Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 3–12

Contents lists available at SciVerse ScienceDirect

Best Practice & Research Clinical

Endocrinology & Metabolism
journal homepage: www.elsevier.com/locate/beem

History of oral contraceptive drugs and their

use worldwide
Sophie Christin-Maitre, MD, PhD, Professor a, b, *
a
Department of Endocrinology, AP-HP, Hospital Saint-Antoine, University Pierre et Marie Curie, Paris VI, France
b
Inserm U 933, Paris, France

Keywords:
The first hormonal pill, called EnovidÒ, was approved by the
hormonal contraceptives Federal Drug Administration (FDA) in May 1960. It contained
oral contraceptive drugs mestranol and norethisterone. Over the years, oral contraceptives
combined oral contraceptive have evolved through gradual lowering of ethinyl estradiol (EE)
vaginal ring content, introduction of 17b estradiol, and many different
implants progestins. The standard regimen allows for 21 days of pill con-
microprogestins taining steroids and a pill-free interval of 7 days. Recently,
continuous or extended regimens have been approved. In order to
improve compliance, alternative routes of combined oral contra-
ceptive (COC) administration have been developed such as vaginal
or transdermal routes.
In 2009, according to the United Nations, the mean global
percentage using contraception in women who are married or in
union was 62.7%. COC represented 8.8% of contraceptive preva-
lence, reaching 15.4% in more developed countries. More than 100
million women worldwide use COCs. However, each year, many
unintended pregnancies occur, indicating that contraception still
needs to be promoted.
Ó 2012 Elsevier Ltd. All rights reserved.

History

Egyptians are recognized as one of the first civilizations using birth control.1 From as early as 3000
BC ancient drawings depict men wearing condoms. However, the earliest known illustration of a man
using a condom during sexual intercourse is painted on the wall of a cave in France and is 12,000 to
15,000 years old.1 Egyptians developed many contraceptive strategies, such as vaginal pessaries or

* Department of Endocrinology, Hôpital Saint-Antoine, 184 rue du faubourg Saint-Antoine, 75012 Paris, France. Tel.: þ33 1
49282400; Fax: þ33 1 49283195.
E-mail address: sophie.christin-maitre@sat.aphp.fr.

1521-690X/$ – see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.beem.2012.11.004
4 S. Christin-Maitre / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 3–12

