Men & Women
Hormones can be a bit of a mystery to figure out. They are part of a very complex, multi-layered system. To make things more difficult, there is a large amount of misinformation out there, often put forth from physicians who do not specialize in hormone therapy and who do not understand the history of the controversies and do not understand that these controversies have been resolved by scientific investigation. A major confusing factor is that even professionals in the medical and scientific communities misuse the terms referring to hormones, which makes understanding the issues that much more difficult. In order for women to understand the issues and to gather the information for informed decisions, they need good information. To explain hormone care, we have to clarify some terminology.
Bio-identical hormones is a term that, in its simplest sense, means “hormones that are, at the level of the molecule, identical to those found in the human body.” When referring to women’s reproductive hormones, this means that at the molecule level, the structure of the chemical is identical to what the ovaries produce. For men they would be the hormones identical in molecular structure to the structure of testosterone, for example. In a bigger sense, the meaning also includes the idea that the hormones are being administered in a way that comes as close as possible to the way they occur in the human body (in nature).
Even in the technical medical literature, you see terminology around hormones being misused. This ends up being a big problem. As an example, for decades, medical studies reported progesterone was linked to breast cancer when given as part of hormone therapy. The word progesterone has a specific meaning. It signifies the exact (bio-identical) form of the hormone that occurs in the human body. When a doctor tries to learn about hormones and what the science shows, she runs across headlines and narratives that show studies using progesterone as part of HRT (hormone replacement therapy) had results with a higher risk of breast cancer. Only the discerning reader realizes that the scientist who wrote the article was using the wrong term. To learn the truth, the provider can’t only read the summary (abstract) of what the study showed. She has to examine the data itself. When the data is sorted out, she realizes they weren’t using progesterone at all in the study; they were using synthetic progestin. The word progestin is a broad term used to describe synthetics that, when they were developed, were modeled to be in the same category as progesterone but distinctly different. In fact, those hormones were man-made (synthesized) for the purpose of blocking the real hormone, or preventing the ovaries from producing it. They were originally developed as very potent drugs meant to treat such things as cancers. In this example, it came as no surprise that these forms of progesterone-imitators/blockers were associated with breast cancer, because they blocked the function of natural hormones. All this has made it very difficult for even doctors to figure out what science actually shows.
What I am going to address here are the two biggest controversies that surround hormone treatment in menopause, and what the science actually shows.
First is the belief that taking replacement hormones in menopause increases the risk of breast cancer. Linked to this is the belief that when women do have breast cancer, and if those cancer cells contain normal hormone receptors, that means the hormones caused the cancer. This is an error.
Second is the belief that taking hormones in menopause increases a woman’s risk of heart disease or stroke.
Here’s the discussion:
- The information that causes the misunderstanding that taking hormones in menopause increases the risk of breast cancer stems from this: a very important scientific study out of Europe looking at 86,000 women compared the number of cases of breast cancer among menopausal women who did not use HRT with those who used bio-identical progesterone (in one group) and women who used HRT with a synthetic progestin (in a third group). The data was analyzed at 5 years and again at 8 years. For the entire length of the study, women on bio-identical progesterone had 20% fewer cases of breast cancer than women not on HRT. In the group who were on synthetic progestins, they saw 49% more cases of breast cancer at 5 years, and at 8 years, they saw a 79% increase in cases. Repeat: this was comparing them to women not taking HRT. When compared to each other, women on bio-identical HRT had 69% fewer cases at 5 years and 99% fewer cases at 8 years!
The conclusion of this impressive study could not be expressed in one short sentence. Rather than coming away from the study with the statement, “Women taking HRT have a higher risk of breast cancer,” which is usually what you hear out there, the correct words would be, “Women on synthetic HRT have a significantly higher risk of breast cancer, but women on bio-identical HRT have a decrease in risk.” That’s a big difference!
A physician who is prescribing synthetics is correct if she describes that the HRT she prescribes are associated with breast cancer. This is the case for most physicians, who are mostly not hormone specialists and prescribing commercial pharmaceutical synthetics. But, this is not so for the provider who prescribes bio-identical estrogen and progesterone. (Also bear in mind that bio-identical hormones cannot be patented and therefore there is very little reason a commercial drug company would want to produce them, their profit would be about the same as their own drugs whose patents have expired. At that point profits drop at a tremendous rate.)
