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Week: 558.6 Guest: Dr. Elizabeth Ginsburg, Brigham and Women's Hospital, Boston, MA Topic: The link between alcohol and estrogen Producer/Host: Steve Girard


NEMA: Today, we're talking with Dr. Elizabeth Ginsburg of the Brigham and Women's Hospital in Boston, about a study on what turns out to be a strong relationship involving a popular and important hormone therapy for post-menopausal women, and a bit of social drinking....

GINSBURG: We were interested in looking at interactions between alcohol drinking and estrogen levels in women. So, we admitted 24 patients to a research ward, and 12 of the women were on estrogen replacement, and 12 were not. We gave all the women the identical diets, gave all the women the same amount of alcohol...and the dose was based on body weight, so the amount of alcohol the women could get could vary depending upon how much they weighed. Obviously, a larger person will get the same blood alcohol levels from a larger amount of alcohol than a smaller person will. And then we looked to see what alcohol levels did and what estradiol levels did...that's the kind of estrogen we measured.

NEMA: And what did you find about those levels?

GINSBURG: What we found was that about ten minutes after they began drinking... and alcohol, I should say, is absorbed very rapidly from the stomach... about ten minutes after drinking began, there was already a significant increase in the circulating estrogen levels in the women that were taking estrogen replacement therapy. In women who were not using estrogen replacement therapy, the levels didn't change significantly. And the estrogen levels were almost double when women had absorbed the amount of alcohol you'd find in, say, half a glass of wine, and by 20 minutes after they began drinking, when they had already completed the study drink, estrogen levels had more than doubled. By the time they had the complete drink in their system, about 50 minutes into the study, that's when estrogen levels peaked. And they peaked at levels over three-fold higher than they did at baseline. Which was an interesting and unexpected finding for us. The blood alcohol levels peaked at approximately the same time that the estrogen levels peaked...so there was clearly a relationship there...and then, as blood alcohol levels fell, so did the blood estradiol levels. That's, again, the kind of estrogen we were measuring.

NEMA: Do you know enough to project what the mechanism for the connection is...

GINSBURG: We have some thoughts. We also measured a metabolyte of estradiol...estradiol is the kind of estrogen we gave the women, and it's the same kind of estrogen that women who are pre-menopausal have in their bodies, that's made by their ovaries. The main metabolyte, the main thing that estradiol is broken down into is something called esterone. We also measured esterone levels, to see if there's a change in the way the estradiol is getting metabolized... was it just not getting broken down as much after alcohol drinking? And we did find that, in fact, that was the case...to a certain extent...because after drinking alcohol, women who are on estrogen replacement therapy had less esterone in their system, than the women did after receiving a placebo drink. And we were comparing what the estrogen levels did after drinking alcohol, as compared to after a drink that did not contain alcohol, but had the same amount of calories in it. So, part of the mechanism, we think, is that the estrogens that the women are taking in isn't getting broken down appropriately. But that probably doesn't explain the whole phenomenon because the effect was so rapid. We think that there's probably some kind of release of estrogen into the circulation from some part of the body, we don't really know where. When women take estrogen replacement therapy in pill form, they're not absorbing the whole amount of estrogen they take. There may be something about alcohol that causes the body either to absorb more estrogen, or to somehow release it into the circulation more...we really don't know exactly what is happening.

NEMA: Some reports show an increase in the risk of breast cancer can accompany estrogen replacement therapy...and the same with alcohol...but both estrogen and alcohol seem to decrease risk of heart disease...

GINSBURG: I think there's a real 'catch-22' there. I think the epidemiologic evidence is really pretty good, showing that drinking a drink or more a day probably does increase your risk of breast cancer, whether or not you take estrogen replacement therapy. And there's also evidence, from epidemiologic studies -not this study - showing that if you both drink alcohol and take estrogen replacement, your risk of breast cancer is doubled. And so, I think there is some sort of interaction going on in the body. Usually when you have a couple of risks for something, those risks are not additive. I think there's also good evidence that a drink a day, or two drinks a day decrease your risk of heart disease, so I think there's a real dilemma there. What I've been telling my patients is just sort of look at their risk factors, look at their background, and look at how they feel. Certainly, women who have a strong history of heart disease in their families should be on estrogen replacement therapy when they go into menopause. I think we really haven't sorted out well where the pluses and minuses start ...where you start getting more into minuses in terms of breast cancer risk, and where the minuses outweigh the pluses in terms of breast cancer risk...when you look at both alcohol consumption and estrogen replacement therapy. And I think that we just need to do more epidemiologic studies, looking at family history and personal characteristics...like lipoprotein profile, or cholesterol profile, history of breast disease...family history of breast cancer. How do all those factors come into play when you're assessing risk levels, and we don't really have the answers to that. Think there's a real 'catch-22' that women face when they're thinking about estrogen replacement therapy and whether they should drink alcohol...and how much they enjoy drinking alcohol, and what to do about that.

NEMA: That's where the lines of communication have to be open between the patient and her personal doctor...to check the risks and weigh them with your enjoyment of life...

GINSBURG: For example, a patient who has a strong family history of heart disease, who herself has hypertension, no family history of breast cancer...I think that woman probably would be well served to take estrogen....and possibly also drink alcohol. I think that the question really is whether the absolute changes in estrogen levels that we found are biologically significant. I don't know...we don't really know that yet...we don't know what the reason is that the combination of estrogen and alcohol seem to increase breast cancer. Is it the higher estrogen levels or something entirely different going on?

NEMA: Can you extrapolate a theory on how alcohol reacts with the most popular estrogen therapy drug...premarin?

GINSBURG: Premarin is difficult to study because it contains so many different types of estrogen. It's conjugated equine estrogen, so it's estrogens that are extracted from the urine of pregnant mares. And there aren't commercially available assays to measure all the different types of estrogen that are in premarin. There are five major kinds of estrogen that are in the pill, and then these are broken down into 20 metabolytes or more that have biological activity. So, it's very, very difficult to study that and say, "Ah hah...such and such an estrogen is higher". We're going to do the best we can, but again....that would be something that is nice to do with the company that makes it.

NEMA: You're finding a lot of new information about estrogen, its effects and interactions in the body, but it seems new questions and quandaries pop up all the time....

GINSBURG: Certainly, more research needs to be done to elucidate this more...what's the mechanism of this estrogen increase? And then the next step is, is this kind of estrogen increase important? There's certainly evidence from laboratory studies showing that estrogen probably increases breast cancer cell growth in a dish...so I think that's the reason why it kind of piques our interest, and I think it's worth following...is that there really may be some biological significance to this. But that hasn't been proven yet. So, I think that the study has raised more questions than it's answered.

NEMA: Dr. Elizabeth Ginsburg of the Brigham and Women's Hospital in Boston. As always, if you have questions about this topic, talk with your doctor. I'm Steve Girard.

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TEASE: Just when you think you know it all...you find something new that makes you take a new perspective. A dentist dabbling in dissection has found two new structures in the head and neck that may give us more information about jaw pain, and headaches. Next, on The Heart of the Matter!


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