From 2002 to 2008, reports from the Women’s Health Initiative (WHI) claimed that hormone replacement therapy (HRT) significantly increased the risks of breast cancer development, cardiac events, Alzheimer disease, and stroke. These claims alarmed the public and health professionals alike, causing an almost immediate and sharp decline in the numbers of women receiving HRT. However, the actual data in the published WHI articles reveal that the findings reported in press releases and interviews of the principal investigators were often distorted, oversimplified, or wrong. This review highlights the history of research on HRT, including a timeline of studies that have or have not found a link between HRT and breast cancer; discusses how to distinguish important, robust findings from those that are trivial; closely examines the WHI findings on HRT and breast cancer, most of which are weak or statistically insignificant; reviews the current thinking about possible links of HRT with cardiovascular disease and cognitive functioning; and reports research on the benefits of HRT, notably relief of menopausal symptoms, that affect a woman’s quality of life. On these complicated matters, physicians and the public must be cautious about accepting findings by press release in determining whether to prescribe or take HRT.
The authors begin by addressing statistics, relative risk and data dredging.
Science is a process; it is rare that a single study gives us a definitive answer.Yet the news-hungry media crave breakthroughs and thrive on scare stories. Thus, it is essential to look behind the headlines to the actual data, to try to get a sense of the larger picture that emerges over time and across studies. Sometimes that larger picture yields a clear image; sometimes, as with HRT, it becomes foggier than ever. Two statistical errors common to research on HRT have contributed to that fog: one has to do with how risks are reported; the other has to do with the often inappropriate mining of data, when researchers retrospectively hunt around in their findings for something, anything, that might seem to be a significant risk factor.
Consider, first, the difference between absolute risk and relative risk. The media, following the example of many researchers themselves, tend to report relative risks, which are expressed in percentages that can seem more important than they are. For example, if we tell you that the relative risk of breast cancer is increased by 300% in women who eat a bagel every morning, that sounds serious, but it is not informative. You would need to know the baseline absolute number of new breast-cancer patients. If the number shifted from 1 in 10,000 women to 3 in 10,000 women, that is a 300% increase, but it is very likely a random artifact. If the risk had jumped from 100 to 300 in 10,000, also a 300% increase, we might reasonably be concerned. In large epidemiological studies that generally include tens of thousands of people, it is very easy to find a small relationship that may be considered significant by statistical convention but which, in practical terms, means little or nothing because of the low absolute numbers.
This is why scientists who are working to promote statistical literacy, especially in helping the public and physicians understand actual versus inflated risks of diseases and treatments, emphasize that knowing the baseline of absolute numbers when comparing two groups is essential.Two major consensus projects on the reporting of clinical trials concluded that stating relative risks alone is often deceptive; results should be provided in absolute numbers, not only as percentage changes.
A reliance on relative risks can also create misleading, faulty comparisons. For example, let us say that 3% of the people who eat chocolates develop cavities, and 2% of people who do not eat chocolates develop cavities. The absolute difference between these populations is only 1%. That means that for every 100 people who eat chocolates, 1 extra person will develop cavities (in addition to the 2 who will develop cavities without eating a single truffle). This is not a particularly frightening risk if you enjoy chocolate. But suppose we report the identical conclusion as a relative risk: 1 additional case divided by the 2 baseline cases gives us an increased relative risk of 0.5 or 50%. A 50% increased risk in cavities if you occasionally eat chocolates! Stop at once!
That’s all I’m going to give you. Please read the article for a fascinating look at the research and what the data really shows vs what some have insisted it shows with regards to breast cancer rates, cardiovascular risk, stroke, cancer and death from all causes for women using HRT. What you think you know is probably not the truth.
Really, that was my intention. After all, menopause isn’t a disease any more than pregnancy or menstruation is a disease. It’s a natural part of the life cycle. My fertile years would be over and I would settle into a new life (!) full of wisdom and peace and creativity and freedom and all the joys we women find in our “golden years.” And don’t worry about sex…it will be fine! You’ll still be horny as hell I was told, just look at all those commercials with the bedroom-eyed AARP members! A little vaginal dryness? Nothing a little lube won’t cure!
Horse-pucky.
Let’s be perfectly frank, shall we?
Pure and simple, loss of hormones means loss of sex drive. Anyone that tells you that sex is 90% mental still has all their hormones. Trust me on this. Losing my sex hormones meant feeling like I was an eight-year-old again. No. Really.
It wasn’t that I didn’t want sex. I just never thought about it. Oh yeah, I knew I was supposed to want it. I just didn’t. Gone was the absolute physical craving that came just from thinking about my beloved. I still loved him. No doubt about that. But sex? Didn’t even cross my mind, unless I made it cross my mind. Or it popped in as a note to myself, Girl, how long has it been?
