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| Clinical data | |
|---|---|
| Trade names | Plan B, Plan B One-Step, others |
| Other names | LNG; LNG-EC; d-Norgestrel; d(–)-Norgestrel;D-Norgestrel; WY-5104; SH-90999; NSC-744007; 18-Methylnorethisterone; 17α-Ethynyl-18-methyl-19-nortestosterone; 17α-Ethynyl-18-methylestr-4-en-17β-ol-3-one; 13β-Ethyl-17α-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a610021 |
| Pregnancy category | |
| Routes of administration | By mouth,transdermal patch,intrauterine device,subcutaneous implant |
| Drug class | Progestogen (medication);Progestin |
| ATC code | |
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| Pharmacokinetic data | |
| Bioavailability | 95% (range 85–100%)[8][9] |
| Protein binding | 98% (50% toalbumin, 48% toSHBGTooltip sex hormone-binding globulin)[8] |
| Metabolism | Liver (reduction,hydroxylation,conjugation)[8][10] |
| Metabolites | •5α-Dihydro-LNG[8] |
| Eliminationhalf-life | 24–32 hours[8] |
| Excretion | Urine: 20–67% Feces: 21–34%[10] |
| Identifiers | |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.011.227 |
| Chemical and physical data | |
| Formula | C21H28O2 |
| Molar mass | 312.453 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 235 to 237 °C (455 to 459 °F) |
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Levonorgestrel is ahormonal medication used in a number ofbirth control methods.[7][11] It is combined with anestrogen to makecombination birth control pills.[12] As anemergency birth control, sold under the brand namesPlan B One-Step andJulie, among others, it is useful within 72 hours of unprotectedsex.[7][11][13] The more time that has passed since sex, the less effective the medication becomes.[11] Levonorgestrel works by preventing or delayingovulation 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 onimplantation.[14] It decreases the chances of pregnancy by 57–93%.[15] In anintrauterine device (IUD), such asMirena among others, it is effective for the long-term prevention ofpregnancy.[11] Alevonorgestrel-releasing implant is also available in some countries.[16]
Commonside effects includenausea,breast tenderness,headaches, andincreased,decreased, orirregular menstrual bleeding.[11] When used as an emergency contraceptive, if pregnancy occurs, there is no evidence that its useharms the fetus.[11] It is safe to use duringbreastfeeding.[11] Birth control that contains levonorgestrel will not change the risk ofsexually transmitted infections.[11] It is aprogestin and has effects similar to those of the hormoneprogesterone.[11] It works primarily by preventingovulation and closing off thecervix to prevent the passage ofsperm.[11]
Levonorgestrel was patented in 1960 and introduced for medical use together withethinylestradiol in 1970.[17][18] It is on theWorld Health Organization's List of Essential Medicines.[19] It is available as ageneric medication.[20] In the United States, levonorgestrel-containing emergency contraceptives are availableover the counter (OTC) for all ages.[21] In 2020, it was the 323rd most commonly prescribed medication in the United States, with more than 800 thousand prescriptions.[22]
At low doses, levonorgestrel is used inmonophasic andtriphasic formulations ofcombined oral contraceptive pills, with available monophasic doses ranging from 100 to 250 μg, and triphasic doses of 50 μg, 75 μg, and 125 μg.[23] It is combined with the estrogenethinylestradiol in these formulations.[23] In addition to the single-dose emergency contraceptive, Cipla and later Piramal marketedi-pill Daily, a 21‑tabletcombined daily oral contraceptive intended forregular birth control.[24][25]
At very low daily dose of 30 μg, levonorgestrel is used in someprogestogen-only pillformulations.[23]
Levonorgestrel is the active ingredient in a number ofintrauterine devices including Mirena and Skyla.[23][26] It is also the active ingredient in thebirth control implantsNorplant andJadelle.[23][26]
One of the more common forms of contraception that contains only levonorgestrel is an IUD. One IUD, the Mirena, is a small hollow cylinder containing levonorgestrel and polydimethylsiloxane and covered with a release rate-controlling membrane.[27]
Levonorgestrel is used inemergency contraceptive pills (ECPs), both in a combinedYuzpe regimen which includes estrogen, and as a levonorgestrel-only method. The levonorgestrel-only method uses levonorgestrel 1.5 mg (as a single dose or as two 0.75 mg doses 12 hours apart) taken within three days of unprotected sex. One study indicated that beginning as late as 120 hours (5 days) after intercourse could be effective.[medical citation needed] However, taking more than one dose of emergency contraception does not increase the chance of pregnancy not happening. Planned Parenthood asserts "Taking the morning-after pill (also known as emergency contraception) multiple times doesn't change its effectiveness, and won't cause any long-term side effects."[28]
