Blog of the Society for Menstrual Cycle Research

Cause and Effect

November 11th, 2013 by Paula Derry

Does menopause cause an increase in health problems ranging from heart disease to bone disease to psychological depression? One issue is that many of these claims have been criticized as being overblown both by professionals within the medical community and by critics outside it. Another issue is that when problems are linked to menopause, the suggested solution has often been estrogen supplements (postmenopausal hormone therapy)—since after menopause a woman’s body produces far less estrogen—rather than seeking more complex causes, solutions, and mechanisms.

For example, although heart disease has many causes, during the 1990s many professionals recommended hormone therapy as being uniquely effective at preventing heart disease. At one time, a middle-aged woman who was depressed ran the risk of a professional assuming that she was suffering from a hormone imbalance without a careful evaluation of her distress.

While there is more attention today to looking at what causes problems and the best way to solve them, there is still a fundamental lack of understanding of basic processes. Even if menopause is linked to a problem, that doesn’t in itself tell us the mechanism by which this happens, or the best way of solving the problem. Suppose, for example, it had turned out that research established (it hasn’t, but suppose it had) that a woman’s risk of heart disease increases because of menopause. If this was because changes in estrogen levels result in changes in a woman’s metabolism, then lifestyle changes might solve the problem by revving up her metabolism even though a hormonal change caused it. Further, some other cause might be present. Perhaps some women who feel old or are busy become less physically active at midlife. Or perhaps some women who are depressed start eating more dessert. Or perhaps (as seems to be the case) heart disease risk simply increases as people get older.

For a wide variety of problems related to menopause, it would be great if more research looked at basic causes, complex mechanisms, and individual differences.

Understanding Research: Expert Opinion Isn’t Enough

October 15th, 2012 by Paula Derry

Many of us do our own health research, either because we have a specific question or simply to keep up with the news. If we don’t read the original scientific articles, we rely on experts to provide summaries in newspapers, magazines, or on a variety of websites. It seems as though by choosing sources judiciously we should be able to count on finding information that is accurate. However, relying on authority, whether this authority derives from a writer having scientific or medical training, or the writer being a professional journalist, or some other reason, is not enough.

I thought about this recently when I saw an article on Medscape, a website for health professionals, especially physicians, called “Early menopause doubles CVD risk regardless of race.” A summary of a new journal article, it was highlighted on the Medscape home page for many days. It began: “Women who experience early menopause–before their 46th birthday–are twice as likely to suffer from coronary heart disease and stroke as women who don’t enter menopause prematurely, and this finding is independent of traditional risk factors.”  Johns Hopkins University, where one of the authors is employed, issued a press release entitled “Early Menopause Associated With Increased Risk Of Heart Disease, Stroke” which also begins:  “Women who go into early menopause are twice as likely to suffer from coronary heart disease and stroke, new Johns Hopkins-led research suggests.” Similar articles appeared in Medline+ (a National Institutes of Health and National Library of Medicine website), a Blue Cross Blue Shield healthcare news website, and many print newspapers.

So, what was in the original scientific article? The article was published in Menopause, which, like many journals, does not post its articles free online for non-subscribers. Many academic libraries do not carry this journal. However, if a reader does get the original article, these are some of the details: The women in this research were studied for a number of years. The researchers collected information about many predictors of circulatory problems (smoking, diabetes, etc.). The women were also asked at what age they had reached menopause. If this was when they were younger than 46, they were classified as having an “early menopause” whether menopause was caused by surgery (ovaries removed) or occurred naturally. The researchers looked at whether the women developed heart problems or strokes, and created mathematical models to study which predictors of these problems were important.

