The Ills of the Pill:

Issues with the Approval of the Oral Contraceptive

Benjamin Smith

HIST 2900

December 15, 2020

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The birth of the oral contraceptive pill came from the desire to solve problems. Overpopulation,

a desire for simpler methods of contraception, and wanting to put contraception in the hands of women

were among the many problems that the contraceptive pill was set to solve. However, the pill may have

caused more problems than it fixed. Today, around 14 percent of women in the United States are

currently on the pill knowing full well of the side effects that come with it. 1 Use of the oral contraceptive

pill is often accompanied by nausea, severe headaches, depression, weight loss and weight gain, among

other side effects.2 For those that take the pill, the benefits seem to outweigh the negatives. However,

when the pill was first approved in the United States and in England as a contraceptive, the side effects

were much worse than they are now. The early contraceptive pill was not tested for long enough or on a

wide enough scale to be considered a safe contraceptive. The approval was done too hastily and with

too little data and thus resulted in numerous cases of thrombosis, cancer, and death in extreme cases. 3

Had the pill been tested for longer and been proven safe before being approved to be prescribed as a

contraceptive, it would have saved countless women from suffering the brutal side-effects that it

originally caused.

The advertised purpose of the pill had not always been for contraception. In the 50s, the pill was

advertised in medical journals to treat a variety of illnesses, most of them regarding menstrual

disorders.4 Even then the contraceptive properties of the pill were known to the public, but women

were unable to get prescribed the pill as an oral contraceptive until 1960. 5

1
Kimberly Daniels and Joyce Abma, “Current Contraceptive Status Among Women Aged 15–49: United States,
2017–2019,” Centers for Disease Control and Prevention. National Center for Health Statistics,
https://www.cdc.gov/nchs/products/databriefs/db388.htm (October 20, 2020)
2
Akshara Shulka, Rohitash Jamwal, and Kumud Bala, “Adverse Effects of Combined Oral Contraceptive Pills,” Asian
Journal of Pharmaceutical and Clinical Research 10 No. 1 (2017): 17
3
Lara Marks, Sexual Chemistry: A History of the Contraceptive Pill (New Haven, CT: Yale University Press, 2010),
127.
4
Marks, 5
5
Sophie Christin-Maitre, “History of Oral Contraceptive Drugs and Their Use Worldwide,” Best Practice & Research
Clinical Endocrinology & Metabolism 27, No. 1 (2013): 3
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The earliest testing of using the hormone progesterone in an attempt to suppress ovulation,

which was done on animals, began in 1951 in the United States. 6 Once it was clear that these

experimental hormones could effectively inhibit ovulation in women, it was known that it could be used

in some way as a contraceptive, and small-scale testing could begin.

The first small-scale trials began in 1953 testing multiple different compounds of the combined

oral contraceptive pill on women in Massachusetts. 7 The trials involved administering progesterone to

inhibit ovulation. These trials involved only 60 women, a fracture of which had provided the accurate

data they were supposed to contribute. This is because the trials required women to administer

themselves the progesterone, whether it be orally, through injection, or through a vaginal suppository,

collect their own urine samples to test the hormone balance, take their body temperature, and have

monthly endometrial biopsies, among other things. 7 Due to the low number of women in the trial and

the even lower number of women who carried out the trial in the intended way, the results of these

early trials were far from providing a definite result.

