The Pill. The universal nickname says much about the place of oral contraceptives in our society.
Introduced 20 years ago, oral contraceptives or "birth control pills" have been used by an estimated 150 million women around the world. Their impact on sex, families and population control has been immeasurable. Yet their safety is still an open question.
"It's a very difficult public health problem," said Dr. Heinz Berendes, director of epidemiology and biometry at the National Institute know any comparable example in mankind -- or peoplekind -- of millions of healthy people using an agent where the safety isn't assured."
The federal government is about to publish a major study that was designed to define the pill's effect on women's health -- especially its influence on the risk of heart attack, stroke, blood clots, cancer and other serious illnesses. The $8.5-million study was conducted by a medical team in Walnut Creek, Calif., that recorded and analyzed the health of more than 16,000 women over 12 years.
The study's overall findings were widely publicized last fall as proving the pill's health hazards to be "negligible." The report contradicted other research by concluding that healthy women did not raise their risk of getting these diseases, or of dying from any cause, by taking the pill.
But some experts on contraception who have reviewed the study say it failed to find many of the serious side effects reported elsewhere -- not because they don't exist, but because the project was not designed to find them. It contained too many women who had stopped using the pill, the critics say, and not enough who were actually taking it while they were being studied.
Despite the years and dollars poured into this study and others, scientists still do not know the overall danger of taking the pill at different ages, or whether past use has consequences later in life. If anything, the questions loom larger than ever.
According to a number of scientists familiar with research on oral contraceptives, there no longer is any doubt that the pill's side efects include potentailly fatal diseases: heart attacks, strokes, blood clots, brain hemorrages. Its relation to cancer is more confusing. The pill apparently raises a woman's risk of getting some kinds of cancer, but may lower her risk for other kinds -- and it will be years before its real impact on cancer is certain.
For all these illnesses, the hazards of the pill are weighted by other aspects of a woman's behavior, including smoking, sex and even sunbathing.
Answering questions about the pill's safety is a long, hard process. It is made harder by the fact that both the pill and the women who take it have changed continuously over the two decades since its introduction -- often in response to news to newly discovered side effects.
Few scientific issues are more emotionally loaded than birth control. "Positions are more ridgidly held than in most areas of research," said one scientist at the National Institutes of Health. Many researchers charged with evaluating the pill, he said, have " . . . a strong emotional commitment, that this [the pill] is an enormously good thing." On the other side are scientists "who set out to find things wrong with the pill -- and they find them. One has to be suspicious of both sides."
Pill manufacturers contend that the side effects of birth control pills must be weighed against their benefits, which include the medical, social and economic advantages of preventing unwanted pregnancies and controlling the size of families.
"Taking the pill is safer than having babies," said a spokesman for G.D. Searle and Co., one of the biggest pill manufacturers and the first company to market an oral contraceptive. "The risks involved with taking the pill are clearly identified on the patient package insert."
"We can do all the research . . . butthe final analysis is up to a woman and her own physician as to whether the risks are greater than the benefits," he said. "There's no flat answer for every woman, which is why we offer other forms of contraception."
"Here is what scientists have learned about the pill's major side effects, and some of the questions that still concern them: HEART ATTACKS
Dr. Howard W. Ory, chief epidemilogist at the Centers for Disease Control's family planning division, has estimated that 310 American women die each year from heart attacks, strokes or blood clots, which would not have occured if they had not been on birth control pills.
A recent study of American nurses found that those on the pill were three times as likely to be hospitalized with a heart attack as those who were not on the pill and had no other risk factors. But a woman's individual risk depends strongly on her age, on whether she smokes, and on other factors that contribute to heart disease.
One British study of the pill's effects when combined with other risk factors -- smoking, high blood pressure, diabetes, and high fat content in the blood -- found that pill-takers who had two of the other risk factors had 128 times as high a risk of a heart attack as women who had none of the risk factors, including using thepill.
While a woman takes the pill, her chances of a heart attack are raised no matter what her age. Because heart disease is so rare in young women, the chances remain very low until age 30, but they rise rapidly from then on.
Dr. Martin Vessey, a British public health expert who has done landmark research on pill risks, believes that oral contraceptives are "remarkably safe and effective" for younger women, but that after 35 the dangers become too great. Many American authorities use 30 as a cutoff age.
"In very young women, under 20, it probably doesn't matter what they do -- thier risk of having a heart attack is so small," said Dr. Bruce Stadel, a medical officer in the contraceptive evaluation branch at the Center for Population Research. But he added that in any woman who smokes or has other risk factors, "You worry about it."
Until recently scientists believed the pill heightened the danger of a heart attack only while the woman was on it. But there is now troubling evidence from two studies that the risk remains heightened after a woman stops taking it, for as long as 10 years.
"If there is an effect of long-term pill use that persists, then we've got a problem that goes beyond what we currently see," Stadel said. BLOOD CLOTS, STROKES
Blood clots in leg veins were one of the first serious hazards of pill use to be recognized. They can be fatal if a piece of the clot breaks off and travels to the lung (a pulmonary embolism), and clots can also form in the brain or travel there, causing strokes.
In a review of research on the pill's contribution to these diseases, Vessey cited a number of studies that found that blood clots were from 2 to 8 times as likely to occur in women taking the pill, and that strokes were 6 to 26 times as likely. Stroke risk is higher in women who smoke or have high blood pressure. Like heart attacks, these hazards increase with age, but they sometimes occur in younger women.
