ORWH Podcast: May, 2007

P R O C E E D I N G S

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MALE ANNOUNCER: From the National Institutes of Health in Bethesda, Maryland, America's premiere medical research agency, this is Pinn Point on Women's Health with Dr. Vivian Pinn, Director of the Office of Research on Women's Health.

Now here's Dr. Pinn.

DR. PINN: Welcome to this episode of Pinn Point on Women's Health. Each month on this podcast we're taking a look at the latest developments in the area of women's health and the medical research that affects our lives.

I'm pleased to welcome Dr. Jacques Rossouw, who is Chief of the Women's Health Initiative Branch of the National Heart, Lung, and Blood Institute here at the National Institutes of Health. Today, Dr. Rossouw will talk to us about some recent findings from the Women's Health Initiative and he'll tell you in just a few minutes what the Women's Health Initiative is. But first some hot flashes from the world of women's health research coming up in 60 seconds when we continue with Pinn Point on Women's Health.

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DR. PINN: Welcome back to Pinn Point on Women's Health. As promised, it's time to take a look at some of the hot flashes in the news or to be in the news regarding women's health research.

First, hot flash: what is vulvadinia? Do you know what vulvadinia is? Have you heard the term? Have you heard women refer to feminine pain or the pain down there? Well, it turns out that vulvadinia is chronic discomfort or pain of the vulva area which is in the pelvic area for women in the area outside of the vagina. Probably because of its location, it's a very sensitive topic for so many women, and it's also a condition that is often not recognized by women or their physicians.

The Office of Research on Women's Health, the National Institute of Child Health and Human Development and other institutes at the NIH, working in association with the National Vulvadinia Association, is developing right now an educational campaign for primary health care providers, patients and the general public about vulvadinia, its symptoms, its diagnosis and its treatment options.

I wanted to make the members of the audience aware of this topic because it is an important one for women who have this constant pain and are unable to find relief. Let me refer you to the ORWH website which has information on vulvadinia and can provide a source of information for you. That website is at orwh.od.hih.gov and then look for a link to vulvadinia. We're hoping to have education packets available for you in the very near future, but all of that information will be available on our website and in addition, we're continuing to fund research here at the NIH to help us have a better understanding of vulvadinia, its causes, its treatments so that this pain which women often don't like to talk about, but which can really cause great discomfort can be addressed and eliminated for those who suffer from this condition, vulvadinia.

Another hot flash has to do with visual impairment, that is problems with seeing in women. There was a recent article interview with Dr. Janene A. Smith who is a researcher here at the National Institutes of Health, published in The Journal of Women's Health. In this interview with Dr. Janene Smith, she points out that in the National Institutes of Health supported report, vision problems in the United States, there are more than one million legally blind adults using the strictest definition and 70 percent of those who are legally blind are women. Another 3.4 million adults are visually impaired, that means having some problem with seeing. And of those, almost two thirds are women.

There are a number of reasons that contribute to these problems with seeing for women. I recommend the article to you and we will put the link on our website, but aside from that let me just use this opportunity to say based upon the discussion with Dr. Smith and looking at the causes of visual impairment in women, women, because vision is so important and some of the causes of blindness can be prevented with early care, take care of yourselves, go and get your eyes checked. Make sure that you're taking care of your eyes, just as you're taking care of your family.

We'll have more updates in the next podcast, but coming up next I want to visit with Dr. Jacques Dr. Rossouw for a discussion about the Women's Health Initiative, one of the most important studies that's ever been funded by the National Institutes of Health.

Ladies, it has to do with our health and our post-menopausal years. So we'll be right back with more Pinn Point on Women's Health.

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DR. PINN: Welcome back to Pinn Point on Women's Health. And we're delighted to have with us Dr. Jacques Rossouw, Chief of the Women's Health Initiative Branch of the National Heart, Lung, and Blood Institute.

Dr. Rossouw, we want you to tell us about some of the recent findings that were published from the Women's Health Initiative, but first could you just remind our audience what the Women's Health Initiative is?

