In reviewing the data for the 10th interim analyses on May 31, 2002, the DSMB found that the adverse effects in cardiovascular diseases persisted, although these results were still within the monitoring boundaries.  However, the design-specified weighted log-rank test statistic for breast cancer (z = -3.19) crossed the designated boundary (z = -2.32) and the global index was supportive of a finding of overall harm (z = -1.62). Updated analyses including 2 months of additional data, available by the time of the meeting, did not appreciably change the overall results.  On the basis of these data, the DSMB concluded that the evidence for breast cancer harm, along with evidence for some increase in CHD, stroke, and PE, outweighed the evidence of benefit for fractures and possible benefit for colon cancer over the average 5.2-year follow-up period.  Therefore, the DSMB recommended early stopping of the estrogen plus progestin component of the trial.  Because the balance of risks and benefits in the unopposed-estrogen component remains uncertain, the DSMB recommended continuation of that component of the WHI.  Individual trial participants have been informed.

---

A 41 percent increase in strokes 
A 29 percent increase in heart attacks 
A doubling of rates of venous thromboembolism (blood clots) 
A 22 percent increase in total cardiovascular disease 
A 26 percent increase in breast cancer 
A 37 percent reduction in cases of colorectal cancer 
A one-third reduction in hip fracture rates 
A 24 percent reduction in total fractures 
No difference in total mortality (of all causes) 

---

USA - USA Today
http://www.usatoday.com/news/healthscience/health/cancer/2002-07-09-hormone-cancer.htm
U.S. stops study on hormone therapy
By Rita Rubin, USA TODAY 

WASHINGTON — In a rare move, the government has halted a major study of hormone therapy three years earlier than planned because of a slightly increased risk of invasive breast cancer, researchers said Tuesday.

The new findings, to appear today in The Jou nal of the American Medical Association, shoot down the deeply engrained belief that estrogen reduces older women's risks of chronic diseases. (Women who have not had a hysterectomy also take progestin to protect the uterine lining from estrogen's cancer-causing effect.)

Last week, JAMA published research from the Heart and Estrogen/progestin Replacement Study (HERS) that showed no benefit for women with heart disease after nearly seven years of treatment.

In response, the leading organizations of obstetrician/gynecologists noted that the HERS findings might not apply to healthy postmenopausal women. Only the Women's Health Initiative, the groups said, could answer that.

http://www.medicalpost.com/article5.html july 11

"The real story here is that, upon hearing about the termination of this trial, scared women are going to make quick decisions with potentially bad consequences," Dr. Wulf Utian, reproductive endocrinologist at the Cleveland Clinic in Cleveland, Ohio, told the Medical Post. 
   "This morning, when the local paper broke the story, frightened women started calling the clinic at a rate of eight to 10 per hour asking what they should do," Dr. Utian said. "The fact is that we don't know if they really have anything substantial to fear from this dual hormone therapy. The researchers got caught by their own overly strict guidelines for risk evaluations. What we could have learned from a few more years of this study is lost." 
   
Shares of Wyeth Pharmaceuticals, of Collegeville, Pa., fell more than 22% to a two-year low. The company manufactures Prempro, an estrogen-progestin pill, used by millions of women for symptoms of menopause. 
   "While the study provides important information, it did not evaluate the benefits of combination (hormone replacement therapy) in the treatment of menopausal symptoms," the company said in a statement. "As stated in the NIH news release, for women taking combination (hormone replacement therapy) for the short-term treatment of symptoms, the benefits are likely to outweigh the risks." 

SYDNEY, Australia - 

Australia issued an urgent warning Thursday against long-term hormone replacement therapy, following U.S. findings that its risks outweigh its benefits.

The Australian Medical Association said 600,000 women are on some form of hormone treatment and that the government's warning was premature.

"It will unnecessarily, in our view, panic more women," said the association's federal vice president Trevor Mudge.
 