Twice the number of women with “early menopause” had heart problems compared with women who reached menopause later. This is what is called “relative risk.” The “absolute risk” numbers were: 3% of the women with early menopause had heart problems compared with 1.4% of those who did not; for stroke, the numbers were 2.6% vs. 1%. This is still a difference, but not as dramatic as a twofold increase. In addition, the way the strength of the association was mathematically computed was to first predict heart problems and stroke with more usual predictors: age, risk factors like diabetes. The difference in risk due to menopause was in the uncertainty left after all these other factors had already been taken into account. Further, we don’t know whether the “early menopause” group had other associated characteristics leading to a health difference—if they were unhealthy in other ways. The authors, for example, state that if a woman had a family history of heart problems, and if this was mathematically taken into account before looking at menopause, then early menopause was no longer a predictor of her having a problem. In accounting for results, the article cannot distinguish between surgical and natural menopause, which differ in many ways.

It is true that, in the media accounts of this research, if a reader reads the entire article, qualifiers do appear embedded in the article in some of the sources. Some do say that the number of women in the study who developed heart problems or strokes was small; that this was a correlation, not a cause-and-effect association; or that when family history of cardiovascular disease was taken into account the relationship disappeared (although in Medscape, the author of the study was quoted as saying that “the pattern was still similar”). A piece of misinformation that reappeared in some of the sources was that the increased risk was similar whether the women had early menopause naturally or because their ovaries had been surgically removed. The research article clearly states that the authors did not have sufficient power (in research this means, basically, enough subjects to get an accurate answer to the question) to determine this.

I was puzzled why so much publicity was given to this study.  In my opinion, it did provide some interesting, suggestive results and contributed information about women from a range of ethnic groups (who have been understudied in the past), but the study’s results were modest and inconclusive.  However, what the article did do was to claim to support the underlying assumption that menopause and heart disease are related, an idea that keeps re-occurring in the professional literature, even stated as though it is a fact, although the evidence for it has been at the very best arguable and weak.  A recent SMCR blog post by Chris Hitchcock analyzed media misreporting of the results of another research project intended to test this relationship. In the study I am discussing, highlighting weak data that seems to suggest a relationship between menopause and ill health, blurring the distinction between natural and surgical menopause, contribute to this meta-message.  Ages 40 to 45 would be considered within the normal age range for menopause by many professionals, but is here defined as creating health risks.  I would hate to think that meta-messages promoting ideas that menopause is unhealthy and causes risk of heart disease contributed to the perceived importance of the article.

Reference

Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis.  Melissa Wellons, MD, NCMP, Pamela Ouyang, MBBS, Pamela J. Schreiner, PhD, David M. Herrington, MD, and Dhananjay Vaidya, PhD, Menopause: The Journal of The North American Menopause Society, 2012.  Vol. 19, pp. 1081-1087

Musings on Menopause and Heart Disease

August 27th, 2012 by Paula Derry

A recent article by Swift et al. looked at the effects of aerobic exercise on heart health. Midlife women with high blood pressure were assigned to one of three exercise groups—a program of exercise that met National Institutes of Health (NIH) guidelines, one that was half the amount of exercise recommended by the NIH, or one that was 150% of the NIH recommendations. The study did not examine who actually got heart disease. Instead, the researchers looked at the ability of arteries to function normally, which is a precursor to disease. Specifically, the researchers measured one component of artery health called “flow mediated dilation” (FMD)—the ability of arteries to respond normally to changes in blood flow by dilating (getting larger), which is one indicator of “endothelial (the inner lining of the artery) function.” The authors found that aerobic exercise improved flow mediated dilation. The amount of exercise was not important—the authors suggest that once some minimum amount of exercise exists, improvements will occur. They also found that women with problems benefited from exercise, but not those with normal FMD.

Well, I have to admit this isn’t an area of my expertise. I’m not going to evaluate how solid the methodology was, how close to normal the improvements brought the women, compare these results with the entire body of knowledge, all of which are important to really understanding the import of a study. However, I’d like to share some musings that the article triggered.

