hormonal medicine used for birth see
not to be confused with Norgestrel
Levonorgestrel is a hormonal medicine which is used in a number of parturition control methods. [ 5 ] It is combined with an estrogen to make combination birth control condition pills. [ 6 ] As an hand brake parentage master, sold under the sword identify Plan B among others, it is utilitarian within 72 hours. This should not be confused with EllaOne which can be effective within 120 hours ( 5 days ) of unprotected sex. [ 5 ] The more clock time that has passed since sexual activity, the less effective the medication becomes, and it does not work after pregnancy ( implantation ) has occurred. [ 5 ] It decreases the chances of pregnancy by 57 to 93 %. [ 7 ] In an intrauterine device ( IUD ), such as Mirena among others, it is effective for the long-run prevention of pregnancy. [ 5 ] A levonorgestrel-releasing implant is besides available in some countries. [ 8 ] common side effects include nausea, summit softheartedness, headaches, and increased, decreased, or irregular menstrual bleed. [ 5 ] When used as an emergency contraceptive, if pregnancy occurs, there is no attest that its consumption harms the baby. [ 5 ] It is safe to use during breastfeed. [ 5 ] Birth master that contains levonorgestrel will not change the risk of sexually transmitted infections. [ 5 ] It is a progestin and has effects alike to those of the hormone progesterone. [ 5 ] It works primarily by preventing ovulation and closing off the cervix to prevent the passage of sperm. [ 5 ]

Levonorgestrel was patented in 1960 and introduced for medical use together with ethinylestradiol in 1970. [ 9 ] [ 10 ] It is on the World Health Organization ‘s List of Essential Medicines, the safest and most effective medicines needed in a health system. [ 11 ] It is available as a generic medicine. [ 12 ] In the United States, levonorgestrel-containing emergency contraceptives are available over the rejoinder ( OTC ) for all ages. [ 13 ] In 2016, it was the 223rd most normally prescribed medicine in the United States, with more than two million prescriptions. [ 14 ]

aesculapian uses [edit ]

Birth master [edit ]

At low doses, levonorgestrel is used in monophasic and triphasic formulations of compound oral contraceptive pills, with available monophasic doses ranging from 100 to 250 µg, and triphasic doses of 50 µg/75 µg/125 µg. [ 15 ] It is combined with the estrogen ethinylestradiol in these formulations. [ 15 ] At identical first gear daily venereal disease of 30 µg, levonorgestrel is used in some progestogen-only pill formulations. [ 15 ] Levonorgestrel is the active component in a count of intrauterine devices including Mirena and Skyla. [ 15 ] [ 16 ] It is besides the active ingredient in the birth control implants Norplant and Jadelle. [ 15 ] [ 16 ] One of the more common forms of contraception that contains only levonorgestral is an IUD. One IUD, the Mirena is a small empty cylinder containing levonorgestral and polydimethylsiloxane and covered with a exhaust rate controlling membrane. [ 17 ]

Emergency parturition see [edit ]

Levonorgestrel is used in emergency contraceptive pills ( ECPs ), both in a compound Yuzpe regimen which includes estrogen, and as a levonorgestrel-only method. The levonorgestrel-only method acting uses levonorgestrel 1.5 milligram ( as a single dose or as two 0.75 magnesium doses 12 hours apart ) taken within 3 days of unprotected sex, with one sketch indicating that beginning equally late as 120 hours ( 5 days ) after sexual intercourse could be effective. [ medical citation needed ] The primary coil mechanism of action of levonorgestrel as a progestogen-only emergency contraceptive pill is, according to International Federation of Gynecology and Obstetrics ( FIGO ), to prevent fertilization by inhibition of ovulation and thickening of cervical mucus. [ 18 ] [ 19 ] [ 20 ] [ 21 ] FIGO has stated that : “ inspection of the testify suggests that LNG [ levonorgestreol ] ECPs can not prevent implantation of a fertilize testis. Language on implantation should not be included in LNG ECP product label. ” [ 22 ] [ 23 ] In November 2013, the European Medicines Agency ( EMA ) approved a change to the label saying it can not prevent implantation of a fertilize egg. [ 24 ] other studies still find the testify to be unclear. [ 25 ] While it is improbable that hand brake contraception affects implantation it is impossible to completely exclude the hypothesis of post-fertilization effect. [ 26 ] In November 2013, the EMA besides approved a change to the label for HRA Pharma ‘s NorLevo say : “ In clinical trials, contraceptive efficacy was reduced in women weighing 75 kilogram [ 165 pounds ] or more, and levonorgestrel was not effective in women who weighed more than 80 kg [ 176 pounds ]. ” [ 24 ] [ 27 ] [ 28 ] In November 2013 and January 2014, the FDA and the EMA said they were reviewing whether increased slant and body batch index ( BMI ) reduce the efficacy of hand brake contraceptives. [ 24 ] An analysis of four WHO randomised clinical trials, published in January 2017, showed pregnancy rates of 1.25 % ( 68/5428 ) in women with BMI under 25, 0.61 % ( 7/1140 ) in women with BMI between 25 and 30, and 2.03 % ( 6/295 ) in women with BMI over 30. [ 29 ] These values yield an octuple reduction in efficacy for women with BMI over 30 compared to women with BMI under 25. however, hand brake contraceptives remain effective regardless of BMI .