But, lack of desire, okay… that could be dealt with. After all, I loved my husband. I would just make a more conscious effort. And I told him what was going on. Communication with your S.O. during this time is critical.* I told him about the “not thinking about it” issue, told him that it was no reflection on him and that if he wanted “time with me” he’d just have to ask. Because honestly, I said, I’m not thinking about it. And I was willing. And my nerve endings, well, they all functioned just as before, if you know what I mean. No problem there.
But there was a problem. About two-plus years ago intercourse began to be a real problem. Vaginal dryness began to rear it’s ugly head and it continued to get worse. But again, nothing a little Astroglide™ couldn’t fix, and so we soldiered on. The thing is, even with the lube, intercourse was becoming increasingly painful until finally I began to bleed. Even with lube. It wasn’t just a little bit of vaginal dryness. My vaginal walls were atrophying, and the result was terribly painful intercourse.
I’m fifty-four and far too young to be putting that part of my life on the shelf. I’m active and full of passion for all kinds of issues, causes, people. Most of all, I am passionate for my beloved and our life together.
So you see, this was a problem. A big one.
I must tell you, menopause was a roller coaster; for me as well as my husband and family. In order to mitigate the ups and downs and to get some even-ness back into my life I tried all kinds of over-the-counter remedies. I drank soy drinks, I took black cohosh, and other herbs, I diligently took Estroven. Nothing helped. And now this show-stopper made things very clear to me. I didn’t want this if I could make it go away.
And so I began to think about hormone replacement therapy. I considered what are commonly referred to as “bio-identicals” but I had reservations. First of all, determining a level of treatment when hormone levels can fluctuate from one day to the next meant that “personalizing” my dosage wouldn’t be any more effective than getting a standard dose. Also, regardless of the source, hormone replacement therapy could entail some risk whether it was “bio-identical” or not. All my body would know is that estrogen and progesterone were being reintroduced to my body. Further, the unregulated nature of compounding pharmacies was a red flag for me. pause. While our regulatory agencies in this country aren’t perfect, they are better than nothing.
I knew about the Women’s Health Initiative study of 2002 that showed increased rates of breast cancer for women using HRT. But I’d also read that they’d gone back and sorted through the data a bit more, and the risks were not as high as originally thought for women like me: Women just entering the post-menopausal period and not yet sixty.
Because the WHI study included women from ages 50 to 79, the initial results were a combined tabulation of all age groups together. But Goldstein says that when data was re-analyzed to focus on the youngest members alone, an entirely different risk-to-benefit ratio of HRT began to emerge.
“What we discovered is that if a woman is between the ages of 50 and 55 when she starts taking hormones, or if she begins HRT less than 10 years after she started menopause, she has less heart disease and less death from any cause, compared to the placebo group,” says Goldstein.
Those results were published in April 2007 in the Journal of the American Medical Association – and then again reinforced by similar research published in The New England Journal of Medicine the following June.
Here researchers focused on younger women who had a hysterectomy, and took estrogen alone. These results suggested that in these women HRT may also have protective effects on the heart.
“Women who were in their 50s in the estrogen-alone trial tended to have less coronary artery calcium if they received estrogen compared to placebo. And coronary artery calcium is … a strong predictor of future risk of coronary heart disease, so these results lend support to the theory that estrogen may slow early stages of arteriosclerosis,” says researcher JoAnn Manson, MD, DrPH, chief of preventive medicine, Brigham and Women’s Hospital, and professor of medicine and women’s health, Harvard Medical School, Boston.
Unfortunately, Goldstein says neither message seems to have been relayed to women or even their doctors, and as a result many women are suffering unnecessarily, afraid to use hormones to quell menopause symptoms in order to protect their heart.
“We have strong evidence to show that if it is less than 10 years since you started menopause, using HRT on a short-term basis is not likely to harm you, and it can help you; you shouldn’t be afraid,” he says.
The conclusion isn’t so clear when it comes to breast cancer, so, this is a bit of a risk for me, but one that I’m taking, given my family history of breast cancer (none).
But Smith says the back-story linking hormone use and breast cancer goes far beyond just connecting a few incriminating dots. It’s a complex relationship, she says, that is still not fully explained – or explainable.
“What we have learned since the WHI is that for most women taking hormones short term — for two or three years for symptom relief — there won’t be an increase in breast cancer in the short term, but this doesn’t necessarily mean these women won’t see an increase in breast cancer in the long term,” says Smith.
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At the same time, however, Goldstein notes that at least one reanalysis of the WHI findings published in JAMA in 2006 found that women who had a hysterectomy and used estrogen-only therapy for an average of seven years had no increase in breast cancer rates.
“In fact, risks of at least one type of breast cancer were reduced in these women,” says Goldstein.
