About HRT & Oestrogen

I recently shared a social media post in which I identified hormonal replacement therapy (HRT) as one of the most profound therapies I have ever used. But I have been roundly scolded for it. Many, many of us believe HRT to be dangerous. I did, too, for a very long time. We all have been scared by media headlines touting links to breast cancer.

I do not want to suggest that breast cancer is not rapidly increasing or not a serious concern for every woman. Indeed, it is now the most commonly diagnosed cancer in the world. But I am not impressed that breast cancer has any particular connection to HRT. So many women fear HRT, perhaps unnecessarily, and are suffering today as a result. Indeed, I believe that the HRT has been both inappropriately blackballed by scientists who wish the truth were different and inappropriately headlined by a press that is looking for ‘sensational’ stories. In truth, the research evidence now indicates that HRT, when appropriately prescribed and overseen by a physician, is not only safe but also demonstrably supportive of our physical and cognitive health.

But before I dive deeper into the arguments around HRT, let me start with a question: Do you remember, during the COVID pandemic, the many pleas on social media and traditional news channels to ‘trust the science?’

I applaud all of the scientists and medical practitioners who worked so hard then to protect and heal all of us in need. The speed with which the disease was analysed and the vaccines developed was breathtaking. Kudos to them all! To me, they were and still are heroes.

But the appeal that we 'trust the science' is, in my mind, almost always inappropriate, if not downright dangerous. Science does not ‘deserve’ blind faith. Science should stand up for itself, offering convincing evidence in support of its hypotheses. It is critical that we always demand that evidence and scrutinise it carefully, being perhaps even somewhat cynical, because ‘science’ can make mistakes, as can all good scientists. Indeed, mistakes are made all the time. Scientists are human after all.

I was very fortunate to have been able to earn my doctorate at one of the world’s finest universities. Perhaps because of this personal experience, I am only too aware of how human and flawed the world’s scientists and their research can be. We, researchers (I include myself in this group), make mistakes all of the time. Sometimes, we make these mistakes because we’re not quite as bright as we think or would like to hope we are. (Academia is a magnet for egotists. ;-) But, sometimes, we make these mistakes because we want and need the answer to come out a particular way.

This is a very real and very serious issue. Science itself may be objective but few scientists are. We all have vested interests. I’m sure you’ve heard the saying that scientists must ‘publish or perish.’ It’s true. Every academic needs his or her research to succeed. Each paper published polishes the CV and builds the scholarly reputation, contributing significantly to career mobility and earnings potential. Sadly, some academics can and will flagrantly manipulate their data and their results. More often, I believe, we researchers can, completely innocently, make mistakes that work in our favour.

In his award winning book, The Mismeasure of Man, Stephen Jay Gould illustrates beautifully how this can and seems indeed to have happened in the laboratory of Dr. Samuel George Morton, a 19th-century physician and scientist who collected and measured hundreds of human skulls to determine cranial capacity. Morton believed that cranial capacity was directly related to intelligence and used his data to argue that white people had larger brains and were therefore more intelligent than people of other races. Interestingly, Gould discovered an array of methodological flaws, including simple arithmetic mistakes in Morton’s calculations, that biased Morton’s work. Perhaps not surprisingly, these errors all tended to support Morton's hypothesis that whites had larger cranial capacities (and therefore higher intelligence) compared to other racial groups. Weren't those errors convenient!

But, of course, the world, or at least the scientific community of the time, was ready to believe and support Morton’s conclusions because Morton was a scholar of significant standing - and because his findings were attractive to the power elite. Sadly, ‘mistakes’ and misrepresentations like these are made all the time.

And, so it may have been with the scientists researching HRT.

Indeed, the above has been a very long lead-up to a discussion of the research surrounding HRT and, more specifically, the research conducted as part of the Women’s Health Initiative (WHI) in the 1990s and early 2000s.

The WHI, launched in 1991, was one of the largest and most ambitious studies ever conducted in the field of women’s health. Its aim was to explore the effects of HRT on postmenopausal women, focusing on its potential benefits and risks, including the risk of cancer. However, the first phase of study was halted precipitously in 2002. The National Institutes of Health posted a press release noting that ‘The National Heart, Lung, and Blood Institute of NIH has stopped early the Women’s Health Initiative . . . due to an increased risk of invasive breast cancer.’ A similar press release was issued by JAMA (Journal of the American Medical Association) noting not only the increase in breast cancer risk but also increased risks of ‘coronary heart disease, stroke, and pulmonary embolisms.’ Dr. Garnet Anderson, a co-principal investigator, claimed the study had demonstrated that ‘breast cancer rates were markedly increased among women assigned to the oestrogen plus progestin group’ v the placebo.’

