Hormone Replacement "Bombshell" is Not and isolated incident

Hormone Replacement “Bombshell” is Not and isolated incident

Wednesday, July 10, 2002

Until a “bombshell” study overturned hormone replacement treatment (HRT), Premarin was the most prescribed drug in U.S. in the last decade (45 million Rx in 2001) and Prempro the most prescribed estrongen / progesterone combination (22 million Rx in 2000). The popularity of this treatment was not supported by scientific evidence demonstrating a favorable risk/ benefit ratio. The shocking news about HRT is not an aberration in American medicine. It is but the latest example demonstrating how medical practice guidelines, research designs and the reported findings are all influenced (some would say, corrupted) by drug industry hype that floods the media and overwhelms the professional literature.

Even after The New England Journal of Medicine published two reports that estrogen increased the risk of cancer, mainstream medicine and the public were deluded by the drug manufacturer’s promotional campaigns and false claims. As it turns out, HRT did not decrease the risk of cancer, heart disease and stroke–it increases the risks of all of the above.

The New York Times reports that the promotion of estrogen began in 1966, “when an enthusiastic doctor, Robert Wilson, wrote a best-selling book. He called it ‘Feminine Forever’ and flew around the country promoting it, telling women and doctors alike that estrogen, the feminine hormone, could keep women young, healthy and attractive. ” What Dr. Wilson didn’t tell them was that Wyeth-Ayerst had paid all the expenses of writing “Feminine Forever”, paid Wilson and his wife to lecture to women’s groups, and financed his organization, the Wilson Research Foundation.

The Times reports: “There were reams of scientific papers. Many fell short of absolute rigor, but in sum they pointed mostly in one direction, that of benefit. There were compelling marketing campaigns by drug companies. There was also the eager adoption of the drug combination by doctors and women who wanted to believe it worked.”

According to Dr. Jay Cohen, author of “Over Dose: The case Against the Drug Companies,” Dr. Janet Woodcock, Director of the FDA’s Center for Drug Evaluation and Research, acknowledged that: “The predominant use of Premarin is a practice pattern of American physicians, probably resulting from advertising.” (p. 77). Did Dr. Woodcock and the FDA know the claims made in the ads were untrue?

An investigative reporter who examines the scientific basis for the claims made about other highly promoted drugs is likely to find a pattern of deceptive pronouncements –particularly when serious adverse side-effects have been detected. Drug companies tend to embark on ever bolder strategies to expand the market while masking negative attributes with increased hype. “Each time there was anything negative about the drug, a new claim arose to keep it alive.”

The scenario that obscured the truth about hormone replacement is being replicated in the marketing of psychotropic drugs. Take antidepressants, for example, a string of controlled studies has found these drugs are no better than placebo in alleviating depression while the risks and adverse side effects linked to antidepressants are severe, and for some patients, life-threatening.

“St John’s Wort, Placebo, and Antidepressant Trials,” JAMA, April 2002 at:

http://jama.ama-assn.org/issues/v287n14/ffull/jtw20010.html

“The Emperor’s New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration” by Irving Kirsch, Thomas J. Moore, et al, in Prevention and Treatment, July 15, 2002 : http://journals.apa.org/prevention/volume5/toc-jul15-02.htm

See, for example, “Deliberate self-harm and antidepressant drugs Investigation of a possible link,” by Stuart Donovan and Richard Madeley, British J of Psychiatry, 2000, v. 177, 551-556;

Murder, suicide. A bitter aftertaste for the ‘wonder’ depression drug Antidepressant Seroxat under scrutiny as firm pays out $6.4m Sarah Boseley, health editor, The Guardian, Monday June 11, 2001 http://www.guardian.co.uk/Print/0,3858,4201752,00.html

Yet, carefully staged, misleading advertising and aggressive marketing that defies medical ethics, has succeeded in creating hugely profitable drugs by keeping the buyers unaware of the truth. The Times’ article ends with the following observation by Dr. Utian of the Menopause Society, who revealed precisely why medicine needs to independent oversight and a system of audits that are not controlled by the stakeholders:

“There are an awful lot of interests at stake here beyond women’s health,” he said. “There are investigators with research grants, N.I.H. grants and grants from the pharmaceutical industry. There are academics with careers to build.” Added to that, he said, are medical specialists – gynecologists are comfortable with hormones, internists with statins to lower cholesterol and protect against heart disease, bone experts with drugs like bisphosphonates to protect against osteoporosis. “It’s not just a matter of what the data says,” Dr. Utian added. “Truth is opinion.”