First, the article assumes that menopause and the menopausal transition increase a woman’s chances of getting heart disease by modifying her precursors and risk factors. The title of the article is: “The Effect of Different Doses of Aerobic Exercise Training on Endothelial Function in Postmenopausal Women With Elevated Blood Pressure”. The introduction states that their research is important because menopause is associated with worsening of heart disease risk factors. However, they are not studying postmenopausal women. They are studying overweight, sedentary women with high blood pressure who are old enough to be postmenopausal. It used to be more commonly stated, as though it is a fact, that menopause increases a woman’s chances of getting actual heart disease. However, this assertion does not appear to be supported by the facts. A recent paper in the British Medical Journal concluded that aging rather than menopause was key: “Heart disease mortality in women increased exponentially throughout all ages, with no special step increase at menopausal ages”. In 2011, the American Heart Association issued the Effectiveness-based Guidelines for the Prevention of Cardiovascular Disease in Women—2011 Update. These guidelines include a long list of risk factors and suggestions for how to prevent disease, such as modifying lifestyle factors like cholesterol and inactivity. Menopause is not included as a risk factor and is mentioned in just one sentence in the document. The line of research that has now arisen which states with equal certainty that risk factors and precursors to heart disease increase with the menopausal transition thus must be looked at critically. Do these changes in precursors really co-vary with menopause? Do they lead to actual disease? How important are they relative to other factors leading to heart disease, like aging or lifestyle?

The article does not, however, suggest that these menopause-related precursors and risk factors doom women to increased heart disease risk. Indeed, the point of the article is that they can be modified through lifestyle changes, here, aerobic exercise. A lifestyle change that can increase health seems like a good thing. However, what also did strike me was something about the meaning of a healthy lifestyle. Sometimes healthy lifestyle is presented as though it is something that is “added on” to normal daily life. Sometimes it’s almost analogous to a medical prescription—take 20 minutes of exercise daily. However, in the article the women who benefited, in terms of improved endothelial function, were the women who had abnormal function. The authors found that a small amount of exercise did the trick, with no additional benefit from increased exercise. So is it that supplementary exercise cured the problem, or was the problem an abnormal lifestyle deficient in exercise? As an analogy, if I don’t have enough vitamin C I might get a disease called scurvy, because my body needs vitamin C. Once I meet my body’s need, I won’t get the disease, I don’t need twice the requirement. The 2008 federal guidelines recommend that adults up to age 65 will get substantial health benefits from two and a half hours a week of moderate aerobic physical activity. Examples of moderate activity are gardening, walking briskly, ballroom dancing, shoveling snow, and stair walking. Maybe the idea is that our bodies need to move, and if we deny them a minimum amount of movement we have an unhealthy lifestyle. Maybe physical movement and activity are bodily needs, along with other components of a healthy diet and lifestyle.

“Death Loves Menopause”: Heart and Stroke Foundation Sends Wrong Message

February 8th, 2012 by Laura Wershler

The Heart and Stroke Foundation of Canada has inaccurately branded menopause as a killer of women. I will not be sending them a donation.

Last October, the foundation launched a fundraising campaign called Make Death Wait. Magazine and TV ads personify death as a man with a disembodied voice (he sounds like a stalker) who says he loves women (and men) and is coming to get them.

Eileen Melnick McCarthy, director of communications for the foundation, wrote to me in an email that the intent of the campaign is to “wake up Canadians to the threat of heart disease and stroke.” The campaign – urging viewers to “make death wait” by making a donation – has drawn both support and criticism.

Note the stereotypical hot flash reference: The thermostat is set at 15 C (60 F) but reads 23 C (73 F).

Photos of the ad by Laura Wershler

I think the TV ads are creepy, but what disturbed me more was the Death Loves Menopause message in the December issue of Chatelaine, Canada’s oldest women’s magazine. The small print reads: “He loves that menopause makes women more vulnerable to heart disease and stroke.” But is this statement defendable?