DR. ROSSOUW: Yes. The Women's Health Initiative was established in 1991 to study the causes and prevention of the more common diseases afflicting older women, post-menopausal women such as breast cancer, colorectal cancer, hip fracture, heart disease and stroke. And so three trials were launched, one, a low-fat diet to prevent cancer; and one of calcium and vitamin D to prevent fractures; and one of hormone therapy to prevent coronary heart disease. The new findings relate to the hormone therapy trials, and perhaps the listeners might remember that early in the 1990s, hormone therapy was commonly being advocated and recommended by professional bodies for prevention of heart disease.

Prior to that, hormone therapy was recognized by the FDA for the treatment of hot flashes and night sweats, and systems of vaginal atrophy and for osteoporosis prevention. But it was also now being recommended for chronic disease prevention, particularly, coronary heart disease. But then were non-medical uses such as the perceived prolongation of life and keeping feminine forever by replacing a presumed hormone deficiency after the menopause.

So we set out to study where the hormone therapy has more risks than benefits and our main findings from the trials, if I may continue before we get into the new findings --

DR. PINN: Yes, please do.

DR. ROSSOUW: Were that in the trial of estrogen versus progesterone, that's in women with an intact uterus, the risk of cardiovascular conditions such as heart disease, stroke, venous strombosis, were increased, rather than decreased, and also the risk of breast cancer was increased. There were some benefits, but the risks certainly far outweighed the benefits and also interestingly dementia risks was increased. And so that trial was stopped early because of these increased risks.

And then the trial of estrogen only, women who had had a hysterectomy was also stopped early in that case because of no benefit for heart disease and increased risk of stroke, so after WHI the original publications came out, the recommendations changed completely and hormone therapy is now no longer used for preventing heart disease. In fact, women are advised not to use it for prevention of heart disease and prescriptions have dropped by some 60 percent since 2002, which leads me into the new findings because this drop in prescriptions was in both younger women who were presumably mostly using it for treatment of vaso-motor symptoms, hot flashes and night sweats, and in older women.

It was our perception that perhaps some of the legitimate uses of hormone therapy were getting short-shrift, whereas appropriately it was no longer being used for chronic disease prevention.

DR. PINN: So what you're saying is that and in accord with what the Food and Drug Administration recommends, that we do still believe that hormone use in menopausal women is good in terms of treating the symptoms of menopausal transition like hot flashes, but that the WHI showed that it did not seem to have benefits for prevention of chronic diseases such as cardiovascular disease when the first results were published.

Is that a correct summation?

DR. ROSSOUW: Yes, that is correct. When we first announced those results, we were looking back on our press statement at the time. We were very clear that this was not a trial of treatment of symptoms. And this was a trial of prevention of chronic disease in older women. And our findings did not -- we thought should not influence the choice of women, whether they wanted to use for a short term use for relief of symptoms.

However, we perceived that probably many women were afraid to use it and we tried to address that, even for relief of symptoms and we tried to address that in previous publications of the individual trials and there were some suggestions that this increased risk of heart disease, in particular, was not present in younger women or women closer to menopause, but those were inconclusive results, whereas the risk, of course, was increased in women over 60 or more distant from the menopause.

So in this publication, we set out to look at these data more definitively and what's new here is that we combined the two trials to get more statistical power.

DR. PINN: When you say you combined the two studies, you're saying you combined the data of the results from which two trials of the Women's Health Initiative?

DR. ROSSOUW: We combined the results of the trial of estrogen only in women who had had a hysterectomy and estrogen plus progesterone in women with an intact uterus. Now although the results of the trials are somewhat different, you know, in the estrogen-only trial no increase in coronary heart disease and estrogen plus progesterone trial increase in coronary heart disease. What we were looking at here is whether there was a trend across decades of age or decades since the menopause. These trends were quite similar in the two trials and we could combine the trends.

And by doing this statistical analysis, we found a rather clear indication that there does not appear to be an increased risk of coronary heart disease within ten years of the menopause, compared to an increase in the risk as women grow more distant from their menopause.

