What Does Drinking Soy Milk Do to Hormone Levels?

The vast majority of breast cancers start out hormone-dependent, where estradiol, the primary human estrogen, “plays a crucial role in their breast cancer development and progression.” That’s one of the reasons why soy food consumption appears so protective against breast cancer: Soy phytoestrogens, like genistein, act as estrogen-blockers and block the binding of estrogens, such as estradiol, to breast cancer cells, as you can see at 0:24 in my video How to Block Breast Cancer’s Estrogen-Producing Enzymes.

Wait a second. The majority of breast cancers occur after menopause when the ovaries have stopped producing estrogen. What’s the point of eating estrogen-blockers if there’s no estrogen to block? It turns out that breast cancer tumors produce their own estrogen from scratch to fuel their own growth.

As you can see at 1:03 in my video, “estrogens may be formed in breast tumors by two pathways, namely the aromatase pathway and sulfatase pathway.” The breast cancer takes cholesterol and produces its own estrogen using either the aromatase enzyme or two hydroxysteroid dehydrogenase enzymes.

So, there are two ways to stop breast cancer. One is to use anti-estrogens—that is, estrogen-blockers—like the soy phytoestrogens or the anti-estrogen drug tamoxifen. “However, another way to block estradiol is by using anti-enzymes” to prevent the breast cancer from making all the estrogen in the first place. And, indeed, there are a variety of anti-aromatase drugs in current use. In fact, inhibiting the estrogen production has been shown to be more effective than just trying to block the effects of the estrogen, “suggesting that the inhibition of estrogen synthesis is clinically very important for the treatment of estrogen-dependent breast cancer.”

It turns out that soy phytoestrogens can do both.

Using ovary cells taken from women undergoing in vitro fertilization, soy phytoestrogens were found to reduce the expression of the aromatase enzyme. What about in breast cancer cells, though? This occurred in breast cancer cells, too, and not only was aromatase activity suppressed, but that of the other estrogen-producing enzyme, as well. But this was in a petri dish. Does soy also suppress estrogen production in people?

Well, as you can see at 2:34 in my video, circulating estrogen levels appear significantly lower in Japanese women than Caucasian American women, and Japan does have the highest per-capita soy food consumption, but you can’t know it’s the soy until you put it to the test. Japanese women were randomized to add soy milk to their diet or not for a few months. Estrogen levels successfully dropped about a quarter in the soy milk supplemented group. Interestingly, as you can see at 3:04 in my video, when the researchers tried the same experiment in men, they got similar results: a significant drop in female hormone levels, with no change in testosterone levels.

These results, though, are in Japanese men and women who were already consuming soy in their baseline diet. So, the study was really just looking at higher versus lower soy intake. What happens if you give soy milk to women in Texas? As you can see at 3:29 in my video, circulating estrogen levels were cut in half. Since increased estrogen levels are “markers for high risk for breast cancer,” the effectiveness of soy in reducing estrogen levels may help explain why Chinese and Japanese women have such low rates of breast cancer. What’s truly remarkable is that estrogen levels stayed down for a month or two even after the subjects stopped drinking soy milk, which suggests you don’t have to consume soy every day to have the cancer protective benefit.

Wait, soy protects against breast cancer? Yes, in study after study after study—and even in women at high risk. Watch my video BRCA Breast Cancer Genes and Soy for the full story.

 What about if you already have breast cancer? In that case, see Is Soy Healthy for Breast Cancer Survivors?

 And what about GMO soy? Get the facts in GMO Soy and Breast Cancer.

 Okay, then, Who Shouldn’t Eat Soy? Watch my video and find out.

What else can we do to decrease breast cancer risk? See:

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In health,

Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations:

Lowering Your Cancer Risk by Donating Blood

Back in the early 1980s, a pathologist in Florida suggested that the reason premenopausal women are protected from heart disease is that they have lower stores of iron in their body. Since oxidized cholesterol is “important in atherosclerosis, and oxidation is catalyzed by iron,” might the lower iron stores of menstruating women reduce their risk of coronary heart disease? “The novel insight suggesting that the longevity enjoyed by women over men might relate to the monthly loss…of blood is remarkable,” but is it true? I discuss this in my video Donating Blood to Prevent Heart Disease?.

