to make sure that you achieve optimal peak bone mass during the growth years. This means that as a young person you need to have lots of calcium and vitamin D in your diet, and do weight-bearing exercises regularly. Even if you missed out on building healthy bones as a child and teenager, it is never too late to start, but if you are a parent it is important to remember that the stronger the bones your children build today, the longer and healthier their lives are apt to be. We'll talk more about this in the section on Kids and Calcium on page 308.

Copyright © 2005 Dr. Leon Root

About the Author

Dr. Leon Root is an orthopedic surgeon at the Hospital for Special Surgery in New York, where he also serves as the Director of Rehabilitation Medicine and Director of the Back School Program. A Professor of Clinical Orthopedics at the Weill College of Medicine, Cornell University and a frequent guest on national media, he lives in New York City.