/ 30 June 2000

A Pill to cure our ills?

The Pill is 40 years old and in that time it has mostly received a bad press because of health risks – we hear less of the benefits. Tania Unsworth celebrates one of the defining inventions of the 20th century

The Pill turns 40 this year, and during the course of its life it has been hailed as many things. A miracle of birth control. A facilitator of women’s independence. A vast medical experiment carried out by men on women. A saviour. A killer. An economic liberator. A device described by the Economist as possibly the single most defining invention of the 20th century, and by others as nothing more than a four- letter word. No other drug has been so examined, caused more enthusiasm, fright and fury. The name itself seems loaded with significance. Singular, mysteriously capitalised: of all the tablets and potions we take, this is the Pill.

Of the 11-million women of reproductive age in the United Kingdom, an estimated three million are on the Pill. To users of the drug, the little rattling packet is as familiar as their toothbrush. A series of innocuous pastel pellets lying in rows or arranged like flower petals around a plastic disc. Sufficiently large to be felt on the tongue, tiny enough to cause a moment of panic if accidentally dropped. Each in its allotted place, marked by the day of the week; charting, by slow degrees, the months and years of a woman’s reproductive life.

Familiar as the Pill is, however, an uneasiness with it remains, a lurking fear that it must carry with it some dangerous catch. But the Pill a woman takes today is not the same as the one her mother took. It is far safer. It also has the power to protect against certain deadly diseases. In ways that the drug’s inventors could not have anticipated, the Pill has benefits that go far beyond simple birth control. Put simply, it can save your life. And the reason it can do this is perhaps one of the greatest medical ironies of the 20th century.

From the start, the very idea of the Pill was troublesome. To give a drug every single day for years to a large, healthy population of young women seemed to go against most people’s notions of how – and why – drugs should be used. The majority of women do not take the Pill to ward off life-threatening disorders, or to alleviate pain, or to control unpleasant symptoms caused by unavoidable disease. They don’t even take it – primarily, at least – simply to avoid pregnancy. The truth is that most women take the Pill because they wish to have sex – without worry and the uncertainty of condoms and diaphragms.

The concept of sex without worry took a serious blow, of course, with the arrival of Aids, but women in monogamous relationships still take the Pill so that they can enjoy a sexual freedom unknown to previous generations. It’s hardly surprising that the drug has always inspired a mixture of love and loathing. Carl Djerassi, the chemist who first synthesised a steroid oral contraceptive in 1951 and who is sometimes described as ”the father” of the Pill, also links our ambivalence towards the drug to the era in which it was first introduced to society: ”In the mid- to late 1960s, the three most important social movements were the women’s movement, the rise of environmental protectionism and consumer advocacy. All were immensely beneficial, but all were, to some extent, suspicious of technology, almost anti-science.”

But although the Pill became one of the symbols of the 1960s, its creation was influenced far more by the cultural concerns of the previous decade. When it was invented, the Pill was designed to be taken in a cycle consisting of three pill-taking weeks, followed by seven ”free” days to allow a woman an episode of bleeding that corresponded to normal menstruation. This is still the method used today. But few Pill-users know that there is no real medical justification for taking it this way. In theory, the drug might have been designed to free women from the obligation of having a period every single month. The decision to create a method of birth control that mimicked women’s normal menstrual cycles was based on a patronising assumption – that women wanted to continue having periods every single month. That it was comforting to them. That there was, in short, a need to bleed.

The idea that menstruation is valuable has a long pedigree. The ”father of medicine”, Hippocrates himself, gave his opinion that it was desirable. Not fully understanding how a woman’s monthly cycle worked, he observed that the onset of menstruation seemed to alleviate the headaches and tension experienced in the days leading up to the release of blood, and therefore concluded it was important. It’s been suggested that the habit of bloodletting for both men and women that dominated the practice of medicine up until the 20th century was inspired by the so- called beneficial effects of menstruation. By the time the Pill came to be created, such beliefs had, of course, been discredited, but the idea that a monthly period was normal and healthy persisted. It also happened to fit nicely with the concerns of one of the Pill’s inventors.

