INFOGRAPHIC INFOGRAPHIC

SIXTY YEARS OF THE COMBINED

RISKS WITH TAKING COMBINED ORAL CONTRACEPTIVES DISCOVERY AND DEVELOPMENT
COCs increase the risk of blood clots and some cancers, but reduce the risk OF THE PILL
of other cancers.

ORAL CONTRACEPTIVE PILL

Progesterone was first synthesised
Venous thromboembolism (VTE)
in the 1950s and was licensed as an
VTE risk is increased but is small compared with
Breast cancer the risks during pregnancy and immediately after oral contraceptive in 1960.
In the UK, around giving birth. The risk varies depending on the type of
1% of breast progestogen in the pill. The risk of VTE is highest in the 1950s 1951: Carl Djerassi, a
chemist at pharmaceutical
The first combined oral contraceptive pill was licensed for ‘menstrual cancers in women
are associated with
four months following initiation of COCs
company Syntex, creates
irregularities’ in 1957, and contraception three years later. Since then, oral contraceptives Women not using a combined
hormonal pill/patch/ring and not
About 2 out of 10,000
women
a progesterone pill by
synthesising hormones from yams
millions of women have taken ‘the pill’. pregnant
1952: Chemist Frank Colton at the
COC containing levonorgestrel, About 5–7 out of 10,000
pharmaceutical company Searle also
Ovarian cancer norethisterone or norgestimate women
DAWN CONNELLY develops a synthetic progesterone pill
The risk of COC containing etonogestrel About 6–12 out of 10,000
Hypothalamus (ring) or norelgestromin (patch) women
ovarian cancers 1954: Biologist Gregory Pincus and
HOW COMBINED ORAL CONTRACEPTIVES WORK Pituitary gland is reduced by 50%
COC containing drospirenone,
gestodene or desogestrel
About 9–12 out of 10,000
women gynecologist John Rock conduct the
Oestrogen component of COCs after >5 years of COC COC containing chlormadinone, Not yet known first human trials on 50 women in the US.
Combined oral contraceptives (COCs) contain suppresses ovulation by stopping the dienogest or nomegestrol The pill is contaminated with oestrogen
synthetic versions of the sex hormones oestrogen Brain release of follicle-stimulating hormone Cervical cancer Pregnancy 29 per 10,000 women during synthesis but purifying it leads to
and progesterone, steady levels of which convince the (FSH) and luteinising hormone (LH) Cervical cancer risk years breakthrough bleeding so it is retained
pituitary gland of a pregnancy. is doubled after Immediate postpartum period 300–400 per 10,000
women years 1956: After large clinical trials in Puerto Rico,
>5 years of COC
the pill is found to be 100% effective
Hormones and the menstrual cycle
1957: Enovid 10mg (9.85 mg norethynodrel
FSH causes an egg to High oestrogen levels trigger and 150 µg mestranol; Searle) is approved
mature in an ovary and a sharp rise in LH causing the TYPES OF PILLS by the US Food and Drug Administration
stimulates the ovary to mature egg to be released There are two main types of COCs: monophasic (contain the same amount of (FDA) for “menstrual irregularities”. It is
release oestrogen released onto the British market as Enavid
hormones in each pill) and phasic (contain different amounts of hormones).
1960: The FDA approves contraception as
If you start the combined 1960s an additional indication for Enovid 10mg
1 Men
28 2 stru pill on day 1 of your
27 3 ation
If you start Zoely, 26 menstrual cycle, you will be 1961: Conovid 5mg is approved by the
Eloine, Daylette 25 protected from pregnancy British Family Planning Association. Serious

4
LH or Qlaira on day straight away concerns are raised after three fatal cases

24

5
FSH 2 or later, you will
ovulation

of blood clots in women taking COCs

23
LH need additional

6
FSH contraception for 7 1967: Epidemiological studies link the pill
ESTRADIOL

22

7
oestrogen days (9 for Qlaira) with thrombosis
FEEDBACK Unless you have a short

21
cycle, starting the pill on

8
Second generation pills are launched,
progesterone 1970s
the fifth day or before will which contain lower amounts of hormones

20

9
protect you straight away
Day 1 Day 14 Day 28 Uterus 1974: Free contraception is introduced

10
19
If you start the pill 18
11 in the UK leading to increased uptake
The ovary secretes progesterone on any other day, you 17
will need additional 12
and oestrogen to continue to 16 13 Third generation pills are launched to reduce
15 14 1980s
prepare the uterus for pregnancy contraception until you have tion androgenic and metabolic side effects
Fallopian Ovul a
tube taken the pill for seven days

ENDURING POPULARITY OF THE PILL Ovary 1990s

1995: The UK Committee on Safety of
Medicines says third generation COCs should
There has been little change in the proportion of women Missed pill advice not be used first line because of the risk of
using oral contraceptives over the past ten years. If only one active pill is missed, take the missed pill blood clots. This “pill scare” is thought to lead to
Missed pills on week 1: an increase of 9% in the abortion rate in 1996
straight away and further pills as usual. No extra
60% Endometrium • Take the most recently missed
Progesterone also thins precautions are needed. If more than one pill is missed,
Progesterone pill straight away and further 1999: The Medicines Commission
the lining of the womb, follow advice below. This advice doesn’t apply to Qlaira,
50% component causes pills as usual says third generation pills can be
making it difficult for an Zoely, Eloine and Daylette — consult product literature.
mucus in the • Extra precautions (condoms) prescribed first line after all
Uptake of oral contraceptives*

neck of the womb egg to implant

40% are needed for the next 7 days
(endometrium) to Missed pills on • Emergency contraception is 2001: The EMA reviews third generation
week 2: 2000s
30% thicken, making it recommended if there has COCs and confirms a small increased risk of
difficult for sperm to • Take the most been unprotected sex VTE compared with second generation pills.
20% reach an egg recently missed pill Fourth generation COCs are released
straight away and Missed pills on week 3:
10% further pills as usual • Take the most recently missed 2009: The first COC containing the
• Extra precautions pill straight away and further oestrogen estrodiol is launched
0 (condoms) are pills as usual
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015** 2016 needed for the next • Omit the pill-free interval (or
* Data show uptake of oral contraceptives for women in contact with sexual and reproductive health 7 days 2013: The EMA reviews third and fourth
inactive pills) 2010s
services in England. **Methodology for determining method of contraception changed in 2014–2015. generation COCs and concludes that
• Extra precautions (condoms)
their benefits continue to outweigh their
Editorial adviser: Nuttan Tanna, pharmacist consultant, women’s health and older people, London North West Healthcare NHS Trust, Harrow, London are needed for the next 7 days
risks, and the well-known risk of VTE with
Sources: British National Formulary, NHS Digital, European Medicines Agency, Medicines and Healthcare products Regulatory Agency, Faculty of Sexual and Reproductive Inactive pills
Healthcare. Illustration: Alex Baker. Infographic: Maria Gonzalez all COCs is small

146 THE PHARMACEUTICAL JOURNAL VOL 299 NO 7905 SEPTEMBER 2017 SEPTEMBER 2017 NO 7905 VOL 299 THE PHARMACEUTICAL JOURNAL 147