As time went on, to come up with any sort of conclusive results that would allow the pill to be

approved as a contraceptive, more large-scale trials needed to be done. For this, Puerto Rico was chosen

for several reasons. There were no contraceptive laws in Puerto Rico at the time, the island was close to

the United States, and the island had a fairly stable population. 8 Even in early large-scale trials, however,

only a handful of women could adhere to the medical examinations and tests that were expected of

them. For the Rio Piedras trials in Puerto Rico, they had only been able to collect urine samples from 42

women and had only been able to collect blood samples from 39. 9

6
Marks, 91.
7
Marks, 96.
8
Marks, 101.
9
Marks, 108.
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These trials had less than desirable results. Initially, the pills that were administered during the

Puerto Rico trials were surprisingly well tolerated. However, within the first few months, women

reported nausea, headaches, and dizziness. This resulted in as many as 17 percent of those in the Rio

Piedras trials in Puerto Rico experimenting with the pill to leave the trials early. 10 In other places where

trials had been setup in the late 1950s, such as in Mexico City and in Los Angeles, there was a similar

trend with women discontinuing their participation in the trials. Mexico City averaged a 10 to 30 percent

dropout rate, and Los Angles had a 66 percent dropout rate, with at least 37 percent of those women

leaving due to the unpleasant side-effects of the pill. 9

In the United States during this time, many drugs were approved despite having many adverse

side effects, even if fatal.11 In the case of the pill, it seemed that the Food and Drug Administration, or

the FDA, was more concerned with whether the pill functioned according to its purpose, that is

inhibiting ovulation and preventing pregnancy, rather than making sure that the pill was completely

safe. For instance, the original approval submitted for Enovid, the first prescription of the pill in the

United States, to be used as an oral contraceptive only cited data from 897 women who were on trial for

the pill, and only 132 of them had taken the pill for over a year. 10 This raised a problem in that the time

frame that most women took the pill was not nearly enough time to test the pill’s potential of harmful

side effects. For instance, one of the most known side effects of the early pill, thrombosis, usually takes

longer than 12 months to appear.12 The side-effects and their severity are dependent on a variety of

factors, including the chemical composition and hormone balance of each pill, the length of time the pill

is taken, and susceptibility of each woman taking the pill, among others. This means that trials lasting

several years are necessary to establish the safety and effect of each oral contraceptive pill. 13

10
Marks, 105.
11
Marks, 110.
12
Ellen Grant, The Bitter Pill: How Safe is the ’Perfect Contraceptive’?, (London: Elm Tree, 1985), 33.
13
Ellen Grant, “Venous Effects of Oral Contraceptives,” British Medical Journal 4, No. 5675 (1969): 79.
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On the contrary, the pill was being tested in a time when rules and regulations on drugs were

not very strict. In 1962, controversies surrounding the drug thalidomide caused there to be more

rigorous testing and stricter guidelines when approving a drug in the United States and elsewhere. 14

Since the first oral contraceptive was approved a few years earlier, these rules and regulations were not

yet in place. While the pill was met with much controversy regarding inadequate testing, the trials and

approval of the pill was still on-par or even exceeded the testing of most drugs at the time. 13

One of the first adverse side effects of the pill to be widely known to the public was the

potential for venous thrombosis, also known as blood clots. Not only did the pill cause the platelets in

the blood to be abnormally sticky, causing the blood to clot, but the pill also decreased antithrombin III,

a protein in the blood that prevents blood clotting. 15 Changes in the artery wall had also been seen in

those that were taking the pill, indicating changes in blood flow that can result in thrombosis. Changes in

blood pressure due to taking the pill that can lead to hardening of the arteries and kidney damage was

also observed.16 A 1968 study found that the likelihood of admissions into the hospital for venous

thrombosis was nine times greater in those that are taking the pill than those who were not. 17

The pill also made users experience changes in their mood. Due to dramatic changes in hormone

levels, many pill users experienced depression and loss of libido, among other negative side-effects after

taking the pill.18 This was evident in the earliest trials of the pill in London when, despite success in

preventing pregnancies, many of the pill users were complaining of migraines, depression, and loss of

libido, among other symptoms.19 A 1968 Oxford and Family Planning Association study also showed pill