The Pill was developed by a team of scientists, of whom the leading figures were Carl Djerassi, biologist Gregory Pincus, who demonstrated the drug’s efficacy on animals, and Harvard-based gynaecologist John Rock, who conducted the clinical trials on humans. Journalist Malcolm Gladwell, writing in The New Yorker, suggests that the form the Pill took, from the start, was influenced, to a large degree, by Rock’s belief that the drug was a ”natural” form of birth control. The Pill contains synthetic versions of two naturally occurring hormones, pro-gesterone and oestrogen. Under normal circumstances, the levels of these hormones fluctuate throughout a woman’s menstrual cycle, resulting in the release of an egg from the ovary and the growth of the uterine lining in preparation for the fertilised egg. On the Pill, however, the hormones are given in a steadily, preventing ovulation from occurring. To Rock, what was natural about the Pill was that it did not introduce anything into a woman’s body that didn’t already exist there, albeit in a more intermittent fashion.

To many, these arguments over the ”naturalness” of the Pill might seem little more than a matter of semantics. To Rock, however, the question was a critical one because, as an ardent Catholic, he passionately wanted the Catholic Church to approve of his invention (it never has). The decision to create the Pill around a monthly cycle that would mimic a woman’s natural menstrual pattern belonged, in part, to the same impulse. The less disruptive the Pill appeared, the more acceptable to women and the church.

Djerassi, however, downplays the role of the church in the Pill’s genesis. ”Having a monthly cycle was normal and reassuring,” he says. ”To women, regular periods meant not being pregnant. It still does.” There’s another reason, too, why continuing to have monthly bleeding might seem important to women. Periods are associated with fertility, with femininity itself. Girls of 12, 13 or 14, faced with their first period, are commonly reassured by their mothers that it means that they are now ”women”. The (surely unintended) implication being that, once those periods end, the girl will – by some unhappy transformation – be a woman no longer.

Hadine Joffe, a reproductive psychiatrist at Harvard Medical School who specialises in the effects of hormones in the brain, finds that taking the Pill continuously (that is, without the usual monthly breaks) can be beneficial for some patients. These are women with severe mood disorders that worsen around the time of their period and that don’t respond to other treatments. ”The question they ask is: ‘Will I still be fertile when I come off the Pill?”’ says Joffe. ”Women associate a lack of periods with menopause.” Whether the bleeding occurs through natural menstruation or being on the Pill, it remains a potent sign to women that they still have reproductive potential.

But there’s no reason to suppose that, given enough information, many women on the Pill would not prefer to have fewer periods. Although it does lighten monthly bleeding and helps alleviate many of the symptoms of normal menstruation, it does not eliminate them. Patricia Sulak, a medical researcher at Texas A&M University, recently published a paper in the United States journal, Obstetrics And Gynecology, that evaluated the physical cost of monthly bleeding for women on the Pill.

In the dry jargon of academic medicine, the study ”confirmed significant symtomatology during the hormone-free interval, including headaches, pain, breast tenderness, and bloating or swelling”. Add to that the cost of tampons and towels, the loss of working hours from debilitation, and the sheer nuisance of bleeding for one week every month, and one has to wonder why women were denied the option of choosing fewer bleeding intervals when the Pill first came out. Nor why it is not widely known that such an option exists.

It seems that, for all the vast research focused on the Pill, there is still a gap. We know a great deal about the safety of taking the drug in its current three-weeks-on, one-week-off form, but there has been little investigation into how many, or how few, periods of bleeding are actually necessary. Regardless of the discomfort and cost of bleeding every month, such research appears to have been given little priority. Studies have shown that blood lipid levels, as well as certain relevant clotting factors, tend to return to normal during the Pill-free week, suggesting that the safety of the Pill may be enhanced by regular breaks, but whether such breaks are needed every single month is still unknown. John Guillebaud, professor of family planning and reproductive health at University College, London, and author of The Pill (OUP, fifth ed 1997) confirms that the pattern of having 13 breaks a year (the current norm for Pill-takers) is ”amazingly safe, healthwise”, but suggests that fewer might also be safe. ”Tri-cycling – which is three or four packets in a row followed, by the seven- day break – might be a reasonable compromise. It gives just four or five annoying bleeds per year, yet at least some breaks.”

