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The combined oral contraception pill (hereafter referred to as the pill or COCP) is often
regarded as one of the most important pharmaceutical innovations of the 20th Century. It is
commonly argued that the pill instigated and/or catalysed the sexual revolution of the 1960s
which brought forth many instances of social equality and liberation (Warsh, 2011). These
include the normalisation of pre-marital sex, lesbian-gay-bisexual-transgender (LGBT) rights
and marriage, and the legalisation of abortion in many countries. These were all large cultural
and societal changes in Western societies such as the United States, Europe and other
European settlements (including Australia) where Judeo-Christian religion was highly
prevalent, and society was constrained by religious (particularly catholic) measures enforced
millennia ago.
The 2011 independent film, The Pill is a light hearted romantic comedy that inadvertently
explores many of the aforementioned themes, such as the importance and prevalence of
COCP in todays society, and how religion can affect peoples attitudes towards forms of
contraception and abortion. After an unprotected one night stand, Fred discovers that his
sexual partner, Mindy, was not on the pill. The film follows Freds struggle of encouraging
Mindy, who is Catholic, to take the second dose of the morning-after pill to avoid an
unwanted pregnancy. In addition to exploring these ideas, the pharmacology of COCP will be
heavily discussed including the pros and cons of such medication, and the significance of the
pill in controlling a sustainable world population and population growth rate.
The pill has a large number of non-contraceptive benefits, such as its social use for family
planning, or pharmacological management of acne. Admiring COCP for its pharmaceutical
effects alone would be a mistake, as its value and its social applications are far more
widespread than as a simple contraceptive measure. The world has a growing population, and
in addition to government intervention and education, the pill has had a phenomenal effect on
reducing the rate of population growth.
Pharmacology
Watkins (2012) writes, Hormonal contraceptionin which synthetic hormones, either
progesterone alone or in combination with estrogen, prevent ovulationwas the truly
innovative contribution made by the Pill. This is what sets the pill apart from other methods
of contraception. COCP is aptly named as it has two components; both progestogen and
oestrogen elements which have independent pharmacodynamics, pharmacokinetics and
contraindications; however work together (often in varying proportions) to provide the best
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pharmacological effects based on both the patients intended use of COCP and their
susceptibility to certain contraindications.
Pharmacodynamics
Progestogens are responsible for the primary contraceptive effects in COCP. The lowest dose
of progestogen which inhibits ovulation is 300mg/day (between cycle days 5 and 25); and
they work via an intricate mechanism that interferes with follicle-stimulating hormone (FSH)
and LH at both hypothalamic and pituitary levels and inhibition of the preovulatory LH peak
which has a direct effect on ovulation (Foran, 2015; Kuhl, 2005). Progestogen decreases
ovarian sensitivity to FSH, decreasing oestradiol production, preventing the ovarian follicle
from maturing (Christin-Maitre, 2013; Foran, 2015). Progestogens also thicken the cervical
mucus, preventing sperm penetration, and limiting sperm viability (Christin-Maitre, 2013).
Oestrogen enhances the above hormonal effects, but its main role is to regulate endometrium
proliferation, and to replace the oestrogen that wouldve been produced if not for the antigonadotropic effects of progestogen (Christin-Maitre, 2013). It is hence oestrogen that is
responsible for the pills effects as a menstrual regulator its first intended marketed use
(as a pill prescribed for the use of oral contraception was still illegal) (Warsh, 2011).
Breakthrough bleeding is a common side effect of COCP which is influenced by the
progestogen component of the pill; the oestrogen component stabilises the endometrium
helping to minimise these side effects (Foran, 2015).
Pharmacokinetics
Ethinylestradiol, the primary oestrogen source of COCP, and progestogens undergo hepatic
metabolism by Cytochrome P450 enzymes in the liver (Life Science Weekly, 2004).
Ethinylestradiol is often administered as the prodrug, mestranol, which is biologically
converted to ethinylestradiol at about 60% efficiency (Foran, 2015). Both drugs are very
effective in small doses, as evidenced by their gradual decreased dose since their synthesis in
1960.
Disadvantages of COCP
There are however several contraindications associated with the use of COCP. The most
significant contraindication is the increased risk of venous thrombosis (VT). The pill can
increase the risk of VT between 3-6 times compared to non-users (Lidegaard, 2013).
Lidegaard (2013) also recognises the increased risk of arterial end points, thrombotic stroke

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and myocardial infection, but highlights that the increased risk of VT is the major
contraindication of the pill (compare that COCP only increases risk of arterial thrombosis
1.5-2 times).
There are several lesser known adverse interactions that COCP can have with patients of a
certain nature, or patients prescribed to other medications. Minor oestrogen associated side
effects include breast tenderness, nausea and fluid retention (Foran, 2015). The broad
spectrum antifungal drug griseofulvin, and broad spectrum antibiotic rifampicin reduce the
efficacy of COCP due to induced hepatic enzyme activity (Weaver & Glasier, 1999) and
hence the two should not be taken simultaneously. There is less evidence about the
interactions between other broad spectrum antibiotics and COCP, however, it suggests that
other contraceptive methods be used for short courses of antibiotics given the serious
consequences of unwanted pregnancy (Weaver & Glasier, 1999). Due to the large number of
uninformed women who take the pill, this is a serious issue, as many women are unaware of
the circumstances that can cause COCP to fail. Doctors and pharmacists alike should strive to
inform women of scenarios, and times when the pill is most likely to fail, and encourage
other forms of contraception to be used alongside it.
Note that the pill was the first, and remains one of very few drugs that are (normally) taken
by otherwise healthy individuals, over a long-term basis. This is an accomplishment in itself.
This communicates that the advantages of COCP heavily outweigh the disadvantages, and
secondly, that it is a relatively safe drug. There are several non-pharmacological methods of
contraception that can supplement or replace (arguably less effectively) the pill. Its continued
use is a testament to its safety. Another indication of the pills commercial and scientific
success is that it is one of the few drugs whose chemical composition remains significantly
unchanged after its initial introduction to the market (Djerassi, 2007). This may simply be
attributed to the fact that the drug already works, and drug discovery and development is an
expensive process (Djerassi, 1989). Nevertheless, it seems feasible to assume that such a
widely used drug with so many applications wouldve been improved had it been a simple
task. Recent research indicates that with better understanding of progestogens and their
mechanisms of action, there may be a better way to better target the endometrium for
purposes of contraception (Lessey, 2003).

