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Is this drug a cure or killer?
A Tragic death has brought calls to ban the abortion pill. But women taking it to treat illness say it's saving their lives.
SELF, April 2004
by Laura Fraser
Winner,2005 Excellence in Women's Health Research Journalism Award
Emily Mulheran's hallucinations began in her early 20s. She could feel hot breath on her neck. A finger poked her on the shoulder. And voices whispered unimaginable taunts and insults in her ears. "Drive your car off a bridge embankment," one urged. "You're a coward for not killing yourself long ago." Twice, she gave in to the malevolent voices, overdosing on Tylenol PM and prescription drugs.
Doctors eventually diagnosed Mulheran, a 33-year-old website designer in Pittsburgh, with psychotic depression. She has been hospitalized for her illness and has taken many medications, most of which haven’t worked. It wasn’t until last year, while researching her condition on the Internet, that Mulheran came across a clinical trial for a new treatment that she says saved her life: mifepristone. “I was at the end of my rope,” she says. “Mifepristone made all my delusions and hallucinations go away. It’s like a miracle drug.”
Mifepristone, also known as RU 486, is approved in the United States only for ending pregnancies of up to seven weeks. But researchers say the drug--brand name Mifeprex--has the potential to treat intractable diseases, including several forms of depression, breast and uterine cancer, the hormonal disorder Cushing’s Syndrome, fibroids, endometriosis and even some brain tumors.
More research is needed, and any FDA approval for these uses would be years away. But patients like Mulheran have had remarkable results in clinical trails. And 84 women and 27 men with life-threatening illnesses have taken the drug under a
"compassionate use” program sanctioned by the FDA and administered by the Feminist Majority Foundation in Arlington, Virginia.
If another medication showed the same promise, doctors might rush to prescribe it off-label to otherwise untreatable patients, and doing so would be perfectly legal. But FDA rules for mifepristone are unusually strict: Physicians can't use it for anything but abortion. Nor can patients pick up the drug at a pharmacy; they must get it directly from qualifying doctors.
Now, after the death in September 2003 of a California teen who took the abortion pill, some lawmakers want to revoke the drug's approval altogether. If that happens, scientists warn, research may grind to a halt--and desperate patients would pay the price. "This drug has many potentially important uses completely unrelated to abortion," says gynecologist Steve Eisinger, M.D., who has conducted trials using mifepristone to treat fibroids at the university of Rochester in New York. "It would be a shame if politically motivated efforts prevented it from getting to the American public."
Researchers call mifepristone a breakthrough drug, with the unprecedented ability to block the effects of two powerful hormones, cortisol and progesterone. Cortisol regulates stress, and having too much of it is linked to depression, alcoholism, anorexia and Cushing's syndrome, a debilitating disease that 10 to 15 out of every 1 million people develop each year and that is marked by severe fatigue, depression, thin skin and obesity. A study at the National Institutes of Health in Bethesda, Maryland, found the drug controlled or reversed the syndrome in more than half of those who took it. And at Stanford University in California, Mulheran and other patients with psychotic depression--a condition for which the most effective treatment is currently electroshock therapy--showed "significant reductions" in psychosis in as little as four days on the medicine. Other small studies indicate that people with obsessive-compulsive or bipolar disorder may also benefit.
But mifepristone's promise extends far beyond its mental-health applications. It is the first in a new class of medications that may be able to fight diseases related to the female hormone protesterone. Mifepristone fits into progesterone receptors like a key into a lock, so the hormone can't come in. When used as an abortion pill, mifepristone causes a miscarriage because progesterone is essential for continuing a pregnancy; without it, the lining of the uterus breaks down and, with the help of a drug called misoprostol, the fertilized egg is expelled. Taken early enough, mifepristone prevents an embryo from being implanted. It's been tested in low doses as an emergency contraceptive in China and Great Britain, and British studies suggest it could be the basis of a once-a-month birth control pill. (Dosages used to treat disease vary, but in all cases, researchers make sure women aren't pregnant because of the risk of miscarrying.)
Ayear-long study by Dr. Eisinger of 40 women with uterine fibroids--tumors stimulated by female hormones--found that mifepristone typically shrank tumors by half. At least one in four American women have symptomatic fibroids. Large tumors can cause severe pain as they press on nearby organs, as well as anemia from very heavy periods. Most women with bad cases resort to hysterectomy, but Dr. Eisinger says mifepristone may shrink tumors enough that women could avoid surgery. And the treatment appears to have fewer side effects than the antiestrogen drugs doctors prescribe for fibroids, which cause hot flashes and bone loss.