The [Australian] media, medical and political reaction to this report has been nothing short of extraordinary. Radio, television and newspapers have devoted an amazing amount of space to the subject. Even the Prime Minister paused his European perambulations to urge women back home not to panic. I can't remember when society has ever been so concerned about a women's health issue. 
<snip>
.....yet a close reading of the study (available at the Journal of the American Medical Association's Web site, jama.com) shows a more complicated, and far less worrisome, picture.

It is a shame the report did not address the question of how the women with breast cancer were responding to treatment. For women grappling with whether to discontinue HRT such information would have been useful. Breast cancer is a terrible affliction, one that kills almost 2600 Australian women every year, but many more are able to be successfully treated. 

At the weekend, Professor John Eisman, of the Garvan Institute, condemned as "criminal" that the trial was stopped. "The answer could be that those women who used HRT and developed breast cancer actually overall had a better outcome," he was quoted as saying. "But we'll never know that now ..."
<snip>
I know a lot of women who take HRT - myself included - but I don't know a single one who is taking it in order to prevent heart or other diseases. Some women take it to keep their bones strong (which is effective, according to the study), some take it so they can still enjoy sex (some husbands insist on it) and some take it to keep their skin supple. The trouble is that many women who initially take it for menopause relief find the fringe benefits so alluring they want to stay on it - perhaps forever.

By age 50 we might, as Colette put it, have the faces we deserve but many women would prefer to stop the aging process right there rather than watch their skin sag, their hair thin and all the other bits deteriorate as our bodies stop producing oestrogen. 

Once the choice was to risk pregnancy or take the pill. Now it's risk cancer with a little pill that allows us to get on with our lives. It's a devil of a choice - but we women should be the ones to make it for ourselves.

---

Forget the facelift. Get the hysterectomy.

You think I'm kidding? Read on.

Two years ago in this space I wrote, "What's a girl to do? To HRT or not to HRT, that is the question?"

This week, the question was answered definitively when a major, government-funded U.S. study showed that HRT significantly increases risk of breast cancer, heart disease and stroke. 

At least, when I read the embargoed study on Monday, I thought the question was answered definitively. And about time, too. Millions of women have been taking a drug that had never been tested in a large-scale, long-term randomized controlled clinical trial — the gold standard for evidence-based medicine.

But now I'm not so sure the case has been made. And not because the study is inconclusive or questionable. It isn't.

The problem is that there are two enormously powerful motivations to downplay or obfuscate the results and both are at work now: vanity and greed.
<snip>
Billions of dollars of marketing have helped to reposition HRT not as a drug to control symptoms, not even as a drug to prevent disease in healthy women (a questionable proposition itself) but as a lifestyle drug promising better skin, better attitude and better sex. This hasn't been articulated in so many words; the preferred phrase is "quality of life."

---

You'd think she'd be happy. After more than 15 years of challenging the dogma that all women need hormone replacement to prevent heart disease and bone breaks after menopause, Maryann Napoli has been vindicated. 
<snip>
"I just wish there had been more caution about giving women this drug combination in the first place," she says, looking up at the shoes passing by the window of her tiny, donated office space in a West Village basement. Instead, "they turned a stage of life into a disease for which you're supposed to take drugs every day for the rest of your life," she says. "It was a pharmaceutical industry's dream come true." 

For many women, though, the treatment of menopause has been a nightmare. Greed and misogyny dovetailed in a massive marketing campaign for products that turned out to be both dangerous and unnecessary.................... 

---

Hormone replacement therapy 
Findings of women's health initiative trial need not alarm users

...............................Survival of the human species over two million years implies that female sex hormones by themselves are not dangerous to health. If harm is established, we must therefore examine the types of substitutes that we use and their means of delivery.

..............................Hormone replacement therapy regimens using different oestrogens and progestogens, and different routes of administration, may be similar in their effects on the breast, bowel, and skeleton. But the metabolic effects of different regimens are clearly different, and this is most likely to have an impact on their cardiovascular effects. Indeed, the women's health initiative trial also has an oestrogen-alone arm for women with hysterectomies, which has not been stopped. We need to see these findings to know whether the medroxyprogesterone acetate is causing the harm. It is most unhelpful that this point about different oestrogens and progestogens was not appreciated by the recent recommendations of the Committee for Safety of Medicines and the Medicines Control Agency,7 which were inappropriate with respect to cardiovascular disease. Particularly for coronary heart disease, the dose (and possibly type) of oestrogen and the type of progestogen may be crucial. Similar studies using different types of hormone replacement therapy than the one used in this trial must be carried out. 

