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NEAL CONAN, host:

This is TALK OF THE NATION. I'm Neal Conan in Washington. Our main focus this hour is on news of a steep decline in breast cancer. Last week, a study reported that about 14,000 fewer women got breast cancer in 2003 than in 2002 and that the most likely reason is that millions of older women stopped using hormone replacement therapy. Questions and answers about menopause, mammograms, HRT and breast cancer a little bit later in the program.

But we begin with a disturbing case that involves allegations of mass murder by AIDS.

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CONAN: Excuse me. Earlier today, a court in Libya issued death sentences for five Bulgarian nurses and a Palestinian doctor who were convicted of deliberately infecting 426 children with AIDS back in 1999. More than 50 of the children are now dead.

Backed by expert testimony, the defendants argue that they are scapegoats. The HIV virus was present before they started work at a hospital in Benghazi, they say, and they blame the spread of the disease on unsanitary conditions.

Among the evidence against them are written confessions the defendants say were extracted under torture. The Libyan government wants Bulgaria to pay more than $10 million for each infected child. The Bulgarian government refuses, saying that that would be an admission of guilt.

The United Nations, international human rights organizations and several Western governments have raised questions about the trial and the sentences. Bulgaria's foreign minister is in Washington, D.C., today, where he joined Secretary of State Condoleezza Rice in denouncing the death sentences.

Ivaylo Kalfin is deputy prime minister and minister of foreign affairs in the Republic of Bulgaria, and we had hoped that he would be able to join us now by phone, but apparently he's tied up on another line. And in the meantime, we will presumably try to get to another subject, excuse me, and take a drink of water so I can maybe get rid of this cough in my throat. Hold on just a second.

All right. Since the foreign minister of Bulgaria is apparently not available, we're going to go back to our main subject this hour, which is of course breast cancer and questions about breast cancer.

If you have questions about the results of a study that was issued last week, and that includes, of course, the finding that the breast cancer rates dropped substantially between 2002 and 2003, those of course are the last dates for which statistics are available, and that the reason for that drop in breast cancer was the widely reported study at the time, which caused many women, older women, to stop using hormone replacement therapy to battle the ills of menopause. And many women stopped using hormone replacement therapy.

If you have questions about the issues raised by this new study that showed a stark decline in breast cancer rates, give us a phone call. Our number is 800-989-8255. That's 800-989-TALK, and our e-mail address is talk@npr.org.

The study released last week - researchers at the University of Texas, M.D. Anderson Cancer Center, reported the results of that study last week. What they found, suggests again, that the drop in breast cancer rates between 2002 and 2003 is due to fewer women taking hormone replacement therapy.

Again, if you have questions about the elimination or the drop in the use of hormone replacement therapy - about menopause, mammograms and the issues of breast cancer, give us a call at 800-989-8255, 800-989-TALK, and our e-mail address is talk@npr.org.

Joining us now here in Studio 3A is NPR healthcare correspondent Joanne Silberner. Joanne, thanks for racing in to bail me out at the last minute. We appreciate it.

JOANNE SILBERNER: Good to see you, Neal.

CONAN: And first of all, tell us: How significant were the results of that study that were issued last week?

SILBERNER: Review it a little for me.

CONAN: This was the issue - this was the study that showed the drop in breast cancer rates.

SILBERNER: Yeah, it's very important. I mean, I think it was about a seven percent decline. It was statistically significant. It was - it might have been a little more than that. It was a very dramatic decline. Something is going on.

CONAN: And the study raised questions about saying that this was due to the drop in the number of women using hormone replacement therapy. Is there a direct cause and effect here?

SILBERNER: Absolutely not. And it may be - there's scientific reason to believe that it may be - but you have to do more careful studies to determine that.

CONAN: And are those studies underway? Are they being done?

SILBERNER: I believe someone out there's going to do them now, if they're not starting on them already. It's very important to find out, because if it is hormone replacement therapy, then you know that it's done. If it's something else, then you want to make sure that people know that. Because whatever it is, if it can keep on going on, maybe we can really see a significant decline.

CONAN: As I understand it, though, not all women who used hormone replacement therapy were - there was a subset of women for whom this was...

