WARNING!
This is an older article that may not reflect Dr. Mercola’s current view on this topic. Use our search engine to find Dr. Mercola’s latest position on any health topic.
By Dr. Mercola
Dr. Sylvia Wassertheil-Smoller is a professor at Albert Einstein College of Medicine in the Department of Epidemiology and Population Health. She's also the principal investigator of the Women's Health Initiative1 (WHI), which is one of the largest studies ever to examine an array of women's health issues.
Hormonal supplementation, for example, is a relatively controversial subject that WHI was able to shed light on—especially with respect to women who have not had a hysterectomy.
But hormone therapy is just one facet of the Women's Health Initiative. It has delved into many other issues as well, including the impact of multivitamins and vitamin D on cancer, and the effects of excessive sitting.
"The Women's Health Initiative has been just a wealth of information and knowledge in health," Dr. Smoller says.
“We have a few ancillary studies that are ongoing. For example, we have something called the Long Life Study (LLS), where we paid a home visit a couple of years ago, to nearly 8,000 women who were over the age of 63 in 2012.
We’re going to see what factors protect and are helpful in later life. We also have something called Life and Longevity After Cancer (LILAC), which is a study of breast cancer survivors.
There are all kinds of things that are coming out of the Women's Health Initiative. And, of course, all our genetic studies."
What the Women's Health Initiative Revealed About Hormone Therapy
The Women’s Health Initiative, which enrolled women in 1993-1998 , included four clinical trials and one observational study. Altogether, more than 160,000 post-menopausal women were enrolled in 39 clinical centers throughout the United States, and the study resulted in over 2,000 peer reviewed scientific papers being published to date.
There was a clinical trial of low-fat diet compared to usual diet, a trial of calcium and vitamin D supplementation compared to placebo and two trials of hormone therapy—one for women who had had a hysterectomy and one for women who had an intact uterus.The hormone therapy trials looked at:
- Estrogen alone for women who have had a hysterectomy versus placebo2
- Estrogen plus progestin (synthetic progesterone) versus placebo for women who had not had a hysterectomy3 These women with an intact uterus had to have progesterone added to the estrogen to protect their uterus from developing endometrial (uterine) cancer
Women tend to have much lower rates of heart disease while they're menstruating, and generally develop heart disease about 10 years later than men do.
In the 1990s when the study started, researchers believed that women's hormones were the protective factor, but the Women's Health Initiative showed that replacing those hormones once they were no longer being manufactured in the body did not protect women from heart disease.
This was truly a landmark finding that made the front page of every major media in the world when they announced their findings in 2002. They actually stopped one leg of the study as it was clear that the hormone therapy was prematurely killing many of the women and resulted in increases in strokes, heart attacks, dementia and breast cancer.
As noted by Dr. Smoller:
"These trials are monitored by a safety monitoring board that's not connected with the study, but that gets access to the data and monitors it for either harm or benefit.
In this case, the results were so clear to them that they advised NIH to stop this trial so it was stopped. There was an enormous amount of publicity about it."
Women who had undergone a hysterectomy and took estrogen alone had a more favorable profile. They still got heart disease, but it wasn’t obvious whether the estrogen was responsible for it. They also had a slightly reduced rate of breast cancer, but they were still at higher risk for stroke and dementia than the women taking placebos.
WHI Hormone Study Turned Standard of Care on Its Head
So what's responsible for this relative protection that menstruating women seem to have? Some researchers believe that it's related to the monthly loss of blood, which lowers your iron level, and iron serves as a prooxidant that can cause a lot of oxidative damage in your body.
"That's certainly probably a good part of it,” Dr. Smoller says. “I think it may be other mechanisms at work as well. Estrogen earlier on in life may be somewhat protective. But the iron hypothesis is one that’s fairly well established....
But there are all kinds of different things that go on in a woman's body when she's still menstruating, and it's the balance of the various hormones [that is important]...
We're looking at genetics, blood biomarkers, and at all kinds of things to elucidate the mechanism [behind adverse effects to hormone therapy]. It's still elusive; we still haven't quite found why this is happening... We do know it's not protective. The combination of estrogen plus progestin does not protect you from heart disease, stroke, or breast cancer...
Estrogen alone is not protective for stroke, dementia, or many of the other things that happen to women as they age. We know you certainly shouldn't take it to prevent disease. That's what the hope was initially—that [hormone therapy] would prove to be a preventive measure, but it isn't."
The findings from the Women's Health Initiative resulted in a rapid reversal of the standard of care recommendations with regards to hormone therapy in 2002. Prior to that, hormones were regularly prescribed to decrease a menopausal woman's risk of heart disease, dementia, and stroke.
Sadly, this information has not been adopted by many physicians, especially gynecologists. Changing the standard of care in medicine can be like trying to turn the Titanic however, and some doctors are still prescribing hormone therapy to women who may not be good candidates for it.