vaginal sponges. Pessaries were made of crocodile dung, honey and sodium bicarbonate. Women used
cotton-lint tampons soaked in the fermented juice of acacia plants to prevent pregnancy. In order to be
spermicidal, vaginal sponges used to be soaked in lemon juice or vinegar.
In the 4th century BC, Aristotle was the first Greek writer to mention contraception. The philoso-
pher recommended that women “anoint that part of the womb on which the seed falls” with olive oil in
order to prevent pregnancy. Another method recommended by the ancient Greeks was to exert
pressure on the abdomen in order to expulse semen from the vagina. Various plants were used by
Greek women to prevent pregnancy such as pomegranate, pennyroyal, and pine. Later, Peter of Spain,
who was elected Pope John XXI in 1276, offered advice on birth control by giving recipes using different
herbs that induced menstruation.2 Women in Sri Lanka are reported to eat a papaya a day to prevent
pregnancy. It contains an enzyme papain which interacts with progesterone. Centuries ago, Chinese
women used to drink lead and mercury to control fertility which often resulted in sterility or death.
Intrauterine devices (IUDs) have been used as a method of contraception for over 2000 years, although
their use became more common in the second half of the 20th century.
In Europe, condoms were used from the 16th century, firstly to prevent syphilis and then to prevent
pregnancy. They were originally made from fish or animal gut. However, in 1944 Charles Goodyear
patented the vulcanization of rubber. This procedure facilitated the mass production of condoms. Other
than the use of condoms, the main methods of birth control used before the 20th century included
mainly abstinence, infrequent coitus, coitus interruptus, breastfeeding and induced abortion.
Real improvements in birth control occurred in the 20th century, thanks to several women,
including Dr Marie Stopes from Scotland. She wrote a guide to contraception entitled “Wise Parent-
hood” and opened the first of her birth control clinics in Holloway, Northern London in 1921. The
dawning of hormonal contraception involved two women, the Americans Margaret Sanger and
Katharine McCormick, and a man Gregory Pincus. Margaret Sanger founded the American Birth Control
League which became Planned Parenthood. She was probably highly motivated as her mother had 18
pregnancies, 11 children and died at the early age of 50. She claimed that “No woman can call herself
free who does not own and control her body. No woman can call herself free until she can choose
consciously whether she will or will not be a mother”.3 She met Katharine McCormick, the wife of the
inventor of the mechanical harvester, as they were both involved in women’s rights. McCormick, who
had a large fortune, funded Gregory Pincus’s research into developing a birth control pill. He is
considered as the creator of the first contraceptive pill. The total of McCormick’s gifts to the research
reached $2,000,000.1 She funded the first clinical trials of the Pill, which were conducted by Dr John
Rock, an eminent Catholic gynecologist. He first treated his patients in his private practice. Rock, who
came to be regarded as a co-developer of the Pill, worked with Planned Parenthood staff on a closely
reasoned book, The Time Has Come: A Catholic Doctor’s Proposals to End the Battle over Birth Control.
Pincus and Rock were able to benefit from Carl Djerassi’s research on steroids. Djerassi had synthesized
a progestin, called norethisterone, in his laboratory in Mexico City which remained effective when
taken orally, and was much stronger than natural progesterone. Doses over 5 mg of progestin in a 21-
day regimen could suppress ovulation but caused unacceptable bleeding. With the discovery that the
contaminant mestranol reduced breakthrough bleeding, mestranol, and subsequently its active
metabolite ethinyl estradiol (EE), were added to contraceptive pills.
The first hormonal pill was called EnovidÒ. It was approved by the Federal Drug Administration
(FDA) in 1957 as treatment of menstrual disorders. Its capacity to regulate birth was only recognized
several years later and it was not until 1959 that the pharmaceutical company Searle applied to the FDA
for approval of a pill that would be marketed as a contraceptive. In May 1960, approval was granted.4
Nowadays, COCs are used by more than 100 million women worldwide.

Combined oral contraceptives

The first combined contraceptive pill, called EnovidÒ contained mestranol and norethynodrel.5
Mestranol is an estrogen, the 3-methyl ether of EE. It is a prodrug as it is demethylated to EE in the
liver. Its dose in the first pill was 150 mg. Knowing that 50 mg of mestranol is pharmacokinetically
bioequivalent to 35 mg of EE, the initial dose of estrogen contained in the pill was very high. Nor-
ethynodrel is a progestin; its initial dose was 9.85 mg per pill.
 S. Christin-Maitre / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 3–12 5

In the first clinical studies, EnovidÒ’s contraceptive efficacy was excellent; reaching 100% but this
drug induced many side effects. In studies performed in Puerto Rico under the supervision of Dr Edris
Rice-Wray, 17% of women presented with nausea, dizziness, headaches, stomachaches and vomiting.
The dose of northynodrel was lowered to 5 mg and the dose of mestranol to 75 mg. However, in 1961,
the Lancet reported the death of a woman from thrombosis who was taking the pill. In less than a year,
the FDA had received reports of 6 deaths and 20 non-fatal cases of thromboembolism.
Over the years, oral contraceptives have evolved through gradual lowering of estrogen content,
introduction of new progestins, new regimens of biphasic, triphasic or quadriphasic Pills as well as
fixed or flexible extended regimen and alternative routes of COC administration, such as vaginal or
transdermal, have been developed.