On the other hand, the increased risk of stroke was present irrespective of the years since menopause. So that has to be kept in mind.

Also, there appears to be an increased risk of breast cancer on estrogen plus progesterone even in women who are within ten years of their menopause.

DR. PINN: Now what were the greatest surprises from looking at this combined data?

DR. ROSSOUW: That's a good question, because the lack of an increased risk coronary heart disease was suggested by previous analyses of the individual trials. We could now just get a firmer estimate of that. The surprise here was that we found that the increased risk in older women, women older than 60 or more than 10 years since their menopause, was basically confined in those older women who had hot flashes and night sweats.

You know, between five and ten percent of women continue to have moderate to severe hot flashes and night sweats into older ages. And it was in those women that there was an increased risk of coronary heart disease. That was unexpected. We tested that, of course, because that is the main reason why women would want to use hormone therapy -- women with hot flashes and night sweats.

And so what we found is that women with those symptoms, okay to use in the short-term within ten years of the menopause, four to five years of use. But not okay to use to use it if you have persistent symptoms after that. And the reason why these women, older women, with symptoms have more risk is unclear, but we could look at whether they had more risk factors or not and they did. They were more likely to have high blood pressure, high blood cholesterol, overweight, diabetes, and so forth.

So part of the explanation is that older women with symptoms seem to be at higher risk inherently, and they should focus on identifying and treating their risk factors rather than considering whether to use hormone therapy. They should not use hormone therapy.

DR. PINN: Now let me see now. If I am a woman listening to this podcast, and I'm just approaching menopause, entering the menopausal transition. So let's say I'm about 50 years old and I am trying to decide whether or not I should be taking hormones. Based upon your re-analysis or your analysis of the combined studies, your advice to me would be?

DR. ROSSOUW: So if you have symptoms, if you have severe symptoms such as they interfere with your life, basically, that's the criteria. They are so severe that you really can't tolerate them. Then hormone therapy is far and away the most effective treatment of those symptoms. Seventy-five to 80 percent of women will respond to hormone therapy. There are other treatments but they are less effective.

And so your choice should be based on how severe your symptoms are, and then use for four to five years, which is what our data indicates -- four to five years, is not attendant with a higher risk of coronary heart disease. However, there is always a caveat in these things. You should certainly continue to have your mammograms if you are hormone therapy, and you should certainly check your risk factors, in particular high blood pressure -- your blood pressure, because the increased risk of stroke may still be there.

Now, I must also say that the risk of stroke is very low at younger ages. But nonetheless, you don't want to have it if you can avoid it and you can avoid it.

DR. PINN: Good. So now let's take the other stance and if I am an older woman, I am post-menopausal. I'm about 65, 66 years old and I am still debating whether or not I should be taking hormones, continuing to take them, or start to take them. What does this study mean for me?

DR. ROSSOUW: Our data really specifically looks at starting hormone therapy at an older age versus at a younger age. Because this was a trial, and most of these women had not used hormones before entering the trial. So our data speaks to initiation of hormone therapy at older ages versus younger ages, and the data is pretty clear on that.

Our data do not speak directly to the issue of whether you start -- if you start hormone therapy at a younger age and continue it for a very long period of time, whether any benefits will persist or not. And really that's an issue that cannot be sensibly addressed in the clinical trial because you need a huge clinical trial, horrendously expensive, and in fact impossible to do because long-term compliance, you know, 15 or 20 years which is impossible to achieve. So it is what I would like to call the unknown and the unknowable.

However, since we know that starting hormone therapy at an older age is not a good thing, you know, one needs to on the basis of what we know, we need to advise women not continue hormone on the long-term, particularly since the risk of breast cancer increases with duration of use.

DR. PINN: And I should add that I think what you just stated is certainly consistent with what the Food and Drug Administration has recommended in terms of the recommended use of menopausal hormones. But with the analysis in this new publication, are there any real new changes in recommendations for the use of post-menopausal hormone therapy?