Some still believe in prescribing estrogen and progestin for women suffering with menopausal symptoms, and these hormones do tend to ameliorate menopausal symptoms such as hot flushes and vaginal dryness, but truly, there are safer ways of addressing such symptoms. To learn more, please review my previous article, Your 7-Minute Guide to Natural Menopause Survival.
“Prescriptions went down by something like two-thirds when the news was first released, but it’s very hard to change a behavior and to change conceptions and attitudes. There was definitely a backlash.
Particularly many in the OB-GYN community said, “Ah, you were giving them too late. If you gave them just at the time that the woman was perimenopausal, that would be protective.” We didn’t find evidence for that in the estrogen plus progestin group,” Dr. Smoller says. “But all the women in our study were post-menopausal; we did not have any perimenopausal women.
You have to understand, women who are in their 40s to 50s have very low rates of these events to begin with. It's very difficult to show that [giving hormones during perimenopause] would make any difference, because there is such a thing as relative risk and absolute risk.
In other words, you could have a 40 percent higher risk of stroke relative to not taking hormones, but still the absolute number of strokes that people get is still very, very small, so forsome events, it’s very hard to show the difference...
But even in absolute terms, though it’s a small number, the fact is that when you multiply that by the number of post-menopausal women and the number who are taking these pills, it translates into millions of lives saved by not taking them.
For example, we calculated that there would be eight more strokes per year per 10,000 women taking estrogen plus progestin than for those not on hormones. If you multiply that by the many tens of thousands of women there are who might be taking hormones, and by the many years they might be on these hormones, you can see that by not taking them a lot of strokes can be avoided.
And I think we have to remember that menopause is not a disease – it is a stage of life. And postmenopausal symptoms do eventually go away. If the symptoms are really severe, then hormones might be appropriate but at the lowest dose and for the shortest period of time, as the FDA labeling says. ”
Bioidentical Estrogen versus Premarin
The estrogen provided to the women participating in the Women's Health Study was Premarin, manufactured by Ayerst. Premarin is conjugated equine (horse) estrogen (CEE), or estrogen extracted from mare's urine. While this sounds "all natural," horse estrogen is not identical to human estrogen. I recommend avoiding all animal estrogens for hormone replacement, as there are excellent human bioidentical estrogen hormones easily available through any compounding pharmacist.
Your body recognizes these as "normal" and virtually identical to the hormones produced in your body, which makes them far safer than synthetic prescription versions. There are three types of estrogens commonly used in bio-identical hormone replacement therapy: estrone, estradiol, and estriol. A common mixed formulation known as Tri-est includes 80 percent estriol with 10 percent each of estrone and estradiol. Estradiol is the primary human female hormone found in all premenopausal women, whereas estriol is produced in significant amounts during pregnancy.
Estriol is considered the safest of the three and is the most commonly prescribed. It has been used safely for decades, and I believe it's particularly useful when you've had a hysterectomy. Unfortunately, as noted by Dr. Smoller, there are many different hormone preparations, and studies cannot be done for each and every one. For example, no trials have been done on bioidentical estrogens. As a result, effects of other estrogens are inferred, based on the trials in which Premarin was used, and hence bioidentical estrogens have also gotten a bad rap.
Natural versus Synthetic Progesterone
I also recommend using natural progesterone in lieu of synthetic progestins, which were used in the Women's Health Initiative study. There's reason to believe that synthetic progestins (like Provera) are responsible for many, if not most, of the detrimental side effects of hormone therapy. For example, one meta-analysis published in the British Medical Journal in January 20054 found that synthetic hormone therapy is linked to an increased risk of stroke, typically ischemic (caused by blockages of blood flow to your brain).
In fact, synthetic hormone therapy may boost your risk of stroke by almost one-third, and your risk of fatal or disabling stroke by more than half. Natural progesterone is made from a substance called diosgenin, which is commonly extracted from wild yams or soybeans. Even though it may be extracted from soy it is a highly purified hormone and there are absolutely no remnants of soy substances that would lead to any problem. To learn more, please refer to this previous article on the use of natural progesterone.
How Beneficial Are Multivitamins and Mineral Supplements?
One of the findings from the observational study in the Women’s Health Initiative was about multivitamins and mineral supplements. Since it was an observational study, it shows correlation but cannot tell us whether there is actually a causal relationship. Nevertheless, about 100,000 women participated in it, giving us some compelling clues.
Looking at cancer and cardiovascular disease rates in women, they found that, on average, there was no difference in the incidence of these diseases between those who took vitamins and those who did not. However, when they looked at women who were already diagnosed with breast cancer, they found that multivitamins with minerals did protect against mortality from breast cancer.
