Popular menopause drugs made in part from estrogen found in the urine of pregnant horses have caused breast cancer in thousands of Canadian women, according to allegations in a new report by the Canadian Cancer Society’s top epidemiologist.
“The body of evidence to date overwhelmingly points to a causal connection between the use of Premplus and the development of invasive breast cancer in women,” the society’s Prithwish De wrote in a report to be filed in a Canadian class-action lawsuit against drug manufacturer Wyeth Canada, now owned by Pfizer.
The drug manufacturer states that its products are “safe and effective when used as directed” and they do not cause breast cancer. A trial date is set for October in a Vancouver court.
According to the report, hormone replacement therapy was the main risk factor in an estimated 12,000 new Canadian breast cancer cases detected between 1994 and 2006 at a time when Wyeth’s products, Premarin and Premplus, dominated the market. The drugs remain on the market, but in more recent years they have contained strong warnings and are also prescribed in lower doses.
In the lawsuit against Wyeth, women like Hamilton’s Rose Scarff, 70, say they were not properly warned of breast cancer risk when the drugs — prescribed to relieve menopausal symptoms such as hot flashes, night sweats and vaginal dryness — were packaged by the drug firm and prescribed by doctors.
“I never suspected there was anything wrong with taking it,” said Scarff, who developed an aggressive form of breast cancer after taking combined hormone replacement therapy continuously for 10 years.
Like millions of other women in North America, Scarff said she wanted to recapture a youthful zest extolled in health literature — “you’d feel like a younger woman,” Scarff recalled of articles about menopause relief treatments — as she entered menopause at age 49.
American courts have dealt with these allegations for years. Pfizer, which in 2009 acquired Wyeth, has paid $1.7 billion to settle nearly all of the 10,000 hormone replacement therapy claims against the drug manufacturer. Pfizer said it makes no admission of liability in the American settlements.
Since 2004 Health Canada has revised the product safety information for the drugs to list potential side effects including coronary heart disease, gynecologic cancers, breast cancer and dementia.
Two medications, Premarin and Premplus, are at the core of both De’s study and a Canadian class action suit for which he was hired as a hormone replacement therapy expert. The estrogen in the drugs comes from the urine of pregnant mares, mostly produced by a Pfizer plant in Manitoba.
Pharmaceutical giant Pfizer responded for comment on the civil suit with an email to the Star stating that “the court has made no ruling on the merits of any class member’s claim.”
In pleadings filed in response to the class action claims, Wyeth Canada (now a division of Pfizer) states that “Premarin and Premplus do not cause breast cancer.”
“The cause of breast cancer is not known. The vast majority of women who take hormone therapies such as Premarin and Premplus do not develop breast cancer,” according to the pleadings filed by Wyeth Canada in a British Columbia court.
The Wyeth documents also note Premarin and Premplus “are proven treatment options for menopausal symptoms and postmenopausal osteoporosis.”
Premarin is a very old drug that went on the market in Canada and the United States about 70 years ago. Premarin contains the equine estrogen hormone extracted from pregnant mare urine. Its name has long been considered a play on its plentiful natural source — PREgnant MARe urINe — but Pfizer staff could not confirm that is true.
Premplus is a combination product containing the equine estrogen and another hormone called progestin in a single medication. Premplus was approved for sale in Canada in 2000. Premarin and progestin can also be prescribed for use as separate tablets.
There are about 2,000 horses stabled at 20 Pregnant Mare Urine (PMU) ranches in Manitoba and Saskatchewan. Back in the 1990s, at the height of the drugs’ popularity, Wyeth had approximately 25,000 to 30,000 mares producing urine, according to a finding of fact in a U.S. patent lawsuit where Wyeth successfully sued to protect a trade secret.
Pfizer contracts ranchers to collect the urine for initial processing at its plant in Brandon, Man. To amass the urine, mares are kept in stalls with flexible pouches hanging between their hind legs to capture every drop.
Foals are removed from the mother when they are young. Some horse welfare advocates claim the PMU offspring often end up in a slaughterhouse. In response to slaughter claims, the ranching association stated its members “are contractually obligated to sell their horses to productive markets” in which horses can be competitive, ridden for pleasure or used to work on farms.
The ranching association website reports 50 per cent of foals are sold privately, 30 per cent go to auction and 20 per cent are purchased by breeders.
Women responded enthusiastically when Premarin came to market, making it the top-selling menopause drug in North America.