SILBERNER: That's right, that's right. There are two different kinds of breast cancer, and they're treated differently. You know, one is - there are receptors on the cancer cells that are sensitive to estrogen. So you treat it differently, because if you can block those receptors. You can, you know, kill the cancer. There's others that are not. Those cancers are more difficult to treat.

CONAN: And intriguingly, the study seemed to find that the hormone replacement therapy did not necessarily start tumors, but if there were tumors, it seemed to feed them.

SILBERNER: Yes, and it make it more difficult to treat.

CONAN: And given all of that, what's the future for hormone replacement therapy?

SILBERNER: Well, it really depends on whether that connection is made... Hormone replacement therapy is already on the significant decline, a big decline. Fewer women are using it. But there are so many things that need to be explained. Was it women who used hormones at a very particular time? Was it women who used hormones over many, many years? Was it something else? You know, was it something else interacting that may be related to hormone replacement therapy but isn't? Until they know exactly what it is, I don't think that they can act on it. But I do think that women paying attention to this will be a little more reluctant to go onto hormone replacement therapy.

CONAN: Dr. Deborah Armstrong joins us now to help explain more about what all of this means and answer your questions. She's an associate professor of oncology, gynecology and obstetrics at Johns Hopkins University and joins us now from the studios of production company Clean Cut, in Baltimore. And Dr. Armstrong, thanks very much for coming in.

Dr. DEBORAH ARMSTONG (Johns Hopkins University): My pleasure.

CONAN: And how big a deal is this?

Dr. ARMSTRONG: Well you know, first of all, it's really data right now from one year, 2003 - although there actually is starting to be some data to suggest that some of that reduction in the incidence of breast cancer is extending into the data from 2004.

So first of all, I think, you know, it looks real. We - you know, I think it's very difficult for us to know exactly what the cause of it is. But because of the temporal relationship, with the publication from the Women's Health Initiative about, you know, the risks of hormone replacement therapy - probably being better defined than they ever had been before - and the large number of women and physicians who decided that those risks really weren't offset by the benefits. A large number of women stopped taking hormone replacement therapy at that time, and certainly that's a reasonable hypothesis as to why we're seeing that decline.

CONAN: But not for sure?

Dr. ARMSTRONG: Oh absolutely not for sure. I don't think we have the chicken or the egg yet.

CONAN: Neither the chicken nor the egg. Nevertheless, 14,000 fewer women with breast cancer - hats in the air. This is good news.

Dr. ARMSTRONG: Absolutely. It's huge. I think - if we knew exactly why the reason was, I think we would all be quite happy. I think right now we have to say this is a very good thing, and we're going to try to figure out exactly what the cause of it is.

CONAN: Now does this study suggest that HRT, hormone replacement therapy, was causing cancer?

Dr. ARMSTRONG: Well, you know, I think that whole issue of causing cancer is probably - you know, it's a little bit sort of erroneous to look at it in that way. It's not quite that simple. I mean, women throughout their reproductive lives are exposed to ovarian hormones, I mean, that's - and that's a natural thing. We know that things that change those hormone levels - such as pregnancy, breastfeeding - change your risk of breast cancer. And what hormone replacement therapy does - menopausal hormonal therapy does - is it basically extends that window of time that women get exposed to those ovarian hormones. And I think it's probably not surprising that continued exposure for a longer than, you know, normal period of time impacts breast cancer incidents.

I think the issue is that we've really been on shifting sands over the last couple of decades. If you go back, you know, now 20 to 30 years, most women, if they took hormone replacement therapy, took it in the form of an estrogen alone. We then found that that's associated with an increased risk of uterine cancer. So we then started using estrogen in combination with progestins. And the data that we have from five years or so, ago now, suggest that that combination is associated with a pretty significant increase in breast cancer risk. It didn't protect the heart. And so some of the things that we thought were beneficial, perhaps from the days when we were using estrogen alone, just weren't there.

CONAN: Mm hmm. And what do you tell the women who, those years ago, followed what was the best advice at the time and got breast cancer?

Dr. ARMSTRONG: You know, one of the questions women always want to know when they have breast cancer is - why did I get it? And I think we have to be honest with most women - is that, you know, we don't know for sure what caused an individual woman's breast cancer. We can certainly say, now, as a whole, that by taking hormone replacement therapy with an estrogen-progestin combination after the time of natural menopause, that the risk for women as a group who do that is - of breast cancer, is increased. But for an individual woman, can I say: If you didn't take that hormone replacement therapy would you have not gotten breast cancer, it's very difficult to say.