The primary mechanism of action of levonorgestrel as a progestogen-only emergency contraceptive pill is, according toInternational Federation of Gynecology and Obstetrics (FIGO), to prevent fertilization by inhibition ofovulation and thickening of cervical mucus.[29][30][31][32] FIGO has stated that: "review of the evidence suggests that LNG [levonorgestreol] ECPs cannot prevent implantation of a fertilized egg. Language on implantation should not be included in LNG ECP product labeling."[33][34] In November 2013, theEuropean Medicines Agency (EMA) approved a change to the label saying it cannot prevent implantation of a fertilized egg.[35]
Other studies still find the evidence to be unclear.[36] While it is unlikely that emergency contraception affects implantation it is impossible to completely exclude the possibility of post-fertilization effect.[37]
In India, levonorgestrel for Emergency birth control was sold under the brand namei-pill. Introduced in 2007 byCipla as anover-the-counter (OTC) medication, I‑Pill is marketed as amorning-after pill and remains one of the most widely used emergency contraceptive brands in India.[38][39] The brand has become so prominent that its name is often used synonymously withbirth control pills among women in India.[40] The i-pill brand was sold toPiramal Healthcare Ltd in March 2010. Since then, Piramal Healthcare holds the manufacturing and marketing rights for i-pill in India.[41]
In November 2013, the EMA approved a change to the label forHRA Pharma'sNorLevo saying: "In clinical trials, contraceptive efficacy was reduced in women weighing 75 kg [165 pounds] or more, and levonorgestrel was not effective in women who weighed more than 80 kg [176 pounds]."[35][42][43] In November 2013 and January 2014, the FDA and the EMA said they were reviewing whether increased weight andbody mass index (BMI) reduce the efficacy of emergency contraceptives.[35]
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.[44] Hence, while there are differences, emergency contraceptives remain effective regardless of BMI.
Levonorgestrel is used in combination with anestrogen inmenopausal hormone therapy.[23][45] It is used under the brand nameKlimonorm as acombined oral tablet withestradiol valerate and under the brand nameClimara Pro as acombined transdermal patch withestradiol.[23][45]
As a type of emergency contraception, levonorgestrel is used after unprotected intercourse to reduce the risk of pregnancy.[46] However, it can serve different hormonal purposes in its different methods of delivery. It is available for use in a variety of forms:
Levonorgestrel can be taken by mouth as a form of emergency birth control. The typical dosage is either 1.5 mg taken once or 0.75 mg taken 12–24 hours apart.[47] The effectiveness in both methods is similar.[47] The most widely used form of oral emergency contraception is theprogestin-only pill, which contains a 1.5 mg dosage of levonorgestrel.[46] Levonorgestrel-only emergency contraceptive pills are reported to have an 89% effectiveness rate if taken within the recommended 72 hours after sex.[48] The efficacy of the drug decreases by 50% for each 12-hour delay in taking the dose after the emergency contraceptive regimen has been started.[48]
Estradiol with levonorgestrel in the form of a skin patch is used under the brand name Climara Pro forhormone replacement therapy in postmenstrual women, treating symptoms such ashot flashes orosteoporosis.[49] The simultaneous delivery of aprogestogen such as levonorgestrel is necessary for the protection of theendometrium.[50][51]
The levonorgestrel intrauterine system (LNG-IUS) is a type of long-term birth control that releases the progestin into the uterine cavity.[52][27] Levonorgestrel is released at a constant, gradual rate of 0.02 mg per day by the polydimethylsiloxane membrane of the device, which renders it effective for up to five years.[52] Because it is inserted directly 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 only 1.35 ng.[52] This high level of levonorgestrel impedes the function of the endometrium, making it hostile for sperm transport, fertilization, and implantation of an ovum.[52]