DR. ROSSOUW: So these findings are very consistent with the current recommendations. But I think they serve to sharpen the recommendations in that they are somewhat reassuring that it is okay to use hormone therapy close to the menopause in the short-term for severe vasomotor symptoms. The recognized indication, but now we're saying yes, that indication is okay to use it for that -- in younger women, but it's not okay to use in older women.

See, the recommendations currently don't distinguish age at which you use hormone therapy for treatment of vasomotor symptoms. And now we're saying yes, it's okay to use it but only at a younger age for treatment of vasomotor symptoms. And it further underlines the current recommendation is don't use it for chronic disease prevention, which is of course a concern of older women, rather than younger women.

So it's consistent and I think it serves to sharpen the current recommendations.

DR. PINN: I'm going to put you on the spot with another question, Dr. Rossouw. In our last podcast, we addressed some of the recent research related to breast cancer. You have mentioned here that the studies still show that there may be an increase in breast cancer with the use of hormone, menopausal hormone therapy.

In our last podcast, it was mentioned that there have been some recent studies suggesting that the decline in the incidence of breast cancer may be related to the fact that after the Women's Health Initiative results, there was a decline in use of menopausal hormones.

Could you comment on that or would you comment on that?

DR. ROSSOUW: Yes, certainly. It's a very interesting topic. There have been two separate studies showing that the breast cancer incidence rate dropped by about 10 percent after 2002. In the same period, hormone prescriptions dropped by 60 percent and the drop in hormone therapy prescriptions has continued up to 2006, the most recent data we have. So it is persistent.

So there was a big change in prescriptions and an impressive drop in breast cancer diagnosis. Is it cause and effect? Now, you know, that one can't be sure of. The drop was rather sudden. I mean, it coincided almost exactly with the drop in prescription, so if it is related than it may be that the sensation of hormone therapy is slowing the growth of existing tumors and then for a while there will be a drop in diagnosis and eventually they might emerge again.

You know, it's also possible there was during this decade there has been a decrease in mammography screening prevalence, perhaps because fewer women are using hormone therapy. So there is some issues, but certainly it looks like it might be more than just coincidence that these drops in hormone therapy and breast cancer coincided.

We know, of course, that reproductive hormones are strongly related to breast cancer, so it certainly makes sense. But I would just repeat that even if this finding is true or not it needs to be repeated and is being repeated in other countries. There are other good reasons to reconsider the use of hormone therapy in the long term.

DR. PINN: I think what you just said is very important, so I want to have you re-emphasis a couple of points. First, we do hear a lot about so-called synthetic versus natural hormones. Could you just define those again for us, at least how that terminology is used so that women listening to this podcast will understand when people use those terms what they are trying to imply

DR. ROSSOUW: Yes, so when people use the term natural hormones, then they are talking about the hormones produced in a women's body, esterile (Phonetic) progesterone. These can also be derived from plant sources, and that is another plant origin also has a good connotation in the minds of many. Whereas synthetic is something is that produced, you know, purely in laboratory by synthesis by chemistry or from pregnant mares' urine in the case of Premarin. So that is so-called synthetic.

From the medical perspective, one has to keep in mind that there are only drugs that work and are safe and drugs that don't work or are not safe. And the origin, where they come from, is quite irrelevant. So these terms bio-identical, natural, synthetic versus these others, these are marketing issues. They are not really medical issues.

DR. PINN: Estrogen is estrogen.

DR. ROSSOUW: Estrogen is estrogen as far as we know.

DR. PINN: And you did comment a bit for us on the bio-identical hormones, and we know that there are many who feel that if they have "bio-identical" hormones they will avoid the risk that have been identified with the use of the hormones, for example, in the Women's Health Initiative and other studies. Just make very clear what science says about that at the present time.

DR. ROSSOUW: So a more recent data suggests that hormones, the hormones we use, which are so-called synthetic hormones, don't appear to have an increase of coronary heart disease if used in the first ten years after menopause. So that appears to make a difference. But and the same probably applies to other, you know, hormones, be they synthetic or so-called natural.

