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The Body Engineers

FROM THE DECEMBER 2007 ISSUE

The Body Engineers

Hormone researchers seek new life for old brains and bones.

Thursday, December 13, 2007

RELATED TAGS: AGING, ALTERNATIVE MEDICINE

Panelists Marc Blackman, Andrea Dunaif, Ginger Constantine, Sara Rosenthal, Adrian Dobs, Michael Thorner.

Photograph by Mackenzie Stroh

In most of the world, people are living longer than ever, and one consequence is that they are living old longer than ever—more frail, less mobile, less mentally acute. Hormones seem central to the process. Muscle atrophies as growth hormone declines; bones get fragile as estrogen declines; sex drive dwindles as testosterone declines. More and more evidence suggests that returning those hormones to the blood can turn back the biological clock. So DISCOVER brought together six leaders in hormone research at the 2007 meeting of the Endocrine Society in Toronto to explore whether hormone therapy could halt or even reverse the aging process.

Participants were Marc Blackman, chief of the endocrine section at the National Center for Complementary and Alternative Medicine at NIH; Andrea Dunaif, chief of endocrinology at Northwestern University; Ginger Constantine, vice president of women’s health and bone repair at Wyeth Research; Sara Rosenthal, bioethicist and medical sociologist at the University of Kentucky; Adrian Dobs, professor of medicine at Johns Hopkins University; and Michael Thorner, professor of medicine at the University of Virginia. DISCOVER executive editor Corey S. Powell moderated the discussion.

Let’s start with the fundamentals: What role do hormones play in controlling, and potentially preventing, the aging process?

Dunaif There are a lot of endocrine processes that have an aging component. For women, the most striking one is gonadal hormone: Women stop menstruating. Interestingly, in both women and men, adrenal function starts to go down with age. The question that we get into is, if you replace those hormones, are you going to prolong life? And is it appropriate to do?

Dobs I see a lot of men who, as they get older, don’t have the same kind of sexual function they had when they were younger, and the same thing goes for women. And of course the question is, “Well, how much of that is natural and should be left alone?” One can look at it in different ways. One can say that sexual function is an important component of quality of life, and we should try to preserve it as long as possible. The other side of the coin is that there are other aspects of life. I think it was Socrates who that said that he was glad he didn’t have the same libido that he had when he was younger; he could finally get some work done.

Blackman I would step back and define the difference between biological aging and chronological aging. We all know that there are people who are youthful folks in their seventies, eighties, and even beyond, physically and mentally, and people who we feel are prematurely old, either from disease or just because the ravages of time have worked more quickly on them. It’s the loss of functional independence, whether for hormonal reasons or complex other reasons, that is the adverse consequence of aging.

Dobs It’s a tough balance how much can be medically treated and how much is lifestyle oriented. So many of the diseases that we talk about—being overweight, getting diabetes, a lot of the chronic diseases—we think about in terms of taking a magical pill. But in reality, many of the diseases can be treated and prevented from a lifestyle point of view.

Thorner There’s a study now being done of older minority women. Half of them have been asked to go to school five days a week to help children learn to read and so on. Their health outcomes are better and their life expectancy is better than for the other half. And so an involvement in society is important in influencing aging. Physical exercise is important. You can’t just say there’s one magic bullet. It’s got to be part of a whole program.

Blackman One of the leitmotifs of this discussion is that aging is not really about hormones; it’s about more complex issues. Hormones are a part of the mix, but hardly the whole story.

Dunaif I think that one of the major reasons the antiaging industry is so appealing is precisely because it promotes taking a pill instead of changing a lifestyle. People are so drawn to the quick fix that you could probably spend the next 50 years trying to get them to do the crossword puzzle and walk around the block, and that’s not going to happen.

But there still has to be a fundamental biological process behind aging, so can’t endocrinology find ways to let us live longer, better lives?

Constantine I think we can perhaps affect aging, but can we affect life span? That’s a huge question. Estrogens definitely prevent osteoporosis. Osteoporosis is one of the most debilitating and disabling diseases that we know of. In the Women’s Health Initiative —a massive study of 161,808 women over 15 years—there was a decrease in mortality among the women in the 50- to 59-year-old group who took estrogen alone or with progesterone. There was also a decrease in cardiovascular disease, though there’s some debate as to whether it’s statistically significant. But we have to look at what we’re doing with our hormones. Are we treating disease? Are we preventing disease? Are we preventing aging?

Thorner I think of aging as a process which probably is inevitable but almost certainly can be slowed—and the objective is not to extend life but to be able to do whatever we want to do until the day that we drop, rather than becoming increasingly dependent. Endocrinology has the tools right now to be able to have a huge impact on aging and on being able to allow people to remain vibrant for as long as possible.

Dunaif But you don’t want the bogus stuff. You don’t want this big industry that’s playing on all these fears, hyping this [hormone therapy] stuff and doing harm.