For years these complications have been blamed exclusively on estrogen, one of the two hormones present in the pill, which makes blood clot more easily. Manufacturers have repeatedly reformulated pills no lower the amount of estrogen they contain.
But scientists are now deeply concerned by the discovery that progestogen, the other hormone in the pill, also has actions that could contribute to heart attacks, blood clots and strokes. It raises blood pressure and lowers high-density lipoprotein (HDL), a blood fat thought to protect against heart disease and blood vessel damage.
Berendes said these findings are prompting a new look at the formulas of all birth control pills now on the market. "We had primarily thought that pill complications were related to estrogen," he said. "This opens up new questions about the mechanism." Cancer
"Cancer, to my way of thinking, is still the big unknown about the pill," Berendes said. He added that although most studies of cancer and the pill have been reassuring so far, cancer "is a disease which we know usually does not occur until many years after exposure to a carcinogen."
"We do have enough data to be clear that there is not a large, overall, immediate effect of oral contrtaceptives on breat cancer," Stadel said. He said most studies have revealed no increase in breast cancer among pill-users. But one found a higher rate of breast cancer in women with benign breast disease who used the pill for six or more years, and in those who took it before the birth of their first child.
Scientists now believe breast cancer takes so long to develop that the 10 to 12 years that have elapsed since large-scale studies of pill-users began may not be long enough to show any influence of the pill on the disease.
If taking the pill as a young woman triggers breast cancer later in life, it could take another decade for a higher cancer rate to appear. "The asbestos effects [on lung cancer] didn't show until you cut the data at 25 years," said Dr. Nicholas Wright, who until Jan. 1 headed the contraceptive evaluation branch at the institute.
The federally sponsored study and several others indicate that the pill may somewhat lower a woman's chances of developing cancer of the ovary or endometrium (the lining of the womb), perhaps because it alters the feedback system of hormones circulating between these organs and the pituitary gland. But the protection is so slight that there is no validity to the argument that it might offset the pill's risks, according to Dr. Philip Coffman, director of the Center for Population Research.
A number of researchers have discovered a higher rate of early cancer and precancerous changes of the cervix (the mouth of the womb) among pill-users. Part of the increase may be caused by the fact that women on the pill are usually more sexually active than those who are not. Cervical cancer behaves much like a veneral disease, increasing in proportion to the number of men with whom a woman has sex. But Vessey, the British researcher, said he believes sexual behavior does not entirely account for the finding, indicating the pill itself may be playing a roll.
The federal study's most startling discovery, according to Berendes, was that pill-users had a significantly increased chance of developing melanoma, a dangerous form of skin cancer. "When we saw this we were concerned," Berendes said.
Since sun exposure is a major risk factor for the disease, the researchers theorized that pill-users might sunbathe more than other women. But other research, being conducted to determine whether the pill promotes cancer by heightening skin cells' sun sensitivity, has not been completed. Other Side Effects
A number of other diseases show an increase among users of the pill. High blood pressure is a side effect that becomes more significant the longer a woman takes oral contraceptives, although blood pressure appears to return to normal once she stops. Many researchers found more urinary infections, more gall bladder disease, and more vaginal infections among pill-users, and some have found an increase in headache, skin problems and hay fever.
Depression is more common among women who are on the pill than in those who are not, according to many researchers. Although some argue this is because women who take birth control pills either are more unstable or more likely to consider depression a side effect of their medicine, two studies have found that pill-users also have a higher rate of suicide and self-poisoning.
Despite concern that women might impair their later fertility by taking the pill, research so far has shown only that a woman may experience a few months' delay in getting pregnant after she goes off oral contraceptives. However, because there is evidence that women with a history of irregular menstrual periods may have more trouble with their periods after taking the pill, many doctors advise such women to avoid it. Overall Risk
These who make health policy on birth control often compare the death rate among pill-users to that of women who use other contraceptives, or no birth control. Besides considering side effects, the death rate for each method includes a woman's risk of dying during pregnancy or childbirth if her contraceptive fails.
Thus, a recent article in Family Planning Perspectives concluded: "The risk to live among pill-users under age 30 who do not smoke is very small and is virtually the same as that among users of the IUD, diaphragm or condom . . . "
But such estimates assume that the IUD will fail to prevent pregnancy twice as often as the pill, and the condom or diaphragm will fail five to seven times as often, even though the authors note that couples who use these methods correctly and consistently will not have such a high failure rate. They also do not consider nonfatal but disabling hazards such as stroke, or less serious side effects that can still affect daily life. Much more important to the decision whether to use the pill is a woman's past health history and habits.
The validity of information on the pill is limited by the fact that the age and other characteristics of women taking it now are vastly different from those of the women who scientists have studied. For instance, 70 percent of the women in the federal study were 30 or older in 1968, when the project began. But since the mid-1970s, when pill use in the United States was at its peak and the risk of heart attack was first reported, use patterns shifted so that now few pill-users are over 30, and many are in their teens. Virtually nothing is known about the pill's long-term effects on women who first take it as teen-agers.
Wright said that in deciding whether to take birth control pills, a woman should invoke the same rule he follows for medications in general. "If you don't need a drug," he said, "don't take it."