Confusion Over Hormone Replacement Therapy

Women are confused, and can you blame them? Ever since the Women's Health Initiative (WHI), hormonal replacement therapy (HRT) has become an extremely controversial topic, especially since a lot of physicians themselves have a problem explaining the results.

Recently, I had the pleasure of talking to a group of women at The Women's Right Information Center in Englewood, New Jersey. We were there to discuss a very interesting book by Barbara Seiman, titled "The Greatest Experiment Ever Performed on Women: Exploding the Estrogen Myth." After the book discussion, the audience had many interesting questions regarding estrogen replacement therapy, so I got to thinking, “Let me ask an expert his or her view on this controversial topic.”

Dr. Andrea Vidali is Director of the Reproductive Endocrinology and Infertility Division at Hackensack University Medical Center in Hackensack, NJ, and Director of the Reproductive Endocrinology and Infertility Division at Saint Vincent’s Catholic Medical Center in New York City. Dr. Vidali is also an active member of the American Society of Anti-Aging Medicine (A4M). You can read Dr. Vidali's blog at

Question: What is the theory behind hormone replacement therapy (HRT) in menopausal women?

Dr. Vidali: When it comes to disease, restoration of low thyroid, insulin and cortisol is the standard medical treatment. Thus, it seems logical to also replace estrogen, progesterone and testosterone when a person has low levels of those hormones. However, the evidence leaves clinicians at a loss for clear direction, because different studies, using a variety of types of hormones, methods of hormone administration, and women of different ages, have produced conflicting results.

Question: What are the Normal Hormone Ratios?

Dr. Vidali: There are three predominant estrogens in non-pregnant, pre-menopausal women: estrone (E1), estradiol (E2) and estriol (E3). These naturally occur in different relative amounts. Typically, E1 will make up 10 to 20 percent of total estrogen, E2 will make up another 10 to 20 percent and E3 will comprise the remaining 60 to 80 percent of total estrogen.

This ratio is protective, because the bulk of estrogen is comprised by the weakest estrogen, E3, which is also the most protective against blood clots and breast cancer. E2 is the strongest estrogen, and E1 is the storage form of estrogen. E1 is sometimes considered the "least desirable" estrogen, because it can stimulate breast tissue production and blood clots. E1 can be safely metabolized and excreted by the liver, but if the liver systems are overwhelmed or if vitamins B12 and folic acid are deficient, E1 is converted to quinines. These can be mutagenic and carcinogenic, and thus could ultimately lead to cancer and other health problems.

Question: What are bio-identical hormones and how can they mimic protective ratios?

Dr. Vidali: Estrogen-like hormones can be obtained from horses, soy and yams, but these hormones do not fit exactly into the human receptors. By contrast, bio-identical hormones are an exact match, molecule for molecule, to the hormones produced naturally by a woman's body. They fit the hormone receptor just like a key fits into its lock, and the body cannot distinguish between a bio-identical hormone and the hormones it makes itself.

Bio-identical hormones can be made in several ways. Sometimes they are created by modifying soy or yam hormones — any molecule that does not exist on the human hormone counterpart is removed. They can also be produced synthetically in the laboratory to make things like estrogen patches, which contain bio-identical 17-beta estradiol.

Question: According to this principle, how are bio-identical hormones prescribed by doctors who use them today?

Dr. Vidali: The goal is to re-establish the normal protective ratio, a 20:80 ratio of E2 to E3, and avoid E1 altogether. Estrogen that comes in the form of a patch mimics normal ratios better than estorgen that is taken in pill form, because the estrogen pill first has to pass through the liver, where 50 percent is converted into E1 ("bad" estrogen) before being circulated to tissues.

Estrogen applied through a patch enters the blood at the same ratio in which it is applied to the skin, with no chance for alteration by the liver. Many studies suggest that estrogen administered through a skin patch decreases thrombosis, blood pressure, triglycerides and vascular resistance, as opposed to the pill form of estrogen, which is known to increase these effects and can also cause other problems.

Question: Going back to the large hormone replacement studies that, four years ago, raised questions about the health risks associated with traditional menopause treatment, what has happened since then?

Dr. Vidali: The Women's Health Initiative (WHI) was a large study, sponsored by the National Institute of Health, which greatly influenced how American doctors prescribe hormones and how American women receive them. Millions of women stopped hormone replacement therapy (HRT) because of the study's findings.

But, as with any medical study, there were many problems. The researchers did not take "quality of life" into account. They did not use estrogens in favorable ratios and they did not test hormones that were administered via a patch. The estrogen used by women in the study was a synthetic, non bio-identical progestin, which is known to increase the risk of thrombosis and cancer.

Another problem with the study was the age of the women involved. The researchers should have started women on hormone therapy before they developed significant vascular disease, by age 55, instead of at an average age of 63 and higher.

Finally, the researchers should have insisted on media coverage of some of the positive findings they later discovered in their data analysis. Since that study, many American women and their doctors have found an alternative treatment via the bio-identical hormone approach.

Unfortunately, there are no studies comparable to the size of the WHI study available yet. While there is no question that more studies on bio-identical hormone therapies are needed, a large body of evidence points to the potential advantages of the bio-identical approach.

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Dr. Manny Alvarez serves as Fox News Channel's senior managing health editor. He also serves as chairman of the department of obstetrics/gynecology and reproductive science at Hackensack University Medical Center in New Jersey. For more information on Dr. Manny's work, visit