When corrupt business practices displaced medical ethics, honesty ceased to be a priority in medical research. Transparency is desperately needed to restore the integrity of the entire medical enterprise. Public trust has been badly shaken. In the wake of disclosures of corporate financial misconduct, President Bush vowed to reform business ethics, to “end the days of cooking the books, shading the truth and breaking our laws.” Nowhere is the need for reform greater than in that sphere of endeavor affecting our health and our lives.

~~~~~~~~~~~~~~~~~~~~~~~~

THE NEW YORK TIMES

http://www.nytimes.com/2002/07/10/health/10HORM.html?pagewanted=print&position=top

July 10, 2002
Hormone Replacement Study a Shock to the Medical System
By GINA KOLATA with MELODY PETERSEN

[excerpt]
The announcement yesterday that a hormone replacement regimen taken by six million American women did more harm than good was met with puzzlement and disbelief by women and their doctors across the country. A rigorous study found that the drugs, a combination of estrogen and progestin, caused small increases in breast cancer, heart attacks, strokes and blood clots. Those risks outweighed the drugs’ benefits – a small decrease in hip fractures and a decrease in colorectal cancer. Many of the 16,000 women in the study, supported by the National Institutes of Health, opened letters yesterday telling them to stop the drugs. In light of the findings, the study had come to a halt.

Hearing the news, some said the findings had persuaded them. “I may have taken my last pill this morning,” said Dr. Deborah Bublitz, a pediatrician in Littleton, Colo.

Others agonized over the consequences of suddenly stopping drugs that help prevent bone loss and relieve menopause symptoms. Would they suffer torrential night sweats and embarrassing hot flashes? Or were the scientists simply exaggerating the risks, which were, after all, minuscule for an individual woman? Until recently, medical authorities were telling doctors to encourage almost every woman who had not had a hysterectomy to start taking the drugs when she reached menopause and to take them for years, even for life. Now the growing consensus seems to be that women should carefully consider whether they want to start the drugs at all. Those who take them for more than a few years should be aware of the risks, which, if slight, are real.

The news of the study’s findings came as such a surprise that doctors were inundated yesterday with calls from patients. Some medical experts on the hormone therapy said they had given up and taken their phones off the hook. “I’m just letting all my calls go onto the answering machine,” said Dr. Wulf Utian, executive director of the North American Menopause Society. But for Dr. Utian and others, this was a defining moment in medical history. “This is the biggest bombshell that ever hit in my 30-something years in the menopause area,” Dr. Utian said.

It was a powerful scientific counterattack to years of strong promotion of hormone replacement. There were reams of scientific papers. Many fell short of absolute rigor, but in sum they pointed mostly in one direction, that of benefit. There were compelling marketing campaigns by drug companies. There was also the eager adoption of the drug combination by doctors and women who wanted to believe it worked. The new study was different from the rest because it involved thousands of healthy women and had a control group, with half the women taking dummy pills. In addition, it looked for evidence of disease like heart attacks and cancer rather than indirect indicators like cholesterol levels, which can be misleading.

“This is definitive evidence,” said Dr. Deborah Grady, who directs the Mount Zion Women’s Health Clinical Research Center at the University of California in San Francisco. The tale of estrogen therapy began in 1966, when an enthusiastic doctor, Robert Wilson, wrote a best-selling book. He called it “Feminine Forever” and flew around the country promoting it, telling women and doctors alike that estrogen, the feminine hormone, could keep women young, healthy and attractive. It was just so natural – women would be replacing a hormone they had lost at menopause just as diabetics replace the insulin their pancreas fails to make.

“At age 50, there are no ova, no follicles, no theca, no estrogen – truly a galloping catastrophe,” Dr. Wilson wrote in 1972 in The Journal of the American Geriatric Society, referring to the eggs and surrounding tissue. But, he continued, estrogen can save these women. “Breasts and genital organs will not shrivel. Such women will be much more pleasant to live with and will not become dull and unattractive.” Dr. Wilson died in 1981, but his son, Ronald Wilson, said yesterday that Wyeth-Ayerst had paid all the expenses of writing “Feminine Forever” and financed his father’s organization, the Wilson Research Foundation, which had offices on Park Avenue in Manhattan.

Mr. Wilson, who lives in Cary, N.C., said the company had also paid his parents to lecture to women’s groups on the book. Wyeth said it could not confirm the account because it was so long ago. By 1975, Wyeth’s product, Premarin, had become the fifth leading prescription drug in the United States, said Nadine F. Marks, an associate professor at the University of Wisconsin at Madison, who co-wrote a research paper on hormone therapy. “Even textbooks for gynecologists and obstetricians in the 1960’s would explain how a woman’s life could be destroyed if she didn’t have estrogen in her body,” Dr. Marks said.

