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:

    1. Estrogen alone for women who have had a hysterectomy versus placebo2
    2. 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.