Blog of the Society for Menstrual Cycle Research

When breast cancer treatment leads to early menopause

April 14th, 2016 by Editor

In the same month I went from menstrual cramps to hot flashes overnight.

By Sheryl E. Mendlinger, PhD

Sheryl Mendlinger cut her hair short before undergoing treatment for breast cancer in 1994.

Sheryl Mendlinger cut her hair short before undergoing treatment for breast cancer in 1994.

In 1994, at the age of 43, I was diagnosed with stage 1 invasive breast cancer. At that time, treatment options were very limited, it was more a “one size fits all,” unlike the targeted therapies available now 20 years later. Taking into account the size of the lump—1.5 centimeters; my age—young enough that I was still pre-menopausal; and lymph nodes that all tested negative, my oncologist recommended I undergo a lumpectomy, a procedure that removed the lump and the surrounding breast tissue, followed by adjunctive chemotherapy and six weeks of daily radiation treatment. I became a statistic; although chemo was not a necessity, I was told that it would increase my chances of long term survival. I had been married to the love of my life for almost 22 years and had two teenage children, a son, 19, and my daughter Yael, 17. When I heard my diagnosis, I welcomed all options on the table, even the most extreme, as an answer to the frightening diagnosis of cancer, with hopes for a long life to see my own children grow into adulthood.

The doctor informed me only about some of the side effects of chemotherapy including: nausea, loss of appetite, hair loss and the possibility that my period might cease during treatment. However, no one addressed the fact that I would most likely go into overnight early onset menopause, which meant that not only would my ovaries stop working and vaginal dryness would set in, but my brain and cognitive abilities would experience a major shut down as well. One day I was bleeding and puking my guts up from the chemo, while days later I started to wake up in the middle of the night, in a pool of sweat, sheets kicked off the bed and I soon realized they were hot flashes. Menopause had arrived in full force.

At the end of her treatment she had short white hair and a full face.

At the end of treatment she had short, thin, white hair and a full face.

Whether from the chemo treatments or menopause, I started to gain a lot of weight and most of the clothes that hung in my closet no longer fit properly. As I wrote in my book Schlopping: Developing Relationships, Self-Image and Memories

“I ballooned from a size 8-10 to a 12-14. The additional fifteen to twenty pounds on my short frame and the new menopausal body made me feel extremely self-conscious, and the only way to continue to look good and feel better was to hide the bulges under baggy clothes, oversized blouses, or sweaters and leggings. The only pants that fit over my rounded belly were those with stretch elastic waist like old ladies wore….I dealt with the extra weight by buying clothes that fit my new changing body. I just accepted the changes that were taking place because it was a sign of me getting well….I felt the additional weight was good for me…and that my body was overcoming the illness… At the end of the treatments, I had very short, thin, white hair and a very puffy, fat, and full face…”

I remember approaching my oncologist very early in my chemo treatments and telling him that I felt my brain was fuzzy and that the connectors didn’t seem to be connecting; it was as if the entire “hard drive” in my brain had crashed and all the information was deleted. At that time, in the 1990s, doctors were convinced that “chemo does not pass the brain membrane.” To say the least, it was a strange, frightening, and terrible experience. I began to forget sentences in mid-thought in addition to having a lot of other medical problems. This memory loss happened at the onset of chemo, even when I was still getting my period. Once my period ceased, near the end of treatment, my cognitive abilities seemed to take a turn for the worse.

Several years after my treatments, in 2000, when I saw one of the first papers on “cognitive function and chemotherapy” in which the word “chemo-brain” was used, I felt a sense of relief that I was not the only person to have experienced this. Although this concept has finally been accepted in the medical world, and scientific research is being conducted in the area, there are still questions as to what causes the cognitive decline. Is it the inflammation from the cancer itself, is it the chemo, is it changes in thyroid functioning or B12, or is it the sudden loss of estrogen with the early onset of menopause? When speaking to young women who have undergone hysterectomies, they too complained of many of the same issues of cognitive decline.

Early onset menopause can affect so many aspects of overall health and the quality of life. More research, knowledge and information will better equip young women in coping with their changing bodies and understanding that it’s not “only in their heads.”

Sheryl E. Mendlinger, PhD, is an author, advocate for women’s health, daughter, wife, mother, and grandmother. She co-authored, with her daughter Yael Magen, “Schlopping (schlep+love+shopping): Developing Relationships, Self-Image and Memories” a book about finding answers to life’s challenges through schlepping with a loved one while shopping. Sheryl’s expertise is inter-generational transmission of knowledge and health behaviors in mother-daughter dyads from multicultural populations with a focus on menstruation.  

Premenopause / Early Menopause / Primary Ovarian Insufficiency (or Failure) / Perimenopause / Menopause / Postmenopause: Why these names matter

April 5th, 2016 by Editor

Making sense of the many names for women’s reproductive aging by Dr. Jerilynn C. Prior

Jerilynn C. Prior BA, MD, FRCPC, ABIM, ABEM is a Professor of Endocrinology and Metabolism at the University of British Columbia in Vancouver, B.C. She is the founder (2002) and Scientific Director of the Centre for Menstrual Cycle and Ovulation Research(CeMCOR).