Hormone therapy [edit ]

Levonorgestrel is used in combination with an estrogen in menopausal hormone therapy. [ 15 ] [ 30 ] It is used under the stigmatize name Klimonorm as a combine oral tablet with estradiol valerate and under the sword mention Climara Pro as a combine transdermal temporary hookup with estradiol. [ 15 ] [ 30 ]

available forms [edit ]

As a type of emergency contraception, levonorgestrel is used after unprotected sexual intercourse to reduce the risk of pregnancy. [ 31 ] however, it can serve unlike hormonal purposes in its different methods of pitch. It is available for use in a variety show of forms :

By mouth [edit ]

Levonorgestrel can be taken by mouthpiece as a shape of emergency birth control. The typical dose is either 1.5 milligram taken once or 0.75 mg taken 12–24 hours apart. [ 32 ] The effectiveness in both methods is similar. [ 32 ] The most widely use form of oral emergency contraception is the progestin-only pill, which contains a 1.5 milligram dose of levonorgestrel. [ 31 ] Levonorgestrel-only hand brake contraceptive pills are reported to have an 89 % potency rate if taken within the recommend 72 hours after arouse. [ 33 ] The efficacy of the drug decreases by 50 % for each 12 hour delay in taking the acid after the emergency contraceptive regimen has been started. [ 33 ]

Skin spot [edit ]

estradiol with levonorgestrel in the form of a bark eyepatch is used under the brand name Climara Pro for hormone substitute therapy in postmenstrual women, treating symptoms such as hot flashes or osteoporosis. [ 34 ] The coincident rescue of a progestin such as levonorgestrel is necessity for the protective covering of the endometrium. [ 35 ] [ 36 ]

Intrauterine device [edit ]

The levonorgestrel intrauterine system ( LNG-IUS ) is a character of long-run give birth control that releases the progestin into the uterine cavity. [ 37 ] [ 17 ] Levonorgestrel is released at a changeless, gradual pace of 0.02 mg per day by the polydimethylsiloxane membrane of the device, which renders it effective for up to 5 years. [ 37 ] Because it is inserted immediately into the uterus, levonorgestrel is present in the endometrium in much higher concentrations that would result from a LNG-containing oral pill ; the LNG-IUS delivers 391 ng of levonorgestrel to the inner uterine region while a comparable oral contraceptive delivers lone 1.35 ng. [ 37 ] This high horizontal surface of levonorgestrel impedes the affair of the endometrium, making it hostile for sperm transport, fertilization, and implantation of an ovum. [ 37 ]

implant [edit ]

hypodermic implants of levonorgestrel have been marketed as birth restraint implants under the mark names Norplant and Jadelle and are available for use in some countries. [ 38 ] [ 15 ]

Contraindications [edit ]

Known or suspected pregnancy is a contraindication of levonorgestrel as an emergency contraceptive. [ 39 ]

side effects [edit ]

After an consumption of 1.5 mg levonorgestrel in clinical trials, very park english effects ( reported by 10 % or more ) included : hives, dizziness, hair-loss, headache, nausea, abdominal pain, uterine pain, delayed menstruation, big menstruation, uterine shed blood, and tire ; common side effects ( reported by 1 % to 10 % ) included diarrhea, vomiting, and afflictive menstruation ; these side effects normally disappeared within 48 hours. [ 40 ] [ 41 ] however, the retentive term side effects common with oral contraceptives such as arterial disease are lower with levonorgestrel than in combination pills. [ medical citation needed ] Levonorgestrel as a contraceptive intrauterine device is associated with a higher hazard of summit cancer than with non-use. [ 42 ]

Overdose [edit ]

Overdose of levonorgestrel as an emergency contraceptive has not been described. [ 39 ] Nausea and vomit might be expected. [ 39 ]

