50th Anniversary of the pill – What does this story teach us?

Key words:

• Pill
• Oral contraceptive
• History
• Perception
• Media
• Counselling

Many readers of the Journal have lived and witnessed a fascinating chapter in the history of medicine. The 50th anniversary of the pill is therefore an appropriate occasion to think about the influence this product has had on women at large, society, the medical profession, and daily clinical practice.

The development of the pill: A multidisciplinary effort

First of all, the story of the pill demonstrates that major breakthroughs in medicine are the result of contributions from various disciplines, which then interact with prevailing social, political and cultural conditions.

Ludwig Haberlandt's physiological research in the 1920s laid the grounds for understanding the role of the ovaries. The latter were already known to produce oocytes; it now appeared that ovulation no longer would occur once a pregnancy is established.

The ‘signals’ from the ovary were studied, their nature elucidated, and the molecules concerned or others derived from these finally synthesised by eminent biochemists. Adolf Butenandt isolated oestrone in 1929, for which he received the Nobel Prize in 1939, and Walter Hohlweg and Hans H. Inhoffen developed ethinylestradiol and ethisterone, thus providing the basic ingredients for hormonal contraception.

Another group of eminent ‘fathers and uncles’ of the pill, like Russell E. Marker, Carl Djerassi and F. B. Bolton, among others, followed this line and synthesised steroids that would become components of oral contraceptives (OCs). However, moving from simply having the right components at hand, to being able to use them for birth control was met with great difficulty at first. As is sometimes the case when science confronts society, there were clashes, resistance, controversies, irrational beliefs, ideological positions to deal with, and, in this case, a fight for women's sexual and reproductive rights. In many societies birth control was regarded as a criminal act, against the values of society and against divine will. It took a coalition of eminent feminist women like Margaret Sanger and Katherine McCormack, on the one hand, and biologists, chemists and clinicians (Gregory Pincus, Min-Chueh Chang, Hudson Hoagland, John Rock), on the other hand, to finally make a visionary concept come true. The path was not always straight. Notably, the scientists in 1957 were forced to have the combination of 150 μg mestranol and 10 mg norethynodrel licensed for regulating the cycle and treating menstrual disorders¹,². Only on 11 May 1960, could this combination in a lower dosage (75 μg mestranol and 5 mg norethynodrel) finally be licensed under the trade name Enovid®, as the first birth control pill. Women thus gained control over their reproductive potential by means of a method that was easy to handle, independent of men's control, and discrete.

This success story teaches us that a multidisciplinary approach involving not only sound scientific research, but also advocacy for women's reproductive and sexual rights, is a basic and mandatory condition for making any progress in the domain of women's health. Family planning professionals always have been and will continue to be involved in the political struggles for the recognition and implementation of these rights.

No treatment is devoid of risk

A second lesson the story of the pill teaches us is that there is no ‘free meal’ in any medical intervention; in other words, that there is no benefit without any risk. The first case of a severe complication was reported by Dr W. M. Jordan, a Suffolk family doctor, in a letter to the Lancet in November 1961. A 40-year-old nurse with endometriosis, who had been treated with Enovid®, developed severe vomiting and bilateral pulmonary embolism. A bit later the Royal College of General Practitioners started its oral contraceptive study, which was supported by a grant of £38,000 to investigate prospectively over a five-year period the health risks of the pill³. More studies followed, whose reports indicated that there was an increased relative risk for deep vein thrombosis and thromboembolism in pill users, compared to non-users⁴. However, if expressed as the absolute number of attributable cases, this risk was low (4–8 per 100,000 women per year) and was considered acceptable with respect to the benefit of OCs. These reports were later followed by studies looking into other, possible health risks including myocardial infarction⁵, stroke, breast cancer^6–8, and cervical cancer, which either produced controversial results or showed only a minimal risk increase.

It became clear that establishing a measure of mass prevention by means of a drug – such as a widely distributed hormonal contraceptive – demanded new efforts from the public health sector and epidemiologists.

Here again, we had a lot to learn. First of all, clinicians had to learn how to read studies and interpret statistics, and how to translate their newly acquired knowledge into clinical practice and counselling. The second important lesson to learn was that results of epidemiological studies can be quickly picked up as ‘scientific sensations’ by the media, always prone to publishing bad news. This may lead to mass behavioural changes resulting in new health problems. The several pill scares, brought about by the press, led each time to a sudden and sizeable increase in unwanted pregnancies and abortions. Later studies looking into the health benefits and the preventive potential of the combined hormonal contraceptives (including protection against ovarian and endometrial carcinoma) did not, by far, elicit as much public attention as reports about their health risks. Handling this complicated duality inherent to medical progress is a constant challenge for family planning professionals in their everyday practice.

There is no easy way

The third lesson to learn is that once a therapeutic or preventive action is established, progress is not easy and demands competitive efforts from pharmaceutical companies. While the first Puerto Rican and Mexican trials were simple and cheap, adapting combinations and dosages, developing new hormonal compounds, and exploring other systems of administration, required enormous scientific and financial efforts. The results of these efforts were lower dosages, new progestogens with different profiles, and transdermal and vaginal administration methods. All these efforts widened the choice for women and created the possibility of individualising contraceptive counselling. At the same time, this development was accompanied by increased competition for the contraceptive market. Was one pill safer and better than the other? Is there a best pill?

This again demanded basic science research and epidemiological studies, with possible biases and confounders, leading to progress in our knowledge, but also and again to public controversies (the progestogen controversy) and insecurity among women. Another aspect of this competition was the increase in marketing activities focusing on benefits like beauty, that have caused some critics to claim that the whole field of hormonal contraceptives had become a commercialised life-style business.

This has taught us that access to more contraceptive options is in itself a progress for women, but it must be accompanied by high-quality post-marketing research that continuously generates information regarding use in the population we care for. It is not the randomised controlled trial which will solve this problem, but rather the high-quality field study looking into everyday practice.

Perception of the pill

This brings us to lesson four. The socio-cultural image of the pill is changing continuously: it fluctuates between the ‘biggest revolution in women's health’ to a ‘dangerous and manipulative invention of the pharmaceutical industry’. In the beginning, as mentioned before, the pill was welcomed by feminists worldwide and condemned by the Catholic Church because it would dissociate sexuality from reproduction and thus go against God's word concerning sex. Later, women's organisations became more critical. They started viewing the pill as a commercial and unnatural product, and a source of profit for the pharmaceutical industry; some were inclined to turn towards more natural methods. However, some of the Church-supported international organisations are advocating hormonal contraception as a very important means of improving women's health, especially in developing countries.

These contradictory reactions within society reveal the ‘social’ nature of the pill: it is used in specific socio-cultural contexts and the latter have to be taken into account. We must understand that the pill is, somehow, albeit indirectly, a product with a ‘sexual’ connotation. Sexuality again is a complex phenomenon showing much variability within and between countries and societies This means that contraceptive counselling is not just about providing information on the different methods, their efficacy, the risks and side effects associated with their use, but also about understanding the individual woman, with her sexual and reproductive health needs, her bio-psychosocial profile, and her family planning objectives.

Conclusion

The story of the pill can teach the medical community many lessons. Learning these lessons and applying into practice the knowledge acquired will help in optimising the use of the pill for the greater good of women's sexual and reproductive health⁹.

Declaration of interest: The author is a member of advisory boards of Bayer Health Care, MSD, Johnson and Johnson, and Grünenthal; he has been an invited lecturer for Bayer Health Care, MSD, Janssen-Cilag, and Grünenthal. The author alone is responsible for the content and the writing of this paper.