Estrogen in COC

Over the years, in order to decrease the cardiovascular risk of the pill, the dose of estrogen has
progressively decreased. In the majority of COCs available nowadays, the estrogen component is EE or
17a estradiol. In the 1970s, the dose of EE decreased from 50 to 30–35 mg. Subsequently, formulations
containing 20 and even 15 mg were developed. Pills available nowadays are usually sorted into
concentrations of EE higher or lower than 30 mg, with pills containing less than 30 mg considered as low
dose Pills. This decrease has been made possible thanks to the availability of new progestins.
The concept of using the natural 17b estradiol (17 bE2) in combined pills arose in the 1970s. More
than 15 different attempts were made by different companies.6–9 However, no satisfactory combina-
tions were available for many years. In many cases, the pills containing 17 bE2 were contraceptive but
their tolerance was low, as women experienced bleedings. Mono-, bi- or triphasic combinations have
failed over the years. However, two formulations delivering estradiol (E2) have recently been mar-
keted. A quadriphasic COC combining E2 valerate and dienogest has been newly approved in Europe
and USA. E2 valerate is a synthetic estrogen, which is metabolized into 17 bE2. The second pill is
a monophasic COC combining 17b E2 with nomegestrol acetate, a progesterone-derived progestin. It is
now available in several European countries.10,11 A pill containing estetrol, a synthetic estrogen iden-
tical to an endogenous fetal estrogen, is currently under development.12 This molecule is a Selective
Estrogen Receptor Modulator (SERM) and has estrogenic activity on bone and on the endometrium but
anti-estrogenic activity on the breast.

Progestins in COCs

In the different combined pills available nowadays, the progestin component in the pill inhibits
luteinizing hormone (LH) peak, decreases ovarian sensibility to follicle stimulating hormone (FSH) and
therefore decreases estradiol production. The estrogenic component regulates endometrium prolifer-
ation and compensates estrogenic deficiency induced by the anti-gonadotropic effect of the progestin.
Progestins are classically characterized according to their structural origins. They bind to proges-
terone receptors, but progestins may also bind to other steroid receptors, such as androgen, gluco-
corticoid and mineralocorticoid receptors. Most of the progestins contained in COCs were initially
derived from testosterone, and are called 19-nortestosterone derivatives. Norethisterone is an estrane,
and norethisterone acetate and norethynodrel are gonanes. Few pills containing first generation
progestins are still available. Their side effects, such as acne, oily skin and decreased high density
lipoprotein (HDL), mainly due to their androgenic proprieties, are the main cause for their progressive
withdrawal. Over the years, progestins with less androgenic effects have been developed. Among them,
are the second and third generation progestins. Levonorgestrel and norgestrel are second generation
progestins. Third generation progestins include desogestrel, with its active metabolite 3-keto-des-
ogestrel (also named etonogestrel), norgestimate (and its active 17-deacetylated metabolite, nor-
elgestromin) and gestodene. The most recent were released in the mid 1980s.13
Different progestins used in COCs are derived from progesterone. Molecules such as chlormadinone
acetate, cyproterone acetate and medroxyprogesterone acetate are called pregnane derivatives, as they
are derived from 17OH progesterone.14 Some newer progestins have been available more recently in
oral contraceptives, such as drospirenone. This progestin possesses anti-mineralocorticoid and weak
6 S. Christin-Maitre / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 3–12

anti-androgen proprieties. Dienogest, is referred to as a hybrid progestin, as it is derived from the

estrane group but does not exert the androgenic effects of the testosterone derivatives.
A Cochrane Review evaluated the effectiveness and side effects of different progestogens.15 Thirty
trials with a total of 13,923 participants were included, generating 16 comparisons. Overall the quality
of trials was low. The conclusion of this Cochrane Review mentions that women using COCs containing
second generation progestogens may be less likely to discontinue than those using COCs containing
first generation progestogens. Based on one small double-blind trial, third-generation progestogens
may be preferable to second generation preparations with regard to bleeding patterns but further
evidence is needed.