I think one of the good pieces of news that we do have from a number of studies is that once women stop taking hormone replacement therapy the risk really starts to go down pretty quickly. So - and that's actually some of the data that were presented at the San Antonio meetings about - that remarkable drop off in 2003 - may really be a correlative of that, which is that stopping can have a pretty quick impact on breast cancer risk.

CONAN: And that's a surprise, given the way these things tend to trend, isn't it?

Dr. ARMSTRONG: It is, but remember, you know, cancer's a complex thing. And what we know is that most cancers develop because there's a series of mutations that happen, and that, you know, if hormones are driving some or even all of those mutations when you stop the hormones - you may have gotten two thirds of the way to cancer but you can't get the last third of the way. So it's possible that really even stopping it in the late steps will have an impact. It's also possible that maybe it's just slowing down the rate of cancer formation and, you know - maybe it's some of those women if the reductions that have been seen are due to stopping hormone replacement therapy - they may eventually get cancer but maybe they'll get it at a later date. So I think these are all things that we just really don't know yet.

CONAN: Dr. Armstrong, stay with us if you will. When we come back we'll get questions from callers. 800-989-8255. 800-989-TALK. E-mail is talk@npr.org. Joanne Silberner, in baseball parlance, you get credit for a save. Thank you very much for being with us here in Studio 3A. I'm Neal Conan. We'll be back after the break. It's the TALK OF THE NATION from NPR News.

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CONAN: This is TALK OF THE NATION. I'm Neal Conan in Washington. Today, questions and answers about breast cancer. That following release of a study, last week, which reported a significant drop in breast cancer rates between 2002 and 2003 - the last two years for which reliable statistics are available. Our guest is Dr. Deborah Armstrong. If you'd like to join us: 800-989-8255, 800-989-TALK. The e-mail address is talk@npr.org. And let's begin with Cheryl(ph). Cheryl calling us from Phoenix.

CHERYL (Caller): Hi. My question is: I've been on the birth control pill, actually, for about 20 years and I'm wondering if there's any kind of correlation between using birth control for that length of time and having breast cancer risk. And if not, why not?

Dr. ARMSTRONG: Well, that's actually a good question. There have been studies that have shown that there's a very, very slight increase in the incidence of breast cancer while women are taking oral contraceptives. But if you think about it, most women who are taking oral contraceptives are taking them in their 20s or their 30s, and that's a time when the risk of breast cancer is actually quite low. It doesn't really start to go up until women get closer to menopause. And so because the number of breast cancer cases in that age range is so small that even significant increase in the percentage - even the doubling - really doesn't mean very many cases.

And so what we call the attributable risk - meaning like how much breast cancer can you attribute to birth control pills - is almost zero.

CHERYL: Thank you.

Dr. ARMSTRONG: So the first issue is that we feel that oral contraceptives are not an unreasonable thing for women to use if they need birth control or if they have other reasons to take them, and that their risk of breast cancer is not significantly elevated related to that. Now, there's a couple of provisos there. Number one, is that some women take what's called low-dose birth control pills as they're approaching menopause, and if you keep taking them you're not really going to know when you get to menopause. So we're talking really about birth control pills when women are fully pre-menopausal. The low-dose birth control pills around menopause really function like hormone replacement therapy.

So if you've been taking them for 20 years and you're approaching the age where you might be naturally going through menopause, you and your gynecologist might want to talk about, you know, when is a time when we would think about tapering off of these medications.

The other important thing about birth control pills, is that many women who are at risk for breast cancer are also at risk for ovarian cancer, and we do know that birth control pills quite significantly reduce the risk of ovarian cancer.

CHERYL: That's good news.

CONAN: Cheryl, thanks for the call.

Dr. ARMSTRONG: Thanks Cheryl.

CONAN: Let's go now to - this is Patty(ph). Patty with us from Orlando in Florida.

PATTY (Caller): Hi. I just wanted to say that I'm one of the people that did give up the HRT. I was on Primarin after a hysterectomy for cervical cancer. I got cancer back in '87 and I took the Primarin for about five years and I really couldn't afford to go out and buy the pills every month so I stopped taking it. And I'll tell you, as far as saving money that's great, and I only go through hot flashes maybe once every couple of months.