Interactions [edit ]

If taken together with drugs that induce the CYP3A4 cytochrome P450 liver enzyme, levonorgestrel may be metabolized faster and may have lower potency. [ 43 ] These include, but are not limited to barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, diphenylhydantoin, rifampin, St. John ‘s wort and topiramate. [ medical citation needed ]

pharmacology [edit ]

Levonorgestrel ( LNG ) is a progestin and has effects like to those of the hormone progesterone. [ 5 ] It works chiefly by preventing ovulation and close off the cervix to prevent the passage of sperm. [ 5 ]

Pharmacodynamics [edit ]

Levonorgestrel is a progestin ; that is, an protagonist of the progesterone sense organ ( PR ), the main biological aim of the progestin arouse hormone progesterone. [ 2 ] It is besides a unaccented agonist of the androgen receptor ( AR ), the chief biological target of the androgen sex hormone testosterone. [ 2 ] Levonorgestrel has no other important hormonal activity, including no estrogenic, glucocorticoid, or antimineralocorticoid bodily process. [ 2 ] The miss of significant mineralocorticoid or antimineralocorticoid activity with levonorgestrel is in hurt of a relatively high affinity for the mineralocorticoid sense organ of arsenic much as 75 % of that of aldosterone. [ 2 ] due to its progestogenic bodily process, levonorgestrel has antigonadotropic effects, and is able to suppress fertility and gonadal sex hormone output in both women and men. [ 2 ] [ 44 ]

Relative affinities (%) of levonorgestrel and metabolites
Compound PR AR ER GR MR SHBG CBG
Levonorgestrel 150–162 34a, 45 0 1–8 17–75 50 0
5α-Dihydrolevonorgestrel 50 38a 0 ? ? ? ?
3α,5α-Tetrahydrolevonorgestrel ? ? 0.4 ? ? ? ?
3β,5α-Tetrahydrolevonorgestrel ? ? 2.4 ? ? ? ?
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PR, metribolone (a = mibolerone) for the AR, E2 for the ER, DEXA for the GR, aldosterone for the MR, DHT for SHBG, and cortisol for CBG. Sources: See template.

androgenic natural process [edit ]

Levonorgestrel is a decrepit androgenic progestin and in women may cause androgenic side effects such as decrease sex hormone-binding globulin ( SHBG ) levels, decreased HDL cholesterol levels, weight gain, and acne. [ 2 ] [ 45 ] In combination with a potent estrogen like ethinylestradiol however, all contraceptives containing androgenic progestins are negligibly androgenic in clinical drill and can in fact be used to treat androgen-dependent conditions like acne and hirsuteness in women. [ 45 ] This is because ethinylestradiol causes a commemorate increase in SHBG levels and thereby decreases levels of detached and hence bioactive testosterone, acting as a functional antiandrogen. [ 45 ] Nonetheless, contraceptives containing progestins that are less androgenic increase SHBG levels to a greater relative extent and may be more effective for such indications. [ 45 ] Levonorgestrel is presently the most androgenic progestin that remains used in contraceptives, and contraceptives containing levonorgestrel may be less effective for androgen-dependent conditions relative to those containing early progestins that are less androgenic. [ 46 ] [ 47 ] [ 48 ]

other activity [edit ]

Levonorgestrel stimulates the proliferation of MCF-7 breast cancer cells in vitro, an action that is independent of the classical PRs and is rather mediated via the progesterone sense organ membrane component-1 ( PGRMC1 ). [ 49 ] [ 50 ] Certain other progestins act similarly in this assay, whereas progesterone acts neutrally. [ 49 ] [ 50 ] It is indecipherable if these findings may explain the different risks of breast cancer observed with progesterone and progestins in clinical studies. [ 51 ]

Antigonadotropic effects [edit ]

In men, levonorgestrel causes marked suppression of circulating testosterone levels secondary coil to its antigonadotropic effects. [ 52 ] Because of this, and due to its androgenic activity being only weak and hence insufficient for purposes of androgen replacement in males, levonorgestrel has potent functional antiandrogenic effects in men, and is able to produce consociate adverse effects like decreased libido and erectile dysfunction among others. [ 52 ] In relative to this, levonorgestrel has been combined with an androgen like testosterone or dihydrotestosterone when it has been studied as a hormonal contraceptive in men. [ 44 ] [ 52 ]

Pharmacokinetics [edit ]

