Hormone Replacement Therapy: Behind the Headlines

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For many women hormonal imbalances become a central issue in their lives as they approach menopause and beyond. With diminishing levels of estrogens and progesterone, it only makes sense that hormone replacement therapy (HRT) would come as a welcome relief. However, since the Women’s Health Initiative (WHI) results were reported, linking HRT to heart disease and stroke, a shadow has been cast over all HRT. The fact that the WHI was reflective of “synthetic” hormones got lost in the story. Yet, it cannot be stressed enough that the results of the WHI do not pertain to “natural” hormone replacement and the research to prove it is consistent. Unfortunately, the numerous studies clearly demonstrating that natural hormone therapy has health benefits, have not received the same media attention. The extensive comparative research of the hormone therapies has revealed several key insights as to the roles of hormones in diseases such as cancer, cardiovascular disease (CVD), and stroke.

Before delving into the subject further, let’s review the basics. Since it’s the estrogen and progesterone levels that decrease as women approach menopause, they are the hormones that are usually central in replacement therapy. Testosterone is important too, but not in this discussion. Premarin is a synthetic form of estrogen that’s derived from pregnant horse’s urine; thus the name, “pre (pregnant)–mar(horse)- in(urine)”. Provera is the most commonly used form of synthetic progesterone (known as progestins). Various combinations of the natural and synthetic hormones have been compared in studies, all showing that natural hormones do not carry the disease risks of synthetic HRTs, Premarin and Provera.

Cardiovascular Disease and Stroke

Since hormones play a role in CVD and stroke, it is important that they are used in a way that is protective against these conditions. Research demonstrates multiple ways in which natural hormones provide cardioprotective effects, in sharp contrast to their synthetic counterparts. The WHI investigators found that when they added Provera (MPA) to Premarin it increased the risks of heart attack and stroke, rather than merely negating estrogen’s cardioprotective benefits. In a number of other studies, coronary artery spasms were reduced with the combination of natural progesterone and estrogen, yet when Provera was combined with estrogen, vasoconstriction occurred. With increased vasoconstriction comes the increased chance of a cardiac event.

The difference in natural vs. synthetic hormones can potentially translate to the difference between life and death as evidenced in a study with 18 monkeys. After removing the monkey’s ovaries in order to induce menopause, the monkeys were put on estrodiol and then treated with either Provera or natural progesterone. Four weeks later, the animals were injected with a substance to trigger vasoconstriction. The Provera monkeys would’ve died within minutes had they not been promptly injected with another drug that was protective. In contrast, those that were on natural hormones were fine. One can imagine how this type of situation might play out in an already compromised person. In other research, hormone effects on vasoconstriction and exercise were studied using post –menopausal women with coronary artery disease. The purpose was to compare the time between endurance exercise and myocardio ischemia. The results showed that while on the natural hormones, the time to ischemia was longer, indicating reduced risk.

Various other studies with synthetic hormones have also demonstrated increased risk of blood clots, plaque formation, high glucose and insulin levels, type 2 diabetes, and negative impacts on cholesterol, in contrast to the protective effects found with the natural hormones. This information caught the attention of the President of the American Heart Association who stated that “based on the difference of HDL levels alone, a woman who changes from MPA to natural progesterone would reduce her risk for CVD”.


The research pertaining to hormones and cancer risk demonstrate similarly contrasting results. One of the largest studies was on 80,000 women for a period of 8 years, was published in a 2007 issue of Breast Cancer Research. The study showed an association between increased cancer risk and various synthetic hormones. The women who took natural forms of estrogen alone had an increase risk over those who took nothing, yet the risk was even higher with estrogen and synthetic progestin. However, by using natural progesterone with estrogen the cancer risk was eliminated. It was further demonstrated that when estriol (form of estrogen) was used, the risk of breast cancer was reduced to less than with those who took nothing at all. Estriol’s protective benefits have stood out in other studies as well. An analysis of the data from six epidemiology studies showed an inverse relationship between estriol levels and cancer risk. Compared to synthetic Prevarin, which can be carcinogenic, estriol does not covert to a carcinogenic compound in vivo. In an article published in the Journal of the American Medical Association, Dr. Follingstad reported on a study of postmenopausal women with breast cancer who were given estriol, which caused remission or arrest of the disease, for 37% of them. It’s no surprise that based on this study and accumulated evidence, Follingstad strongly supports the use of estriol for women at risk and in need of estrogen replacement therapy.

The conversation would not be complete without acknowledging the significance of progesterone’s protective effects against breast cancer. Even in cases where other risk factors are higher, women with increased levels of progesterone have a reduced cancer risk. Its strong anti-proliferation effect on cells is one of the reasons why. Had natural progesterone been used in the WHI it is likely that the outcomes would have been different, as would many women’s lives. Clearly safe alternatives are available, but women must also become aware of them in order to benefit.

For even more information on synthetic and bioidentical hormone replacement therapy, watch this video.

1. Available at: http://holtorfmed.wpengine.com/download/natural-hormone-replacement/Natural_vs_Synthetic_HRT_Literature_Review.pdf/ Accessed on March 30, 2016.

2. Available at: http://holtorfmed.wpengine.com/download/natural-hormone-replacement/BHRT_and_Risk_of_Breast_Cancer.pdf/ Accessed on March 30, 2016.