The great irony is that, in the years since the Pill was invented, what used to seem normal and ”natural” is revealing itself to be just the opposite. Rock thought he was maintaining a status quo by allowing women their monthly period. What he did not know was that later research would fundamentally challenge this status quo. For while it is true that modern women are used to menstruating once a month, the same cannot be said of their ancestors. It now appears that far from being natural, constant menstruation is an abnormality in evolutionary terms.

During the 1980s scientist Beverly Strassmann studied the reproductive life of women in the Dogon, an African tribe whose lifestyle had remained largely unchanged since anti-quity. She wanted to form a picture of what women’s biological patterns might have been like before the advent of modernity. What she discovered was that Dogon women spent most of their fertile years either pregnant or breastfeeding, both of which suppressed their ovulation for long periods. As a result, they only experienced, on average, 100 menstrual periods before they reached menopause. By contrast, the average contemporary woman in the West has between 300 and 400 periods.

This phenomenon is relatively recent. Only a few generations ago, it was normal for women to spend much of their reproductive life giving birth to children. But in the West today, the fertilisation of an egg is a far more rare occurrence in an individual’s life. Of the 5E000 eggs present in the ovaries at birth, an estimated 10 are fertilised and, of these, on average, only one, two or three result in a complete pregnancy. The rest of the time, eggs are released through ovulation and discarded. Women’s lifestyles and expectations may have changed, but it’s now thought that our bodies were simply not designed by evolution to handle such frequent ovulation.

A growing number of experts in contraception is now questioning whether continuous menstruation is necessary or even advisable. ”It is simplicity itself to eliminate menstruation with safe, inexpensive and widely used oral contraceptive tablets,” states a recent essay by Sarah Thomas and Charlotte Ellertson in The Lancet. ”Yet monthly menses continue to be the standard for women. Why?” Contraception researchers Elsimar Coutinho and Sheldon Segal, both leaders in their field, make a bold argument for doing away with constant menstruation altogether in their book, Is Menstruation Obsolete? (OUP, 1999). ”Recurrent menstruation is unnecessary,” they say, ”and can be harmful to the health of women. It is a needless loss of blood.”

Because the Pill suppresses ovulation, it reduces the number of menstrual episodes in a woman’s life. The joke is that, although it was designed to maintain monthly bleeding (without ovulation) for the sake of perceived ”normality”, the drug is, in fact, only normal – in evolutionary terms, at least – for it represses true menstruation. It could be argued, therefore, that, in some ways, being on the Pill is more natural than the constant menstruation experienced by modern women who do not take the drug. And not ovulating all the time carries some important health benefits.

The division and reproduction of cells necessitated by ovulation and the growth of a woman’s uterine lining increases the risk of ovarian and womb cancers. By lessening the frequency of that cell activity, the Pill increases a women’s chances of avoiding these diseases. The advantages are significant. A woman who takes the Pill for 10 years reduces her risk of getting cancer of the womb by about 60% and her risk of ovarian cancer by around 70%. These benefits of the Pill have been known about for decades, but they remain among the most unsung of the drug’s side-effects.

Meanwhile, health scares surrounding the Pill continue to make headlines. When the drug first came out, concerns over its safety proved justified. Serious and even fatal complications occurred among users, prompting more research. Since then, hormone doses in the Pill have been drastically reduced. Today, there is only one hundredth the amount of oestrogen that was in the original. Other modifications have added to its safety. During the 1980s a triphasic version of the drug was introduced, providing three different levels of hormone to be taken over the course of a month and corresponding more closely to a woman’s natural cycle. Despite the safety of the new Pill, however, fears persist.

