Prempro, also known as conjugated estrogen/medroxyprogesterone acetate, was approved by the U.S. Food and Drug Administration (FDA) in November 1995, to relieve menopause symptoms and osteoporosis. It is a combination of two hormones, an estrogen and a progestin, and is used only by menopausal women who have not undergone hysterectomy. Prempro was the first estrogen/progestin combination available for hormone replacement therapy (HRT), and is still one of the most common HRT’s prescribed by physicians today. In 2003, it was estimated that more than 10 million postmenopausal women in the U.S. take estrogen or estrogen-progestin products to treat the symptoms of menopause. Prempro is manufactured by Wyeth-Ayerst Laboratories.
Prempro HRT has been proven to cause serious health risks in women, most notably Breast Cancer. Before 2002, it was believed that Prempro and other HRT therapies protected women against heart disease and osteoporosis and helped to treat symptoms of menopause. Instead, a federal study found that Prempro hormone replacement therapy increases the incidence of Prempro breast cancer by 26 percent, including heart attack by 29 percent, stroke by 41 percent and blood clots in the legs and veins by 105 percent.
A number of other adverse health consequences have been reported including ovarian and gall bladder cancer, breast cancer, lupus, non-hodgkins lymphoma, heart attack, sclerederma, venous thrombosis, pulmonary embolism and asthma. It is estimated that six million American women use Prempro, a combination of premarin (which is estrogen) and progesterone. In 2001, approximately 22.3 million prescriptions were written for Prempro to treat post-menopausal hot flashes and other menopause symptoms
Pfizer has agreed to pay about $330 million to settle more than 2,200 lawsuits charging its Prempro hormone replacement therapy caused women to develop breast cancer, embracing a strategy used by several other drugmakers to cap the cost of growing product-liability litigation that can worry investors. The cases settled for an average of about $150,000, according to Bloomberg News, which first reported the settlement, although a Pfizer spokesman disputed the figures. The move came after a Pennsylvania appeals court reinstated $1.7 million in compensatory damages and $8.6 million in punitive damages against Pfizer in a lawsuit filed by an Arkansas woman, who alleged its Wyeth unit failed to warn that Prempro could cause her to develop breast cancer. The settlement comes just weeks after Ian Read took over as Pfizer CEO, suggesting a desire to put aside an eight-year-long battle over Prempro.
In 1990, Wyeth, the manufacturer, requested that the FDA change the label of their HRT drugs to include that they protect against heart disease. Prempro was approved as HRT by the Food and Drug Administration (FDA) in 1994, but the drug was put on the market even though it lacked a randomized clinical trial.
By the mid-1990s, the labels for Prempro and Premarin hormone drugs claimed that the drugs were approved by the FDA to treat moderate to severe menopause symptoms, such hot flashes, and to prevent osteoporosis.
In July 2002, the National Heart, Lung and Blood Institute (NHLBI) announced that it had stopped a major clinical trial of the risks and benefits of combined estrogen and progestin– Prempro was the only estrogen/progestin combination drug tested in the study. (The study was supposed to continue until 2005.) The NHLBI study found a marked increase in breast cancer for women who were taking Prempro compared to those in the placebo group.
In 2003, following a study conducted by the Women’s Health Initiative (WHI) showing these links, the FDA required Wyeth to change Prempro’s labeling to include information from the WHI study – specifically that the drug may increase the risk of myocardial infarctions (heart attack), stroke, invasive breast cancer, pulmonary embolism (blood clots), and deep vein thrombosis (deep vein blood clots) in postmenopausal women who take the drug for more than 5 years. On December 12, 2009 The New York Times reported that recently examined court documents from HRT lawsuits argued that Wyeth oversold the benefits of its menopausal hormone drugs while failing to warn of their risks. According to the NYT, documents show that Wyeth spent tens of millions of dollars–such as paying influential physicians, scientific publications and celebrity ads–promoting Prempro with positive preventive health messages
In 1991, the National Heart, Lung, and Blood Institute (NHLBI) began a long-term study of ways to prevent heart disease, breast and colorectal cancer, and osteoporosis in women, called the Women’s Health Initiative (“WHI”).Annual sales of Wyeth’s hormone-replacement drugs once topped $2 billion before the Women’s Health Initiative study, sponsored by the U.S. National Institutes of Health, suggested that women on the therapy had a 24 percent higher risk of breast cancer. The WHI consists of a set of clinical studies and an observational study, and involves more than 161,000 healthy, postmenopausal women.
One of the clinical studies involved 16,608 women who took either Prempro or a placebo. The main goal of this study was to see if Prempro would help prevent heart disease and hip fractures. The Prempro portion of that study was cut short three years early, however, because the researchers determined that the risks associated with Prempro, which include breast cancer, stroke, heart disease and blood clots,outweighed its benefits, which include a lower rate of fractures and a reduction in the risk of colorectal cancer. Women had been studied in the trial for over 5 years before it was halted.