Subcutaneous implants of levonorgestrel have been marketed asbirth control implants under the brand names Norplant and Jadelle and are available for use in some countries.[53][23]
Known or suspected pregnancy is acontraindication of levonorgestrel as an emergency contraceptive.[54]
After an intake of 1.5 mg levonorgestrel inclinical trials, very commonside effects (reported by 10% or more) included:hives,dizziness,hair loss,headache,nausea,abdominal pain,uterine pain,delayed menstruation,heavy menstruation,uterine bleeding, andfatigue; common side effects (reported by 1% to 10%) includeddiarrhea,vomiting, andpainful menstruation; these side effects usually disappeared within 48 hours.[55][56] However, the long 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 contraceptiveintrauterine device has been associated with a slightly higher risk ofbreast cancer than with non-use in select studies.[57]
Overdose of levonorgestrel as an emergency contraoceptive has not been described.[54]Nausea andvomiting might be expected.[54]
If taken together with drugs thatinduce theCYP3A4cytochrome P450liverenzyme, levonorgestrel may bemetabolized faster and may have lower effectiveness.[58] These include, but are not limited to barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John's wort and topiramate.[medical citation needed]
Levonorgestrel is aprogestogen with weakandrogenic activity.[8] It has no other importanthormonal activity, including noestrogenic,glucocorticoid, orantimineralocorticoid activity.[8] The lack of significantmineralocorticoid or antimineralocorticoid activity with levonorgestrel is in spite of it having relatively highaffinity for themineralocorticoid receptor, which is as much as 75% of that ofaldosterone.[8]
| Compound | PRTooltip Progesterone receptor | ARTooltip Androgen receptor | ERTooltip Estrogen receptor | GRTooltip Glucocorticoid receptor | MRTooltip Mineralocorticoid receptor | SHBGTooltip Sex hormone-binding globulin | CBGTooltip Corticosteroid binding globulin |
|---|---|---|---|---|---|---|---|
| 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 (%). Referenceligands (100%) werepromegestone for thePRTooltip progesterone receptor,metribolone (a =mibolerone) for theARTooltip androgen receptor,E2 for theERTooltip estrogen receptor,DEXATooltip dexamethasone for theGRTooltip glucocorticoid receptor,aldosterone for theMRTooltip mineralocorticoid receptor,DHTTooltip dihydrotestosterone forSHBGTooltip sex hormone-binding globulin, andcortisol forCBGTooltip Corticosteroid-binding globulin.Sources: See template. | |||||||
Levonorgestrel is aprogestogen; that is, anagonist of theprogesterone receptor (PR), the mainbiological target of the progestogensex hormoneprogesterone.[8] It has effects similar to those of the hormoneprogesterone.[11] As a contraceptive, it works primarily by preventingovulation and closing off thecervix to prevent the passage ofsperm.[11] Theendometrial transformation dose of levonorgestrel is 150 to 250 μg/day or 2.5 to 6 mg per cycle.[8][59][60][61]
Due to its progestogenic activity, levonorgestrel hasantigonadotropic effects and is able to suppress the secretion of thegonadotropins,luteinizing hormone andfollicle-stimulating hormone, from thepituitary gland.[8] This in turn, results in suppression ofgonadal activity, including reduction offertility andgonadalsex hormoneproduction in both women and men.[8][62] Theovulation-inhibiting dose of levonorgestrel inpremenopausal women is 50 to 60 μg/day.[8][59][63]
In men, levonorgestrel causes marked suppression of circulating testosterone levels secondary to its antigonadotropic effects.[64] In healthy young men, levonorgestrel alone at a dose of 120 to 240 μg/day orally for 2 weeks suppressed testosterone levels from ~450 ng/dL to ~248 ng/dL (–45%).[65] Because of its effects on testosterone levels, and due to its androgenic activity being only weak and hence insufficient for purposes of androgen replacement in males, levonorgestrel has potent functionalantiandrogenic effects in men.[64] Consequently, it can produceadverse effects likedecreased libido anderectile dysfunction, among others.[64] Levonorgestrel has been combined with anandrogen liketestosterone ordihydrotestosterone when it has been studied as ahormonal contraceptive in men.[62][64]
Levonorgestrel is a weak agonist of theandrogen receptor (AR), the main biological target of theandrogen sex hormonetestosterone.[8] It is a weaklyandrogenic progestin and in women may cause androgenicbiochemical changes and side effects such as decreasedsex hormone-binding globulin (SHBG) levels, decreasedHDL cholesterol levels,weight gain, andacne.[8][66]