Sequence of COC

Combination pills are categorized as monophasic, or multiphasic, depending on the different

levels of hormones contained in each pill per cycle. The initial pill was monophasic but biphasic and
triphasic pills were introduced in the 1980s. They were initially designed to decrease potential side
effects, such as nausea and headaches. A Cochrane review showed that tolerance is identical
between mono- or multiphasic pills.16,17 A second goal was to mimic the natural human cycle more
closely.
Most COCs have a 28-day cycle. The standard regimen allows for 21 pills containing steroids and
a pill-free interval of 7 days, for eliciting regular withdrawal bleeding and for reassuring women that
they are not pregnant. However, monthly bleeding is not necessary for contraceptive efficacy or safety
issues. Furthermore, several studies have illustrated that ovarian activity occurs during the pill free
interval,18 potentially reducing the efficacy of the pill as follicular growth may occur followed by
ovulation. This phenomenon is mainly observed with the newest pills, as they contain lower doses of
steroids and therefore less gonadotropin inhibition. This threat of contraceptive failure is even higher
in the case of pill omission just after the pill free interval.18 Therefore, in some new pills, the pill-free
interval has been reduced to 4 days. This reduction has been shown to diminish the mean follicular
size. For instance, with the pill containing nomegestrol acetate and 17b E2, the largest follicle diameter
was significantly smaller in the 24/4 day group than in the 21/7 day group [mean (SD) mm in cycle 2:
9.0 (3.0) versus 11.3 (5.3) (p¼ 0.02); in cycle 3: 9.2 (3.0) versus 11.5 (6.0) (p ¼ 0.04)].19 Mean FSH plasma
levels were significantly lower in the 24-day versus the 21 day group on day 24 of cycles 1 and 2.
Over the past years, a strategy has been to add placebo pills instead of having a pill-free interval. The
Coraliance study, enrolling 617 gynecologists in France, followed 3316 patients and showed that during
their previous cycle of COC, 23% women missed a pill at least once.20 Among women on the pill
involving a treatment-free interval, 42% of instances of missing a pill occurred during the first week
following the treatment-free interval. Therefore, a continuous regimen without a treatment free
interval may improve compliance.
In order to reduce the number of unwanted pregnancies, the immediate start or “quick-start”
strategy has been developed. It implies that COCs are started immediately after the healthcare
provider’s visit instead of waiting for the next menses. It has to be associated with back-up birth control
for the first seven days. A Cochrane Review reported limited evidence that immediate start reduces
unwanted pregnancies.21
Another change in the cycle regimen, developed in the past 10 years, is the extended cycle COC.22
This consists of 3 or 4 months of active pill use with a 7-day pill free interval. When the pill-free interval
is avoided it is named continuous regimen as opposed to cyclical regimen. The rationale of extended or
continuous regimens was to avoid menstrual related side effects, such as premenstrual syndrome,
dysmenorrhea or migraine. The second goal was to reduce the number of days of bleeding. In 2003, the
FDA approved an extended cycle COC in an 84/7 dosing regimen, EE 30 mg/levonorgestrel (LNG) 150 mg
(SeasonaleÒ; Duramed Pharmaceuticals, Cincinnati, Ohio), with 84 active pills and 7 placebos. In 2007,
it approved LybrelÒ (Wyeth Pharmaceuticals, Philadelphia, Pennsylvania), which is administered as
a combined active pill containing LNG 90 mg and EE 20 mg in a continuous fashion, 365 days per year.
Several studies have shown that those regimens’ contraceptive efficacy is comparable with the
traditional 21/7 regimen. However, continuous regimens are often associated with increased risk of
breakthrough bleeding versus cyclical COC.
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In some extended regimens, placebo pills have been replaced by low dose of EE. The rationale is to
provide the potential for greater gonadotropin secretion. Furthermore, EE could stabilize the endo-
metrium and reduce bleeding. In May 2006 and October 2008, the FDA approved respectively, a pill
containing 84 active pills with LNG 150 mg and EE 30 mg, followed by 7 days of 10 mg EE pills, and a pill
containing 84 active pills with LNG 100 mg and EE 20 mg, followed by 7 days of 10 mg EE pills. A recent
review has shown that this new extended cycle OC provides patients a low dose, extended regimen OC
option without sacrificing efficacy or tolerability.23
In the past few years, it has been hypothesized that a regimen that extended more than 28 days and
could give women the opportunity to manage their intracyclic breakthrough bleeding would be
appreciated. It was called flexible extended regimen or MIB, for “Manage Intracyclic Bleeding”. Klipping
et al. conducted a multicenter randomized, open-label, parallel group study comparing EE 20 mg/
drospirenone (DRSP) 3 mg in a flexible extended regimen versus a cyclical or a fixed extended regimen
of 124 days.24 With the flexible MIB regimen, women received EE/DRSP for a flexible number of cycles
(minimum three, maximum 13 in 1 year), each of which was separated by a 4-day tablet-free interval.
Over a period of 1 year, the mean number of bleeding/spotting days was significantly lower in the
flexible MIB regimen than with the cyclical regimen (41.0  29.1 (95% CI 38.8–43.3; n ¼ 640) versus
65.8  27.0 (95% CI 62.2–69.4; n ¼ 215) days, p < 0.0001). The mean number of bleeding/spotting days
with the fixed extended regimen was 60.9  51.1 (95% CI 53.9–67.9) days (n ¼ 209). The Pearl Index for
the flexible MIB regimen was 0.64, indicating good contraceptive efficacy. These data have been
confirmed by Jensen et al.25 The management of intracyclic bleeding represents an interesting concept
that could be more developed over the next years.