Most of the women in the Prempro portion of the WHI study did not have prior evidence of heart disease, so the increased risk in healthy women of incidents like heart attack or stroke was a new finding, according to researchers. Unfortunately, because of differences in the formulas of other combination estrogen/progestin products, it was unclear whether the concerns of this study should also be considered for other, similar products.
Wyeth immediately announced supplemental Prempro labeling describing the conclusions from the cancelled WHI study. On August 14, 2002, the Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) announced it was going to review the risks and benefits of Prempro in light of the WHI findings.
The latest data, which was published in the Journal of the American Medical Association, followed 12,788 women since 2002, when the federally funded WHI study that compared HRT with placebos was halted. In the new findings, there were 678 cases of invasive breast cancer, including 385 for women taking hormones and 293 with a placebo. More women who took hormones died from breast cancer – 0.03 percent per year, versus 0.01 percent per year in the placebo group. That amounts to 2.6 deaths per 10,000 women per year versus 1.3 deaths in the placebo group.
After the WHI was released eight years ago, HRT use plummeted and led to a drop in breast cancer rates, with about 100,000 fewer invasive tumors detected from 2002 to 2007 than expected, said lead researcher Rowan Chlebowski, chief of medical oncology at the University of California, Los Angeles, School of Medicine, tells Bloomberg News. Using a 10-year mortality rate of about 20 percent, he calculates the reduction in hormone use may have prevented about 20,000 deaths.
Recent medical article outlining recent findings:
Doctors to cut down on Prempro Use
The findings should cause doctors to cut back on long-term usage to treat hot flashes and night sweats. “I don’t think you can say that now,” Chlebowski tells the news service. “I know some people have to take it because they can’t function, but the message now is that you really should try to stop after a year or two…Women should think critically about if they need this, if their symptoms are significant and if they would persist.”
In an accompanying editorial in JAMA, Peter Bach, a physician at Memorial Sloan-Kettering Cancer Center, writes that, “given the substantial population of women who seek relief from menopausal symptoms and the large potential burden of disease that could be created if medications given to alleviate symptoms today cause cancer and other deaths tomorrow, it seems that additional randomized trials are needed specifically to determine whether lower doses or shorter durations of hormone therapy could alleviate menopausal symptoms without increasing cancer risk.”
Prempro, manufactured by Wyeth, is the primary drug involved in HRT lawsuits. Over the last seven years, 13,000 people have sued Wyeth (and are now suing Pfizer, the world’s biggest drugmaker, which acquired Wyeth), alleging that Prempro and other hormone drugs caused breast cancer and other health problems.
The Superior Court of Pennsylvania issued the ruling Monday, reversing a 2007 trial court decision to grant Wyeth a new trial and throw out the compensatory damage award. The appellate panel concluded no “fraud on the court took place here and a new trial should not have been granted,” according to the Superior Court of Pennsylvania.
In November 2009, a Philadelphia jury ordered Pfizer to pay $6.3 million in compensatory damages to an Illinois breast cancer survivor after finding menopause drugs Premarin, Provera and Prempro caused the disease.
In October 2009, a jury in a Pennsylvania state court awarded a woman $75 million in punitive damages from Wyeth on top of compensatory damages of $3.75 million. The suit asserted that Wyeth oversold the benefits of menopausal hormones and failed to properly warn of the risks.
In October 2007 a Nevada jury awarded $134.5 million to three women who developed breast cancer following use of Prempro and Premarin. The verdict was the largest against drugmaker Wyeth related to its hormone replacement therapy. A fourth woman settled before trial and passed away in April 2007 at the age of 59.
In February 2007, a jury in Philadelphia found that Prempro caused Jennie Nelson’s breast cancer and awarded her and her husband $3 million in damages. Nelson previously had been awarded $1.5 million by a jury in October 2006, but a mistrial was declared after the verdict had been returned.
In January 2007 a Philadelphia jury found that Prempro was responsible for Mary Daniel’s breast cancer and ordered Wyeth to pay $1.5 million in compensatory damages. The jury concluded that Wyeth was negligent in failing to provide adequate warnings about the risk of breast cancer associated with Prempro.
Pfizer has now lost eight of 15 Prempro cases that were decided by juries since trials began five years ago. However, Pfizer has succeeded in having some verdicts tossed after a trial or had awards reduced. Some verdicts, meanwhile, were settled and some are on appeal. Pfizer also won dismissals of more than 3,000 cases before these went to trial.
Even though Wyeth has received thousands of warnings and lawsuits linking Prempro to breast cancer, strokes and other serious illnesses, the drug remains on the market. Experts believe that Wyeth has known of the adverse events caused by Prempro for many years, but it has chosen profits over safety–in 2006 and 2007, Prempro sales were over $1 billion.