Interesting research on breast cancer

A series of studies performed at the Eppley institute for Research in Cancer and Allied Diseases in 2008 shed new light on the possible causes of breast cancer and what can be done to lower the risk of developing this disease.

It is known that estrogen, whether produced in the body or taken as a supplement, is carried through the bloodstream to the liver where it is gradually broken down and eventually eliminated. In this process, the liver releases a variety of estrogen breakdown products, some of which are harmless or even protective of good health, and others that are highly toxic and can cause cancer.

Although genetics also play a part in this, exposure to a variety of chemicals triggers the liver to overproduce toxic forms of estrogen. One of the studies showed that these toxic estrogen breakdown products are found in significantly higher concentrations in women who have breast cancer or who are at high risk of developing it (Int J Cancer, 2008 May 1;122(9):1949-57).

Two other studies show that the antioxidants N-Acetylcysteine (NAC) and Resveratrol (RES) have a balancing effect on liver function, and that this results in an improved ratio of healthy forms of estrogen to cancer-causing ones (J Steroid Biochem Mol Biol, 2008 Mar;109(1-2):22-30, Free Radic Biol Med, 2008 Apr 8).

Both NAC and RES have been shown to increase the liver’s production of glutathione, a protein the liver needs to eliminate toxins from the body. In today’s environment liver stores of glutathione can become depleted leaving us at greater risk for a variety of adverse health events, not just breast cancer. Therefore I feel that NAC or RES (or both) should be a part of everybody’s “survival kit” in this day and age.

Are natural hormones really better?

Until very recently, every woman going through menopause or past it was told she should take hormones. There seemed to be no good reason not to do so; hormones helped women feel better, they were believed to protect their hearts, their bones, and even their brains from the effects of aging. The fact that these hormones came from horses and were very different from human hormones didn’t seem to raise many suspicions. After all, that’s what the doctors were prescribing and what pharmaceutical companies wanted to sell.

A small group of physicians with an interest in nutritional medicine had always favored natural, so-called bio-identical hormones; but at the time few people took notice. These hormones are synthesized from plant materials and – unlike hormones from horses – are identical to hormones produced in the human body. Because they cannot be patented and so cannot be used to make enormous profits, pharmaceutical companies have never had an interest in them.

Twenty years after the fact, we discovered that the old studies about the benefits of hormone replacement were all wrong. New research started to surface and was broadcast everywhere showing that everything that was believed about hormone replacement was incorrect. Not only do hormones not protect women from heart disease, they can cause it – and besides that, they can cause cancer too.

Many of the “natural hormone” doctors felt vindicated and, before they knew it, their practices were booming with women wanting to stop the dangerous horse hormones and replace them with something natural. However, natural does not always mean safe, and there have been no safety studies to date on natural hormones. The doctors’ contention has been that natural hormones must be safe because they are identical to those produced in the human body. A compelling argument, but one that never quite convinced me in the absence of confirming studies.

Now an interesting study from the UK (Environ Health Perspect 112: 1137-1142 (2004)doi: 10.1289/ehp.7028 available from voices that very same suspicion. The study compared growth-promoting effects on uterine tissue of synthetic estrogen, natural estrogen and genistein, a plant estrogen found in soy. If these effects are not substantially different, it is likely that all of these compounds might have the same effect in promoting uterine cancer. The researchers did find that all three compounds acted in a similar manner and they concluded that “the case is yet to be made for regarding synthetic estrogens as presenting a unique human hazard.”

Hormone replacement therapy

Everybody’s heard about this study and it’s really old news by now, but after seeing a TV ad by a local doctor promoting “natural” hormones I decided to put in my own two cents. Could it be that menopause is really the only natural way to go?

Here’s the background: one of the largest and best-designed studies on hormone replacement therapy was halted when it was found that the women who were on the hormones had a higher rate of breast cancer, heart attack, stroke and blood clots than those on placebo (JAMA 2002;288:321-333). The hormones in the study were Premarin, a horse-derived estrogen, and Progestin, a synthetic analog of progesterone.

In fact, there was nothing so surprising about this study other than the enormous news coverage it received. Previous studies, some of them covered in earlier issues of this newsletter, had reached similar conclusions but received little public attention.

So should women take “natural” hormones instead? So-called natural hormones are actually synthetically reacted from a common plant steroid. The plant material is not itself a hormone in humans, but it can be manipulated in the laboratory to make any sex hormone. These plant-derived hormones are actually best defined as “bio-identical” in that they are exactly the same as hormones produced naturally in humans.