Dr. Jerilynn Prior, endocrinologist and scientific director of the Centre for Menstrual Cycle and Ovulation Research, wrote in an article about women’s risk for cardiovascular disease that the assumption heart disease in women is caused by estrogen deficiency associated with menopause  is a myth:

The reasoning behind this notion goes like this—young women have lots of estrogen and don’t get heart attacks. Older menopausal women are “estrogen deficient” and get heart attacks. Therefore, lack of estrogen causes women’s heart disease. That is like saying that headache is an aspirin-deficiency disease!

 

It is true that heart disease and stroke is the #1 killer of women, but the ad’s assertion that it is menopause that makes women more vulnerable raised the ire of women’s health experts I asked for comment.

Joan Starker, a PhD clinical social worker specializing in midlife, menopause, and aging issues, called it “an appalling and shocking advertisement.” Starker says she and her colleagues have “worked hard to shatter negative conceptualizations of menopause and aging. When I viewed this ad, I was left with only one horrifyingly toxic message – menopause equals death – which is ageist and sexist.”

Barbara Mintzes, assistant professor at the University of British Columbia, calls the ad “misleading and inaccurate” and says “there is no sudden shift in the rate of heart disease post- versus pre-menopause (or around age 50), as would be expected if menopause was a major risk factor for heart disease.  As women age our risks of heart disease gradually increase, similarly to ageing in men.”

My fellow blogger, Paula Derry, is a PhD health psychologist who critiques, analyzes, and theorizes about menstruation research/theory, with menopause being one of her specialties. “The idea that women’s risk of heart disease increases after menopause is a common one, yet there is little evidence for any increase in risk, much less that menopause is a key cause of heart disease and death,” she says.

Derry cites a 2011 paper in the British Medical Journal - Ageing, menopause, and ischaemic heart disease mortality in England, Wales, and the United States – that concluded aging rather than menopause was key: “Heart disease mortality in women increased exponentially throughout all ages, with no special step increase at menopausal ages.”

Last March, the American Heart Association issued the Effectiveness-based Guidelines for the Prevention of Cardiovascular Disease in Women—2011 Update. These guidelines present a long list of risk factors such as obesity, poor diet, physical inactivity, high cholesterol, hypertension and diabetes. Menopause is not included as a risk factor and is mentioned in just one sentence in the document.

As Derry says, “If I were going to donate money to an organization it would not be to one that tried to scare me with what I understand to be inaccurate facts.”

The Heart and Stroke Foundation of Canada should “wake up” to the truth about heart disease and menopause.

Cardiovascular deaths increase with steady aging, not menopause

September 27th, 2011 by Chris Hitchcock

Earlier this month, researchers published a statistical analysis of mortality data in England, Wales and the United States, disproving the common statement that, after menopause, women face increased rates of mortality from heart disease. There are other studies that have come to similar conclusions, but there are a few things that make this study different. One is that it drew on epidemiological data from three different parts of the world, which reduces the likelihood of a local coincidence. A second is that they took care to create longitudinal data sets, comparing women born in different birth decades with the appropriate mortality over time. In doing so, they avoided the problems of cross-sectional data.

The authors found that there was a steady exponential increase in risk with age, and that there was no sign of accelerated risk at the typical age of menopause (50). They compared different versions of mortality curves, and were able to show that a two-stage model of mortality with a hinge at menopause was not a good fit to the data.

These findings have received national and international coverage, and are a major blow to the argument that menopausal women require premenopausal hormones to retain premenopausal protection from cardiovascular risk. Menopausal women are older than premenopausal women, and that is why they are more likely to die from cardiovascular disease, not because of the hormonal changes of menopause.

More news about irregular cycles

November 22nd, 2010 by Elizabeth Kissling

Last week, we reported that new research shows a relationship between irregular menstrual cycles and sleep difficulties. Now we learn that irregular menstrual cycles are associated with a higher risk of both type 2 diabetes and coronary disease.  As we’ve said many times, the menstrual cycle doesn’t happen just in the uterus and vagina; it is part of a complex system, affecting nearly every other bodily system, and a window into women’s health.