Dr. ARMSTRONG: Yeah, and I think some of it depends on the age that you were when you had your surgery - you know, how close someone is to natural menopausal impact on how severe the hot flashes are. And I think what Patty's talking about is that, as treatment for cervical cancer, she had a hysterectomy-and presuming that her ovaries were removed as well. So in that situation you're really sort of replacing estrogen, in the form of Primarin that your ovaries would normally be making. And what a lot of people do is they might start that and then decrease the dose slowly over a period of time, so that it really mimics more natural menopause. I'm sorry Patty.

PATTY: Oh I'm sorry, go ahead.

Dr. ARMSTRONG: I was going to say we don't - with cervical cancer, we don't worry about the effects of hormones, because they don't seem to impact on the risk of recurrence or even frankly the development of cervical cancer. So hormones are probably safe in somebody's had a history of cervical cancer.

PATTY: I was 36 when I went through that and...

Dr. ARMSTRONG: Clearly an age when menopause would be premature. And so, that would be - that would be a very typical scenario. But I think - I'm glad you got off of them, because I think, one of the issues that we do try to encourage people to do is to - you know, you get on this medication sometimes people don't even think about it. But to say, you know, why am I on this? How is it helping me, and is it time for me to be thinking about other things that may be increasing in terms of risk, and should I get off of this medication?

PATTY: I was - when that study came out I was concerned - you know, I'd rather go through a hot flash than have to deal with breast cancer.

Dr. ARMSTRONG: Yeah.

CONAN: The comparison of the two isn't even close, Patty. But how would I know? Thanks very much for the call.

PATTY: Thank you.

CONAN: Bye-bye. Good luck to you.

Dr. ARMSTRONG: Thanks Patty.

CONAN: Let's go now to Beth. Excuse me, I hit the wrong button. There it is. Beth - Beth calling us from Charlotte, North Carolina.

BETH (Caller): Yes, I have a question about this mix of hormonal cocktails that a lot of us have ended up taking. I took Primarin for a while, and then, thank heavens, just intuitively decided, uh uh, I'm going off of this. Four years ago I was diagnosed with breast cancer and because it's the kind that's very responsive to estrogen, I am now on medication to wash all of the estrogen out of my body - to clear it out as opposed to what the Primarin did. But I'm curious, like a lot of women who have waited until later to have babies, I also took Clomid. Does that mean I'm - kind of was at a double risk?

Dr. ARMSTRONG: You know, we haven't associated the use of ovulatory-stimulating drugs like Clomid. I mean that's really how they function. They try to help women who are having difficulty with ovulation as the reason they're having difficulty conceiving. Drugs like Clomid, that stimulate ovulation - first of all, as you know, they're given for a very short period of time - so their impact probably isn't going to be nearly as significant. We have not associated that with a significant increase in breast cancer. What has been associated with an increase in breast cancer is women who start their families late - so have their first pregnancy after the age of 30 - and that's going to be pretty common in women who are undergoing infertility evaluations and treatment.

So again, that gets to the chicken and the egg. Was it the infertility or the fact that you didn't - someone didn't start to think about having a family until after age 30 - is that the risk factor or is it the use of the ovulatory-stimulating drugs like Clomid. And we haven't seen that the Clomid itself has been a risk for breast cancer. But having your first pregnancy after Age 30 does slightly increase the risk of breast cancer.

BETH: Not to mention the stress caused by being labeled an elderly (unintelligible).

Dr. ARMSTRONG: And you don't have to be very old to get that label.

BETH: Right. Okay, thank you.

CONAN: Beth, thanks very much for the call.

BETH: You're welcome.

Dr. ARMSTRONG: Thanks, Beth.

CONAN: Dr. Armstrong, what do you tell women who are interested, these days, in hormone replacement therapy?

Dr. ARMSTRONG: Well first of all, you know, I think one of the things that the data that we've been able to get over the last five to ten years - one of the things is - I think it actually fairly clearly defines for us in a much more clear-cut manner, who benefits. In other words, what symptoms should you be using these for? What problems should you being using hormone replacement therapy for? And what does it not do? So what I generally - the way I counsel women is, you know, what is the reason that you're using it? Are you using it because you think your skin looks younger? Well there's not much data in support of that, number one. Number two, is that worth an increase in your risk of breast cancer? And for most women, that answer's going to be no.