Not at all surprisingly, Dr. Anderson’s press conference and the press releases themselves caused widespread confusion and panic among physicians and patients alike. Within a short time, the prescription rate for HRT fell some 70%.

It is fascinating that the WHI’s reported research results do not seem to agree with Dr. Andersons’s statements at all. According to the expose compiled by Avrum Bluming, a medical oncologist, and Carole Tavris, a social psychologist, in their book, Oestrogen Matters, the publicly documented WHI results revealed that women who were randomly assigned to take oestrogen on its own experienced no increased risk of breast cancer at all. Those who were assigned to take both oestrogen and progestin did reveal a small increase in the risk of breast cancer cancer (1.26) compared to those in the placebo group; however, this increased risk was neither statistically or practically significant.

Robert Langer, another principal investigator later reported, that ‘highly unusual circumstances prevailed when the WHI trial was stopped . . . The investigators most capable of correcting the critical misinterpretations of the data were actively excluded from the writing and dissemination activities.’ It seems Dr. Anderson, who had always believed ardently that HRT was dangerous, had significant control and pushed her conclusion to the utmost.

And . . . the damage was done.

Very importantly, a follow up report compiled and released in 2006, found no increased risk of breast cancer at all within this oestrogen/progestin group compared to placebo. But news of this followup was not widely disseminated, nor did it seem anyone was much interested. The world had moved on.

Fortunately, more time has now passed and further follow-ups and re-analyses have been added to the study’s data bank. Indeed, the WHI Extension Study, completed just this past year, has helped to clarify the risks and benefits of HRT. The report summarising this study concludes:

Age Matters: Younger women (those in their 50s) who begin HRT closer to the onset of menopause have a different risk profile compared to older women. For these younger women, the benefits of HRT can significantly outweigh the risks. These women are less likely to develop heart disease and may even have a reduced risk of osteoporosis and colorectal cancer.  However, for women in their 60s and 70s, the WHI findings support the use of hormone therapy for the treatment of menopausal symptoms in women in early menopause without contraindications.  In her statement on these most recent WHI results, Dr. Joanne Manson. an investigator and professor at Harvard Medical School, notes:   

This is a US Food and Drug Administration (FDA)–approved indication for hormone therapy. The WHI findings really should never be used as a reason to deny the use of hormone therapy to women who are presenting with bothersome vasomotor or other menopausal symptoms and seeking treatment, especially when they are in early menopause and free of contraindications. 

Individual Risk Assessment: Not every woman has the same risk factors, and decisions about HRT should be personalised, taking into account each woman’s health history, preferences, and concerns.

Type of Hormone Therapy: The type and route of administration of hormone therapy also matter. Newer formulations, different types of hormones, and various delivery methods (such as patches or gels) may offer benefits with lower risks compared to the regimens used in the original WHI study.

Duration of Use: Short-term use of HRT (for a few years) to manage severe menopausal symptoms is generally considered safe for most women. The risk of long-term use needs to be carefully weighed against the benefits.

Clearly, these new findings from the WHI Extension Study have led to a more balanced view of HRT. It is now recognised that for many women, HRT can be a safe and effective treatment for menopausal symptoms when used appropriately. This nuanced understanding is crucial because untreated menopausal symptoms can significantly impact a woman’s quality of life.

In my own experience, HRT has been a game-changer. Like many women, I struggled with menopausal symptoms that affected my daily life - and especially my cognitive capability. Yes, I understand brainfog. After careful consideration and consultation with my doctor, I decided to start HRT. The improvement was remarkable. I am aware of the potential risks but I also understand that these risks are relative and that my personal health profile plays a significant role in determining my risk.

Clearly, while science is an invaluable tool, it is not infallible. Or should I say, scientists are not infallible. Studies can be flawed, and interpretations can be biased. It's important to critically evaluate scientific findings, consider the broader context, and make decisions based on the most current and comprehensive information available. For me, HRT has been a tremendously beneficial choice. I feel that I have been both well advised and well introduced to the data and the risks. I hope that every woman can have the same opportunity for such learning and counseling. That's what medicine should provide for us all.