The bioavailability of levonorgestrel is approximately 95 % ( crop 85 to 100 % ). [ 2 ] [ 3 ] The plasma protein tie of levonorgestrel is about 98 %. [ 2 ] It is bound 50 % to albumin and 48 % to SHBG. [ 2 ] Levonorgestrel is metabolized in the liver, via reduction, hydroxylation, and union ( specifically glucuronidation and sulfation ). [ 2 ] [ 4 ] Oxidation occurs primarily at the C2α and C16β positions, while reduction occurs in the A gang. [ 4 ] 5α-Dihydrolevonorgestrel is produced as an active metabolite of levonorgestrel by 5α-reductase. [ 2 ] The elimination half life of levonorgestrel is 24 to 32 hours, although values equally short as 8 hours and ampere bang-up as 45 hours have been reported. [ 2 ] [ 4 ] About 20 to 67 % of a single oral dose of levonorgestrel is eliminated in urine and 21 to 34 % in feces. [ 4 ]

chemistry [edit ]

Levonorgestrel, besides known as 17α-ethynyl-18-methyl-19-nortestosterone or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one, is a man-made estrane steroid and a derivative of testosterone. [ 53 ] [ 54 ] It is the C13β or levorotary stereoisomer and enantiopure form of norgestrel, the C13α or dextrorotary isomer being inactive. [ 55 ] [ 56 ] Levonorgestrel is more specifically a derivative instrument of norethisterone ( 17α-ethynyl-19-nortestosterone ) and is the parent compound of the gonane ( 18-methylestrane ) subgroup of the 19-nortestosterone family of progestins. [ 57 ] Levonorgestrel acetate rayon and levonorgestrel butanoate are C17β esters of levonorgestrel. [ 58 ] [ 59 ] It has a molecular weight of 312.45 g/mol and a division coefficient ( logP ) of 3.8. [ citation needed ]

history [edit ]

Norgestrel ( rac -13-ethyl-17α-ethynyl-19-nortestosterone ), the racemic concoction containing levonorgestrel and dextronorgestrel, was discovered by Hughes and colleagues at Wyeth in 1963 via structural alteration of norethisterone ( 17α-ethynyl-19-nortestosterone ). [ 60 ] [ 61 ] [ 62 ] [ 63 ] It was the inaugural progestin to be manufactured via sum chemical deduction. [ 62 ] [ 63 ] Norgestrel was introduced for checkup function as a compound birth control condition pill with ethinylestradiol under the brand appoint Eugynon in Germany in 1966 and under the brand identify Ovral in the United States 1968, and as a progestogen-only pill under the trade name name Ovrette in the United States in 1973. [ 63 ] [ 64 ] [ 65 ] [ 66 ] Following its discovery, norgestrel had been licensed by Wyeth to Schering AG, which separated the racemic mix into its two optical isomers and identified levonorgestrel ( 13β-ethyl-17α-ethynyl-19-nortestosterone ) as the active agent component of the mixture. [ 10 ] [ 62 ] [ 63 ] Levonorgestrel was first studied in humans by 1970, and was introduced for checkup use in Germany as a combine birth control pill with ethinylestradiol under the brand diagnose Neogynon in August 1970. [ 10 ] [ 64 ] [ 65 ] [ 67 ] [ 68 ] [ 69 ] A more wide used conceptualization, containing lower doses of ethinylestradiol and levonorgestrel, was introduced under the brand name Microgynon by 1973. [ 15 ] [ 70 ] [ 71 ] In addition to combined formulations, levonorgestrel was introduced as a progestogen-only pill under the brand names Microlut by 1972 and Microval by 1974. [ 72 ] [ 73 ] Many other formulations and sword names of levonorgestrel-containing give birth control pills have besides been marketed. [ 15 ] Levonorgestrel, taken alone in a individual senior high school dose, was first evaluated as a kind of emergency contraception in 1973. [ 74 ] It was the second progestin to be evaluated for such purposes, following a study of quingestanol acetate rayon in 1970. [ 74 ] [ 75 ] In 1974, the Yuzpe regimen, which consisted of high doses of a unite parturition master pill containing ethinylestradiol and norgestrel, was described as a method acting of emergency contraception by A. Albert Yuzpe and colleagues, and saw widespread concern. [ 76 ] [ 77 ] Levonorgestrel-only emergency contraception was introduced under the brand name Postinor by 1978. [ 78 ] Ho and Kwan published the foremost study comparing levonorgestrel only and the Yuzpe regimen as methods of emergency contraception in 1993 and found that they had like effectiveness but that levonorgestrel alone was better-tolerated. [ 79 ] [ 80 ] In relation to this, the Yuzpe regimen has largely been replaced as a method acting of emergency contraception by levonorgrestrel-only preparations. [ 81 ] Levonorgestrel-only emergency contraception was approved in the United States under the stigmatize name Plan B in 1999, and has besides been marketed widely elsewhere throughout the populace under other brand names such as Levonelle and NorLevo in addition to Postinor. [ 15 ] [ 82 ] In 2013, the Food and Drug Administration approved Plan B One-Step for sale nonprescription in the United States without a prescription or age restriction. [ 83 ] Levonorgestrel has besides been introduced for use as a progestogen-only intrauterine device under the sword names Mirena and Skyla among others, as a progestogen-only parentage operate plant under the sword names Norplant and Jadelle, as a unite oral pill with estradiol valerate for menopausal hormone therapy under the sword name Klimonorm, and as a compound transdermal patch with estradiol for menopausal hormone therapy under the sword name Climara Pro. [ 15 ] [ 16 ] [ 30 ] Ester prodrugs of levonorgestrel such as levonorgestrel acetate and levonorgestrel butanoate have been developed and studied as other forms of give birth control such as long-acting progestogen-only injectable contraceptives and contraceptive vaginal rings, but have not been marketed for medical use. [ 58 ] [ 59 ]