In the mid-1990s a link was suggested between the third-generation Pill and deep-vein thrombosis. Much was made of the fact that women taking this version had double the chances of death over users of the second-generation Pill. ”In 1995, a lot of women were frightened enough to stop taking the Pill altogether,” says Sheila Hancock, a nurse who has been working in family planning since 1977. ”We saw more unwanted pregnancies and more abortions. We stopped using the third-generation pills for a while, and then the GMC okayed them again.”

A doubling of risk sounds terrifying enough, but what was the actual number of deaths being doubled? On the safer Pill, there were two deaths per million women a year. On the third-generation version, four deaths per million. ”Anybody who drives on the roads for a single hour a year increases their risk of death to one in a million,” claims Professor Guillebaud. ”The difference in risk between the two brands of Pill is the same as going from two hours of driving a year to four.”

Recently, a suggested link between the Pill and breast cancer has been causing debate, and here the risks appear less clear-cut. At the moment, there’s no hard evidence that the drug definitely increases a woman’s chances of developing the disease. But it might. ”The bottom line,” says Guillebaud, ”is that the Pill appears to be a weak co-factor in breast cancer. It’s probably not the cause. If someone has early cancerous changes to the breast, the Pill can move it along.”

The good news is that, once you stop taking the Pill, your risk for breast cancer is unaffected by your former use of the drug. ”Ten years after taking the Pill, your risk goes back to what it would have been had you never taken it,” says Guillebaud. He also points out that the time most women take the Pill – during their 20s and early 30s – are the years in which breast cancer is least likely to occur in a woman’s life. ”Think of a room of 1E000 women,” he says. ”All of them took the Pill for 20 years. Now aged 45, they are all ex-users who have not used the drug for 10 years. Eleven women in that room will have breast cancer. In a room of 1E000 women who have never taken the Pill, 10 will have breast cancer.”

Although there may be a small increased risk of breast cancer associated with the drug, it is offset by the Pill’s protection against different forms of cancer. So, in the lottery of cancer as a whole, Pill users may not be any better – or worse – off than anybody else.

No one is denying that there are drawbacks to the Pill. Side-effects include an increased risk of blood clots, stroke and heart attack, and it can cause headaches, depression, nausea and skin problems. But all drugs have the potential for bad side-effects. Djerassi tells the story of a talk he once gave, in which he described the risks associated with a certain unnamed medication. This drug, he said, sometimes caused gastro-intestinal distress, bleeding in the stomach and, very occasionally, a life-threatening allergic reaction. Given all this information, he asked his audience, would you still take the drug? They said they would have to think carefully before taking the medication. Their need for the drug would have to be high enough to merit such a risk. The name of the offending substance? Aspirin.

”People want the ideal contraceptive,” states Djerassi. ”They want something 100% safe without any side-effects. Well, there’s no such thing. It’s simply not universally possible.”

So why, after four decades of its use, is the Pill still demonised? Why do the fears persist out of all proportion to actual risk? ”When I’m counselling women about whether they should take the Pill,” says Hancock, ”my goal is to give them all the information to date and let them decide. But most of the women I see have far more knowledge about the negative aspects of the drug. Very few know about the cancer benefits. I do wonder sometimes about why we go on having these terrible scares. Perhaps society as a whole is saying, ‘Oh no, the Pill, that’s naughty …”’

”It’s to do with sex,” agrees Guillebaud. ”We’re in the 21st century, but people still have hang-ups. They can’t believe nature won’t bite back in some way. Besides, only the bad news seems to make headlines.”

Will we ever be able to look at the Pill squarely, with true objectivity? The question might one day become quite unimportant. In a future of technology- driven reproduction, where human beings are no longer created in bedrooms and the backseats of cars, but in the carefully controlled environment of the petri dish, current methods of birth control may come to seem quaintly old-fashioned. If that time comes, the Pill will come out of tens of millions of handbags and bathroom cabinets and find a new home: a coyly packaged curiosity in a museum of the 20th century.

Perhaps it’s appropriate that the man who had the first word on the Pill should be allowed the last. ”The Pill was the first step,” says Carl Djerassi. ”It made sex without pregnancy possible. The next step will be to have pregnancy without sex. And when that happens, the Pill will be irrelevant.”