All Forms of Hormone Replacement Therapy (HRT) Increase Breast Cancer Risk

One of the most common questions that I am asked is if there are any safe forms of hormone replacement therapy (HRT) for women who are experiencing severe symptoms associated with menopause. Since the release of the preliminary results of the pivotal Women's Health Initiative study, in 2002, which clearly showed that standard combination HRT (containing the two primary female sex hormones) was associated with a significant increase in the risk of developing breast cancer, a number of alternative "safer" forms of HRT have been proposed. These alternative forms of HRT have included transdermal estrogen patches (which are placed on the skin) and other forms of "bioidentical" HRT hormones.

Advocates of transdermal estrogen patches note that the adverse effects of estrogen-based HRT pills on cholesterol, as well as their association with an increased risk of life-threatening blood clots, may be lower with transdermal patches when compared to oral HRT medications.

Proponents of "bioidentical" HRT, in which the active ingredient is the same chemical form of estrogen (estradiol) that is manufactured in the ovaries prior to menopause, have also made abundant health-related claims for this form of HRT when compared to the more commonly prescribed cocktail of mixed forms of estrogen derived from the urine of pregnant mares. Unfortunately, there is almost no solid clinical research evidence available to support these claims that "bioidentical" HRT is safer, or more effective, than the more commonly prescribed "conjugated equine estrogens." (Within the estrogen-sensitive cells of a woman's body, estrogen receptors really don't care much whether estrogen-like hormones come from horse urine or from the human form of estrogen; nor do they care whether or not estrogen-like hormones enter the body in the form of a pill versus being absorbed into the bloodstream through a transdermal patch.)

As the Women's Health Initiative study's breast cancer risk findings were far more robust for the combination HRT pill that has been commonly prescribed for menopausal women (because estrogen-alone HRT increases the risk of uterine cancer, as well...), many patients, and their doctors, have held out the hope that low-dose estrogen-only HRT might be a safer alternative to traditional combination HRT. However, a recently published research paper from the enormous European EPIC public health study casts serious doubt about the assumption that alternative forms of HRT are safe from the standpoint of breast cancer risk.

This research paper, which has been published in the International Journal of Cancer, is an update of the huge European Prospective Investigation into Cancer and Nutrition (EPIC) study, in which 134,744 postmenopausal women throughout Europe were evaluated. After nearly 9 years of follow-up, on average, 4,312 new cases of breast cancer were diagnosed within this extremely large group of patient volunteers.

When compared to women who had never used HRT, the women who were currently using combination HRT during the course of this clinical study experienced a 77 percent increase in the relative risk of developing breast cancer (similar to what has been shown in the Women's Health Initiative study, and in other similar prospective clinical research studies). However, the greater contribution of this study to our understanding of the risks of HRT was the finding that estrogen-only HRT also increased the risk of breast cancer, as there was a 42 percent increase in the relative risk of breast cancer among the women who were taking various forms of estrogen-only HRT. Moreover, this increased breast cancer risk among users of estrogen-only HRT was the same for both oral and transdermal forms of estrogen-only HRT.

The results of this giant, multi-national prospective public health study are of great importance, as it is many times larger than most of the studies that have preceded it, including the Women's Health Initiative study. These results from the ongoing EPIC study emphasize the point that I have made to patients for almost two decades, now: The biology of the receptors in cells that respond to estrogen, and other estrogen-like molecules, has been well understood for decades now. Any substance that stimulates these estrogen receptors automatically sets off a cascade of biochemical reactions with the same end biological result. We have long known that prolonged exposure to estrogen (whether from a woman's own ovaries, or from HRT medications) increases the risk of breast and uterine cancer, and also increases the risk of blood clots, gallstones, and other serious illnesses. (More recent data has also implicated combination HRT in the development of cardiovascular disease and dementia in women.)

Based upon the findings of this very large prospective public health study, my advice to women remains the same as it has been for almost 20 years. If you are going through menopause, do not use HRT medications. If you are already using HRT medications, then ask your doctor to help in weaning you off of them. If you are one of the approximately 3 to 5 percent of postmenopausal women who have unbearably severe hot flashes, or other severe symptoms of menopause, and you are currently using some form of HRT medication, then work with your doctor to reduce the dose of your HRT medicine to the lowest possible level that adequately treats your symptoms.

To learn more about the critical role of hormone replacement medications and the risk of cancer, look for the publication of my new landmark book, "A Cancer Prevention Guide for the Human Race," in the summer of this year.