Priscilla Putnam, a 51-year-old school administrator in Rochester, participated in the fibroid study. For years, she'd suffered heavy menstrual periods, back pain, bloat, and frequent urination. After trying other treatments without success, she took mifepristone and, she says, "the results were amazing. The fibroids shrank, and I felt so much better.” When the study was over, however, she had to go off the medication--and the fibroids grew back. She understands that the FDA needs more data before approving it as safe for treating fibroids. But she adds, “I’m concerned that this medical treatment will get mixed in with the whole anti-abortion movement. They’re two separate issues.”
Under the terms of the compassionate-use program, Putnam can’t get mifepristone because the FDA doesn’t consider fibroids potentially fatal. But Doris Laird, a retired professor in Tallahassee, Florida, has been taking mifepristone for 10 years to treat meningioma, a type of brain tumor that has progesterone receptors. Her tumor had wrapped around her optic nerve; three marathon brain surgeries had not been able to fix the problem. Today, CT scans reveal that the tumor has stopped growing. Clinical studies on this treatment have been inconclusive thus far, but Lair is convinced: "Mifepristone has saved my life and my sight," she says.
Because some cancer cells have progesterone receptors, mifepristone may also work to arrest forms of breast and uterine cancer, says Lois Ramondetta, M.D., a gynecologic oncologist at the University of Texas M.D. Anderson Cancer Center in Houston. In a trial there with patients who have recurrent and late-stage endometrial cancer, the drug appeared to stabilize a disease that is usually, at that point, unstoppable. Mifepristone offers valuable new clues to progesterone's role in cancer, Dr. Ramondetta adds: “We’re learning a lot about progesterone receptors, but it’s very early. Once we learn a little more, we should make some big differences.”
The death of 18-year-old Holly Patterson imperils this research just as it begins. Patterson was nearly seven weeks pregnant when she went to Planned Parenthood Golden Gate in Hayward, California, on September 10, 2003. She took mifepristone, according to a county coroner's report, and was told to take misoprostol the next day. On September 14, she went to a local hospital complaining of abdominal pain. The ER docs performed a pelvic exam, treated her with painkillers and released her. She returned to the ER on September 17 and died that afternoon of septic shock, a system-wide shutdown triggered, the coroner found, by inflammation in Patterson's uterus. the report did not specifically link the drug to the infection.
The American College of Obstetricians and Gynecologists in Washington, D.C., continues to call mifepristone, used in combination with misoprostol, a safe and effective alternative to surgical abortion for very early pregnancy termination. More than a million women in 29 countries have taken the drug since it was introduced in France in 1988; clinical trials in the United States lasted two years and involved 2,121 women; and since the FDA approved the drug in the fall of 2000, about 200,000 American women have used it.
Danco Laboratories, the company that distributes Mifeprex, reports two deaths among those cases: Patterson's and one other due to a ruptured ectopic pregnancy (a danger the drugmaker warns doctors to screen for). Any fatality is reason for concern. But to put the numbers in perspective, there are roughly 12 pregnancy-related deaths per 100,000 live births in this country. And Viagra caused five deaths for every 100,000 prescriptions as of 1999, according to the Journal of the American Medical Association. "Childbirth, abortion or miscarriage can all create conditions that can result in infection," says Danco spokeswoman Health O'Neill. "There is no medical evidence that Mifeprex presents a special risk."
Nevertheless, seven weeks after Patterson's death, U.S. Representative Jim DeMint, a South Caroline Republican with strong antiabortion views, introduced a measure to take the drug off the market for at least six months while the General Accounting Office reviews the process that led to its FDA approval. A similar bill is pending in the Senate. "If there is an error, you ground the fleet and investigate the safety problems," says DeMint's spokesman, John Hart.
Hart says the mifepristone bill would affect only its use in abortions. But suspending the drug's approval could put other patients in jeopardy. Danco, which supplies the drugs for U.S. clinical trials at a discount, has only one product, Mifeprex. If the company couldn't sell the medication, it's hard to see how it could remain in business. And if Danco failed, the drug wouldn't be available in this country. (Foreign companies manufacture mifepristone, but past experience suggests they'd face boycotts if they tried to sell it here.)
Already the political climate has discouraged researchers interested in the drug, says Beth Jordan, M.D., medical director of the Feminist Majority foudnation. "Researchers have trouble getting supplies and funding to study the drug," Dr. Jordan says. "Taking it off the market would prevent leading scientists from conducting research for life-threatening conditions."
Patients like Mulheran hope the drug remains available and that Danco can amass enough evidence to seek FDA approval for other uses. After Mulheran's clinical trial ended, mifepristone's effects lasted six months before her delusionsreturned. Frantic, she tried to get the drug from a clinic, but doctors there couldn't give it to her because of FDA rules. She ended up having electroshock therapy, which she says didn't work as well and affected her memory so much that she couldn't function.
Mulheran now hopes to get mifepristone through the compassionate-use program. Meanwhile, she has e-mailed her representatives to oppose any new restirctions. "If Congress bans this drug," she says, "they're effectively telling people like me that we're not worth helping."