The New Pill in Town 
NEWSDAY 
By Roni Rabin 
January 25, 2004

Controversial form of birth control delays monthly cycle

The coming-out party for the extended-cycle birth control pill was choreographed as carefully as a wedding.

Pleated pink invitations were mailed out weeks in advance. The event was held in November at a hip Manhattan loft space filled with installation art; black cars idled out front waiting for guests to depart. "Sex and the City" author Candace Bushnell was a guest speaker. As they left, reporters were handed lavender press kits suggesting clever ways to convey the message that monthly periods are, well, so last year.

"What's In? Winter White, and Labradoodles," said one news release. "What's out? A monthly period."

Like other oral contraceptives on the market, Seasonale, the new birth control pill, prevents pregnancy. But the new pill's ability to suppress periods for months at a time is the focus of the sales pitch the manufacturer, Barr Laboratories is emphasizing to women on other contraceptives, those with menstrual disorders and a third group: healthy girls and women who simply want the convenience of fewer periods, even if they're not sexually active.

Seasonale provides hormone pills for 84 days, instead of the traditional 21, followed by a 7-day sugar pill break. The result is four "seasonal" menstrual periods.

"This is for the high school athlete whose heavy periods affect her performance," said Dr. Patricia Sulak, an obstetrician-gynecologist and professor at Texas A&M University System Health Science Center College of Medicine in Temple, Texas, who was paid by Barr to address the media at the kickoff. "It's for the law student who may not be sexually active but doesn't want to have cramps during the test. It is truly a breakthrough."

But a Newsday examination of Barr Laboratories' statements about Seasonale found many of its claims are not supported by the evidence, and that it overstated both the number of women participating in its clinical trial of Seasonale as well as the negative impact that menstruation has on women's lives, self-esteem and achievements.

Barr Labs, based in Pomona, N.Y., and Woodcliff Lake, N.J., has repeatedly said Seasonale was tested on 1,400 women in year-long controlled clinical trials and an extension to the trial. Actually, only 456 of the trial participants were receiving Seasonale and so many dropped out or suffered adverse effects before the trial ended that only 271 were observed for a full year. The other 944 women were either in a study of a different,lower-dose extended-cycle pill or in control groups for comparison. Barr spokeswoman Carol A. Cox said the original numbers were satisfactory.

None of the data from the extension trial have been made public; Barr spokeswoman Carol Cox said the results have not been analyzed yet.

Many advocates for women's health have called for more studies on the long-term safety of Seasonale, even though the U.S. Food and Drug Administration has not required them and approved Seasonale in September.

Dr. Susan Rako, a physician who raised concerns about menstrual suppression in her book "The Blessings of the Curse: No More Periods?" warns that tinkering with the reproductive cycle could have negative, long-term consequences on a woman's health.

"Hormones have an effect on every organ system in the body," Dr. Rako said. "It's reckless for doctors to be passively signing on to something that involves dosing young, healthy, fertile girls and women with hormones that do away with their natural cycle, for no medical reason."

But proponents of menstrual suppression espouse a controversial theory suggesting that decades of monthly periods are a relatively recent historic phenomenon in women's lives, because women in earlier eras were frequently pregnant, breast-fed for long periods and were not well nourished, and therefore menstruated less.

The theory, popular among gynecologists, suggests women in earlier times suffered less from disorders aggravated by normal menstruation, such as anemia, endometriosis and ovarian cancer. "Menstruation is not a normal, healthy thing to happen," said Dr. David Grimes, a researcher with a large nonprofit international health organization, Family Health International, who subscribes to the theory. "In hunter-gatherer societies, women didn't have a period every month."

Critics say women in hunter-gatherer times lived far shorter lives than women today. The non-profit National Women's Health Network said there is no scientific evidence it is healthier to have fewer periods and said it's important Barr "not get ahead of the research and science."

Taking oral contraceptive pills won't restore women to their earlier physiological conditions, said Christine Hitchcock, a researcher at the Center for Menstrual Cycle and Ovulation Research at the University of British Columbia, because the pills increase the level of estrogen; lactating and malnourished women have low estrogen levels.

"There has been natural selection on the menstrual cycle," Hitchcock said. "The idea that we could just guess at how to suppress the menstruation system and there wouldn't be negative consequences is hubris."

Some women's health advocates fear the implications of promoting a product that "cures" women of their monthly periods, saying this harkens back to archaic notions of menstruating women as impure or unclean. Barr's publicity calls periods a costly "nuisance" that makes women feel "messy."

