Kent Holtorf, M.D.

There is a lot of confusion about the meaning of the recent study known as the Women’s Health Initiative, which was testing the effects of the most prescribed drug combination hormone replacement therapy for menopausal women, Premarin (conjugated equine estrogens) and Provera (medroxyprogesterone acetate). This study was halted because the use of the study drugs, Premarin and Provera (also in PremPro), increased the risk of breast cancer, heart attack, blood clots, and stroke. This was actually an expected outcome for this particular medication, which combines an oral horse estrogen and a synthetic progestin, because this combination has been shown on numerous occasions to have precisely these problems. For years, many doctors have been discouraging patients from taking synthetic hormones and encouraging them to switch to natural prescription hormones that are shown to be more beneficial and to not have the risks associated with the synthetic hormones. I have discouraged the use of this combination for many years and have gotten my patients off this combination and onto prescription natural estrogen and progesterone that are bioidentical to a woman’s natural hormones. These natural hormones do not have the negative side-effects or carry any of the risks demonstrated in the recent and past studies. The natural combinations have been shown to decrease the risk of stroke and heart attack by 50% (Premarin and Provera increase it) and reduce the risk of breast cancer by 80% (Premarin and Provera increase it). The natural hormones also reduce the risk of osteoporosis by 50%, reduce the risk of Alzheimer’s by 80%, reduce the risk of osteoarthritis by 40%, and reduce the risk of colon cancer by 40%.

There is a long history of studies showing that when a synthetic progestin (Provera) is used, there will be an increase in breast cancer, while the use of natural prescription progesterone will have a powerful protective effect against breast and other cancers. Studies show that women with low levels of progesterone are up to 10 times more likely to develop cancer and 5 times more likely to develop breast cancer. Natural progesterone has strong anti-cancer effects while synthetic progestins are carcinogenic. In fact, women taking natural estrogen and natural progesterone are provided protection against breast cancer and are at less risk of developing cancer when compared to women who are not on any hormone replacement therapy.

Progesterone is naturally produced by a woman, but because the drug companies cannot patent this natural hormone, they must first alter the molecule so they can patent it to make it financially worth while to market and sell. When this was done, some of progesterone’s effects were retained, while other effects were opposite of those produced by natural progesterone. For instance, progesterone is secreted in high doses by women during pregnancy to promote fetal growth. On the contrary, progestin during pregnancy will kill the fetus. The main ingredient in The Morning After Pill to terminate pregnancy is progestin. It was shown that Provera could protect the uterus from cancer from unopposed estrogen, and this is how it was approved. It was not known at that time, however, that it would not protect the breast from cancer like natural progesterone does. In fact, synthetic progestins such as Provera promote cancer. The alteration of the natural progesterone also changed the vasodilator effect of natural progesterone, which decreases the risk of heart attack and stroke, to a compound that constricts coronary arteries and other vessels, significantly increasing the risk for heart attack and stroke. It is also clear from numerous studies that taking synthetic progestins, such as Provera, will increase a woman’s risk for heart disease and will negate many potential positive benefits of estrogens. On the contrary, natural progesterone will augment the positive benefits. Provera has also been associated with increased fatigue, weight gain, and decreased exercise tolerance, while natural progesterone demonstrates none of these problems. Over the past 10 years there has been so much evidence that the synthetic progestins, such as Provera, are harmful that it would never have been approved by the FDA if the drug companies had sought approval in more recent years.

The Premarin used in the study added fuel to Provera’s toxic fire. Premarin, the most popular estrogen replacement therapy (ERT,) is derived from pregnant horses and contains mostly estrone and a number of equine (horse) estrogens that are not natural to humans. Many of these foreign estrogens bind very tightly to the human estrogen receptors, making them highly stimulating and carcinogenic. A combination of the natural estrogens, estriol and estridiol have been shown to actually protect against breast cancer and result in a reduction in breast cancer risk. When this is added to natural progesterone’s powerful breast cancer risk reduction, one would expect a significant reduction in breast cancer in women on natural hormone replacement than in women on no therapy. The hormones estriol and progesterone rise very high during pregnancy, which results in a successive decreasing risk of breast cancer the more times one is pregnant.

Also when Premarin is given orally, it passes through the liver and significantly increases clotting factors and risk for stroke and heart attack. This results in a multiplied heart attack risk when Provera is added. When estrogens are given transdermally patch or cream this problem is avoided. Synthetic progestins are toxic no matter which form is prescribed.

This study has unfortunately surprised many physicians even though this was truly an expected result of these synthetic hormones. In the many years that I have been preaching the dangers of Premarin and Provera many patients have asked me why then are so many doctors prescribing these hormones. The answer is multifactorial. First, many doctors are not aware of the studies showing the significant risks of this combination. Many people think that doctors are able to sit around and read medical journals, but unfortunately, most doctors do not have the time. Many rely on pharmaceutical representatives (the ones selling the drugs) to bring them new studies on their drugs, and obviously nothing negative is brought in. There are no pharmaceutical representatives selling natural prescription estrogens and progesterone. Secondly, drug selection by physicians is driven by insurance companies, who decide which drugs the physicians may use by deciding which drugs are on their formularies. Insurance companies encourage the use of Premarin, Provera and PremPro because they are economically priced and they have been the standard treatment for many years. They make it difficult for a doctor to choose another drug. Thirdly, many doctors are creatures of habit. Once they become comfortable with a drug it is difficult to get them to change. Many doctors also felt that the problems were not that bad and besides everyone else was using them.

In summary, this study has opened the eyes of many, but it has also closed the eyes of many. In that some will understand what this study indicates, while others will misinterpret the study and come to the wrong conclusion that women are better off not on any hormone replacement therapy. Consequently, many women will needlessly suffer and be at increased risk for heart disease, stroke and multiple cancers. There is a fast growing interest in the natural hormones, despite the fact it is not backed by a multi-billion dollar drug company because they don’t have the risks associated with their synthetic counterparts. Many more women are demanding them and many more doctors are prescribing them for their superior properties and safety. I recommend women find a doctor who is well versed in these natural bioidentical prescription hormone replacement therapies.