society and polish [edit ]

Generic names [edit ]

Levonorgestrel is the generic mention of the drug and its INN, USAN, USP, BAN, DCIT, and JAN, while lévonorgestrel is its DCF. [ 15 ] [ 53 ] [ 54 ] It is besides known as d-norgestrel, d(–)-norgestrel, or D-norgestrel, deoxyadenosine monophosphate well as by its developmental code names WY-5104 ( Wyeth ) and SH-90999 ( Schering AG ). [ 15 ] [ 53 ] [ 54 ] [ 72 ]

Brand names [edit ]

Levonorgestrel is marketed alone or in combination with an estrogen ( specifically ethinylestradiol, estradiol, or estradiol valerate ) under a multitude of brand names throughout the world, including Alesse, Altavera, Alysena, Amethia, Amethyst, Ashlyna, Aviane, Camrese, Chateal, Climara Pro, Cycle 21, Daysee, Emerres, Enpresse, Erlibelle, Escapelle, Falmina, Introvale, Isteranda, Jadelle, Jaydess, Jolessa, Klimonorm, Kurvelo, Kyleena, Lessina, Levlen, Levodonna, Levonelle, Levonest, Levosert, Levora, Liletta, Loette, Logynon, LoSeasonique, Lutera, Lybrel, Marlissa, Microgynon, Microlut, Microvlar, Min-Ovral, Miranova, Mirena, My Way, Myzilra, Next Choice, Nordette, Norgeston, NorLevo, Norplant, One Pill, Option 2, Orsythia, Ovima, Ovranette, Plan B, Plan B One-Step, Portia, Postinor, Postinor-2, Preventeza, Ramonna, Rigevidon, Quartette, Quasense, Seasonale, Seasonique, Skyla, Sronyx, Tri-Levlen, Trinordiol, Triphasil, Triquilar, Tri-Regol, Trivora, and Upostelle, among many others. [ 15 ] [ 54 ] [ 84 ] These formulations are used as emergency contraceptives, normal contraceptives, or in menopausal hormone therapy for the discussion of menopausal symptoms. [ medical citation needed ] As an emergency contraceptive, levonorgestrel is much referred to colloquially as the “ morning-after pill ”. [ 85 ] [ 86 ]

handiness [edit ]

Levonorgestrel is identical widely marketed throughout the world and is available in about every nation. [ 15 ] [ 54 ]

approachability [edit ]

Levonorgestrel-containing hand brake contraception is available over-the-counter in some countries, such as the United States. [ 83 ] A policy update in 2015, required all amerind Health Services -run pharmacies, clinics, and emergency departments to have Plan B One-Step in stock, to distribute it to any charwoman ( or her congressman ) who asked for it without a prescription drug, old age verification, registration or any other prerequisite, to provide orientation trail to all staff regarding the medicine, to provide unbiased and medically accurate information about hand brake contraception, and to make person available at all times to distribute the pill in case the primary coil staff member objected to providing it on religious or moral grounds. [ 87 ]

research [edit ]

Levonorgestrel has been studied in combination with androgens such as testosterone and dihydrotestosterone as a hormonal contraceptive for men. [ 44 ] [ 52 ]

References [edit ]

  • Levonelle manufacturer’s product information from Schering
  • Monograph for levonorgestrel – Uk Medicines Information
  • “Levonorgestrel”. Drug Information Portal. U.S. National Library of Medicine.