In combination with a potent estrogen likeethinylestradiol however, all contraceptives containing androgenic progestins are negligibly androgenic in practice and in fact can be used to treatandrogen-dependent conditions like acne andhirsutism in women.[66] This is because ethinylestradiol causes a marked increase in SHBG levels and thereby decreases levels of free and hence bioactive testosterone, acting as a functionalantiandrogen.[66] Nonetheless, contraceptives containing progestins that are less androgenic increase SHBG levels to a greater extent and may be more effective for such indications.[66] Levonorgestrel is currently the most androgenic progestin that is used in contraceptives, and contraceptives containing levonorgestrel may be less effective for androgen-dependent conditions relative to those containing other progestins that are less androgenic.[67][68][69]
Levonorgestrel stimulates theproliferation ofMCF-7breast cancercellsin vitro, an action that is independent of the classical PRs and is instead mediated via theprogesterone receptor membrane component-1 (PGRMC1).[70][71] Certain other progestins act similarly in this assay, whereasprogesterone acts neutrally.[70][71] It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins inclinical studies.[72]
Thebioavailability of levonorgestrel is approximately 95% (range 85 to 100%).[8][9] Theplasma protein binding of levonorgestrel is about 98%.[8] It is bound 50% toalbumin and 48% to SHBG.[8] Levonorgestrel ismetabolized in theliver, viareduction,hydroxylation, andconjugation (specificallyglucuronidation andsulfation).[8][10]Oxidation occurs primarily at the C2α and C16β positions, while reduction occurs in the A ring.[10]5α-Dihydrolevonorgestrel is produced as anactive metabolite of levonorgestrel by5α-reductase.[8] Theelimination half-life of levonorgestrel is 24 to 32 hours, although values as short as 8 hours and as great as 45 hours have been reported.[8][10] About 20 to 67% of a single oral dose of levonorgestrel iseliminated inurine and 21 to 34% infeces.[10]
Levonorgestrel, also known as 17α-ethynyl-18-methyl-19-nortestosterone or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one, is asyntheticestranesteroid and aderivative oftestosterone.[73][74] It is the C13β orlevorotatorystereoisomer andenantiopure form ofnorgestrel, the C13α or dextrorotatory isomer being inactive.[75][76] Levonorgestrel is more specifically a derivative ofnorethisterone (17α-ethynyl-19-nortestosterone) and is theparent compound of thegonane (18-methylestrane or 13β-ethylgonane) subgroup of the19-nortestosterone family of progestins.[77] Besides levonorgestrel itself, this group includesdesogestrel,dienogest,etonogestrel,gestodene,norelgestromin,norgestimate, andnorgestrel.[78]Levonorgestrel acetate andlevonorgestrel butanoate are C17βesters of levonorgestrel.[79][80] Levonorgestrel has amolecular weight of 312.45 g/mol and apartition coefficient (logP) of 3.8.[81][82]
Norgestrel (rac-13-ethyl-17α-ethynyl-19-nortestosterone), theracemic mixture containing levonorgestrel anddextronorgestrel, was discovered by Hughes and colleagues atWyeth in 1963 viastructural modification ofnorethisterone (17α-ethynyl-19-nortestosterone).[83][84][85][86] It was the first progestogen to be manufactured viatotal chemical synthesis.[85][86] Norgestrel was introduced for medical use as acombined birth control pill withethinylestradiol under the brand nameEugynon inGermany in 1966 and under the brand nameOvral in the United States 1968, and as aprogestogen-only pill under the brand nameOvrette in the United States in 1973.[86][87][88][89] Following its discovery, norgestrel had been licensed by Wyeth toSchering AG, which separated the racemic mixture into its twooptical isomers and identified levonorgestrel (13β-ethyl-17α-ethynyl-19-nortestosterone) as the active component of the mixture.[18][85][86] 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 nameNeogynon in August 1970.[18][87][88][90][91][92] A more widely used formulation, containing lower doses of ethinylestradiol and levonorgestrel, was introduced under the brand nameMicrogynon by 1973.[23][93][94] In addition to combined formulations, levonorgestrel was introduced as a progestogen-only pill under the brand namesMicrolut by 1972 andMicroval by 1974.[95][96] Many other formulations and brand names of levonorgestrel-containing birth control pills have also been marketed.[23]