If women are taking it because they have such bad hot flashes that they can't sleep at night, and they then, like, are falling asleep at the wheel during the daytime, I mean, that's - hot flashes in a small percentage of women can be that bad that they really interfere with your normal functioning. And that's the group of women where the use of menopausal hormone replacement therapy is probably has the best indication. But even in that situation, I think - what I counsel people is if you go on this medicine you should go on it with a plan to taper yourself off over some period of time. And that can be a year or two years, but most women will be able to get off of these medications, or at least get to a lower dose with repeated attempts at trying to cut the dose.

So, that's what I usually tell women. Now some women may want to use estrogen for other reasons in menopause - there's vaginal dryness, which could lead to difficulties during intercourse. It can lead to problems with bladder infections. And for those women we can use vaginal estrogen preparations, which really don't expose the rest of the body to very significant levels of estrogen. So I think that that's one way out, if people are taking estrogen or hormones for that reason. So we can start to work around what's the reason you're taking it, what's the lowest dose, the safest dose that we can use, the safest way of using it for your particular problem.

CONAN: Since the study's release, last week, doctors and researchers have been discussing other possibilities that might account for the decline in breast cancer rates. Dr. Richard Wender is among them. He is a primary care physician and president of the American Cancer Society. He joins us now, from his office in Philadelphia. Pleasure to have you on the program today.

Dr. RICHARD WENDER (President, American Cancer Society): Glad to be here.

CONAN: And I know you're concerned that there might, in fact, be just as many breast cancers but they're not getting detected.

Dr. WENDER: Well exactly. I think that the very striking evidence that has been discussed over the past few days, probably is representing something biologically very real. But it's important to understand that we're talking about the incidence of breast cancer, and sometimes people don't quite understand what incidence means. They think that it means that it means that that's the cancers that started in that year. But as you've discussed, these are cancers that probably started some years before. And then it takes some time for them to grow big enough for us to actually be able to find them.

And it's actually not until we find the cancers that it counts towards the rates that are being discussed in this new data. So we're concerned that, yes, it looks like this decline in use of estrogen probably has had a significant impact but that it's not the only factor. And the other factor we're particularly concerned is an eroding and steady decline, gradual though, of the number of women who are up to date with screening mammograms.

And if you don't have a screening mammogram, you're not going to be able to find a very early cancer before somebody can feel it. So in order to count toward these rates it's important to keep up with the screening.

CONAN: And Dr. Wender, I know that you're also concerned about systemic weaknesses in our ability to continue to detect those cancers through mammography, and that partly, is a result of declining numbers of radiologists.

Dr. WENDER: Well, exactly. We've seen a steady decline in the number of women who are up-to-date with their mammogram, which is recommended by the American Cancer Society every year after age 40. And that's been going on now, for about six or seven years. And there's a lot of reasons for it.

The percent of women who are uninsured is creeping upward, and they're less likely to have a mammogram. But the interest among the radiology community in devoting time to doing a mammography has declined as other attractive options for imaging become available to the radiology community. The reimbursement rates is not as good as many radiologists feel that should be, the number of facilities is not distributed well throughout the country. And a result, waiting times are very long, which makes it less likely for a woman to actually do it.

CONAN: And one of the important lessons that I think you derive from last weeks study, good news. I think everybody says that. But you can take away the wrong message - that, hey, this is the declining problem.

Dr. WENDER: Absolutely correct. In fact, it's important to remember that a great number of women who never took an estrogen pill in their lives, develop breast cancer, and will continue to develop breast cancer. Just eliminating the use of - or significantly reducing the use of post-menopausal estrogen, will not eliminate the problem of breast cancer.

So women absolutely, in partnership with their physicians, need to keep up on the screening, which includes annual mammography after age 40 and an annual physical exam.

CONAN: Thanks very much, Doctor. Appreciate your time today.

Dr. WENDER: My pleasure.

CONAN: Doctor Richard Wender is president of the American Cancer Society and joined us today from his office in Philadelphia. Questions and answers today about breast cancer. You're listening to TALK OF THE NATION from NPR News.