Gross sales of Premarin in the United States grew from over $500 million to in excess of $2 billion during the period of 1992 to 2001, according to Wyeth’s 2002 patent lawsuit submissions in a Minnesota court. The Star was unable to find Canadian sales information.
The Canadian class action suit follows years of litigation (thousands of cases with similar breast cancer claims) launched against Pfizer in the United States. Pfizer has won some of those suits, lost others and settled many.
Pfizer paid victims $1.7 billion (U.S.) to settle nearly all 10,000 hormone replacement therapy claims against it as of Dec. 31, 2013, according to the pharmaceutical manufacturer’s most recent annual financial report. The settlements included breast cancer, ovarian cancer, stroke and heart disease claims.
The Canadian class action was filed in 2004 by Dianna Stanway, a 68-year-old woman from Sechelt, B.C., and is only now coming to court.
Stanway, the lawsuit’s leading claimant, alleges she developed breast cancer after using Premarin in combination with the hormone progestin for about eight years. She, on behalf of 209 plaintiffs and others who can still join, are suing Wyeth Canada for general and punitive damages, costs and other relief as the court sees fit. No dollar amount is listed in the suit.
Stanway’s allegations include: Wyeth suppressed study results that indicated “significant health risks” associated with Premarin and Premplus use; Wyeth failed to conduct proper drug safety testing; the company oversold the drugs’ effectiveness; long-term use was promoted when the drug maker knew that serious risks outweighed their “limited benefits” and that Wyeth “deliberately chose to value their own profits over public safety” by its conduct.
In its response to the allegations, Wyeth states in its pleadings that “for the vast majority of women, the potential risks associated (with Premarin and Premplus) are outweighed by the benefits of treatment.” Wyeth provided information on risks to doctors and “acted appropriately” at all times when testing, manufacturing and marketing the drugs, the pleadings state.
The allegations have not been tested in a Canadian court. Similar claims about Pfizer’s family of hormone replacement therapy drugs have been tried in American courts.
For example, in 2007 a Philadelphia jury found Prempro — a Pfizer product — caused breast cancer in an Arkansas woman who took the medication from 1999 to 2001 and awarded her $1.7 million in compensation. In 2010, another Philadelphia jury rejected a claim that Prempro caused breast cancer in two Pennsylvania women.
A written statement from Pfizer to the Star said the American settlements are confidential “but they do not contain admissions of liability.”
“The company believes it has strong defences to the claims in this litigation and has prevailed in a substantial number of the cases that have gone to trial. Any previous settlements are a desire by the company to focus on the needs of patients and prescribers,” the statement said.
As part of the Canadian lawsuit, Prithwish De was hired by the plaintiff’s law firm, Klein Lyons, to produce a report. In addition to De’s role with the Canadian Cancer Society, he is an associate professor of epidemiology at the Dalla Lana School of Public Health at the University of Toronto.
De reviewed national and international studies of women using the Wyeth products named in the legal claim in his 25-page report for the lawsuit.
Hormone replacement therapy, used in combination prescriptions like the Wyeth products, was the major risk factor in new breast cancer cases among Canadian women from 1994 until 2002, De writes, referring to research from a 2010 Canadian study he reviewed for his report.
By the 1990s, red flags were popping up regarding health concerns related to Wyeth’s menopause medications, according to information filed by lawyers in the class action.
The world’s first extensive, long-term randomized controlled trial study was commissioned by the U.S. National Institutes of Health in 1991. De describes randomized controlled trials as the gold standard of clinical drug testing.
The Women’s Health Initiative study involved 16,000 healthy post-menopausal women aged 50 to70 who had not had a hysterectomy. Half the women took combined hormone replacement therapy drugs, the other half had placebos. The study was halted prematurely in 2002; researchers feared there were more risks (such as breast cancer, blood clots, strokes) than benefits among the group using the hormone replacement therapy drugs. The women’s study also reported the medications’ beneficial effects, such as reduced risk of colorectal cancer and fewer fractures.
De notes the dramatic decline of combined hormone replacement therapy use began in 2002 after the Women’s Health Initiative published findings from its long-term study about the medications’ serious side effects (including breast cancer).
Scarff said she believes her breast cancer was tied to hormone replacement therapy. “I’m positive that was the cause of it,” she said.
Mary Ormsby can be reached at firstname.lastname@example.org or 416-869-4373