The process of aging of women’s reproductive system, like puberty and most biological transitions, occurs in a generally standardized but variable way and over many years. Also, there are broad age ranges at which we consider something normal or not. Then add on top of that cultural presuppositions, chief among them that “menopause means estrogen deficiency” (rather than that menopausal estrogen and progesterone levels are normally low), and we have real confusion and a situation that is not helpful1 for women or for their communication with health care providers.

I will do my best to describe some of these standardized ways that women’s physiology changes during reproductive aging. I will mention the current terms and the words that have some physiological relevance and should be used. Because I am a physician, I believe that understanding of “the story” of life phases and the “why” of experiences is helpful. It is also necessary to appreciate the whole woman in her social, cultural, physical and experiential environments markedly influence her experiences.

After extensive research to understand mine and my patient’s puzzling midlife experiences, I learned that the ovaries start to make less Inhibin (really Inhibin B) while cycles are still regular2;3. Inhibin is small hormone made in the follicular cells surrounding stored eggs; its job is to control levels of follicle stimulating hormone (FSH). Because FSH stimulates follicles to grow, Inhibin is necessary to limit the number of stimulated follicles and to prevent us having litters. As shown (Figure below), by very early perimenopause there are fewer remaining ovarian follicles (B), Inhibin is decreased and this allows higher FSH levels and more stimulated follicles. Since each recruited follicle makes some estrogen, levels rise and the higher estrogen levels are also not reliably able to control FSH3.

menopauseDiagram

Legend: The ovaries are shown as a stylized oval with follicles in various degrees of maturation. A. shows what is occurring in the follicular phase of a premenopausal ovary; B. illustrates the normal changes that occur in perimenopause. Reprinted from Prior Endocrine Reviews 1990

The same normal reproductive aging pattern of lower Inhibin, higher FSH and estrogen occurs when the ovary is injured; this can be by chemotherapy or radiotherapy for cancer, partial removal, more rapidly than normal after hysterectomy or tubal ligation/removal and in those with immune or genetic problems. The chaos of women’s reproductive aging occurs for these Inhibin-related reasons but also because the hypothalamic-pituitary ovarian feedbacks are disrupted (so a normal midcycle estrogen peak may not trigger the luteinizing hormone (LH) peak or the LH peak may not stimulate ovulation4). An FSH level, even one that is taken on cycle day 3, is not diagnostic of perimenopause. That estrogen levels average 20% higher in perimenopausal than in premenopausal women 3, I learned from a systematic review of studies within each of several centres; but symptomatic women may have double or triple normal cycle phase-specific levels that create the “perimenopausal ovarian hyperstimulation syndrome” because this situation resembles an adverse effect that may occur in IVF 3.

With this understanding we can define the three terms for normal reproductive life phases, the term used for perimenopause or menopause that comes too early and also identify some inappropriate labels.

Premenopause is the entire time (usually 30-40 years) from the first menstruation (menarche) until the changes of perimenopause start.

Perimenopause begins when cycles are still regular (called very early perimenopause and this phase lasts 2-5 years) but an observant woman notices typical experience changes5. Because the current official classification of reproductive aging begins with irregular cycles6, no one knows at what age on average this may start; likely it is normal from as young as age 35. At least three of nine typical experience changes, especially the start of night sweats, sleep problems or heavy flow, can be used to determine that you have begun this phase5. Additional potential perimenopause changes are: increased cramps, increased premenstrual physical and emotional unwanted experiences, shorter cycles (usually ≤25 days), increased or new breast tenderness, increased or new migraines and weight gain without important changes in exercise or food intake7. Perimenopause’s early menopausal transition starts when cycles become irregular and lasts a year or so; the late menopause transition begins with the first skipped cycle (60 days without flow) and late perimenopause is the year after the last flow.

Menopause is the life phase that lasts from a year after the final flow for the rest of women’s lives. It is normal for both estrogen and progesterone levels to be low. Hot flushes/flashes and night sweats may continue for many years but heavy flow, cramps, breast tenderness, premenstrual-type symptoms and severe migraine are usually gone.  (The term “postmenopause” is sometimes used interchangeably with menopause but is double-speak and refers to an erroneous use of the word “menopause” to mean the literal final menstrual flow).

Early Menopause Caused By Makeup?

November 8th, 2012 by Heather Dillaway

It turns out that phthalates – chemicals found in cosmetics, hairspray, packaged food, household cleaners, and other common plastic items – are causing early menopause. At least according to one new study that is getting a lot of hype in the past week or two. A team of researchers from Washington University in St. Louis, MO, studied phthalate levels in blood and urine for over 5,000 women, and those women with the highest levels of pthalates apparently went into menopause an average of at least two years before others.