As strange as it may seem, bio-identical hormones have never been adopted in medicine as the standard for hormone replacement therapy. Instead, some hormones were taken from horses (and the horses were treated very inhumanely in the process) and others were manufactured from chemicals. The reason is that natural, or bio-identical, hormones cannot be patented and pharmaceutical companies have no interest in promoting them.

But the question remains: are natural hormones safe? Unfortunately, there is not a single study evaluating their safety, primarily due to lack of funding. These substances have been approved for use simply because they are natural and, consequently, presumed to be safe.

Some experts hold that they are safe because they are from a natural source, plants, and are identical to those made by the human body. This type of reasoning never completely satisfies my curiosity – is menopause then a mistake? A well-known fact among researchers is that early menarche and late menopause are themselves risk factors for breast cancer. Actually, for every year that menopause is delayed, the risk of cancer goes up (see Lancet Oncol 2001;2(3):133-40 and Breast Cancer Res Treat 2002;72(2):107-15 among others).

This does not imply that women’s sex hormones are unhealthy. It means that if exposure to these hormones becomes excessive or goes beyond a certain natural term, they may endanger a woman’s health. In this respect, menopause could be understood as a protective mechanism of nature.

Of course, the symptoms of menopause can be incapacitating. In most cases I have found herbal medicines to be very effective, especially if they are expertly selected and combined. Herbs are the only true natural solution for the symptoms of menopause, and they are a solution that has been used for thousands of years. For women who do not respond to herbal remedies, I would suggest using natural hormones until the symptoms subside.

Hormone Replacement Therapy linked to breast cancer

A recent study published in the Journal of the American Medical Association (February 13 2002;287 (6):734-41) found a clear association between long-term hormone replacement therapy (HRT) in women and an increased risk of breast cancer.

The study looked at 705 women who had been diagnosed with breast cancers of all types between 1990 and 1995 as well another 692 randomly selected age-matched women. Researchers concluded that those who had been on long-term HRT, both on estrogen alone and estrogen plus progestin, had a risk of contracting breast cancer of any type that was 60% to 85% higher than that of women who had not been on long-term HRT. When considering only the lobular type of breast cancer, the risk was more than three times higher for the HRT group.

Natural progesterone and sleep

A study published this year (J N Am Menopause Soc, 2001;8(1):3-4) looked at how natural progesterone and medroxyprogesterone (Provera) affect sleep in post-menopausal women. The study concluded that, when women take natural progesterone, they fall asleep faster and wake up less frequently during the night. The average sleep time increases by more than 40 minutes, which is similar to the effects of many prescription sleeping pills, but with no daytime drowsiness or other side effects. In contrast, no improvement in the quality or duration of sleep is observed in women taking Provera.

Hormone Replacement Therapy (HRT) and Heart Disease

Do you still believe HRT will protect you from heart disease? Think again. The American Heart Association, in an open letter to physicians published in the journal Circulation (July 24, 2001;104:499-503), recommends that heart health should be left out of HRT decisions.

Although HRT has been shown to lower cholesterol levels, preventing heart disease is obviously a far more complex issue. The well-known Heart and Estrogen/Progestin Replacement Study (HERS), a 4-year trial, showed that conventional HRT actually raised the risk of recurrent heart attack and death during the first year, and then lowered it only slightly. Detailed review of this same study suggests that, over longer periods of time, conventional HRT may further increase the risk of heart disease because it promotes inflammation (JAMA 1998;280:605-613). Another study (Circulation 1999;100:717-722) also found that women on HRT had elevated markers for inflammation and, although cholesterol was down, fibrinogen – a protein associated with blood clots – was elevated.

Hormone replacement therapy and heart disease

Contrary to what many women have been told, a new study published in the New England Journal of Medicine (August 24, 2000; 343:522-529, 530-537) reveals that hormone replacement therapy (HRT) does not protect against heart disease.

Researchers studied the effects of two forms of HRT on women with existing coronary artery disease. The two forms of HRT studied were horse-derived estrogen (found in Premarin) and the same estrogen plus synthetic progesterone (progestin). At the end of the 3.2-year study, researchers observed that neither treatment had altered the progression of the disease.

The authors concluded that women with established disease “should not use estrogen replacement with an expectation of cardiovascular benefit.” An accompanying editorial states:

“Evidence is mounting that current postmenopausal hormone preparations may not be effective as secondary prevention for some women. For example, the Heart and Estrogen/Progestin Replacement Study (HERS) (7) found that 4.1 years of treatment with conjugated estrogen plus medroxyprogesterone acetate had no overall effect on the rate of nonfatal myocardial infarction or death among women with established coronary artery disease. However, an increased risk of cardiovascular events was associated with the study regimen in the first year.”