Levonorgestrel, taken alone in a single high dose, was first evaluated as a form ofemergency contraception in 1973.[97] It was the second progestin to be evaluated for such purposes, following a study ofquingestanol acetate in 1970.[97][98] In 1974, theYuzpe regimen, which consisted of high doses of a combined birth control pill containing ethinylestradiol and norgestrel, was described as a method of emergency contraception byA. Albert Yuzpe and colleagues, and saw widespread interest.[99][100] Levonorgestrel-only emergency contraception was introduced under the brand namePostinor by 1978.[101] 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.[102][103] In relation to this, the Yuzpe regimen has largely been replaced as a method of emergency contraception by levonorgrestrel-only preparations.[104] Levonorgestrel-only emergency contraception was approved in the United States under the brand namePlan B in 1999, and has also been marketed widely elsewhere throughout the world under other brand names such asLevonelle andNorLevo in addition toPostinor.[23][105] In 2013, theFood and Drug Administration approvedPlan B One-Step for saleover-the-counter in the United States without a prescription or age restriction.[106]
Levonorgestrel has also been introduced for use as aprogestogen-only intrauterine device under the brand namesMirena andSkyla among others, as aprogestogen-only birth control implant under the brand namesNorplant andJadelle, as acombined oral tablet withestradiol valerate formenopausal hormone therapy under the brand nameKlimonorm, and as acombined transdermal patch withestradiol for menopausal hormone therapy under the brand nameClimara Pro.[23][26][45]Esterprodrugs of levonorgestrel such aslevonorgestrel acetate andlevonorgestrel butanoate have been developed and studied as other forms of birth control such as long-actingprogestogen-only injectable contraceptives andcontraceptive vaginal rings, but have not been marketed for medical use.[79][80]
Levonorgestrel is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name,USPTooltip United States Pharmacopeia,BANTooltip British Approved Name,DCITTooltip Denominazione Comune Italiana, andJANTooltip Japanese Accepted Name, whilelévonorgestrel is itsDCFTooltip Dénomination Commune Française.[23][73][74] It is also known asd-norgestrel,d(–)-norgestrel, orD-norgestrel, as well as by its developmental code namesWY-5104 (Wyeth) andSH-90999 (Schering AG).[23][73][74][95]
Levonorgestrel is marketed alone or in combination with anestrogen (specificallyethinylestradiol,estradiol, orestradiol valerate) under a multitude of brand names throughout the world, includingAlesse, 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.[23][74][107] These formulations are used as emergency contraceptives, normal contraceptives, or in menopausal hormone therapy for the treatment of menopausal symptoms.[medical citation needed]
As an emergency contraceptive, levonorgestrel is often referred to colloquially as the "morning-after pill".[108][109]
Levonorgestrel is very widely marketed throughout the world and is available in almost every country.[23][74]
Levonorgestrel-containing emergency contraception is availableover-the-counter in some countries, such as the United States.[106] On some college campuses, Plan B is available from vending machines.[110]
A policy update in 2015, required all pharmacies, clinics, and emergency departments run byIndian Health Services (for Native Americans) to have Plan B One-Step in stock, to distribute it to any woman (or her representative) who asked for it without a prescription, age verification, registration or any other requirement, to provide orientation training to all staff regarding the medication, to provide unbiased and medically accurate information about emergency contraception, and to make someone available at all times to distribute the pill in case the primary staffer objected to providing it on religious or moral grounds.[111]
Levonorgestrel has been studied in combination withandrogens such astestosterone anddihydrotestosterone as ahormonal contraceptive for men.[62][64]
[Levonorgestrel (24): The product generated by Smith's norgestrel total synthesis was a racemate, so half of each consisted of the left- and the right-handed enantiomer. Chemists at Schering discovered that only the levorotatory enantiomer was effective [49] and developed a biotechnological process for the preparation of the pure levorotatory enantiomer. This was the active ingredient levonorgestrel born. With the single-acting enantiomer, the dose and thus the liver burden could be halved again. The resulting Neogynon® contained 0.25 mg levonorgestrel and 0.05 mg ethinylestradiol and was introduced in 1970.]