Non-oral routes of COC

In order to increase efficacy, compliance and tolerance, alternative routes of combined contraception
have been developed, such as vaginal or transdermal routes. Increased bioavailability implies that lower
steroid doses are needed in these systems. The contraceptive vaginal ring named NuvaringÒ releases
15 mg of EE, and 120 mg of etonogestrel per day.26 It is a flexible, transparent ring with a diameter of
54 mm and a cross section of 4 mm. It is self-administered for 3 weeks, followed by 1 week ring-free
period. It works by inhibiting ovulation. The skin patch called EvraÒ delivers 20 mg EE and 150 mg nor-
elgestromin daily to the systemic circulation.27 It is a once-weekly self-administered patch and its
efficacy is based on ovulation suppression. Both regimens have been approved since the mid 2000s.

COC as emergency contraception

COCs were first used as emergency contraception, as advised by Dr Albert Yuzpe, a Canadian
obstetrician/gynecologist who first published in 1974. This method must be initiated within 72 h
following sexual intercourse. Several COC pills have to be taken 12 h apart.28 This method has been
used by millions of women; however, its tolerance is low, and nausea, vomiting, spotting and head-
aches are frequent side effects. Therefore, in 1999 it was replaced by progestin only emergency
contraception and, more recently, by Selective Progesterone Receptor Modulators (SPRM).

Other types of hormonal contraception

Progestin only pills should be distinguished from COCs. This type of pill does not contain estrogens,
only synthetic progestogens, and are called progestin only mini-pills. These pills have been available
since 1973 and are currently proposed to women with contraindications to use of estrogens, as their
efficacy is lower than combined pills and their tolerance is not always very good, inducing bleedings
such as spotting as well as acne and ovarian cysts.29 The dose of progestin contained in this type of pill
is lower than in COCs. They inconsistently inhibit ovulation and rely mainly on their progestogenic
effect of thickening the cervical mucus, thereby reducing sperm viability and penetration. Therefore,
their ovulation inhibition is lower than with COC.
Injectable progestins were developed a few years after the pill in order to make it possible for
women to use an effective method without taking a pill once a day. Depot medroxyprogesterone
8 S. Christin-Maitre / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 3–12