But one has to keep in mind that even natural substances, including natural hormones, may have risks. All the risk factors for breast cancer that we are aware of are related to a woman's reproductive natural bio-identical hormones. But keep in mind that even natural substances, such as the natural hormones or if you like bio-identical hormones produced in a woman's body can have harmful effects.

They have purposes for reproduction. Whether they have purposes for disease prevention is another issue. We know, for example, that prolonged exposure to these natural hormones are strongly related to risk of breast cancer. That's both esterile (Phonetic) and progesterone. The earlier the menarche (Phonetic) or the later the menopause, there is the longer the period of reproduction, the higher the risk of breast cancer.

We also know that the very high levels of these hormones during pregnancy are associated with a very high risk of venous thrombosis. So natural is not automatically safe.

DR. PINN: So if I am a woman and I am concerned because I am approaching menopause and I want to stay young and I want to be healthy into the elderly years of my life because I know that women are living longer and I want to be active and have my full mental capability and be able to do everything 30 years from now that I could do when I entered menopause. What's the best recommendation we can give women today? Should I take hormones or is there something else that I should think about doing? I'm not talking about symptoms, I'm talking about that thought that some many women have that hormones will keep us young.

DR. ROSSOUW: Yes. Well, that gets back to you know the theory of hormone deficiency and staying feminine forever if you can correct the so-called hormone deficiency. It's making ovarian, the sensation of ovarian function at the menopause which is a normal phenomenon, akin to thyroid failure or pancreatic failure which gives rise to diseases.

Now but those endocrine organs, if they fail, you die, if you don't treat the deficiency. Your ovary stops working, it's normal and you don't die. You might feel miserable for a while,but you won't die.

So what we should stop looking for hormone therapy or any other elixir of life. Aging is going to be aging and I predict safely that in my lifetime, we're not going to solve that issue. But however, we can manage and prevent the risk factors that become more and more common as women age and these are the things like keeping your body weight within a reasonable range; staying physically active; checking and treating your blood pressure, your blood cholesterol; your blood glucose; not smoking. These things are all known to be effective and safe and that's what we should be -- and of course, you should try to be happy in your personal life and your professional life and find satisfaction in most of the things that you do -- not everything. Not everything. And these are the key, I think.

DR. PINN: So healthy living --

DR. ROSSOUW: Healthy living.

DR. PINN: Healthy living is the key, is the best key we have right now.

DR. ROSSOUW: There's no elixir.

DR. PINN: To aging gracefully.

DR. ROSSOUW: there's no elixir.

DR. PINN: Well, with that in mind and knowing that you've been involved from the beginning with the Women's Health Initiative which I think has been an extremely important study. Would you have other -- knowing that you've been involved with the Women's Health Initiative from its beginning, you've seen the controversies and the surprise findings and the documentation and the reaffirmation of what we found and documented through research and the importance of research that really was well demonstrated by the Women's Health Initiative and the investment of dollars that went into this study and the investment of time of the many, many women who have participated in this study.

So are there other points from the Women's Health Initiative that you'd like to stress to our audience?

DR. ROSSOUW: Generally, which would include the dietary trials and in fact, the hormone trials, I think one of the lessons we've learned is that lifestyle changes take a long time to manifest their benefits. And you know, we're all trying to find the quick fix and certainly if you have a disease, there is a specific treatment that will usually help. But in terms of managing your life so that you live as healthfully as possible as long as possible, that's a lifetime commitment.

And so, for example, in the dietary trial, we found some suggestion that lowering fat, total fat in women who were consuming a high level of fat at (Inaudible) line that there was a reduction of about 20 percent in their breast cancer risk. But overall, the reduction we found at about nine percent was not significant. But maybe you just need to stick with it for more than eight years. But maybe you need to stick with it for 20 or 30 years and you'll find a benefit. So just because a short-term trial or a short-term effort on your part doesn't pay the dividends. That's no reason to give up. You should stick with what we think is the healthy way to go.