{{cite book}}: CS1 maint: overridden setting (link) p. 121:Mechanism of action
Copper-releasing IUCs
When used as a regular or emergency method of contraception, copper-releasing IUCs act primarily to prevent fertilization. Emergency insertion of a copper IUC is significantly more effective than the use of ECPs, reducing the risk of pregnancy following unprotected intercourse by more than 99%.2,3 This very high level of effectiveness implies that emergency insertion of a copper IUC must prevent some pregnancies after fertilization.
Emergency contraceptive pills
To make an informed choice, women must know that ECPs—like the birth control pill, patch, ring, shot, and implant,76 and even like breastfeeding77—prevent pregnancy primarily by delaying or inhibiting ovulation and inhibiting fertilization, but may at times inhibit implantation of a fertilized egg in the endometrium. However, women should also be informed that the best available evidence indicates that ECPs prevent pregnancy by mechanisms that do not involve interference with post-fertilization events.
ECPs do not cause abortion78 or harm an established pregnancy. Pregnancy begins with implantation according to medical authorities such as the US FDA, the National Institutes of Health79 and the American College of Obstetricians and Gynecologists (ACOG).80
Ulipristal acetate (UPA). One study has demonstrated that UP can delay ovulation.81... Another study found that UPA altered the endometrium, but whether this change would inhibit implantation is unknown.82
p. 122:
Progestin-only emergency contraceptive pills. Early treatment with ECPs containing only the progestin levonorgestrel has been shown to impair the ovulatory process and luteal function.83–87
p. 123:
Combined emergency contraceptive pills. Several clinical studies have shown that combined ECPs containing ethinyl estradiol and levonorgestrel can inhibit or delay ovulation.107–110
How does EC work?
In 2002, a judicial review ruled that pregnancy begins at implantation, not fertilisation.8 The possible mechanisms of action should be explained to the patient as some methods may not be acceptable, depending on individual beliefs about the onset of pregnancy and abortion.
Copper-bearing intrauterine device (Cu-IUD). Copper is toxic to the ovum and sperm and thus the copper-bearing intrauterine device (Cu-IUD) is effective immediately after insertion and works primarily by inhibiting fertilisation.9–11 A systematic review on mechanisms of action of IUDs showed that both pre- and postfertilisation effects contribute to efficacy.11 If fertilisation has already occurred, it is accepted that there is an anti-implantation effect,12,13
Levonorgestrel (LNG). The precise mode of action of levonorgestrel (LNG) is incompletely understood but it is thought to work primarily by inhibition of ovulation.16,17
Ulipristal acetate (UPA). UPA's primary mechanism of action is thought to be inhibition or delay of ovulation.2
Can LNG ECPs cause an abortion?
LNG ECPs do not interrupt an established pregnancy or harm a developing embryo.15 The evidence available to date shows that LNG ECP use does not prevent a fertilized egg from attaching to the uterine lining. The primary mechanism of action is to stop or disrupt ovulation; LNG ECP use may also prevent the sperm and egg from meeting.16
Emergency postcoital contraception
Levonorgestrel
Mechanism and efficacy
Levonorgestrel-only emergency contraceptive pills:
• Interfere with the process of ovulation;
• May possibly prevent the sperm and the egg from meeting.
Implications of the research:
• Inhibition or delay of ovulation is LNG ECPs principal and possibly only mechanism of action.
• Review of the evidence suggests that LNG-ECs cannot prevent implantation of a fertilized egg. Language on implantation should not be included in LNG ECP product labeling.
• The fact that LNG-ECs have no demonstrated effect on implantation explains why they are not 100% effective in preventing pregnancy and are less effective the later they are taken. Women should be given a clear message that LNG-ECs are more effective the sooner they are taken.