And still with us is Dr. Deborah Armstrong, associate professor of oncology, gynecology, and obstetrics at Johns Hopkins University in Baltimore. And let's see if we can get another caller on the line. This is Lee. Lee calling us from St. Louis.

LEE (Caller): Hi. I have a strong history, in the family, of both breast cancer and Alzheimer's disease, and a personal history of depression. And had a surgical total hysterectomy in 1999. Well, every time I try to go off the estrogen replacement, my doctor admonishes me that the research indicates that there's protection from Alzheimer's disease by being on the estrogen.

And of course, you know, given the choice, I'd prefer to have breast cancer over Alzheimer's disease. So, I'm just wondering what Dr. Armstrong thinks about protection from Alzheimer's disease by estrogen replacement.

Dr. ARMSTRONG: I think that's actually a really good question, and it was actually, you know, one of the sort of on the list of sort of secondary benefits that people might get from taking hormone replacement therapy. I would have to say that with regard to dementia and Alzheimer's disease that the jury is still out.

The studies have actually not been consistent, in terms of the potential benefits that they've shown the use of estrogen or hormone replacement therapy, in terms of decreasing the risk of Alzheimer's disease.

So, you know, that's not a very solid reason, I would think, as a stand-alone reason, for continuing hormone replacement therapy. I think, you know, in a family where there's a history of breast cancer, you and your physician, you know, need to be somewhat potentially more alert than the average person in terms of, you know, making sure that you're getting good clinical breast exams, that you're doing your monthly breast self-exam, and that you're getting your mammogram and other appropriate screening done in a timely fashion.

The women who have had a hysterectomy, again, usually just need to use estrogen. They don't usually need to use progestin. And the data that we have right now, suggests that if there's an increased risk associated with hormone replacement therapy, it's most potent for the combination of estrogen and progestin.

So, you know, my counsel to someone in your situation would be, you know, to keep the lines of communication open with your doctor, keep talking about the data, about Alzheimer's disease and the risks of breast cancer, use the lowest dosage you can, and think about whether or not there's a time to start thinking about doing a trial off the medication and to see how you feel.

LEE: You know, when I've gone without it I felt no real ill effects, or minor, you know, certainly as has already been stated. What's a hot flash compared to some of these other dread diseases? So, you know, I'm on the low dose and then I think, well, what if I took it every other day? And I don't know whether that's a good idea or a bad idea.

Dr. ARMSTRONG: Well, you know, I think the problem is that, you know, it sounds like one of your main goal would be to minimize your risk of Alzheimer's disease. And I think the problem is that I don't think any of us can say you need to take this dose, this frequency for this duration to reduce your risk of Alzheimer's disease. Because the data just are fairly conflicting, and not even consistent that there's a reduction in the risk of Alzheimer's with menopausal hormone replacement.

So just keep talking to your doctor. And it sounds like the good news is that you can get down to a pretty low dose, and that's going to be beneficial with regard to the breast cancer risk.

LEE: Very good. Thank you so much.

CONAN: And good luck, Lee.

Dr. ARMSTRONG: Thanks, Lee.

LEE: Thank you.

CONAN: Bye, bye. We're going to take another short break and when we come back a couple of more questions for Dr. Deborah Armstrong about breast cancer and about the meaning of the study that was released last week that reported significant declines in breast cancers incidence between 2002 and 2003.

Again, if you'd like to join us 800-989-8255, 800-989-TALK. E-mail talk@NPR.org. Plus later on, Senator-elect Sherrod Brown of Ohio will join us to take your calls.

I'm Neal Conan. This is the TALK OF THE NATION from NPR News.

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CONAN: This is TALK OF THE NATION. I'm Neal Conan in Washington.

In a few minutes our series New Voices in Politics continues with Senator-elect Sherrod Brown of Ohio. What do you want to see from the next Congress. Give us a call, 800-989-8255, 800-989-TALK. E-mail is talk@NPR.org.

But first, let's continue with questions and answer about the drop in breast cancer rates. Dr. Deborah Armstrong is still with us. She's associate professor of oncology, gynecology, and obstetrics at Johns Hopkins University in Baltimore.

And I have to ask you, Dr. Armstrong, another study was released last night, which looked at the herbal supplement, black cohosh, which a lot of women use to try to help relieve hot flashes and other symptoms of menopause. The results of the study were not promising.