"Are you ready for fewer periods and more possibilities?" asks Seasonale's Web site. And Dr. Anita Nelson, an obstetrician-gynecologist flown to New York by Barr to speak to the media in November, said parents should consider Seasonale for teenage daughters because girls who have their periods score lower on the SATs.

Despite repeated requests, Nelson has not provided evidence to support that statement. An e-mail written by Nelson's husband, LeRoy, claimed that Nelson, a professor at Harbor-UCLA Medical Center in Torrance, Calif., did not refer to SATs at the public forum, and cited as a reference a study that found women's navigational skills in a virtual water maze were diminished during the pre-ovulatory phase of their menstrual cycle, which occurs about a week after menstruation.

"I'm concerned about a marketing ploy that treats a natural part of women's life cycle like a bother, an abnormality that ought to be fixed," said Diana Zuckerman, executive director of the National Center for Policy Research for Women and Families, a nonprofit think tank in Washington, D.C.

Teenage girls uncomfortable about their changing bodies are especially vulnerable to such a message, she said, and critics wonder how their developing bodies may be affected by the pill; those under 18 are generally excluded from contraception studies and were not included in Seasonale trials.

And while many obstetrician-gynecologists interviewed expressed enthusiasm about offering women the option of limiting their periods, medical experts specializing in heart disease and cancer have concerns.

Women on the conventional 28-day-cycle pill face an increased risk of cervical cancer, liver tumors and, in recent users under 35, an increased risk of breast cancer, according to the National Cancer Institute, which also notes they face a decreased risk of ovarian cancer.

There's also a rare but elevated risk of stroke and blood clots to the lung, a complication that can cause sudden death.

Under the new regimen, a woman would be exposed to more hormones than with today's 28-day-cycle pills: According to the Seasonale label, a woman would spend nine more weeks each year ingesting hormones. The new cycle would cover 91 days (84 days of a birth control pill, 7 days off), compared to conventional oral contraceptives (21 days on, 7 days off).

Many physicians, including Rako, believe the natural menstrual cycle plays a role in protecting women of reproductive age from heart disease. Oral contraceptives can raise cholesterol levels, said cardiologist Dr. Nieca Goldberg, a spokeswoman for the American Heart Association. Goldberg recommends screening all women for heart disease risk factors before they go on the pill.

Studies of hundreds of women for one, two or even three years "is not powered to look at things like cardiovascular disease, which you would have to follow for many years," Goldberg said. "That's a real small study."

Seasonale is being marketed for the purpose for which it was approved: contraception, said Carol A. Cox, vice president for investor relations and corporate communications for Barr Laboratories Inc. Despite public comments by physicians paid by Barr and news releases, she said, "That's not how our sales reps go out and talk to physicians. We don't market it for women who don't take it for prevention of pregnancy. What the product's indicated for and how it's promoted by Barr is for the prevention of pregnancy." Cox said Drs. Sulak and Nelson's presentations to the press reflected their own practices with patients and were not dictated or condoned by the company. Dr. Nelson "has her own practice and her own opinions and thoughts." Of Dr. Sulak's recommendation that non-sexually active women should take Seasonale, Cox said, "She may be saying that; that's not supported by our clinical study." To enhance the appeal of Seasonale, however, Barr has funded health provider organizations that promote the theory that monthly periods are unnecessary and possibly detrimental to women's health. One is a national association of doctors and nurses that used a Barr grant to develop a course on extended-cycle contraception for health providers. Barr also created The Coalition for Cycle Freedom, a group of female doctors and nurses who discuss the benefits of menstrual suppression.

More than half of women feel "messy, fat and unattractive" during their periods, Barr says in a news release, citing a survey it commissioned. But the results of the Roper ASW poll, which were provided to Newsday, actually found only 33 percent of women said they felt unattractive during their period.

Many women said they feel "healthy" (68 percent), "normal" (60 percent), "feminine" (54 percent) and "fertile" (47 percent) when they have their period. In the same poll, 74 percent said health concerns might prevent them from suppressing their periods, and a third were worried they would not know if they were pregnant without a regular period. Doctors familiar with Seasonale said women may have to rely on other signs, like nausea, or take a pregnancy test.

Many gynecologists say the traditional 28-day-cycle oral contraceptive is one of the most thoroughly studied medications they prescribe and has a good safety record. And they have long been familiar with the so-called "honeymoon trick," in which women planning a special event take hormone-filled pills continuously, skipping a menstrual period. The strategy is also used to treat menstrual disorders or severe menstrual migraines. It is often recommended for women with a family history of ovarian cancer, because studies have linked the pill to a reduced risk of ovarian cancer.