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Managing Contraindications
Many of the disadvantages associated with the newer generation progestogens can be
combatted by prescribing progestogen only pills. In fact, these progestogen only pills not
only reduce the general risk of venous thrombosis, but are also safe in women with other risk
factors including tobacco smokers, those with hypertension, hyperlipidaemia, migraine,
adiposity, diabetes, genetic history of thrombotic or hyper-coagulation disorders (Lidegaard,
2013). There are several conflicting studies as to whether or not newer generation
progestogens increase risk of venous thrombosis embolism (Foran, 2015). These progestogen
only formulae however have lower efficacies than COCP and limited tolerance, causing
increased side effects that oestrogen normally regulates (Christin-Maitre, 2013). Ovulation
inhibition is inconsistent, and hence the progestogen only pill mainly relies on the
progestogen effect of thickening the cervical mucus, diminishing sperm penetration (ChristinMaitre, 2013). It is also safe to use the progestogen only pill amongst pregnant or
breastfeeding women (Kapp et al., 2010).
The newer progestogens (third generation), especially in combination with ethinylestradiol
(oestrogen) are able to inhibit conception at lower doses (Lobo & Stanczyk, 1994). Although
lower doses may lead to less adverse effects associated with oestrogen and progestogen, it
must be noted that COCP containing these newer generation progestogens come with an
increased risk of venous thrombosis; at least three times with the second generation
progestogens and more than six times with the third and fourth generation progestogens
(Lidegaard, 2013).
Non-Contraceptive Benefits
There is scientific evidence indicating that oestrogens produce objective regressions of
human breast cancer (Dorfman, 1980). The oestrogen components of COCP also have
beneficial effects on acne, hirsutism and cycle control (Arowojolu et al., Gallo et al., 2012;
2015).
Furthermore, COCP has been shown to decrease the risk of ovarian cancer by up to 50%, and
there is also limited evidence suggesting that it may also decrease risk of endometrial and
colorectal cancers (Guha, 2013).
A 2004 study estimates that over half a million women die each year from child-bearing
complications (Garca, 2004). This issue is especially prominent in countries such as Africa
where health care is limited, and the study notes that much of this unnecessary death would
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be easily circumvented with more access and knowledge to oral contraceptives (Garca,
2004). Not only would COCP prevent unwanted pregnancies, but by circumventing
pregnancies, there would be less child-birth associated deaths. This would save the lives of
mothers around the world, simultaneously improving familial management. By saving the life
of a mother that would otherwise be taken from child-birth complications, the mother is
better able to take care of her other children, greatly improving their childhood health and
education.
Social Effects
COCP has created waves of social reform since 1960. With relevance to the film, it is
understood that much of Mindys reluctance to take the pill was due to her religion.
Christianity the most prevalent religion in America, disagrees with contraception or
abortion in any form. This is for two reasons. Abortion is seen as a form of murder, and it
was Gods will for humans to procreate to directly disobey this is a mortal sin. Djerassi
(2007) comments that no other drug has been able to so swiftly and powerfully change
peoples opinion on a religious view that has previously been strongly reinforced in society.
As Mandy eventually sees reason and takes the pill, many Catholic couples prioritise family
planning and choose to neglect the mortal sin that disagrees with their religion. That is, they
understand the risks associated with unplanned pregnancies and understand that contraception
is more important than this aspect of their religion.
For Fred, an unwanted pregnancy would radically change his life. With the birth of a child
comes the emotional and financial obligations of a father. Although he does not face the same
consequences that a Catholic may (eternal damnation). This is one of the rarer circumstances
where two faiths see eye to eye, and understand the importance of contraception. Ironically,
to best illustrate this point, note that one of the fathers of the pill was a Catholic
gynaecologist, Dr John Rock (Christin-Maitre, 2013).
Recognising that Fred expected Mindy to be on the pill illustrates the social prevalence of
such a drug. It is not a social expectation for a person to be on or open to any other drug on a
regular basis except for maybe alcohol. The pill is taken by over 100 million women
worldwide, accounting for 8.8% of contraceptives (Christin-Maitre, 2013). With
contraceptives to thank, the fertility rate has decreased from 4.7 to 2.6 births between the
early 1970s and late 2000s (Ahmed et al., 2012).

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The path to todays level of equality was no easy feat and we still have a long way to go. For
example, gay marriage is yet to be legalised in Australia, and abortion is still illegal in
countries such as the devoutly Catholic Ireland. Since its realisation, COCP has had a social
and scientific outreach beyond any other drug. Its use amongst healthy individuals, and its
relatively unchanged molecular structure is a testament to its safety and scientific success.
Such a drug revolutionised the sexual revolution, redefined social beliefs, decreases mortality
rates in infants and mothers and has allowed women to become a larger part of the workforce
(Joyce, 2013). The 2011 film, The Pill makes comments on several of these ideas, and
highlight the dichotomy between religious thinking and societys progress towards equality,
relevant to the present sexual revolution, and further illustrates COCPs wide prevalence and
importance in family planning.

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