The consumption of heme iron—the iron found in blood and muscle—is associated with increased risk of heart disease. Indeed, “an increase in heme iron intake of 1 mg/day appeared to be significantly associated with a 27% increase in risk of CHD,” coronary heart disease. But, heme iron is found mainly in meat, so “it is possible that some constituents other than heme iron in meat such as saturated fat and cholesterol are responsible” for the apparent link between heme iron and heart disease. If only we could find a way to get men to menstruate, then we could put the theory to the test. What about blood donations? Why just lose a little blood every month when you can donate a whole unit at a time?

A study in Nebraska suggested that blood donors were at “reduced risk of cardiovascular events,” but another study in Boston failed to show any connection. To definitively resolve the question, we would really have to put it to the test: Take people at high risk for heart disease, randomly bleed half of them, and then follow them over time and see who gets more heart attacks. Maybe it could turn “bloodletting” from the past into “bleeding-edge technology.” In fact, that was actually what was suggested in the original paper as a way to test this idea: “The depletion of iron stores by regular phlebotomy could be the experimental system for testing this hypothesis…”

It took 20 years, but researchers finally did it. Why did it take so long? There isn’t much money in bloodletting these days. I suppose the leech lobby just isn’t as powerful as it used to be.

What did the researchers find? It didn’t work. The blood donors ended up having the same number of heart attacks as the non-donor group. Something extraordinary did happen, however: The cancer rates dropped. There was a 37 percent reduction in overall cancer incidence, and those who developed cancer had a significantly reduced risk of death. An editorial in the Journal of the National Cancer Institute responded with near disbelief, saying the “results almost seem to be too good to be true.” “Strikingly,” they started to see cancer reduction benefits within six months, after giving blood just once. As the study progressed, the cancer death rates started to diverge within just six months, as you can see at 2:46 in my video, but this is consistent with the spike in cancer rates we see within only six months of getting a blood transfusion. Is it possible that influx of iron accelerated the growth of hidden tumors?

I continue this wild story in my video Donating Blood to Prevent Cancer?.

What if you feel faint when you give blood? Don’t worry. I’ve got you covered. Check out How to Prevent Fainting.

What might iron have to do with disease? See The Safety of Heme vs. Non-Heme Iron and Risk Associated with Iron Supplements.

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations:

How Phytoestrogens Can have Anti-Estrogenic Effects

When the Women’s Health Initiative study found that menopausal women taking hormone replacement therapy suffered “higher rates of breast cancer, cardiovascular disease, and overall harm,” a call was made for safer alternatives. Yes, the Women’s Health Initiative found that estrogen does have positive effects, such as reducing menopausal symptoms, improving bone health, and reducing hip fracture risk, but negative effects were also found, such as increasing the blood clots in the heart, brain, and lungs, as well as breast cancer.

Ideally, to get the best of both worlds, we’d need what’s called a selective estrogen receptor modulator—something with pro-estrogenic effects in some tissues like bone but at the same time anti-estrogenic effects in other tissues like the breast. Drug companies are trying to make these, but phytoestrogens, which are natural compounds in plants, appear to function as natural selective estrogen receptor modulators. An example is genistein, which is found in soybeans, which happen to be structurally similar to estrogen. How could something that looks like estrogen act as an anti-estrogen?

The original theory for how soy phytoestrogens control breast cancer growth is that they compete with our own estrogens for binding to the estrogen receptor. As more and more soy compounds are dripped onto breast cancer cells in a petri dish, less and less actual estrogen is able to bind to them. So, the estrogen-blocking ability of phytoestrogens can help explain their anti-estrogenic effects. How do we then explain their pro-estrogenic effects on other tissues like bone? How can soy have it both ways?

The mystery was solved when it was discovered there are two different types of estrogen receptors in the body and the way in which a target cell responds depends on which type of estrogen receptor they have. The existence of this newly discovered estrogen receptor, named “estrogen receptor beta…to distinguish it from the ‘classical’ estrogen receptor alpha,” may be the “key to understanding the health-protective potential of soy” phytoestrogens. And, unlike our body’s own estrogen, soy phytoestrogens preferentially bind to the beta receptors.