But again, Stuenkel reminds us that the duration of hormone use might change that picture, too. She points to results from the Harvard Nurses’ Health Study published in the Archives of Internal Medicine in 2006, which reported that those women who took estrogen only experienced an increase in breast cancer after 20 years of use.
The trick appears to be this: take only what you need to relieve symptoms, and don’t take it for decades. And so, armed with this knowledge, I made an appointment with my doctor. For the first two months she prescribed nightly applications vaginal cream at the lowest dose, which was to be replaced after two months by a vaginal ring that I would change out every 90 days. I also was prescribed a mid-range range patch (.05mg of estadiol) which is changed twice a week. I was worried about the adhesive from the postage stamp-sized patch as I am sensitive to them, but the fact that I change it twice a week and alternate patch locations has meant no irritation from the patch. I also give my self one squeeze of a transdermal estradiol spray.
Off I went to the pharmacist, prescriptions in hand. When I was given my prescriptions, the pharmacist made a huge deal of pointing out to me that these may cause weight gain. Gawd. He said it at least four times and insisted that when I got home to read that part of the pamphlet, even going so far as to circle it with his pen. Yes, dear readers, I went home and read all of it. Would you expect less of me? So I was on the lookout for any side effects. Nausea, bloating, headaches, weight gain.
Here’s what actually happened. I began to feel better almost immediately. Even. Normal. My doctor told me to allow time for my hormone levels to increase and stabilize. I did. No headaches, no nausea, no bloating. Nearly three months in I’ve had no weight gain.
One day, on my drive in to work, I noticed something I hadn’t felt in a long, long time. I was horny! Yeehaw! The time had arrived for a test drive of my refurbished hoohah. All I can say is…
I’ve been back to the doctor, and will continue follow-up visits. It appears we got the dosage right on the first try. Nice. So, while I won’t be able to stay on HRT for decades, for now it is smoothing out my fifties and frankly, has given me back a part of my life that I thought was gone forever. My decision is mine. Not all menopausal women experience vaginal atrophy to the degree that I did. Every woman has to make her own decision about what is right for her and should do it in full and continuing consultation with her physician.
For me, this decision, slowly and carefully made, was right for me.
* For an interesting perspective on what menopause may be like for the other side of the couple equation go here.
Conclusion After a median follow-up of 8.0 and 7.9 yearsin the clinical trial and observational study cohorts, respectively,the Women’s Health Initiative study provided convincing evidencethat multivitamin use has little or no influence on the riskof common cancers, CVD, or total mortality in postmenopausalwomen.
F.D.A. Finds ‘Natural’ Diet Pills Laced With Drugs
. . . But the Food and Drug Administration now says those weight-loss capsules, called StarCaps and promoted as natural dietary supplements using papaya, could be hazardous to your health. In violation of the law, the agency has found, the capsules also contained a potent pharmaceutical drug called bumetanide which can have serious side effects.
And StarCaps are not the only culprits. In a continuing investigation that has prompted consumer warnings and recalls by some distributors, the F.D.A. has determined that dozens of weight-loss supplements, most of them imported from China, contain hidden and potentially harmful drugs. In the coming weeks, the agency plans to issue a longer list of brands to avoid that are spiked with drugs, an F.D.A. spokeswoman said.
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As the F.D.A. continues to investigate, many questions remain to be answered — including who put the drugs in the pills and who knew about it. But some doctors and other experts say the F.D.A. inquiry raises a larger issue: Whether the regulations governing dietary supplements leave consumers who take so-called natural weight-loss supplements to unknowingly play Russian roulette with their health.
Enacted in 1994, the main law on dietary supplements gives the F.D.A. jurisdiction only after the products go on the market. Rather than reviewing the supplements and approving them for sale, as the agency does with drugs, the F.D.A. is limited to spot-checking manufacturers and distributors, and testing products already on store shelves. Even the F.D.A. acknowledges there may be hundreds of other drug-contaminated weight-loss supplements for sale that the agency does not have the resources to identify.
But even when the agency identifies contaminated products, it does not have the ability to remove the pills from stores, because it is initially up to companies to issue a recall. Eventually, though, if contaminated products stay on the market, the F.D.A. can seek injunctions, seize products or file criminal charges.
You would need to know the baseline absolute number of new breast-cancer patients. If the number shifted from 1 in 10,000 women to 3 in 10,000 women, that is a 300% increase, but it is very likely a random artifact. If the risk had jumped from 100 to 300 in 10,000, also a 300% increase, we might reasonably be concerned. In large epidemiological studies that generally include tens of thousands of people, it is very easy to find a small relationship that may be considered significant by statistical convention but which, in practical terms, means little or nothing because of the low absolute numbers.
