The latest FDA approved labeling for Prempro states in part:
"Do not use estrogens and progestins to prevent heart disease, heart attacks, strokes, or dementia. Using estrogens and progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots. Using estrogens, with or without progestins, may increase your risk of dementia, based on a study of women age 65 years or older."
Prempro was approved as a hormone replacement therapy to treat menopause and prevent osteoporosis only. The wide-spread over-prescribing of the drug for other conditions was a result of Wyeth promoting the drug for off-label uses.
Off-label refers to the practice of physicians prescribing an FDA approved medication for uses other than the indications listed on the drug's label. While this practice may be justified in exceptional cases, critics say, HRT illustrates the damage that can occur when off-label prescribing becomes routine.
The widespread myths about the cures of hormone therapy began in 1965, when Dr Robert Wilson, published the book, "Feminine Forever," without revealing that he was a consultant to Wyeth, the maker of the hormone drug Premarin.
By the mid-1970's, a clinical trial showed that Premarin increased the risk of endometrial cancer, and a scientific panel had rejected virtually all of its benefits except for hot flashes and vaginal dryness. When Premarin sales fell, Wyeth added progestin to the pill, and created HRT.
The vast popularity of HRT, was in large part due to Wyeth's successful efforts to promote the off-label use of Prempro through the media by providing information which overstated its benefits and downplayed the cancer risks. For instance, a May 25, 1992, Newsweek article, entitled, "Every Woman for Herself," stated in part, estrogen replacement therapy:
"almost always zaps hot flashes, soothes vaginal dryness, improves bladder problems, evens out mood swings, and clears up short-term memory loss. It also combats the more serious effects of estrogen deficiency: osteoporosis and an elevated risk of heart attacks. The hormone retards bone
loss and cuts death from heart attacks in half."
An article in the October 1997, Ladies Home Journal, stated: "A woman's chance of dying from heart disease is more than five times greater than dying from breast cancer, and HRT lowers that risk."
A story in the September 1998, Better Homes and Gardens, told women, "talk to your doctor about taking estrogen or hormone replacement therapy."
"Research has shown," the article stated, "that estrogen and HRT may reduce the risk of heart attack after menopause by as much as 50 percent."
As part of a Wyeth-sponsored American Heart Association campaign in 1998, the media received a pamphlet entitled, "Take Charge! A Woman's Guide to Fighting Heart Disease."
It listed loss of estrogen first under risk factors for heart disease, and stated: "Estrogen replacement helps protect against coronary heart disease risk."
What critics say is most disturbing, is that the media continued to publish articles with similar statements even after the 1998 Heart and Estrogen/Progestin Replacement Study, which found that women who used HRT actually had a higher rate of heart disease during the first year of therapy.
It got to the point where the National Institute of Health decided that the use of hormones for disease prevention had to be studied precisely because doctors were prescribing the drugs off-label to so many women, even though long-term safety and efficacy had not been established.
In 2002, millions of women quit taking hormone pills, after an 8-year study was halted by the NIH after five years. The study by the Women's Health Initiative included 16,000 women and found that women who received HRT had significant increases in breast cancer, heart attacks, strokes, and blood clots.
The principal investigators of the study reported that further trials to test other estrogen and progestin formulations would be unethical and a waste of tax dollars because there was no reason to believe any other formulations would render a different result.
Similarly, they said, there would be no reason to test HRT for the prevention of heart disease in women 50 to 59-years-old, because one third of the WHI's volunteers were in their 50's, and they had the highest increased risk of stroke.
Within 3 months after the study was released, Wyeth's stock had fallen more than 55%, eroding its $48 billion in market value, according to TradingMarkets.com on February 28, 2007.
Critics of the study claim that it was the type of hormones, the dose, and the method of use which increased the health risks. The study tested HRT with estrogen made from the urine of pregnant horses, and some experts believe that estrogen from plant sources is better suited for treating menopause because it is closer to what the human body produces.
The most common risks associated with HRT, are blood clots, which can cut off the blood supply to vital organs and, in the most serious cases, a pulmonary embolism can occur if a clot travels to the lungs from another area of the body.
A recent study by French researchers in the journal Circulation, compared 271 women who suffered blood clots to 610 women without clots and found that women taking hormone pills orally were over 4 times more likely to develop clots than women who did not take hormones or who received them from patches, gels or creams.
Hormones delivered through the skin cause fewer blood clots, doctors say, because they enter the bloodstream directly, similar to natural hormones. When taken in pill form, the drugs must be metabolized by the liver triggering some of the unwanted side effects before entering the blood stream.
Since the release of the 2002 study, Wyeth's massive off-label promotion of HRT has come back to haunt the drug giant. According to SEC filings, as of December 31, 2006, there were approximately 5,200 lawsuits pending against the company filed on behalf of approximately 8,400 women for injuries related to its HRT, with about 60% of the cases filed in federal courts and 40% in state courts.
The latest lawsuit was filed by Nancey Land, a retired South Carolina teacher, who blames her breast cancer on Prempro, according to The State on March 2, 2007.
Ms Land's attorney, Ken Suggs, won a case against Wyeth in February 2007, when a Philadelphia jury returned a $3 million verdict for a 67-year-old Dayton, Ohio, woman who said Prempro caused her breast cancer which resulted in a double mastectomy, chemotherapy, and radiation.
The woman initially won $1.5 million in October 2006, but a mistrial was later declared after a juror was found to be ineligible, Mr Suggs told The State.
During the retrial, the jury was told that Wyeth knew for decades that HRT could cause breast cancer but failed to warn patients.
In January 2007, Mr Suggs' law firm also handled a trial where the jury awarded $1.5 million to an Arkansas woman.
So far, Wyeth has won two cases in federal court.