acetate (DMPA) was first submitted to the FDA for contraceptive use in 1967. However, although it has
been widely used all over the world, it was not approved until 1992 by the FDA. This long acting
formula needs to be injected every three months.1
Another form of progestin only contraception are implants. The first developed was Norplant,
a multi unit system containing 6 rods, then came Jadelle containing 2 rods.30 Since then several single
or double-rod systems have been developed using four different types of progestin: levonogestrel,
etonogestrel, nestorone and nomegestrol acetate. The most recent one to be launched on the market
was NexplanonÒ. It is a single-rod subdermal implant that is inserted just under the skin of a woman’s
upper arm. The 4 cm by 2 mm rod, named ImplanonÒ, contains 68 mg of etonogestrel which is released
over a three year period. It was first approved in 1988 in Indonesia and in the US in 2006. It has been
replaced by NexplanonÒ because of cases of incorrect insertion of ImplanonÒ by medical personnel.31 It
is essentially identical to ImplanonÒ except that it is radiopaque.
The first IUD containing progesterone was introduced in 1976. However, it was abandoned as its
life-span was only 1 year. In the late 1970s Dr Luukainen designed an IUD delivering levonorgestrel,
called MirenaÒ. It was first approved in Finland in 1990 and has a lifespan of 5 years. Levo-
norgestrel is released into the endometrial cavity initially at a daily dose of 20 mg and then at a dose
of 10 mg.32
Progestin pills can be used as emergency contraception. The most popular form for emergency
contraception is levonorgestrel. Initially two pills of 0.75 mg were administered 12 h apart, although
this regimen has now been replaced by a single pill containing 1.5 mg of levonorgestrel.33 More
recently, SPRMs have been developed as emergency contraception. Initially low doses of mifepristone
have been tested.34 The SPRM available as emergency contraception is ulipristal acetate (UPA),
previously known as VA 29-14 or CDB-2914.35 It is a derivative of 19-norprogesterone and is admin-
istered as a single dose of 30 mg. It was approved in May 2009 by the European Commission and
marketed as an emergency contraceptive within 5 days of unprotected sexual intercourse. This
molecule has also been developed as daily contraceptive; a daily oral administration of UPA is able to
suppress ovulation in a majority of women.36 It is an “estrogen-free” contraceptive with possibly fewer
side effects than contraceptives delivering EE. Currently the Population Council in collaboration with
National Institute of Child Health and Human Development (NICHD) is developing a 3-month
contraceptive vaginal ring containing UPA.37

Prevalence of contraception use

At the 2005 World Summit, Governments committed themselves to “achieving universal access to
reproductive health by 2015, as set out at the International Conference on Population and Develop-
ment” (General Assembly resolution 60/1). This goal is not achieved yet, as illustrated in Fig. 1,
reporting the percentage of women between 15 and 49 years old using contraception according to the
most recent data published by United Nation in 2011.38 Disparities are obvious. In 2009, the mean
global percentage using contraception in women who are married or in union was 62.7%. In more
developed regions, it was as high as 72.4% and as low as 31.4% in lesser developed countries. Looking
more precisely at modern contraceptive methods, the prevalence was 60% for Asia, 67% for the Latin
American and Caribbean region, but only 22% for Africa as a whole and 16% for sub-Saharan Africa.38
Furthermore, in at least 46 countries, 20% or more of the women of reproductive age who are married
or in a union have an unmet need for contraception.
However, a major improvement in contraceptive prevalence has been observed since 1960. In
developing countries this prevalence reached 10% in 1960 and was close to 70% in 2009. The fertility
rate has decreased from 4.7 births in the early 1970s to 2.6 births in the late 2000s, predominantly due
to contraceptive use.39 Using a mathematical model, Ahmed et al. estimated that worldwide, in 2008,
342,203 women died from maternal causes, but that contraceptive use averted 272,040 maternal
deaths (uncertainty interval 127,937–407,134), a 44% reduction, so without contraceptive use, the
number of maternal deaths would have been 1$8 times higher than the 2008 total.39 Contraceptive use
improves perinatal outcomes and child survival by widening the interval between pregnancies.40 In
developing countries, risk of death in infancy (age < 1 year) would fall by 10% and in ages 1–4 years by
21% if all children were spaced by a gap of 2 years.
 S. Christin-Maitre / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 3–12 9

Fig. 1. Percentage of women using any modern method of contraception among those aged 15–49 years who are married or in
a union, in 2009.

What is the prevalence of COC use and types of COC used?