This study is definitely making news. British news sources are reporting on this study as much as U.S. news sources. Women’s reactions to online news stories about this study are mixed. Women hearing about this study are quick to comment online, saying either (1) how quickly they’ll be running out to buy more makeup (to launch themselves into menopause) or (2) discontinuing their use of makeup (to ward against the effects of pthalates). What I find interesting is how divided women are about whether early menopause is good. Reactions to reports on this study definitely show attitudinal differences among women in that women do not think uniformly about menopause or about the importance of using cosmetics. Women are not  thinking uniformly about how damaging phthalates are to our bodies either.

Of course, by all news reports of this study, phthalates also cause cancer, diabetes, and even feminization of boys (really?), so even if you think early menopause is a good thing you might want to hold off on consuming more phthalates.

What this study (and people’s belief in the study) also reiterates is the fact that our bodies are affected by what we eat, use, and do, as well as what we come into contact with, where we live, etc. Some of the articles reporting on this study focus in on the natural, healthy choices we can make when picking beauty products, household cleaners, prepared food, and other common household items. Who knew there was vegan makeup, for instance? This is all worth a second thought. Sure, we might all want to be done with menstruation sooner than later but phthalate-induced menopause should probably not be our goal.

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

Earlier menopause with ovary-saving hysterectomy

November 22nd, 2011 by Chris Hitchcock

Recently Heather Dillaway blogged about the challenges and frustrations of naming, and this blog continues with that theme, looking at a recent article about increased rates of “ovarian failure” following ovary-preserving hysterectomy.

Ovary-saving hysterectomy linked to early menopause,” reads the USA Today on-line headline, and the article opens with the statement that:

Younger women who have a hysterectomy that spares the ovaries are almost twice as likely to go through early menopause as women who do not have their uteruses removed, according to a new study. 

It’s an alarming statement, and one likely to alarm an already anxious woman. The study in question was a longitudinal study following 406 women aged 30-47 at the time of their surgery and a control group of 465 similar-aged women who did not have a hysterectomy. The study will be published in the December 2011 issue of the peer-reviewed journal Obstetrics & Gynecology, and the news coverage was drawn from the Duke University press release, entitled “Hysterectomy Increases Risk for Earlier Menopause In Younger Women”.

The first challenge of naming is in the subtle difference between the press release’s earlier menopause, and the USA today article’s early menopause. Early menopause is defined as menopause that occurs before the age of 40; the earlier menopause in the article is a difference of about 2 years — an important difference.

In women who no longer have menstrual flow, how did the authors establish menopausal status, or “ovarian failure”, as they called it? In women with a uterus, menstrual flow is a convenient landmark, which is roughly aligned with the hormonal changes to decide when menopause (or is it post-menopause?) has begun. We assume that 12 months without menstrual flow likely means that there will be no further flow (although that is not always true), and that it is a good estimate of when ovarian hormonal cycles have stopped. In this article, the authors used an annual blood sample to measure a hormone called FSH (follicular stimulating hormone). FSH is high in menopausal women, and an FSH>40 IU/L was used as a criterion for reaching menopause. However, we have known since 1994 that a high FSH level is not diagnostic of menopause, and, indeed, 6 of the 504 women were excluded because they had a baseline FSH > 40 IU/L, despite having menstruated within the previous three months. Regularly cycling women in their 40’s can have high FSH levels, and later have low FSH levels and ovulatory cycles. In menstruating women, blood samples would also be timed, which is not possible for women who don’t menstruate. It would be interesting to know how the high FSH criterion corresponded to menstrual cycle history in the control group.

Studies like this are hard to do. The authors were careful — they enrolled women prior to surgery and followed control women in the same way. To get 403 women with complete data, they started with over 900 women.  The controls were fairly well matched — similar in age, age at first period, c-section and oral contraceptive history. However, women undergoing surgery were more likely to have had at least one full-term pregnancy (84.5% vs 68.3% in controls), and more likely to have had a previous tubal ligation. In addition, fibroids, endometriosis, ovarian cysts and previous surgery for fibroids were more common in those having a hysterectomy. Both the hysterectomy itself and the history of previous surgery, particularly tubal ligation, may also contribute to a difference between the two groups. Finally, women with hysterectomy were heavier than the control group.

By following the two groups, the authors were able to estimate that hysterectomy accelerated the rate of reaching the FSH threshold by about 2 years. This is consistent with other research, and fits with the finding that hysterectomy and other reproductive surgeries are associated with a lower rate of breast cancer, presumably due to lower estrogen exposure.

So, how does this fit with the frustration and complexity of naming? One frustration is with the persistent use of the value-laden term “ovarian failure” in the medical literature. But in this particular population, a large part of the frustration is technical. Perimenopausal hormones are changeable, and without menstrual flow as a landmark, it is even harder to estimate where a particular woman is on her transition into her menopausal years. We might learn more with daily hormone samples over a longer period of time, but that would be hard for women to do and would cost too much. If a single high FSH value is one step along the pathway to menopause, and if hysterectomy doesn’t change the timing of that step along the path, and if women scheduled for hysterectomy aren’t already further along that path than the controls, then these data give us some idea of the effect of hysterectomy on when women reach menopause.

There is more I could write about the technical details of this one paper, and perhaps that is another point to make — scientific articles are complicated logical arguments, and critiquing them from within science is challenging to fit into a blog format.

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.