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


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“A critical weekly review of important new research findings for health-conscious readers”


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.


For more information on HRT and cancer, please click on the following links to my previous columns on this topic:

Hormone Replacement Therapy (HRT) & Ovarian Cancer

Hormone Replacement Therapy (HRT) & Breast Cancer; Stool DNA Testing & Cancer of the Colon & Rectum

Breast Cancer Incidence & Hormone Replacement Therapy; Circumcision & the Risk of HPV & HIV Infection

Breast Cancer Recurrence & Hormone Replacement Therapy (HRT); Carotid Artery Disease: Surgery vs. Stents?; Statin Drugs & Cancer Prevention

Medication & Risk of Death After Heart Attack; Hormone Replacement Therapy (HRT) & Mammogram Results; Selenium: Cancer, Heart Disease & Death

Minority Women, Hormone Replacement Therapy & Breast Cancer; Does Health Insurance Improve Health?

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.

Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity

Dr. Wascher is an oncologic surgeon, a professor of surgery, a cancer researcher, an oncology consultant, and a widely published author

For a different perspective on Dr. Wascher, please click on the following YouTube link:

I and the staff of Weekly Health Update would like to take this opportunity to thank the more than 100,000 new and returning readers who visit our premier global health information website every month.  As always, we enjoy receiving your stimulating feedback and questions, and I will continue to try and personally answer as many of your inquiries as I possibly can.


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9 Comments on "All Forms of Hormone Replacement Therapy (HRT) Increase Breast Cancer Risk"

  1. Doctorwascher on Sun, 18th Jul 2010 6:56 pm 

    Vitamin D Reduces Risk of Cognitive Decline & Dementia…

    Weekly Health Update:

    Vitamin D Reduces Risk of Cognitive Decline & Dementia

    “A critical weekly review of important new research findings for health-conscious readers…”

    By, Robert A. Wascher, MD, FACS

    Updated: …

  2. Alexis on Tue, 20th Jul 2010 12:58 pm 

    I have to say I can’t agree – none of the types of studies regularly accepted are done on bio-identical hormones prescribed in proper proportion because they aren’t patentable so there is no financial incentive. Numerous doctors have been prescribing them with a good track record for over 20 years and when done properly they have seen no increase in breast cancer. AND – compounded bio-identical estrogen (which I take) is generally a small amount of estradiol and a large proportion of estriol which has been shown to be PROTECTIVE against breast cancer. REAL progesterone – not the drug company progestins which are the most dangerous of all – is also necessary and sometimes testosterone – as someone whose body simply can’t make many hormones who was going through hell despite a great diet, supplements and exercise I take exception to the idea that I should quit and go back to migraines every week, vaginal atrophy, horrible hot flashes and the bone loss, skin sagging and other things that go along with hormone deficiency. I get tired of hearing this when there is so much evidence to the contrary but it is ignored by the “mainstream” – of course if bio-identical hormones are kept from us the drug companies can sell more antidepressants, pain killers, dangerous osteoporosis drugs and I’m sure plenty of other things they would invent to poison us. Even IF there were a SLIGHT risk of increased breast cancer there is the issue of quality of life. If a man had to experience what some menopausal women did believe me they would be opting for hormones! I just see red when I see all the evidence ignored that bio-identical hormones ARE much safer than drug company crap (that has been changed molecularly so it can be patented and they can earn money). Try asking thousands of women and the doctors that take the time to learn about bio-identicals what the outcomes are! There is one doctor, well known, who has treated hundreds and hundreds of women over 20 years and only had TWO cases of breast cancer! From what I have read about the odds toward contacting breast cancer that is impressive!

  3. admin on Wed, 21st Jul 2010 7:10 am 

    Dear Alexis,

    While I do not wish to minimize the discomfort that many women experience with menopausal symptoms, your passionate defense of bioidentical hormone replacement therapy offers only anecdotal information. I understand that many women have strong feelings about this topic. At the same time, anecdotes and and generalized tirades against the pharmaceutical industry (or research scientists, or any other large group of people) cannot take priority over high-level clinical research findings, even if you personally disagree with the findings of such studies.

    As to a woman’s choice of accepting a higher risk of breast cancer in exchange for relief from the symptoms of menopause, that is more of an issue of personal choice. The goal of this column is to provide men and women with high-quality clinical research information that can assist them in making choices such as this one. I would also add that, as with our personal decisions to eat too much, to avoid exercise, to allow ourselves to become obese, to smoke, to drink alcohol excessively, or to indulge in other unhealthy behaviors, there are indeed associated costs to such behaviors that potentially affect not only the individual who is indulging in these unhealthy behaviors, but also their loved ones, as well as society in general.

    As the goal of this column is to bring new high-level health research findings to the public, and not to espouse any particular social or philosophical views, I will end this reply by thanking you for expressing your opinions on this column.

