Levonorgestrel

Levonorgestrel is a hormonal medication used in a number of birth control methods.[7][8] It is combined with an estrogen to make combination birth control pills.[9] As an emergency birth control, sold under the brand names Plan B One-Step and Julie, among others, it is useful within 72 hours of unprotected sex.[7][8][10] The more time that has passed since sex, the less effective the medication becomes.[8] Levonorgestrel works by preventing or delaying ovulation so an egg cannot be released. The dosage used for emergency contraception is ineffective when ovulation has already occurred, and has been found to have no effect on implantation.[11] It decreases the chances of pregnancy by 57–93%.[12] In an intrauterine device (IUD), such as Mirena among others, it is effective for the long-term prevention of pregnancy.[8] A levonorgestrel-releasing implant is also available in some countries.[13]

Common side effects include nausea, breast tenderness, headaches, and increased, decreased, or irregular menstrual bleeding.[8] When used as an emergency contraceptive, if pregnancy occurs, there is no evidence that its use harms the fetus.[8] It is safe to use during breastfeeding.[8] Birth control that contains levonorgestrel will not change the risk of sexually transmitted infections.[8] It is a progestin and has effects similar to those of the hormone progesterone.[8] It works primarily by preventing ovulation and closing off the cervix to prevent the passage of sperm.[8]

Levonorgestrel was patented in 1960 and introduced for medical use together with ethinylestradiol in 1970.[14] It is on the World Health Organization's List of Essential Medicines.[15] It is available as a generic medication.[16] In the United States, levonorgestrel-containing emergency contraceptives are available over the counter (OTC) for all ages.[17] In 2020, it was the 323rd most commonly prescribed medication in the United States, with more than 800thousand prescriptions.[18]

Medical uses

Contraindications

Known or suspected pregnancy is a contraindication of levonorgestrel as an emergency contraceptive.

Side effects

After an intake of 1.5 mg levonorgestrel in clinical trials, very common side effects (reported by 10% or more) included: hives, dizziness, hair loss, headache, nausea, abdominal pain, uterine pain, delayed menstruation, heavy menstruation, uterine bleeding, and fatigue; common side effects (reported by 1% to 10%) included diarrhea, vomiting, and painful menstruation; these side effects usually disappeared within 48 hours.[47][48] However, the long term side effects common with oral contraceptives such as arterial disease are lower with levonorgestrel than in combination pills.

Levonorgestrel as a contraceptive intrauterine device has been associated with a slightly higher risk of breast cancer than with non-use in select studies.[49]

Overdose

Overdose of levonorgestrel as an emergency contraceptive has not been described.[50] Nausea and vomiting might be expected.[50]

Interactions

If taken together with drugs that induce the CYP3A4 cytochrome P450 liver enzyme, levonorgestrel may be metabolized faster and may have lower effectiveness.[51] These include, but are not limited to barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John's wort and topiramate.

Pharmacology

Chemistry

Levonorgestrel, also known as 17α-ethynyl-18-methyl-19-nortestosterone or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a derivative of testosterone.[69][70] It is the C13β or levorotatory stereoisomer and enantiopure form of norgestrel, the C13α or dextrorotatory isomer being inactive.[71][72] Levonorgestrel is more specifically a derivative of norethisterone (17α-ethynyl-19-nortestosterone) and is the parent compound of the gonane (18-methylestrane or 13β-ethylgonane) subgroup of the 19-nortestosterone family of progestins.[73] Besides levonorgestrel itself, this group includes

History

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).[84][85][86][87] It was the first progestogen to be manufactured via total chemical synthesis.[86][87] Norgestrel was introduced for medical use as a combined birth control pill with

Society and culture

Research

Levonorgestrel has been studied in combination with androgens such as testosterone and dihydrotestosterone as a hormonal contraceptive for men.[56][58]

External links