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Sixty years of the combined oral contraceptive pill

Sixty years of the combined oral contraceptive pill

The first combined oral contraceptive pill was licensed for ‘menstrual irregularities’ in 1957, and contraception three years later. Since then, millions of women have taken ‘the pill’.

View the full infographic here.

Discovery and development of the pill

Progesterone was first synthesised in the 1950s and was licensed as an oral contraceptive in 1960

1951: Carl Djerassi, a chemist at pharmaceutical company Syntex, creates a progesterone pill by synthesising hormones from yams

1952: Chemist Frank Colton at the pharmaceutical company Searle also develops a synthetic progesterone pill

1954: Biologist Gregory Pincus and gynecologist John Rock conduct the first human trials on 50 women in the US. The pill is contaminated with oestrogen during synthesis but purifying it leads to breakthrough bleeding so it is retained

1956: After large clinical trials in Puerto Rico, the pill is found to be 100% effective

1957: Enovid 10mg (9.85mg norethynodrel and 150µg mestranol; Searle) is approved by the US Food and Drug Administration (FDA) for “menstrual irregularities”. It is released onto the British market as Enavid

1960: The FDA approves contraception as an additional indication for Enovid 10mg

1961: Conovid 5mg is approved by the British Family Planning Association. Serious concerns are raised after three fatal cases of blood clots in women taking COCs

1967: Epidemiological studies link the pill with thrombosis

1970s: Second generation pills are launched, which contain lower amounts of hormones

1974: Free contraception is introduced in the UK leading to increased uptake

1980s: Third generation pills are launched to reduce androgenic and metabolic side effects

1995: The UK Committee on Safety of Medicines says third generation COCs should not be used first line because of the risk of blood clots. This “pill scare” is thought to lead to an increase of 9% in the abortion rate in 1996

1999: The Medicines Commission says third generation pills can be prescribed first line after all

2001: The EMA reviews third generation COCs and confirms a small increased risk of VTE compared with second generation pills. Fourth generation COCs are released

2009: The first COC containing the oestrogen estrodiol is launched

2013: The EMA reviews third and fourth generation COCs and concludes that their benefits continue to outweigh their risks, and the well-known risk of VTE with all COCs is small

Graphic showing how combined oral contraceptives work and the hormones present during the menstrual cycle

How combined oral contraceptives work

Combined oral contraceptives (COCs) contain synthetic versions of the sex hormones oestrogen and progesterone, steady levels of which convince the pituitary gland of a pregnancy.

Graph showing usage of the pill in England from 2006 to 2016

The enduring popularity of the pill

There has been little change in the proportion of women using oral contraceptives over the past ten years.

Contraindications and interactions

Women should not take the combined oral contraceptive pill if they:

  • are pregnant
  • smoke and are 35 or older
  • stopped smoking less than a year ago and are 35 or older
  • are very overweight

Or if they have or have had:

  • a blood clot
  • a heart abnormality or heart disease, including high blood pressure
  • severe migraines, especially with aura (warning symptoms)
  • breast cancer
  • disease of the gallbladder or liver
  • diabetes with complications or diabetes for the past 20 years

The following medicines can interact with combined oral contraceptive pills:

  • antibiotics (rifabutin, rifampicin)
  • antiepileptics (carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide, topiramate)
  • antiretrovirals (ritonavir, ritonavir-boosted protease inhibitors, efavirenz, nevirapine)
  • antidepressants (St John’s wort)
  • others (modafinil, bosentan, aprepitant)

Graph and table  showing risks with taking combined oral contraceptives

Risks with taking combined oral contraceptives

COCs increase the risk of blood clots and some cancers, but reduce the risk of other cancers.

Graph showing when and how to use COCs to avoid pregnancy

Types of pills

There are two main types of COCs: monophasic (contain the same amount of hormones in each pill) and phasic (contain different amounts of hormones).

Graphic showing blister pack and what to do when pills are missed

Missed pill advice

If only one active pill is missed, take the missed pill straight away and further pills as usual. No extra precautions are needed. If more than one pill is missed, follow advice above. This advice doesn’t apply to Qlaira, Zoely, Eloine and Daylette — consult product literature.

Combined oral contraceptives available in the UK
Type of COCBrand nameOestrogenProgestogen
Sources: BNF, MIMS
Monophasic 21-dayBimizza
Gedarel 20/150
Lestramyl 20/150
Munalea 20/150 
Ethinylestradiol 20mcg Desogestrel 150mcg
 Aidulan 20/75
Millinette 20/75
Sunya 20/75
Ethinylestradiol 20mcgGestodene 75mcg 
 Loestrin 20Ethinylestradiol 20mcg Norethisterone acetate 1mg 
Gedarel 30/150
Lestramyl 30/150
Munalea 30/150 
Ethinylestradiol 30mcg Desogestrel 150mcg 
Ethinylestradiol 30mcg Drospirenone 3mg 
Katya 30/75
Millinette 30/75
Aidulan 30/75 
Ethinylestradiol 30mcg Gestodene 75mcg 
Microgynon 30
Ethinylestradiol 30mcg Levonorgestrel 150mcg 
 Loestrin 30Ethinylestradiol 30mcg Norethisterone acetate 1.5mg 
Ethinylestradiol 35mcg Norgestimate 250mcg 
 Brevinor Ethinylestradiol 35mcg Norethisterone 500mcg 
 Norimin Ethinylestradiol 35mg Norethisterone 1mg 
 Norinyl-1 Mestranol 50mcg Norethisterone 1mg 
Monophasic 28-dayFemodene ED Ethinylestradiol 30 mcg Gestodene 75mcg 
 Microgynon ED Ethinylestradiol 30 mcg Levonorgestrel 150mcg 
 Zoely Estradiol (as hemihydrate) 1.5mg Nomegestrol acetate 2.5mg 
 Eloine Ethinylestradiol 20mcg Drospirenone 3mg 
 Daylette Ethinylestradiol 20mcg Drospirenone 3mg 
Phasic 21-dayTriadene Ethinylestradiol 30/40/30mcg Gestodene 50/70/100mcg 
Ethinylestradiol 30/40/30mcg Levonorgestrel 50/75/125mcg 
 Synphase Ethinylestradiol 35mcg Norethisterone 500mcg/1mg/500mcg 
Phasic 28-day Logynon ED Ethinylestradiol 30/40/30mcg Levonorgestrel 50/75/125mcg 
 QlairaEstradiol valerate 3/2/1mgDienogest 2/3mg

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2017.20203625

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