14
Marks, 4.
15
Grant, The Bitter Pill, 29.
16
Grant, The Bitter Pill, 32.
17
Grant, “Venous Effects of Oral Contraceptives,” 73.
18
Grant, The Bitter Pill, 37.
19
Grant, The Bitter Pill, 23.
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users to be four times more likely to admitted into the hospital for attempted suicide than users of the

diaphragm, a mechanical form of contraception. 20

One initial thought that the researchers had when confronted with some side-effects of the pill,

such as nausea, headaches, and depression, was that the women in the trials could be feeling those

symptoms simply because those were the questions that the social workers examining the trials were

asking. Oftentimes, doctors would not even ask questions regarding these symptoms because they did

not want to influence the women in the trial to imagine ‘neurotic’ symptoms. 21 This resulted in

inconsistent reporting and dismissal of related symptoms during the early trials.

Another issue with the safety and approval of the pill regarded the dosage given in the first

version of the pill prescribed in the United States. Although at the time of the pill’s approval lower doses

of the pill were proven to be more safe and just as effective, the pharmaceutical company that

developed Enovid still had to get approval for the 10mg version of the pill before they could get

approval for any lower dosage versions.10 Although later studies showed that the changes in

formulations of the pill did not have much effect on things like the risk of breast cancer, 22 studies by The

Committee on Safety of Drugs showed that the higher dosed pills were more likely to cause other side-

effects, such as thrombosis.15

In her 1985 book on the safety of oral contraceptives, Dr. Ellen Grant, who had worked closely

with the initial London trials of the pill, wrote this about the early trials:

We found repeatedly that varying either the dose of progestogen or oestrogen changed the

women’s symptoms from breakthrough bleeding to vein effects, to arterial effects like headache

and high blood pressure, to weight gain, to depression. So-called ‘neurotic’ symptoms like

20
Grant, The Bitter Pill, 36.
21
Grant, The Bitter Pill, 22.
22
Ralph Paffenbarger et al., “Cancer Risk as Related to Use of Oral Contraceptives during Fertile Years,” Cancer 39,
No. 4. (1977): 1889.
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tiredness, anxiety and irritability were most marked with the mid range pills which had a higher

balance of oestrogen. All pills were producing numerous side-effects sooner or later. The results

of our London Trials, it seemed to me, were that high doses caused a wide range of side-effects

while low doses caused as many pregnancies as mechanical methods of contraception. 23

What this shows is that the early trials of the pill had many tribulations. It seems that, at the

time, no pill that they had developed yet was ‘safe’. While some of the pills conjured some side-effects,

the pills created to combat these side-effects would just produce different side-effects. Dr. Grant

claiming that all pills were producing numerous side-effects shows that approval at this stage was not a

smart decision if the health of those taking the pill was the main priority.

Another evident side effect with taking certain formulations of the pill is fluctuations in weight.

When taking the pill, the changes in hormones in the body can interfere with normal functions of

thyroid activity and metabolism.24 Because of this, many women on the pill experience drastic changes

in weight. This effect depends on the individual as well as the formulation of the pill, but women on the

pill often experienced rapid weight gain, gradual weight gain, or complete loss of appetite, resulting in

weight loss.23

Potentially one of the most serious and well-known side effects discussed with use of the pill is

the increase in risk of cancer. Although the issue seems to be widely contested, many studies have

shown an increase in the risk of cancer in pill users. This was not as evident in earlier trials of the pill

because the cancer risk seems to increase the longer a woman is taking the pill. 25 In the early London

trials for the pill, of the first 200 women to be enrolled, only one instance of breast cancer was

developed.25 This could very well have been unrelated to taking the pill, however later studies of women

taking the pill for longer periods of time produced far more troubling results. For instance, in 1968, two
23
Grant, The Bitter Pill, 48.
24
Grant, The Bitter Pill, 50.
25
Grant, The Bitter Pill, 92.
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American studies in World Medicine showed evidence of higher numbers of cervical cancer in those

taking the pill, and one study by a Professor Weid estimated a six-times increase in risk for those that

had been taking the pill for five years or more. 26 A 1977 study found a significant risk in cases of breast

cancer for those taking the pill for 2 to 4 years, however showed little to no increase in risk for time

periods shorter than 2 years.27 Furthermore, contrary to the two studies in World Medicine, the study

found no increase in risk for former pill users when compared to non-users. Assessing cancer risk is not

always easy due to the fact that cancer usually takes years to develop, and a time span as short as 15 or