For instance, within eight hours or so of eating about a cup of cooked whole soybeans, genistein levels in the blood reach about 20 to 50 nanomoles. That’s how much is circulating throughout our body, bathing our cells. About half is bound up to proteins in the blood, so the effective concentration is about half the 20 to 50 nanomoles. What does that mean for estrogen receptor activation?

In my video Who Shouldn’t Eat Soy?, I feature a graph explaining the mysterious health benefits of soy foods. Around the effective levels we would get from eating a cup of soybeans, there is very little alpha activation, but lots of beta activation. What do we find when we look at where each of these receptors are located in the human body? The way estrogen pills increase the risk of fatal blood clots is by causing the liver to dump out extra clotting factors. But guess what? The human liver contains only alpha estrogen receptors, not beta receptors. So, perhaps eating 30 cups or so of soybeans a day could be a problem, but, at the kinds of concentrations we would get with just normal soy consumption, it’s no wonder this is a problem with drug estrogens but not soy phytoestrogens.

The effects on the uterus also appear to be mediated solely by alpha receptors, which is presumably why no negative impact has been seen with soy. So, while estrogen-containing drugs may increase the risk of endometrial cancer up to ten-fold, phytoestrogen-containing foods are associated with significantly less endometrial cancer. In fact, protective effects are found for these types of gynecological cancers in general: Women who ate the most soy had 30 percent less endometrial cancer and appeared to cut their ovarian cancer risk nearly in half. 

Soy phytoestrogens don’t appear to have any effect on the lining of the uterus and can still dramatically improve some of the 11 most common menopausal symptoms (as compiled by the Kupperman Index).

In terms of bone health, human bone cells carry beta estrogen receptors, so we might expect soy phytoestrogens to be protective. And, indeed, they do seem to “significantly increase bone mineral density,” which is consistent with population data suggesting that “[h]igh consumption of soy products is associated with increased bone mass…” But can soy phytoestrogens prevent bone loss over time?

In a two-year study, soymilk was compared to a transdermal progesterone cream. The control group lost significant bone mineral density in their spine over the two years, but the progesterone group lost significantly less than that. The group drinking two glasses of soymilk a day, however, actually ended up even better than when they started.

In what is probably the most robust study to date, researchers compared the soy phytoestrogen genistein to a more traditional hormone replacement therapy (HRT) regimen. Over one year, in the spine and hip bones, the placebo group lost bone density, while it was gained in both the soy phytoestrogen and HRT estrogen groups. The “study clearly shows that genistein prevents bone loss…and enhances new bone formation…in turn producing a net gain of bone mass.”

The main reason we care about bone mass is that we want to prevent fractures. Is soy food consumption associated with lower fracture risk? Yes. In fact, a significantly lower risk of bone fracture is associated with just a single serving of soy a day, the equivalent of 5 to 7 grams of soy protein or 20 to 30 milligrams of phytoestrogens, which is about a cup of soymilk or, even better, a serving of a whole soy food like tempeh, edamame, or the beans themselves. We don’t have fracture data on soy supplements, though. “If we seek to derive the types of health benefits we presume Asian populations get from eating whole and traditional soy foods,” maybe we should look to eating those rather than taking unproven protein powders or pills.

Is there anyone who should avoid soy? Yes, if you have a soy allergy. That isn’t very common, though. A national survey found that only about 1 in 2,000 people report a soy allergy, which is 40 times less than the most common allergen, dairy milk, and about 10 times less than all the other common allergens, such as fish, eggs, shellfish, nuts, wheat, or peanuts.

What if you’re at high risk for breast cancer? See BRCA Breast Cancer Genes and Soy

What if you already have breast cancer? See:

What if you have fibroids? See Should Women with Fibroids Avoid Soy?.

What about hot flashes? See Soy Phytoestrogens for Menopause Hot Flashes.

What about genetically modified soy? See GMO Soy and Breast Cancer.

Not all phytoestrogens are beneficial, though. See What Are the Effects of the Hops Phytoestrogen in Beer? and The Most Potent Phytoestrogen Is in Beer.

How deleterious is hormone replacement therapy? See How Did Doctors Not Know About the Risks of Hormone Therapy?.

Synthetic estrogens used in animal agriculture are also a concern. For more on this, see Zeranol Use in Meat and Breast Cancer.

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations: