Women’s Health Initiative, Estrogen (Premarin), Breast cancer

Estrogen Vindication, Part 1: Estrogen and the WHI

By Devaki Lindsey Berkson, DC

Please box/shade the following notice:

This article has been abridged from the original. Full article and references available at townsendletter.com

Summary

Estrogen was once an extremely popular hormone. Estrogen replacement was used as an anti-aging drug by multiple millions of women in the United States and all over the world. Estrogen therapy was even standard of care to treat certain breast cancers. However, once the Women’s Health Initiative. (WHI) hormone trials were prematurely stopped due to early negative conclusions (July 9, 2002), claiming prescribed estrogen caused cancer and heart disease, these scary headlines prompted many doctors and women to become estrogen-phobic.

Nonetheless, as crazy as it seems, within only months after the WHI first published negative estrogen news, re-analyses started to emerge from scientists and statisticians at prestigious institutions. These new “look-sees “of the WHI statistical data painted completely different stories.

But the emerging “good news” never made headlines like the initial “bad news.” The bad news? Estrogen can “cause” breast cancer. This turned out to be “wrong news.”

The good news: Estrogen therapy in healthy women significantly “protects against” breast cancer. This good news continued to accumulate over the past two decades, without influencing “standard of care,” without entering the clinical trenches of most doctors or the understanding of most women. Until December 2019.

In December 2019, a 19-year reanalysis—looking back from an almost 20-year vantage point with new statistical in-depth collaborative investigation—was presented at the San Antonio yearly breast cancer symposium. Conclusions by a consortium of 12 highly respected cancer centers stated—once and for all—estrogen protects breasts. This re-analysis makes it finally undeniable that estrogen is not the enemy; rather, it protects breasts from cancer. Unfortunately, many doctors and women continue to not know about this news nor translate it into their practices or lives.

Even though no one knows exactly how breast cancer starts, it does not seem to be due to estrogen, but rather to cancer stem cells—a totally different kind of cell that has nothing to do with estrogen. Most older women, who naturally have less estrogen, have higher risks of being diagnosed with breast cancer than younger more estrogenized females. Pregnancy, which is the “highest estrogenic time” of life in any woman, is protective against breast cancer. In fact, there is a 70% decrease in breast cancer risk associated with a full-term pregnancy before the age of 18. It’s also been shown that pregnancy is safe after treatment of breast cancer, even among estrogen receptor–positive women patients (ER+ means pathologists identify estrogen receptors in the tumor). Also, no benefits have been proven for aborting at the time of pregnancy in breast cancer patients, so lowering the levels of estrogen didn’t cause further improvement in outcomes.

Medical practitioners thought tamoxifen worked because it was an anti-estrogen. But tamoxifen works in a wide variety of anti-cancer mechanisms, not just by tamping down estrogen. In fact, tamoxifen can often raise estrogen levels. In the HABITs study (which concluded that hormones cause breast cancer), only the women on tamoxifen turned out to have higher risk of recurrences (though this was not easy to read within the inner depths of the study and was thus was not noticed by many doctors).

The appreciation of estrogen as “foundational” in protecting many aspects of health is rapidly growing. A few examples are estrogen protects bones from fracture, blood vessels from hardening, brain from dementia, shields mitochondria (energy-producing cells) from damage, allows bodies to benefit from lifestyle changes as it promotes epigenetics, makes it easier to keep a smaller waistline, and maintains heart and kidney health.

Estrogen therapy is as close to an effective anti-aging tool that we have, even maintaining life-promoting telomere length. The longer and healthier our telomeres (the tips on our DNA), the longer and healthier we live. In fact, estrogen reduces premature death from quite a large number of possible causes.

My Story

Twenty-six years ago, I was diagnosed with breast cancer. This was not found by mammogram but by self-palpation while in the shower. I was the very first woman in the US diagnosed with a pure mucinous cancer, a very rare cancer back then, more common now. Neither my radiologist nor oncologist had ever treated a pure mucinous cancer at that time.

I was a DES (diethylstilbestrol) daughter, meaning my mother had been given this drug when pregnant with me. DES was banned in 1971 as the most cancer-causing substance ever invented at that time. DES was the first synthetic estrogen (50 times stronger than bio-available estrogen) and given to pregnant women from 1938 to 1971 as a prenatal vitamin or to stop threatened miscarriages. Many DES daughters turned out to manifest breast cancer in their mid-40’s. I was one of the very first ones.

As no one had ever treated breast cancer in a DES daughter before, I kept asking, “How do you know that what you are recommending is right for me?”

They suggested I do standard protocol, like radiation. However, even though my doctors had never treated pure mucinous tumors before, or ever treated a documented DES daughter before, after several weeks of sleuthing (pre-Internet), I found the only two groups (in the Netherlands) with human studies at that time on this type of tumor.

Due to the time changes, I had to call the principal leaders on these investigations in the middle of the night and leave messages about my circumstance. As the fickle finger of fate would have it, one head investigator didn’t call me back until a very dramatic moment: I was sitting on the table getting the grid put on my chest for my first radiation treatment.

This doctor/scientist firmly recommended, “If I were you, I would not do radiation. We have learned that radiation causes fibrosis, which makes it impossible to palpate a tumor in the breast if cancer returns. Totally pure mucinous tumors are never picked up by mammograms, only by palpation. If you have radiation, you won’t be able to monitor yourself appropriately. That’s what we advise all our pure mucinous breast cancer patients to do: not get radiation and do vigilant breast exams.”

I got off the table and told the radiologist I wasn’t going to do radiation therapy. I explained to this female radiologist (wife of one of the local cancer docs) what the experienced researcher had told me. I further explained that this scientist was one of the only two research teams in the world (at that time) studying this unique tumor type. They had published a study on 95 patients with this unique tumor, and understood protective details for patients with this unique tumor.

The radiologist spat angrily back, “F… him!” (I kid you not.) “If you don’t do this radiation, you are certainly going to die!” That was 26 years ago.

Then my cancer doctors told me that I didn’t need chemotherapy. Hmmm. Reading the science, it was becoming clearer to me (even way back then) that stem cells caused cancer more than the daughter cells found mostly in primary tumor loads. I decided to do my own chemo. After a lot of investigation, I found a black-market chemo from Switzerland (called “Ukraine”) that was supposed to eradicate both daughter cancer cells and cancer stem cells, but not harm healthy cells. So, I did 40 rounds of this chemo with a willing local doctor.

Then my cancer doctors recommended tamoxifen. But I was one-of-a-kind—a lone woman with a pure mucinous tumor and a history of DES—so it seemed they didn’t really know if it would help me and this special situation…or not. They were fitting me into the same box that all other breast cancer patients were in.

So I called Craig Jordan, the man who put tamoxifen on the map. Grateful to get him on the phone, I asked: “I have this rare tumor and this rare in-utero exposure to DES. Do you think I’m really a candidate for tamoxifen?” Dr. Jordan was thoughtful and candid, “I have to be honest with you. No one in your situation has ever asked me that. Let me look into this. I’ll get back to you in a week.”

To his credit Dr. Jordan indeed called back within a week and humbly explained, “If I were you, I wouldn’t take tamoxifen. I think it might make DES daughters worse. Not sure, but I don’t have a good feeling about it.” Stunningly enough, I still get yelled at by cancer doctors today telling me I made a mistake not taking it, even though its main scientist suggested otherwise!

After all I read, it made sense to me to take estrogen therapies, even though not one of my colleagues (functional or conventional) agreed with me. I was on my own. I waited five years just to be safe, but at year six Dr. Wright wrote me the first bioidentical script for 2-methoxyestradiol (2 MEO), which I had figured out would reverse the immunosuppressive issues started by DES in the womb. I was the first person in the US to take bioidentical 2 MEO, so Dr. Wright and I had to figure out the dosage. I also began hormonal therapies of estradiol, estriol, progesterone, and testosterone.

When I saw my breast cancer doc for yearly exams over the past two decades, she would say, “You look better than any of my other patients. But stop taking estrogen. It will kill you.”

Thank god, I’ve been well. At my ripe age, when many are winding down, I’m still winding up. My breast cancer doctor is 20 years younger than I am, but truthfully, as smart and nice as she is, she looks 20 years older as she hasn’t taken hormone therapies.

This 19-year reanalysis of the Women’s Health Initiative confirms my own research. (For those who want to know, I take 125 mcg/2MEO methoxyestradiol/day, along with .35 mg estradiol/.75 mg estriol BID labially, along with 3 mg testosterone/day mucosally.)

By the way, there are a lot of nuances to taking 2 MEO. I have a webinar on it available at drlindseyberkson.com. It’s hard to get. I am trying to write the monograph that the FDA requires to help move this along.

I worked at a hormone/nutritional family practice clinic, the Wiseman Family Practice clinic, in Cedar Park, Texas, for six years. I asked Dr. Richard Wiseman, who had been in practice for almost 50 years, what he thought about hormones. He ran several Ironman marathons a year, looked like he stepped out of an Irish Spring commercial, and had been prescribing bioidentical hormones all those years. Dr. Wiseman said, “If you took 100 people who all exercised and ate well, you could still pick out those who were on hormones: they will have shinier skin, more youthful voices, straighter posture, thinner waistlines, look younger, and even appear more confident.”

Hormones protect so many organs—from the collagen in our skin to the volume of our hippocampus (where our memories live in the brain).

I am honored to be able to write this article to spread the word that the science shows estrogen is once again okay to prescribe and safe to take. 

Summary of Criticisms of the WHI

• It only used one protocol of hormones (not individualized or diverse options).

• The age of the participants was older, many years away from hormone exposure.

• The majority of women were obese (which is a significant risk factor for breast cancer).

• The study had an extreme number of dropouts of participants.

• The recommendations could not be validly generalized to all women.

• Many of the WHI’s conclusions were ultimately found to be inaccurate.

Worst kicker of all has just been realized in 2020! The WHI had huge design flaws that when analyzed, the flaws themselves pointed to the protection of estrogen on breast tissue. Dr. Avrum Bluming wrote about these serious statistical defects in the editorial section of The ASCO Post, in early 2020, just after the 19-year re-analysis was presented in San Antonio. Dr. Bluming wrote:

An explanation of the hormone replacement therapy “anomaly’ (huge flaw, Berkson’s comment) was published in 2018. It was caused by a lower-than-expected risk in the control group, against whom the combination hormone replacement therapy population was measured. This lowered risk appears to have resulted from including within the placebo group women who had taken estrogen prior to joining the study and who were randomly assigned to that placebo arm. When the risk was recalculated after these women were excluded, the increased risk observed among those randomly assigned to combination hormone replacement therapy had disappeared.

In other words, some of the women in the control group had taken estrogen therapies earlier in their lives. This protected them against breast cancer. This gave the control group a lower incidence. This made the group on hormones falsely “appear” to have an increased incidence! What a statistical kettle of fish!

“This remarkable analysis,” further states Dr. Bluming, “should have been incorporated into the 19-year interpretation of the results presented in San Antonio and published in The ASCO Post article.”

Wow. This shows just had difficult it is to run randomized trails without “confounding factors” that make results nothing but questionable. Dr. Bluming also states that this may take progestins out of the picture as a risk factors for breast cancer. However, there are plenty of articles linking synthetic progestins to many increased downstream health consequences.

Decline in Breast Cancer

One of the clinchers in the media and even in scientific studies that the WHI’s conclusions were sacrosanct, was the recent decline in breast cancer incidence. Many said, “See, when women went off hormones (after the WHI) they got less breast cancer. This proves the HRT-breast cancer link.”

I realized early on, about 2004 and 2005, that women were going to be missing out on hormones. Scouring the literature, I saw the reanalyzes that were not making headline news. I became passionate about getting the accurate science “out” so women wouldn’t miss out on lifesaving and breast-saving hormones. That’s why I wrote Safe Hormones, Smart Women. All the information inside that book has been vindicated.

As I took a deep dive into the incidence data, it became clear that breast cancer rates started to slow down before the WHI results came out and use of HRT went down! This is critical to understand. They did not go down because estrogen scripts went down. They went down because our surveillance has gone up.

The conclusion that going off hormones secondary to the WHI started the decline in breast cancer incidence is wrong. But this is not known by many, doctors, patients, or pharmacists.

Dr. Christopher L. Li, from the Division of Public Health Science at the Fred Hutchinson Cancer Research Center (one of the cancer center names on the WHI 19-year reanalysis), looked at data from 13 cancer registries from 1995 to 2004 to get a handle on what was causing lowering of incidence of breast cancer cases.

They found that breast cancer rates started to go down around 1998, well before 2002 when the WHI brouhaha hit the media. The decline, they stated, was mostly likely due to more and improved breast cancer screening. The WHI didn’t start the decline, though in fact, now that we see how protective estrogen therapy is on breast tissue, it may very well have contributed to breast cancer incidence by denying women protective hormonal therapies.