• LNG ECPs do not interrupt a pregnancy (by any definition of the beginning of pregnancy). However, LNG ECPs can prevent abortions by reducing unwanted pregnancies.
NorLevo works by stopping your ovaries from releasing an egg. It cannot stop a fertilized egg from attaching to the womb.
Cipla helped create the emergency contraceptive market in India in 2007 when it launched the i‑Pill
Based on animal studies and clinical studies in women, 19‐norderived progestins are known to be potent in terms of gonadotropin suppression (Couzinet et al, 1996). Among this class of steroidal compounds are norethisterone (NET), norethynodrel, and its dextrorotatory isomer LNG (ie, the biologically active form of this progestin). The progestins of this class are known to be potent suppressors of gonadotropin secretion, and when administered to men these compounds induced a profound suppression of sperm production (Frick, 1973). However, a decrease in libido and sexual potency was also reported, presumably due to the suppression of T production secondary to gonadotropin suppression (Kamischke et al, 2000b). Therefore, like other progestins available thus far, nor‐progestins should not be administered alone for male contraception because their residual androgenic activity is not sufficient to maintain androgen‐dependent physiological functions like libido or sexual potency (Kamischke et al, 2000a).
The Population Council also plans to test vaginal rings with two other progestins, ST-1435 and levonorgestrel acetate, alone and combined with ethinyl estradiol (168).
The gonanes share the structural modifications found in the estranes and also possess [an ethyl] group at the position 13 and a keto group at position 3. Norgestrel was synthesized in 1963 and is a racemic mixture of dextro and levorotatory forms. The levorotatory form, levonorgestrel, provides the biological activity.
[Norgestrel] was discovered by Hughes et al. (1963).
Norgestrel, developed by Wyeth and patented in 1964, was the first progestogen to be manufactured by total chemical synthesis. It was subsequently licensed to Schering AG, who separated the racemic mixture into an inactive structural isomer l-norgestrel and the active d-norgestrel -- more usually known as dextronorgestrel and levonorgestrel respectively, because of the optical isomerism that each displays.
In 1964 the pharmaceutical company Wyeth developed norgestrel, the first progestogen to be made from a total chemical synthesis. Subsequently licensed to Schering AG, norgestrel was used to develop levonorgestrel, another active progestogen later used for oral contraception.
[The contraceptive EUGYNON is launched in 1966. NEOGYNON follows in 1970.]
The 1966 marketing campaign for Schering's second contraceptive, Eugynon, [...] (Schering AG Berline 1966, 11). [...] In 1970 [Schering] had already conducted an opinion poll among doctors in the run-up to the marketing campaign for the newly introduced Neogynon. [...]
[Since the safety of ovulation inhibition by levonorgestrel was also proven in the clinical studies, the cycle was extremely stable and the side effects were low, the drug was on August 1, 1970 introduced as Neogynon 21 and Neogynon 28 in Germany on the market.] [...] After the OC market had risen sharply in 1968 and 1969, the launch of Neogynon / Schering and Stediril-d / Wyeth in August 1970 gave the market a fresh boost.]
The results obtained in these series clinically confirmed the findings in animal work on the potency of d-norgestrel, i.e., that the biological activity of norgestrel resides largely in the d-enantlomer (5,6).
Comparison of the effects of Eugynon and Neogynon (.05 mg ethinyl estradiol with .5 mg norgestrel or with .25 mg d-norgestrel, respectively) in 272 women is reported. The 2 preparations were comparable as regards effectiveness (100%), cycle control, and endometrial and cervical morphology. No clinical or biological complications occurred, and the incidence of minor side effects was very small. The d-norgestrel preparation (Neogynon) may be preferable for metabolic reasons because of its lower steroid dose.
There are two main methods involving oral emergency pills, commonly misleadingly described as the 'morning-after pill'. The first older method, developed in the mid-1970s, involves two high-dose combined pills containing oestrogen (50 ug ethinyloestradiol) and progesterone (0.25 mg levonorgestrel): the Yuzpe regime (Schering PC4 or Ovran). The second involves progesterone only (0.75 mg levonorgestrel), and therefore, has a lower incidence of side effects, in particular vomiting (6%).
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