DR. PINN: Well, as we focus on women's health research and talk about it needing to address lifespan issues, I think you've just put your finger on the key to how we can improve our health as girls and women, that is, start early with healthy, life behaviors and continue them through life and of course, look for medications and external things that we take, based upon what research has demonstrated really would be of value in treating or curing diseases.

And when we look for prevention, to see what we can do ourselves to help prevent those chronic diseases that can shorten our lifespan. And when it comes to menopause, one of the most hotly debated topics and for many women one of the most important topics we have learned a lot when it comes to those questions that have been asked for years about whether or not to take hormones and we now have good information to help guide us, make informed decisions.

Any other comments you'd like to make, Dr. Rossouw?

DR. ROSSOUW: I would agree absolutely with what you've just said.

DR. PINN: Well, thank you so much for being with us and presenting. I know just a little from the data from the Women's Health Initiative. There's so much more we could discuss, but that could take up many more podcasts. So hopefully, we'll have you back at some point in the future to discuss some of the other areas, such as dementia and relationship to hormones. But with that, thank you for being with us today.

Coming up next, your final thoughts for this month, when Pinn Point on Women's Health continues.

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DR. PINN: And now a few final thoughts. You may have noticed during this podcast that we kept referring to menopausal hormone therapy rather than hormone replacement therapy or HRT which has been sort of the traditional terminology for the use of hormones in menopausal women. Hopefully, after hearing this interview with Dr. Rossouw, you will understand why we tend not to call it replacement therapy anymore, because the thought is that menopause is a natural time in women's lives and so it is not normal to replace the hormones. And therefore, rather than replacing when we use hormones in menopausal women, we're actually treating with hormones. So we have really made a great effort to move the terminology towards referring to the use of hormones in the post-menopausal woman as menopausal hormone therapy.

Aside from that, you've heard a discussion about the Women's Health Initiative. Again, I think one of the most important studies that's ever been done, because certainly questions related to menopause and especially whether to take or not take hormones during the menopausal transition or during the post-menopausal years has been of great concern to women and their physicians and their nurses and their health care providers for many years.

We finally had a long-term study that has taken a look in a randomized controlled trial of large numbers of women of all ethnic, racial, and geographic backgrounds and locations to help us come up with information for that informed decision-making. And right now, the word seems to be that if you're a younger woman, and you're entering the menopausal transition, then you may wish to consider short-term menopausal therapy to prevent those symptoms.

If you've been in the menopausal years for 10 years or so, you might want to think twice or three times or four times about starting the use of hormones, if you think you're taking those hormones to prevent the development of cardiovascular disease. You need to consider also the risk for breast cancer.

Actually, this gets to be very complicated and hopefully we've cleared up some of these points for you. But I recommend that if you have questions, you can discuss them with your physicians or your nurses, discuss these questions with each other and you may also go to the NHLBI website where there's information on the Women's Health Initiative. We refer to it as the WHI, and you can see these results clearly stated. And we also have a link from our ORWH, Office of Research on Women's Health website, giving the final results of the study and linking to that website for the National Heart, Lung, and Blood Institute.

Well, we hope we haven't left you with more questions, but have provided you with more answers and at least we've given you some good information to think about and I can assure you that research will continue to address the questions that we have and continue to have about menopause, but overall, just remember, women's health research is directed towards helping us learn more about our bodies, our health, and our illnesses, so that we can live a longer life with a better quality of life during those years.

And so now, in a few moments, an announcer will tell you where to send your comments and suggestions for future episodes. I'm Dr. Vivian Pinn, Director of the Office of Research on Women's Health at the National Institutes of Health in Bethesda, Maryland. Thank you for listening.

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ANNOUNCER: You can email your comments and suggestions concerning this podcast to marshalove@lovematod.nih.gov. Pinn Point on Women's Health comes from the Office of Research on Women's Health and is a production of the NIH Radio News Service, News Media Branch, Office of Communications and Public Liaison at the Office of the Director, National Institutes of Health, Bethesda, Maryland, an agency of the U.S. Department of Health and Human Services.

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