Infographic on the chemistry of oral contraceptives. Oral contraceptives contain synthetic versions of two natural hormones: estrogens and progestogens. These trick the pituitary gland into thinking a woman is already pregnant, stopping release of hormones which stimulate ovulation and preventing pregnancy. Progestogens make it difficult for sperm to reach the uterus and also make it harder for an egg to attach to the uterine lining. Progestogens can be used in combination with estrogens or on their own – which is recommended for breast-feeding women as it doesn't affect milk production. Combined pills contain an estrogen and progestogen, and are taken over a 28 day cycle.
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You may have read in the news over the past few days about the passing of Carl Djerassi, the chemist (and later, novelist) who is best known for his discovery of the first oral contraceptive. This discovery led to something of a social revolution, putting the power of contraception firmly in the hands of women, as well as changing sexual attitudes. This graphic looks at the some of the common chemicals used in oral contraceptives, and how they work.

Before the advent of oral contraceptives, it was already well known that sex hormone levels could suppress or prevent ovulation. Further research showed that injected doses of the natural hormone progesterone, the primary progestogen, was linked with suppressed ovulation. However, the issue was that progesterone was very poorly absorbed when taken orally, meaning it wasn’t practical to use it in a formulation as a contraceptive pill.

This changed with Djessari’s discovery. In 1951, he discovered the synthetic progestogen, norethindrone, a discovery which paved the way for a number of other synthetic progestogens and estrogens. The first oral contraceptive to obtain approval was Enovid, a mixture of the compounds norethynodrel and mestranol, in 1961, and several other brands soon followed. Despite this, contraceptive pills were still restricted in terms of who had access to them; in several US states, unmarried women were prohibited from using them until the early 1970s.

How, then, do oral contraceptives exert their effects? They come two different types: progestogen-only pills (also known as the mini pill), or the combined pill, which contains both an estrogen and a progestogen. Both of these types act as contraceptives in a similar manner, though there are some differences.

Primarily, both types of oral contraceptive prevent pregnancy by affecting hormone levels. Ovulation is usually triggered by a peak in estrogen in the body during the menstrual cycle, usually around 14 days in. This peak causes the release of hormones from the pituitary gland, luteinising hormone (LH) and follicle stimulating hormone (FSH), which prompt the ovaries to produce an egg. Taking oral contraceptives containing synthetic estrogens can help keep estrogen levels in the body stable; without this peak in estrogen levels, ovulation does not take place.

Progestogens can also exert this effect in some cases, but they also have other effects which can inhibit pregnancy. Their constant levels in the body as a result of oral contraceptives prevents the thickening of the uterus wall, making it difficult for any eggs that are produced to attach. They also thicken the cervical mucus, making it difficult for sperm to reach the uterus. Ovulation whilst taking oral contraceptives is rare, but if it does occur, these additional mechanisms still make it difficult for pregnancy to occur.

Since their introduction, oral contraceptives have continued to develop. Medical concerns related to the levels of estrogens in the pills led to a gradual reduction of the dosage, and the levels used today are notably lower than those used when they were first made available. They have also been linked to positive health effects, such as a decreased incidence of ovarian cancer.

If taken correctly, the efficacy of oral contraceptives in preventing pregnancy is stated to be 99.9%. They are used by more than 100 million women worldwide, and society’s attitudes towards sex and pregnancy have been heavily influenced by their use since Djerassi’s discovery of norethindrone. It’s something of a oversight for science that, as a consequence of his death, he will never receive a Nobel prize for his society-changing work, as the prizes are not awarded posthumously.



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