WHI Re-Analyzed by 12 Prestigious Cancer Centers

From 1993 to 1998, more than 27,000 postmenopausal women, aged 50 to 79 years, with no prior breast cancer, enrolled in one of two randomized, placebo-controlled WHI trials implemented at 40 US centers, with follow-up through September 2016.

• Women with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/day) plus MPA (2.5 mg/day) or placebo (n = 8102) for a median of 5.6 years.

• Women with prior hysterectomy received CEE alone (n = 5310) or placebo (n = 5429) for a median of 7.2 years.

• After about 19 years of follow-up, CEE+MPA resulted in a significant 29% increased risk of breast cancer.

• Whereas CEE alone resulted in a significant 23% reduction in breast cancer incidence.

• There was a significant 44% reduction in deaths from breast cancer with Premarin.

• There was a 45% increase (borderline significance) in breast cancer deaths with CEE+MPA (Premarin plus the synthetic progestin MPA).

Re-Analysis Presented in San Antonio

On December 13, 2019, at the San Antonio Breast Cancer Symposium (SABCS), an abstract was presented that summarized the 19-year follow-up of the Women Health Initiative. (You can read the entire abstract in the Appendix.) Medscape published an article entitled “Remarkable New Data on Menopausal Hormone Therapy,” summarizing the new research, headed by lead investigator Dr. Rowan T. Chlebowski, MD, PhD, from Harbor-UCLA Medical Center, Torrance, California, and funded by the National Institutes of Health (NIH).

Chlebowski has been a consultant for AstraZeneca, Novartis, Amgen, Genentech, Pfizer, Puma, Immunomedics, and has received NIH grant funding. So Dr. Chlebowski has been studying breast cancer and hormones for a long time from many different perspectives.

The data are “remarkable,” said Dr. Chlebowski. The reanalysis study concluded:

• Estrogens are breast protective against breast cancer, (and this protection can last up to two decades).

• Synthetic progestins promote breast cancer, slightly but significantly. (Other animal and human studies have implicated synthetic progesterone in increasing the risk of heart disease; estrogens do not share the same increased risk.

Dr. Chlebowski was asked if this should change how doctors and patients look at estrogen and how it is prescribed to menopausal women. Dr. Chlebowski replied, “Yes, I would hope so! Women considering estrogen alone should know it’s safe and there may be a breast cancer benefit associated with its use.”

Dr. Chlebowski pointed out:

…none of the approved agents for breast cancer risk reduction . . . have been able to demonstrate a reduction in deaths from breast cancer . . . so this is a very unique finding.

Women should be reassured if they had short-term estrogen exposure they are not at increased risk. In fact, the data suggest there is decreased risk.

Who is saying this besides Dr. Chlebowski? The following esteemed institutions agreed with these findings and put their names on them!

• The Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California;

• Fred Hutchinson Cancer Research Center, Seattle, Washington;

• Brigham and Women’s Hospital, Boston, Massachusetts;

• Stanford Prevention Research Center, Stanford, California;

• University of Washington, Seattle, Washington;

• Pitt Public Health, Pittsburgh, Pennsylvania;

• Karmanos Cancer Institute, Detroit, Michigan;

• Stony Brook University, Stony Brook, New York;

• University of Tennessee Health Science Center, Memphis, Tennessee;

• Albert Einstein Cancer Center, Bronx, New York;

• The Ohio State University, Columbus, Ohio, and

• The UF Health Internal Medicine, Gainesville, Florida.

Their consensus clearly states: after 19 years of the WHI being looked at from 360 degrees, there are two different types of menopausal hormone therapy—estrogen alone and estrogen plus progestin—both of which have “opposite” effects on breast cancer incidence.

Of note, these effects persist long after stopping treatment (up to ten and possibly 19 years).

The data clearly indicate that estrogen—in this case horse estrogen (conjugated equine estrogens, CEE) alone (without synthetic progestins)—significantly decreases breast cancer incidence and deaths from breast cancer.

In contrast, CEE plus a synthetic progestin (MPA, medroxyprogesterone acetate), significantly increases the risk of developing the disease. In both instances, these effects linger for decades after discontinuation.

Part II of this article will discuss the physiology of estrogen and breast cancer, and the WHI and Million Women Study.

BIO in February/March 2020.