Speaking of hype, Suzanne Somers has been prominently pushing bioidentical hormones as a way of slowing the aging process, replacing the hormones that dropoff as we age with natural compounds that are structurally identical.Mainstream researchers are dubious about this approach. Why?

Dunaif You’ve got two issues here. One, if we replace those hormones, does that help? And two, although we don’t have the data with the bioidentical hormones, we know from the Women’s Health Initiative that estrogens were not the fountain of youth that Suzanne Somers sort of claims. They didn’t keep you sharper and heart-attack free. And then you get into this sham argument that because this hormone is not the hormone that was used in the study, because it’s identical to what the body makes, it doesn’t have the side effects. Scientific data do not support that. In fact, what pharmaceutical companies make, because it’s a highly regulated industry, is much safer and much purer than bioidentical hormones.

Somers argues that the reason that we don’t have good data on bioidentical hormones is that they can’t be patented so there’s no industry money behind them. Why aren’t the pharma companies investigating these compounds?

Constantine Why would I test somebody else’s product for safety and efficacy? To say, “They haven’t tested my product” is, quite honestly, a ridiculous argument. I would think the person who’s making the profit has the responsibility for testing, and it’s certainly not the pharmaceutical company; it is the people making the bioidenticals, the people who are selling the books, the people who are on the speaking tours. They’re making a profit off that, I would imagine, and it would behoove them to study it.

Dunaif I think we’ve got a little confusion here, because what Suzanne Somers is talking about—bioidentical estrogen—is the same product that is marketed by a number of pharmaceutical companies. There are studies that are not as big as the Women’s Health Initiative showing that it is equivalent in outcome parameters to Premarin [a pharmaceutical estrogen]. There are no data showing that these different preparations of estrogen differ biologically. The reason bioidentical hormones aren’t getting tested—it is for reasons that I think are just outrageous to the public. The FDA doesn’t regulate this industry, so somebody in a compounding pharmacy is literally making hooch. You don’t know what concentration you’re getting. You don’t know what your blood levels are. And you’ve got somebody selling the idea that because of a great conspiracy, bioidenticals are safer than what the pharmaceutical companies are selling—and that is totally wrong.

Dobs I think the public is sometimes quite naive about the complexity of doing research. First, it is extremely expensive. The Women’s Health Initiative or a comparable study using testosterone in men costs billions of dollars and many years. To do a study like that takes a lot of time, a lot of money, a lot of people willing to volunteer to participate in research like that.

Dunaif Right now we have great examples of the challenges involved. We have Vioxx being pulled off the market. We’ve got rosiglitazone [Avandia] being questioned. On one hand, you’ve got all the newspapers and Congress saying: “You didn’t test it enough. You didn’t do it in 5,000 people to find out there’s a bad effect.” On the other hand, you have people saying: “You’re keeping something from us. This is a conspiracy.”

Which gets back to the idea that people are looking for a miracle pill. Why this obsession with youth? People have been growing old forever—why is fulfilling our biological destiny now considered a disease?

Dunaif The sociological experience of women has dramatically changed in this century, much more so than any century prior, and our biology has not caught up with our social circumstances. We have a number of women who are coming into their careers only in their thirties and forties. We have pushed the envelope in terms of reproductive possibilities into perimenopausal pregnancies, even postmenopausal pregnancies, so there’s tremendous dissatisfaction with an aging body at a very young sociological age—it’s a huge contrast.

Thorner I think the real public-health issue that we’re going to be dealing with is a large number of people in this country who are going to be frail and elderly. In a society where the proportion of the old population is getting larger and larger, it’s not going to be economically possible for all these people to be looked after. It’s a serious issue.

So how far can antiaging therapy take us? Can it address these social and psychological issues in addition to the obvious biological goals of staying vigorous into old age?

Rosenthal Ultimately, we might do a very good job of preserving ourselves physiologically, but there are tremendous problems that people still suffer from in terms of psychological issues and spiritual issues—the absence of a rich life in the parts that you can’t see. In addition, we’re very far away in research from really understanding the aging brain, fixing Alzheimer’s disease, stopping all kinds of dementia-related diseases. We may wind up with large numbers of people who may not have quality of mind even though they have quality of body, and that’s just going to create more problems and more questions.

Dunaif And even though we may have therapies to prevent aging in the future, there are going to be tremendous disparities in who has access to those therapies. We may wind up in a societal dilemma where wrinkles will be a sign of poverty, and lovely-looking skin and great libidos will be a sign of wealth.

Rosenthal When we talk about aging, we’re really not looking at many of the positive sides. Many of us come into the heights of our careers and knowledge only in our forties, fifties, even sixties. The whole point of living is to live and to make a contribution, not to live your life in fear of aging. Life-cycle research has demonstrated that people actually aren’t happiest in their twenties.

Blackman The concept of antiaging is anathema to those who study the aging process, gerontologists or geriatricians. The whole philosophy implies that aging is inherently something to be prevented and avoided rather than understood—rather than learning to live one’s life with grace in each epoch of life. Our country is unusual in that it no longer venerates the wisdom and experience of aging.