- Now, on to the issue of heart disease/stroke, the controversy here was unfortunate from the beginning. Starting in 1990, many studies had come out showing that women who took HRT in menopause had a lower incidence of heart disease, and the effect of the hormones appeared to be preventative. To address this issue, the HERS trial was started in 1998; they stopped and looked at their data in 2002. At that point, they were surprised to find that the women on the study who had begun HRT had a much higher risk of heart attack than women off hormones. Their reaction was to abort the entire study and quickly publish very public, essentially evangelical reports about what they had “found.” Suddenly, there were interviews on Good Morning America, headlines and large print articles in all the women’s magazines; it became high-profile. At that time I was already practicing with an emphasis on hormone issues, and as a specialist who had followed these issues closely, I was very hesitant to believe the conclusions that were being put out. Likewise, many of the stakeholders in the issue, (the American Heart Association, the American College of OB-GYNs, the American Endocrinology Association, etc.) took time to analyze the data, and then stepped forward to state the flaws in the way the study had been put together, arguing that the conclusions they had found were not valid. However, these entities did not get time on Good Morning America to explain, nor were they given space for articles in women’s magazines or in newspaper headlines.
The long and short of it was that the set-up of the study was all wrong. The “rules” of the study were that all women in the study had to have never used hormone replacement, and from there, they were divided into groups to observe outcomes, some continuing without hormones and others continuing as “new starters” of hormones. One of the big issues was that the average age of the women in the study was 65. This is a problem because the effect of hormones in influencing risk for heart disease had been a preventative effect. It had long been recognized that women enter the age group where risk for heart disease is significant at about the age of 60, with the average age of menopause being 50. The conditions that set up the arteries of the heart to become at risk for becoming blocked take about 10 years to develop with ongoing decline. (More about that later.) By becoming “new starters” of hormones at the average age of 65, these women had already experienced 15 years of cumulative decline. It’s hard to do prevention once the problem is already off the ground!
Another flaw in the study was the group of women who were randomized as “new starters” of hormones were placed on oral estrogens. One of the qualities of oral estrogens is they are given in once-daily dosing (so the entire amount of hormone for the day comes into the system all at once), and being taken by mouth means the hormone is going to have to be screened by the liver before it is allowed into the system. The liver “sees” the hormone as a large amount and gets into metabolic gear to metabolize that hormone. The ramp-up of hormone processing at the liver causes a side effect in the liver of increasing production of fibrinogen, which is a protein that is part of the clotting system. When estrogen is given orally, there is a one-year adjustment period when there is more fibrinogen production, which places the woman at risk of spontaneously forming a clot in the bloodstream. That clot may form in a heart or brain artery, which becomes the heart attack or stroke.
The scientists who put the study together inadvertently set it up to cause heart attacks.
Subsequently, many studies have been done that confirm women on hormone replacement have a lower incidence of heart attack and stroke, and the benefit hormones give is in prevention. The short version of that story is this: one of the greatest advantages hormone replacement in menopause gives in lowering the risk of heart attack and stroke is supporting tissue health. As an illustration, the visible effect of hormone loss that everyone is familiar with is aging of the skin on the face. The skin becomes thinner and has less collagen and less blood flow. It becomes weaker so creases that occur with facial motion and lying on our faces while we sleep become permanent creases because the lesser amounts of collagen are no longer able to spring back, and there is less elasticity. The same effect is happening in the entire body, including the arteries. Plaque that forms in a young, healthy artery is unlikely to tear the inner surface of the artery and release its contents into the artery and block it, while in a person with weak tissues (the woman who has been without hormones for a 10-year period) will more likely tear and block that artery. Make sense?
These were the two controversies that have made it difficult to find a physician who will do hormone work, and why most physicians, not being specialists and not following these issues closely, still believe taking hormones in menopause is harmful rather than healthy. Clearing up these misunderstandings paves the way for a productive discussion about the true pros and cons of hormone replacement in menopause so patients can work with their physicians to make informed choices for their health.