The global mean percentage using contraception among women who are married or in union of
62.7% breaks down as follows: 56.1% using modern methods, and 6.6% using any traditional methods.
Modern methods are female sterilization (18.9%), male contraception (2.4%), pill or COC (8.8%),
injection (3.5%), implants (0.3%), IUD (14.3%), condoms (7.6%) and vaginal barrier methods (0.2%). In
2009, COCs represented only 8.8% of contraceptive prevalence, reaching 15.4% in more developed
countries. It is currently used by more than 100 millions of women worldwide, with large variations
depending on country, age and education.
According to a recent study by Hall et al., the proportion of women using sexual and reproductive
health services (SRHs) in the US, increased from 50% (2006–2007) to 54% (2007–2008) and 57% (2008–
2010) [all year odds ratios (ORs) 1.4, p values < 0.03]. Among sexually experienced women, the
proportions using SRH and contraceptive services were unchanged, while sexually transmitted
infection (STI) service use increased from 22% (2006–2007) to 33% (2008–2009) (OR 1.7, confidence
interval 1.1–2.4, p ¼ 0.009).41 Lower proportions of service were used among women of social
disadvantage. A recent American study from Princeton University sought to estimate the prevalence of
types of COCs used among US women. Data were collected by interviewing 12,279 women aged 15–44
years participating in the National Survey of Family Growth.42 Analyses focused on COC use overall, by
pill type, across socio-demographic and health factors. The prevalence of current COC use (88 different
brands) was 17%. The majority of COC users used earlier-formulation COCs: 30 mg (67%) versus <30 mg
estrogen (33%), monophasic (67%) versus multiphasic (33%) dosages and traditional 21/7 regimens
(88%) versus extended or other cycle regimens (12%). Norgestimate (32%) and norethindrone (20%)
were the most commonly used progestins. Socio-demographic, gynecological and health risk factors
were associated with type of COC use.

Conclusion

In 2009, COC use remained low, accounting for 8.8% of global contraceptive prevalence. Although
studies have demonstrated that long acting methods such as IUDs and implants have a very low failure
rate and that their effectiveness is superior to that of contraceptive pills, ring or patch,43 there is still
10 S. Christin-Maitre / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 3–12

room for COCs. Their failure rate is among the lowest, ranging from 1/5 to 1/100 woman per year.
Furthermore, non-contraceptive benefits of COCs have been reported, such as improved acne, head-
aches, menorrhagia, dysmenorrhea and premenstrual menstrual syndrome.44 A recent review of the
literature has reported that fertility after using COC is broadly similar to those reported following
discontinuation of barrier methods or use of no contraceptive method.45 In summary, the health
benefits of COC far outweigh the health risks. The European Society of Human Reproduction and
Embryology (ESHRE) Capri Workshop group recently concluded that although great advances have
been made in recent years in increasing contraceptive needs in women in many countries where
contraceptive prevalence is low or there is a high unmet need for contraception,46 much more can, and
needs to be done. Healthcare providers should be more informed about contraception47 and women
and couples need to make informed choice concerning their contraception.

Practice points

- The first hormonal contraceptive pill, EnovidÒ, was approved by FDA in 1960.
- Doses of ethinyl estradiol have been progressively lowered in order to avoid thrombotic
events.
- The standard regimen of 21 pills containing steroids and a pill-free interval of 7 days is
progressively being replaced by continuous regimens to improve compliance.
- Non-contraceptive benefits of COCs, such as improvement of acne, headaches, menorrhagia,
dysmenorrhea and premenstrual menstrual syndrome should be considered when choosing
a contraceptive method.
- In 2009, COC represented 8.8% of contraceptive prevalence. More than 100 million women
used COCs.

Research agenda

- Research needs to be performed in order to understand the method failures of COC.

- Trials are necessary to test educational programs explaining how benefits outweigh the risks
of COCs.
- Development of new molecules such as progestins or Selective Progesterone Receptor
Modulators for new contraceptive pills, rings or patches.

Funding

None.

Conflict of interest

None declared.

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