"Usually things that are protective like that are also protective in primary prevention," Dr. Smoller says. "In this case, we didn't see that. But nevertheless they definitely – no matter what we did, no matter what we controlled for, no matter how we looked at the data – still showed a benefit in terms of dying from breast cancer... and all-cause mortality as well."
The WHI also looked at vitamin D and its effects, and according to Dr. Smoller, “it’s fairly well accepted that vitamin D is protective against a variety of adverse conditions and that many women have too low levels of vitamin D in their blood.” However, one trial in WHI in which calcium and vitamin D supplements were compared to placebo found no significant protection against colorectal cancer. As for other individual nutrients, it’s quite difficult to study the effects of single nutrients because we don’t eat nutrients; we eat foods, and foods have all kinds of nutrients and synergistic ingredients that interact with each other in them.
As noted by Dr. Smoller:
"It's hard to look at specific nutrients unless there's a big deficiency of them. One of our latest studies showed that dietary potassium is protective against stroke. We're now looking to see whether it's protective against dementia as well. The recommended daily allowance of potassium is something like 4,700 milligrams (mg)… Nearly five grams... But very few people get that. In our study, only about 16 percent got more than 3,500 mg... something like three percent got 4,500 mg."
Some nutrients, such as potassium, you should ideally get from your diet and not from supplements. Dr. Smoller notes that supplemental potassium can be problematic for people with undiagnosed kidney disease. "Too much potassium can be very dangerous. So you shouldn't take potassium supplements without talking to your doctor. But it's not that hard to get adequate potassium in foods because so many foods have potassium. Certainly vegetables and fruits... like bananas, avocados, oranges, apricots, meats even, and yogurt."
Waist-to-Hip Ratio and Sedentary Behavior—Two Potent Predictors of Disease
Another health factor the Women's Health Initiative looked at was waist circumference, body shape, and waist-to-hip ratio. Virtually all of these are better predictors of disease than body mass index (BMI), with the waist-to-hip ratio being the best.
“The other thing that we found in some of our studies is what they call “healthy obese,” i.e. metabolically healthy obese. They are people who are obese and overweight who are metabolically healthy. Their insulin levels, their glucose levels, their cholesterol levels are all okay...Then there are people who are lean but are metabolically unhealthy. Even though they are thin, they have a bad cholesterol profile, they have insulin and glucose problems, and so on. These are the lean, metabolically unhealthy.
Then there are the obese, metabolically unhealthy and the lean, metabolically healthy. There are at least four groups. Among the obese, most people are metabolically unhealthy. There is this smaller group that is metabolically healthy. Some people have shown that if you’re overweight and metabolically healthy and may not yet be showing higher risk of diabetes and cardiovascular disease, eventually you’ll become metabolically unhealthy. It’s an extremely complex situation, but the bottom line is it’s the metabolism that counts.”
Not surprisingly, the self-report in the Women’s Health Initiative also showed that the more exercise women reported getting, the better their health. And, more importantly, the study also found that sedentary behavior independent of regimented exercise is a potent predictor of disease.
This is something I’ve discussed in numerous articles in recent years, as more than 10,000 studies clearly shows that prolonged sitting is an independent risk factor for chronic disease, even if you exercise regularly and are very fit, and that is precisely what was found here as well.
“What we found is that sedentary behavior is associated with cardiovascular risk and cardiovascular diseases,” Dr. Smoller says. “This is apart from the amount of physical activity you get. You could go out to the gym and get your physical activity, but then you spend six or seven hours a day sitting, and that is a risk factor.”
Optimal Health Is Within Your Reach
When it comes to health and longevity, there is no quick fix and no "fountain of youth" that will help you become healthy overnight. Being fit and healthy in order to reach a ripe old age takes effort and attention – this is something that I repeatedly tell my readers. The good news is that relatively simple lifestyle changes you can make a major difference when it comes to optimizing your health and preventing disease.
Your diet is of primary concern, of course, as is getting enough exercise and avoiding prolonged sitting on a day-to-day basis. Ideally, avoid sitting for more than three hours per day. Things like hormone therapy is clearly trickier, and you'd be wise to do your homework before taking hormones. Addressing basic lifestyle issues can go a long way toward preventing any major hormonal imbalances though. For example, the Paleolithic diet, which includes fermented and cultured foods, tends to promote healthy hormone levels, even as you age.
The Women’s Health Initiative has done much to shed light on women’s health, and for that we can be truly grateful. Taxpayer dollars are not always so wisely spent. At the end of the day, a lot of the research shows that if you want to be healthy and prevent disease, lifestyle choices like good nutrition and exercise matter—which really shouldn’t come as any great surprise. Below is an infographic listing my top guidelines for healthy living.
![11 Basic Guidelines for General Health and Longevity Infographic Preview]()
Embed this infographic on your website:
Click on the code area and press CTRL + C (for Windows) / CMD + C (for Macintosh) to copy the code.