Time and Time Again

April 18th, 2010 by Elizabeth Kissling

Guest Post by Paula S. Derry, Ph.D.

Déjà vu

An article in today’s New York Times Magazine recounts the author’s experience with a debilitating depression that began during her perimenopause, the transitional time leading up to menopause.   For her, prescription estrogen was a life-saver that alleviated her symptoms.  The article places her experience in the context of research on the Timing Hypothesis, an idea that arose after the Women’s Health Initiative, or WHI, research project.  WHI clinical trials documented that hormone supplements after menopause did not, as had previously been assumed, lower a woman’s risk of heart disease.  Heart disease risk was not lower, and, in fact, when a number of chronic illnesses were considered together, the medication did more harm than good overall.  The Timing Hypothesis is the idea that the WHI was fundamentally flawed, because hormones must be started right around the time of menopause to have a health-promoting effect and the subjects in WHI were on average over 60; if started when a woman is older, when chronic illnesses have already started, the hormones are actually harmful rather than helpful.  The Sunday New York Times article presents this idea uncritically, without quoting any of the many experts who do not find it plausible or convincing, and, in addition, presents a lurid, unscientific  description of perimenopausal hormonal dynamics with words like “ricocheting hormones” and an “upheaval” that causes a “hellacious strain” on the brain. The author suggests that WHI was  a poorly planned study that asked the wrong questions with the wrong methodology.  The Timing Hypothesis, if true, might lead to a cure for Alzheimers and have other important health repercussions.


Time for a reality check.

Let’s go back in time to before the WHI research. Beginning in the 1980s, professionals asserted that hormone therapies were safe and effective to prevent chronic illnesses, especially heart disease, in postmenopausal women.   This idea was aggressively promoted, and it was not limited to women around the time of menopause.  Clinical trials are required to prove that a new medication is safe and effective before the Food and Drug Administration will approve that medication. However, once approved and available on the market, it is okay for doctors to use their judgment and prescribe the drug for whatever use they believe is reasonable.  Many of the claims for estrogen were for this kind of off-label use because there was no clinical trial proof that estrogens reduced heart disease, made women “feel better,” or improved their lives in many other ways being claimed.  However, other kinds of evidence made it seem plausible. There were “biologically plausible” mechanisms–this means that because of things we know about the body–like the fact that there are estrogen receptors in the brain–it is plausible, we can hypothesize a way that  estrogen would have a certain health effect.  There were the personal experiences of women. There was the idea that menopause was intrinsically unhealthy and that women were not meant to “outlive their ovaries.” Using estrogens was compared by some to using vitamin supplements or to a diabetic using insulin. There was a strong conviction among certain enthusiastic scientists and practitioners, some of them highly respected individuals, that it was all so. Professional groups of various sorts frequently issue opinions about medications; here, many groups offered the opinion that all women be offered hormone treatment.  Physicians were encouraged to prescribe hormones for disease prevention because it was so certain that it would help their patients, rather than waiting for the slow process of clinical trials to take place. Wyeth, a pharmaceutical company,  asked the FDA to approve estrogen for heart disease prevention even without clinical trials.

Typically, what was said was that women would benefit from using hormones. There was little or no discussion that estrogen needed to be started around the time of menopause to be effective. In fact, when the FDA declined Wyeth’s request for approval, the company, in order to provide clinical trial data for the FDA,  financed a study of secondary prevention–giving estrogens to women who already had had a heart attack, the very older sicker women that the Timing Hypothesis says will not benefit–believing that there was a good enough chance that estrogen would be beneficial to warrant their financing the study.

Readers should note that statements published in re: Cycling are those of individual authors and do not necessarily reflect the positions of the Society as a whole.