    Sincerely/ Robert A. Wascher, MD, FACS

  4. Lizette on Wed, 21st Jul 2010 1:42 pm 

    I am wondering why you refer to the study as if it proves bio-identical hormones are not safe when the study did not USE progesterone and estriol but only estradiol and PROGESTIN which is NOT the same molecule and NOT protective? You seem to be coming to a conclusion that the hormones God created a woman’s body to make cause cancer even when in balance when in fact you have no study to prove that. Estrogen domanince is shown to increase cancer even if it’s a woman’s own estrogen but this is remedied with REAL progesterone – not something that has been changed to a different thing that only ACTS like progesterone to a degree – there is a lot of real information that IS left out of this article and is not clarified or differentiated. I’m sure you really believe this is in women’s best interest but there is a lot more to this issue.

  5. Dia on Fri, 23rd Jul 2010 10:23 am 

    I have read the article several times and can’t find anything that says the studies you speak of use bio-identical hormones in the way that has been done for years by a number of forward thinking doctors with good results. Estriol and real progesterone are not mentioned. Is the study using both female hormones one that used the dangerous progestin? I have to agree with the others – I think there is a lot to be learned but it’s not being done in the specific manner (studies) you look to because there is no one to FUND those studies. But ignoring the clinical evidence of years of use by a number of doctors just because it’s not some “study” (studies can and often are proven to be fraudulent) and telling women they should suffer the various effects of aging that come from being low on the hormones that kept them young and healthy (and generally cancer free) for years – to me this makes no sense. If a man gets really low on testosterone I don’t think he would want to live with the consequences either – and on that note – it’s shown more and more that testosterone is not the cause of prostate cancer either! If it were then younger men should get it more than older men.

  6. admin on Sun, 25th Jul 2010 9:57 am 

    Once again, I must emphasize that the biological effects of these hormones, at the molecular level, is the same. Estrogen-like substances and progesterone-like substances that reduce the symptoms of menopause do so by stimulating the very same estrogen and progesterone receptors, and in the same manner as each other. In doing so, these various chemical forms of female sex hormones (whether “natural,” “synthetic,” “human,” “non-human,” “bioidentical,” or “non-bioidentical”) produce the very same biological effects on the tissues and organs that contain the cellular hormone receptors that respond to these various forms of estrogen and progesterone.

    While some hormone-like substances do possess “mixed agonist-antagonist” properties, whereby they may act like sex hormones in some tissues but not in other hormone-sensitive tissues, this is really not the issue that proponents of one form of hormone replacement therapy (HRT) over others are debating. The molecular biology of these various forms of female sex hormones all relieve the symptoms of menopause because, in fact, they have identical biological effects on the estrogen and progesterone receptors associated with these symptoms. These very same sex hormone receptors, and the various forms of sex hormones that bind and activate them, are also directly involved in modulating the risk of breast cancer, and other hormone-sensitive cancers in women.

    Sincerely/ Robert A. Wascher, MD, FACS

  7. admin on Sun, 25th Jul 2010 10:18 am 

    It is not the purpose of this column to dictate to people how they should address important health issues in their lives. Rather, “Weekly Health Update” stands apart from most other health information sites due to its rigorous focus on evidence-based health research findings. We provide updates on clinically meaningful research findings to empower readers to make more informed choices about lifestyle and dietary factors linked to important health outcomes.

    As I have already addressed most of‘s comments in my responses to other readers’ comments on this topic, I will not repeat them in my reply to her comments.

    I do agree with her, however, that individual people (both male and female) are free to make personal health choices for themselves, even if doing so exposes them to increased health risks. (Both men and women often make poor health-related choices.)

    In closing, I will repeat my previous observation that hormone replacement therapy (HRT) is, for some people, a topic that elicits a great deal of passion and interest. At the end of the day, however, passionate anecdotal testimonials, low-quality research or pseudo-research findings, and wildly exaggerated claims (both for efficacy and safety) for any medication, or dietary supplement, or other treatment, cannot substitute for the consistent findings of multiple high-quality research studies that have repeatedly validated our understanding of these issues.

    Yes, I agree that not every research study’s findings will stand the test of time, and I also agree that bias does creep into many high-levels studies as well. However, these are the limitations imposed upon clinical research because human beings are performing these research studies. But, it is stiill the best available approach to separating anecdote and bias from objective observation and fact. (And, if and when high-quality Level 1 research data comes along to contradict any of the findings, in this or other areas, that I have previously commented upon, then I will be the first one to update readers on any such new understandings that arise in the area of HRT.)

    Thank you, readers, for taking the time to express your thoughts on this controversial area, and for your invigorating comments on this topic.

    While the exact release date for “A Cancer Prevention Guide for the Human Race” has not yet been set, I expect this landmark science-based comprehensive cancer prevention book to be available towards the end of August, 2010.

    Sincerely/ Robert A. Wascher, MD, FACS

  8. Maria Karth on Fri, 3rd Jun 2011 6:27 am 

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  9. Debera on Tue, 10th Apr 2012 11:53 am 

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