20 years may not be enough time to accurately assess the risk of cancer. 28

Prior to the 1960s, contraception was a very delicate topic that was not often discussed. Many

doctors opposed the use of contraception and many doctors were not well educated on the subject. For

example, a 1957 survey in England indicated that less than half of medical graduates had received

teaching on contraception.29 Contraception was taught better and was more widely accepted in

America, however many American medical professionals still did not favor having doctors concern

themselves with contraception. This caused much uncertainty in the medical field regarding prescribing

the pill in the 1950s and 1960s.

The approval of the pill as a contraceptive was a huge step for medicine, feminism, and sexual

freedom, however the approval process was done too hastily and was based on insufficient data for the

pill to be considered a safe alternative to other forms of contraception. Had the pill been administered

responsibly and only to treat menstrual disorders until a safer version was developed for widespread

use, fewer women would have suffered the side effects of thrombosis, breast and cervical cancers, and

26
Grant, The Bitter Pill, 93.
27
Paffenbarger, 1890.
28
Paffenbarger, 1887.
29
Marks, 119.
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fatality. Furthermore, how much time must be given and how few side-effects must there be before the

pill is considered ‘safe’? This seemed impossible to determine at the time and still is.

Since the pill was approved so quickly, the responsibility for determining the safety of the oral

contraceptive then rested on the shoulders of the doctors administering the pill and with the women

requesting it. This was made more difficult due to both a lack of knowledge and a lack of testing. In the

past, both doctors and patients were unable to accurately assess the risks involved with taking the pill.

Women deserved a safe and effective form of contraception without the necessity of putting their

health at risk to obtain it. Unfortunately, that is exactly what happened and the women subject to the

early pill paid dearly for it.

Bibliography
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Christin-Maitre, Sophie. “History of Oral Contraceptive Drugs and Their Use Worldwide.” Best Practice &
Research Clinical Endocrinology & Metabolism 27, no. 1 (2013): 3–
12. https://doi.org/10.1016/j.beem.2012.11.004. 

Daniels, Kimberly, and Joyce Abma. “Current Contraceptive Status Among Women Aged 15–49: United
States, 2017–2019.” Centers for Disease Control and Prevention. National Center for Health
Statistics, October 20, 2020. https://www.cdc.gov/nchs/products/databriefs/db388.htm. 

Grant, Ellen. The Bitter Pill: How Safe Is The 'Perfect Contraceptive'? London: Elm Tree, 1985. 

Grant, Ellen C. G. “Venous Effects of Oral Contraceptives.” British Medical Journal 4, no. 5675 (1969):
73–77. https://doi.org/10.1136/bmj.4.5675.73. 

Marks, Lara. Sexual Chemistry:  A  History of the Contraceptive Pill. New Haven, CT: Yale University Press,
2010. 

Paffenbarger, Ralph S, Elfriede Fasal, Martha E Simmons, and James B Kampert. “Cancer Risk as Related
to Use of Oral Contraceptives during Fertile Years.” Cancer 39, no. S4 (April 1977): 1887–
91. https://doi.org/10.1002/1097-0142(197704)39:4+<1887::aid-cncr2820390822>3.0.co;2-i. 

Shukla, Akshara, Rohitash Jamwal, and Kumud Bala. “Adverse Effect of Combined Oral Contraceptive

Pills.” Asian Journal of Pharmaceutical and Clinical Research 10, no. 1 (2017):
17. https://doi.org/10.22159/ajpcr.2017.v10i1.14565.