................................Women who are currently taking continuous combined oestrogen-progestogen should not panic, as it is most unlikely to have caused considerable harm

.................................There is no right or wrong hormone replacement therapy to use in the short term, but in the light of the findings of this trial the use of hormone replacement therapy regimens containing conjugated oestrogens 0.625 mg together with medroxyprogesterone acetate (at any dose) should be avoided in the long term. The findings of this trial may not apply to lower doses of conjugated equine oestrogens, given with or without other progestogens. The long term effects of alternative hormone replacement therapy preparations have not yet been tested in large randomised trials, and this must become a research priority.

New Hormone Program Information 
Since our last update to you, the Data and Safety Monitoring Board (DSMB) has finished another review of all the data from the beginning of the study up to February 28, 2001. The DSMB looked carefully at the safety of women in the study and the value of the study to all women across the nation. They unanimously said we should continue the study, because the overall balance between benefits and risks of hormone replacement therapy (HRT) is not clear.

Study findings as of February 28, 2001
In the spring of last year, we told you that there was "a small increase in the number of heart attacks, strokes, and blood clots in the lungs of women receiving active hormone replacement therapy compared to women taking inactive (placebo) pills. Fewer than l% of WHI women had any one of these problems, regardless of the type of study pills they were taking. Over time these differences between women on active and placebo pills seem to be getting smaller and may disappear." The DSMB has now reviewed the data through February 28, 2001 and has told us that the differences have not disappeared. The number of heart attacks, strokes, and blood clots remains higher in women taking active hormones. We do not know how this might change in future years.

The Balance Between Benefits and Risks
In trying to understand the overall balance of benefits and risks, the DSMB reviews data on many health conditions - including:

What We Are Doing to Understand These Risks
We have checked to see if the heart attacks, strokes. and blood clots in women on active hormones may be related to any individual risk factor (for example age or other health conditions like high blood pressure). So far, we have not found any particular group of women to be at higher risk. Now we are doing laboratory studies using stored blood samples from WHI women to see if we can identify women at risk. Whether or not these laboratory studies give us new information, the DSMB will continue to monitor the progress of the study and the effects of hormones on your health in future years.

The Health of Women in WHI
As a group, women who joined WHI were healthier than average. As a result the number of heart attacks, strokes, and blood clots in the WHI women is lower than in the general population of U.S. women. Each year in the study, less than one half of one percent of women have had a heart attack. The same is true of strokes and blood clots. Even so, more women taking active hormones than women taking placebos developed these conditions.

How You Can Help Maintain Your Health
To help prevent heart attacks or strokes a healthy lifestyle is important, including:

To help prevent blood clots, it is important to:

Remember to keep exercising your legs and feet if you must stay in bed for any reason. You may want to ask your clinic practitioner for the "WHI Update" on blood clots,

What Can You Do Now?
The most important thing you can do is to stay informed. Please read this information carefully and discuss with our staff any concerns that you have. There are many more questions about hormones at this time than there are answers.

Female hormones are the number one selling prescription drugs in the U.S. - and the world. According to a recent survey by the American Heart Association 54% of women believe that hormones prevent heart attacks. However, we still do not know if taking hormones for many years prevents heart atacks and improves health. This study is even more inportant since we told you of the unexpected findings last year. The whole world is waiting for the final results of the WHO. Thank you for your contribution to this study.

Our commitment to you remains. We ask for your continued participation in this effort because we expect WHI to provide answers for women like you and for generations of women to come. As always, your participation is voluntary. We will continue to provide you with new information when it becomes available. And we will do our part to conduct this study according to the highest standards of medical research, so that the results will be as clear and useful as possible.