text: Norgestrel (rac-13-ethyl-17α-ethynyl-19-nortestosterone), the racemic mixture containing levonorgestrel and dextronorgestrel, was discovered by Hughes and colleagues at Wyeth in 1963 via structural modification of norethisterone (17α-ethynyl-19-nortestosterone). It was the first progestogen to be manufactured via total chemical synthesis. Norgestrel was introduced for medical use as a combined birth control pill with ethinylestradiol under the brand name Eugynon in Germany in 1966 and under the brand name Ovral in the United States 1968, and as a progestogen-only pill under the brand name Ovrette in the United States in 1973. Following its discovery, norgestrel had been licensed by Wyeth to Schering AG, which separated the racemic mixture into its two optical isomers and identified levonorgestrel (13β-ethyl-17α-ethynyl-19-nortestosterone) as the active component of the mixture. Levonorgestrel was first studied in humans by 1970, and was introduced for medical use in Germany as a combined birth control pill with ethinylestradiol under the brand name Neogynon in August 1970. A more widely used formulation, containing lower doses of ethinylestradiol and levonorgestrel, was introduced under the brand name Microgynon by 1973. In addition to combined formulations, levonorgestrel was introduced as a progestogen-only pill under the brand names Microlut by 1972 and Microval by 1974. Many other formulations and brand names of levonorgestrel-containing birth control pills have also been marketed.
  Levonorgestrel, taken alone in a single high dose, was first evaluated as a form of emergency contraception in 1973. It was the second progestin to be evaluated for such purposes, following a study of quingestanol acetate in 1970. In 1974, the Yuzpe regimen, which consisted of high doses of a combined birth control pill containing ethinylestradiol and norgestrel, was described as a method of emergency contraception by A. Albert Yuzpe and colleagues, and saw widespread interest. Levonorgestrel-only emergency contraception was introduced under the brand name Postinor by 1978. Ho and Kwan published the first study comparing levonorgestrel only and the Yuzpe regimen as methods of emergency contraception in 1993 and found that they had similar effectiveness but that levonorgestrel alone was better-tolerated. In relation to this, the Yuzpe regimen has largely been replaced as a method of emergency contraception by levonorgrestrel-only preparations. Levonorgestrel-only emergency contraception was approved in the United States under the brand name Plan B in 1999, and has also been marketed widely elsewhere throughout the world under other brand names such as Levonelle and NorLevo in addition to Postinor. In 2013, the Food and Drug Administration approved Plan B One-Step for sale over-the-counter in the United States without a prescription or age restriction.
  Levonorgestrel has also been introduced for use as a progestogen-only intrauterine device under the brand names Mirena and Skyla among others, as a progestogen-only birth control implant under the brand names Norplant and Jadelle, as a combined oral tablet with estradiol valerate for menopausal hormone therapy under the brand name Klimonorm, and as a combined transdermal patch with estradiol for menopausal hormone therapy under the brand name Climara Pro. Ester prodrugs of levonorgestrel such as levonorgestrel acetate and levonorgestrel butanoate have been developed and studied as other forms of birth control such as long-acting progestogen-only injectable contraceptives and contraceptive vaginal rings, but have not been marketed for medical use.