In a phone interview, Sulak, the doctor from Texas who spoke to the press about Seasonale, emphasized the health benefits of all oral contraceptives. Asked about the risks, she said, "I'm about to go get in my car. Nothing in life is without risk."

But clinical trials on the extended-cycle regimen are limited.

Barr has said in media statements that 1,400 women participated in its controlled clinical trials of Seasonale. But the study had four different subgroups, studying different regimens and control groups. It was coordinated by the Jones Institute, which owns the patent to Seasonale and has licensed Barr to develop and market the drug.

An article about the study, which appeared in the August issue of the journal Contraception, says that of 456 women put on Seasonale, 185, or 40 percent, left before the end of the study. Of the 226 in the control or comparison group of the Seasonale study, who were on Nordette, a 28-day-pill with similar chemical composition which is already on the market, only 28.8 percent, or 65 women, did not complete the full-year trial.

Of the participants taking Seasonale, 68 women, or 15 percent, suffered an adverse effect, compared to 22 women, or 9.7 percent, of the control. Most common were unexpected mid-cycle bleeding, increased weight, mood swings and acne. Ten percent of the Seasonale group - 47 women - quit the trial for unknown reasons, compared to 3 percent, or seven women, of the control. In both the Seasonale group and the comparison, about 15 percent of participants were "lost to follow-up," or "other/unknown," a category that includes women who became pregnant or weren't complying with doctors' instructions.

Four study participants became pregnant on Seasonale, which was calculated as a failure rate of just under 1 percent, in line with or lower than other oral contraceptives. Dr. F. Andy Anderson, the chief investigator of the trial, which was conducted at 48 locations, said there is little or no information about the medical status of many women who left.

But the longer cycle "may pose an additional risk of thrombotic and thromboembolic disease," including stroke and blood clots in the leg that can travel to the lungs and be fatal, but "studies have not found an increase," the package information says.

A 39-year-old on Seasonale suffered a pulmonary embolism, or blood clot that travels to the lungs. She had traveled on an airplane and was overweight, both of which increase the risk, Anderson said, but she was not a smoker, another risk factor.

The extension of the trial is observing more than 300 women on Seasonale, including some who were on different birth control regimens or switched over from the control groups after the first year of the trial, Cox and Anderson said.

Dr. LaMar McGinnis, senior medical consultant at the American Cancer Society, said he was concerned about the small numbers and short duration of the trial, because many cancers are hormonally related.

"People will say this honeymoon trick has been used for years and that's true, but there was no study," McGinnis said. "The lesson we learned with hormone replacement therapy [for postmenopausal women] is that we needed a good long-term study to find out that a therapy we thought was providing protection was actually placing women at risk."

Many physicians and contraception experts have embraced the concept of Seasonale, saying women have enough information to make informed choices. "It's a good option for those women who desire control over their period and who are comfortable using hormones," said Wayne Shields, president and CEO of the Association of Reproductive Health Professionals. "It's all about options."

Others say women should weigh the risks and benefits of oral contraceptives.

"It makes sense for women to take them to prevent pregnancy, because pregnancy has risks," Zuckerman said of the National Center for Policy Research. "But if you're taking this for no other reason than not to get your period, the risks have to be a lot lower. For an Olympic swimmer, it may be understandable. But most of us can live with our periods."

Comparing The Pills

The new birth control pill Seasonale offers some potential advantages over traditional oral contraceptives.

Active Ingredient - Both traditional contraceptive pills and Seasonale contain elements of the hormones estrogen and progestin.

How They Work - Prevent ovulation by suppressing hormones that stimulate ovary to release an egg. May also inhibit implantation of a fertilized egg.

How They're Taken - 21-day cycle, then seven-day pause period or 28-day cycle that includes a seven-day inactive pill / 84-day cycle, then a seven-day inactive pill

Total Annual Menstrual Cycles - About 13 / Four

Possible Side Effects - May include irregular menstrual bleeding, nausea, and mood changes. Increased risk of some cancers. Some women also are prone to blood clots. Can treat acne. / No long-term data. Side effects in clinical trial included mood swings, mid-cycle bleeding, weight gain and acne.

Not Recommended For - Both traditional contraceptive pills and Seasonale should be avoided by women who have had heart attacks or strokes, blood clots and some cancers. Women older than 35 who smoke also should avoid them.