Dr. ARMSTRONG: Well, that's correct. The study was actually a really well designed trial and it looked at the use of either black cohosh, either alone or in conjunction with some other biologicals. It looked at the use of a higher dietary soy level. And it also looked at women who were taking hormonal therapy for suppression of hot flashes.

And I guess the bad news is, unfortunately, that it did not show any benefit for any of the groups except the hormone replacement therapy group in hot flashes. The thought was that agents - and like black cohosh - have what are called phytoestrogens in them - and these may be plant-based estrogens - with the thought that these plant-based estrogens may not have the negative effects of typical mammalian estrogens, but they may have enough of an estrogenic effect to suppress hot flashes.

We've never known whether, you know, you can separate out those two. I guess the good news is we may not have to do that since it doesn't look like they really work very well to control hot flashes in this trial.

CONAN: Let's see if we can get another caller on the line. And this is Peter. Peter calling us from Wynona, New Jersey.

PETER (Caller): Yes, hi, Dr. Armstrong, I'm a physician. Something troubles me very much about this whole matter, and that is that thus-to-far, as far as I know, all of these studies have focused on only one type of preparation -Prempro and Premarin. And there have been some very interesting preliminary studies on low estradiol patches, like Vivelle, in which in fact, they believe there may even be a reduction of breast cancer.

Vivelle used as a patch at the lowest dosage twice a week, in combination with progesterone during the first 10 days of each month. Why is it that they think that there is only Prempro and Premarin and all conclusions must be derived from only these two preparations?

Dr. ARMSTRONG: I think it's actually an excellent question. Because if you actually start to look at all the different ways you can use hormone replacement therapy, you really, actually get into very large group groups. The - I have to say in all honesty - I believe these two were used because they were, in terms of testing, because they were the most commonly used and the most frequent dosing of these medications.

But what he's talking about is the fact that, for example, in Prempro, you have a Premarin, which is an estrogen compound and a progestational agent. And you get both of those every day in the medication. You don't have to have a progestin every day to protect the uterus.

So you may only need to take a short, a few days of a progestational agent every month. So you may not even take it every month. And in fact...

PETER: But I am looking at it yet from another standpoint. When you use a low dose estrogen patch like Vivelle, it's more physiological in that it is constantly being dosed, but at a very low dose through the skin, and only has to be replaced twice a week. The patches are very durable and it seems to me much more physiological - not only the preparation is more physiological, but the means of the administration is much more physiological.

Dr. ARMSTONG: Well you know, physiological, I think, it may be - because remember that in normal physiology, estrogen levels actually are varying quite strikingly during the normal menstrual cycle. So physiologic in terms of the variations, it probably doesn't reproduce.

But again, I think that the question is quite legitimate. If you use a low-dose estrogen, whatever means or route of administration you use, and you use it with intermittent progesterones or you use it - for example, in Scandinavian countries, quite commonly women with a uterus will get systemic estrogen either in the form of a pill or a patch, and they'll have an IUD, an intrauterine device, that has progesterone. It's giving progesterones to the uterus, which is really the one organ that needs it for protection, and there's very low levels of progesterones that get to the bloodstream.

So there's lots of different subtleties in terms of this whole issue of hormone replacement therapy and defining risk, and we really, I think - you know, he's right in that the large studies that have been done, such as in the Women's Health Initiative, have really looked at one specific does because you really need it to make sure that differences in the doses weren't the reason for differences in the outcome.

But I think it's an excellent question as to whether you can change the dosing, change the route, change the formulation and reduce risk. But I think we don't know the answer to that at this point in time.

PETER: Thank you very much.

CONAN: Peter, thanks very much for the call.

And Dr. Armstrong, if there seems to be a conclusion from all of this, it's to continue to get screened and to, if you can avoid it, avoid hormone replacement therapy.

Dr. ARMSTRONG: Absolutely. I think like any medication, you have to look at what are the potential benefits, what are the risks, and try and balance those off. And I think the one thing we're doing is better defining what the risks are.

CONAN: Dr. Armstrong, thanks so much for your time today. We appreciate it.

Dr. ARMSTRONG: My pleasure.

CONAN: Deborah Armstrong is an associate professor of oncology, gynecology and obstetrics at Johns Hopkins University and with us today from the studios of production company Clean Cuts in Baltimore.

When we come back, New Voices in Politics.

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