During that time, however, two major studies published in 1975 in The New England Journal of Medicine indicated that estrogen substantially increased the risk of cancer of the lining of the uterus. Soon, doctors and drug companies found an alternative. They began giving estrogen with progestin, which counteracts the effects on the uterine lining, leading to monthly bleeding that resembles a menstrual period. Women who had had a hysterectomy could take estrogen alone. Women who had a uterus could take the hormone combination. The problem was solved, or so most thought. Sales soared again in the 1980’s, Dr. Marks said, after a major advertising initiative by the company, which promoted the hormones for the prevention of osteoporosis.

There was no doubt that the drugs helped many women through a difficult time when their sleep was disrupted by night sweats and their days by hot flashes. “There is nothing else out there that addresses the symptoms of menopause,” said Dr. Victoria Kusiak, vice president of global medical affairs at Wyeth. But scientists and doctors were saying something more – that it could be used for disease prevention.

Many were impressed by evidence from dozens of observational studies in which women who happened to take estrogen were compared to women who did not. The drawback to these studies, however, is that women who decide to take estrogen, studies have shown, tend to be different from those who do not. They are healthier, leaner, less likely to smoke. The question is, does estrogen make women healthy, or do healthy women take estrogen? Nevertheless, many of the studies indicated that those who took the drugs had fewer heart attacks and fewer strokes, that they had stronger bones and fewer fractures. There were also laboratory studies demonstrating effects on animals and cells that seemed to support the observations.

“There was all this mechanistic stuff,” Dr. Grady said. “I have six inches of papers suggesting that it improves coronary vasodilation, that it prevents atherosclerosis.” In fact, she said, the accumulating evidence for a heart disease benefit, although indirect, seemed overwhelming. Even a large study by the National Institutes of Health seemed to support the notion of benefit. It looked not at disease but at markers for disease, cholesterol levels and bone density. Women who took hormones had better cholesterol levels and denser bones than those taking a placebo.

“If you look at this evidence – and it’s part of the mind-boggling aspect of this whole story – boy, the evidence for estrogen looked really strong,” Dr. Grady said. She and other experts were so persuaded that they wrote guidelines for the American College of Physicians recommending that women at high risk of heart disease take estrogen after menopause.

Dr. Marcia Stefanick, the principal investigator of the new federal study, said that not long ago medical groups were recommending that as soon as a woman turned 50, she should have a frank discussion with her doctor about hormone replacement therapy and that her doctor should encourage her to take the drugs. “This was what every 50-plus woman should do to prevent the disease of aging,” Dr. Stefanick said. “They linked up a very beneficial product for treating menopausal symptoms to the answer for treating all of a woman’s aging problems.” Even when some observational studies indicated that estrogen, and more so the combination of estrogen and progestin, might increase the risk of breast cancer, doctors were not dissuaded.

“A lot of people thought it was outrageous that women should worry about breast cancer risk when the heart disease risk is so much higher,” Dr. Stefanick said. Even as some scientists and advocates for women began arguing that at least there should be a more vigorous test of the estrogen hypothesis, it retained its power.

Dr. Stefanick said that when the new study was being planned, doctors and researchers said it was unethical because in the most rigorous studies, a group of women would be taking placebos. They would be denied the benefits of the hormones, these critics said.

All along, as hormone therapy grew in popularity, some refused to be convinced. One group, the National Women’s Health Network, said it was offended by the message and questioned the data. The message, said Cynthia Pearson, executive director of the network, “was sexist and ageist.” It had a constant refrain, she added. “Stay young. Stay healthy. Stay sexually vital. Be less of a pain to your husband.” “The claims were too good to be true,” Ms. Pearson said. “Each time there was anything negative about the drug, a new claim arose to keep it alive.”…. [complete article at:

http://www.nytimes.com/2002/07/10/health/10HORM.html?pagewanted=print&position=top]

Copyright 2002 The New York Times Company | Permissions | Privacy Policy

FAIR USE NOTICE: This may contain copyrighted (© ) material the use of which has not always been specifically authorized by the copyright owner. Such material is made available to advance understanding of ecological, political, human rights, economic, democracy, scientific, moral, ethical, and social justice issues, etc. It is believed that this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, this material is distributed without profit to those who have expressed a prior general interest in receiving similar information for research and educational purposes. For more information go to: http://www.law.cornell.edu/uscode/17/107.shtml