At low doses, levonorgestrel is used in monophasic and triphasic formulations of combined oral contraceptive pills, with available monophasic doses ranging from 100 to 250 μg, and triphasic doses of 50 μg, 75 μg, and 125 μg.[19] It is combined with the estrogen ethinylestradiol in these formulations.[19]
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.[21]
Emergency birth control
Levonorgestrel is used in emergency contraceptive pills (ECPs), both in a combined Yuzpe 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."[22]
The primary 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.[23][24][25][26] 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."[27][28] In November 2013, the European Medicines Agency (EMA) approved a change to the label saying it cannot prevent implantation of a fertilized egg.[29]
Other studies still find the evidence to be unclear.[30] While it is unlikely that emergency contraception affects implantation it is impossible to completely exclude the possibility of post-fertilization effect.[31]
In November 2013, the EMA also approved a change to the label for HRA Pharma's NorLevo 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]."[29][32][33] In November 2013 and January 2014, the FDA and the EMA said they were reviewing whether increased weight and body mass index (BMI) reduce the efficacy of emergency contraceptives.[29]
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.[34] These values yield an eight-fold reduction in efficacy for women with a BMI over 30 compared to women with a BMI under 25. However, emergency contraceptives remain effective regardless of BMI.
As a type of emergency contraception, levonorgestrel is used after unprotected intercourse to reduce the risk of pregnancy.[36] However, it can serve different hormonal purposes in its different methods of delivery. It is available for use in a variety of forms:
By mouth
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.[37] The effectiveness in both methods is similar.[37] The most widely used form of oral emergency contraception is the progestin-only pill, which contains a 1.5 mg dosage of levonorgestrel.[36] Levonorgestrel-only emergency contraceptive pills are reported to have an 89% effectiveness rate if taken within the recommended 72 hours after sex.[38] 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.[38]
The levonorgestrel intrauterine system (LNG-IUS) is a type of long-term birth control that releases the progestin into the uterine cavity.[42][21] 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.[42] 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.[42] This high level of levonorgestrel impedes the function of the endometrium, making it hostile for sperm transport, fertilization, and implantation of an ovum.[42]
Overdose of levonorgestrel as an emergency contraceptive has not been described.[44]Nausea and vomiting might be expected.[44]
Interactions
If taken together with drugs that induce the CYP3A4cytochrome P450liverenzyme, levonorgestrel may be metabolized faster and may have lower effectiveness.[48]
These include, but are not limited to barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John's wort and topiramate.[medical citation needed]
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PRTooltip progesterone receptor, metribolone (a = mibolerone) for the ARTooltip androgen receptor, E2 for the ERTooltip estrogen receptor, DEXATooltip dexamethasone for the GRTooltip glucocorticoid receptor, aldosterone for the MRTooltip mineralocorticoid receptor, DHTTooltip dihydrotestosterone for SHBGTooltip sex hormone-binding globulin, and cortisol for CBGTooltip Corticosteroid-binding globulin. Sources: See template.
In men, levonorgestrel causes marked suppression of circulating testosterone levels secondary to its antigonadotropic effects.[54] 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%).[55] 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 functional antiandrogenic effects in men.[54] Consequently, it can produce adverse effects like decreased libido and erectile dysfunction, among others.[54] Levonorgestrel has been combined with an androgen like testosterone or dihydrotestosterone when it has been studied as a hormonal contraceptive in men.[52][54]
In combination with a potent estrogen like ethinylestradiol however, all contraceptives containing androgenic progestins are negligibly androgenic in practice and in fact can be used to treat androgen-dependent conditions like acne and hirsutism in women.[56] This is because ethinylestradiol causes a marked increase in SHBG levels and thereby decreases levels of free and hence bioactive testosterone, acting as a functional antiandrogen.[56] Nonetheless, contraceptives containing progestins that are less androgenic increase SHBG levels to a greater extent and may be more effective for such indications.[56] 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.[57][58][59]
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).[73][74][75][76] It was the first progestogen to be manufactured via total chemical synthesis.[75][76] 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.[76][77][78][79] 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.[14][75][76] 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.[14][77][78][80][81][82] A more widely used formulation, containing lower doses of ethinylestradiol and levonorgestrel, was introduced under the brand name Microgynon by 1973.[19][83][84] In addition to combined formulations, levonorgestrel was introduced as a progestogen-only pill under the brand names Microlut by 1972 and Microval by 1974.[85][86] Many other formulations and brand names of levonorgestrel-containing birth control pills have also been marketed.[19]
Levonorgestrel, taken alone in a single high dose, was first evaluated as a form of emergency contraception in 1973.[87] It was the second progestin to be evaluated for such purposes, following a study of quingestanol acetate in 1970.[87][88] 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.[89][90] Levonorgestrel-only emergency contraception was introduced under the brand name Postinor by 1978.[91] 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.[92][93] In relation to this, the Yuzpe regimen has largely been replaced as a method of emergency contraception by levonorgrestrel-only preparations.[94] 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.[19][95] 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.[96]
Levonorgestrel is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, USPTooltip United States Pharmacopeia, BANTooltip British Approved Name, DCITTooltip Denominazione Comune Italiana, and JANTooltip Japanese Accepted Name, while lévonorgestrel is its DCFTooltip Dénomination Commune Française.[19][63][64] It is also known as d-norgestrel, d(–)-norgestrel, or D-norgestrel, as well as by its developmental code names WY-5104 (Wyeth) and SH-90999 (Schering AG).[19][63][64][85]
Brand names
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.[19][64][97] 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".[98][99]
Levonorgestrel is very widely marketed throughout the world and is available in almost every country.[19][64]
Accessibility
Levonorgestrel-containing emergency contraception is available over-the-counter in some countries, such as the United States.[96] On some college campuses, Plan B is available from vending machines.[100]
A policy update in 2015, required all pharmacies, clinics, and emergency departments run by Indian 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.[101]
^ abFotherby K (August 1996). "Bioavailability of orally administered sex steroids used in oral contraception and hormone replacement therapy". Contraception. 54 (2): 59–69. doi:10.1016/0010-7824(96)00136-9. PMID8842581.
^ abcdefShoupe D, Haseltine FP (6 December 2012). Contraception. Springer Science & Business Media. pp. 22–. ISBN978-1-4612-2730-4. Archived from the original on 28 August 2021. Retrieved 15 April 2018.
^"Chapter 1". Research on reproductive health at WHO: biennial report 2000-2001. Geneva: World health organization. 2002. ISBN9789241562089. Archived from the original on 2015-09-26.
^ abcRoth K (2014). Chemische Leckerbissen. John Wiley & Sons. pp. 77–. ISBN978-3-527-33739-2. Archived from the original on 2021-08-28. Retrieved 2018-04-18. [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.]
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^ abcFriend DR (October 2016). "Development of controlled release systems over the past 50 years in the area of contraception". Journal of Controlled Release. 240: 235–241. doi:10.1016/j.jconrel.2015.12.043. PMID26732558.
^Trussell J, Schwarz EB (2011). "Emergency contraception". In Hatcher RA, Trussell J, Nelson AL, Cates Jr W, Kowal D, Policar MS (eds.). Contraceptive technology (20th revised ed.). New York: Ardent Media. pp. 113–145. ISBN978-1-59708-004-0. ISSN0091-9721. OCLC781956734. 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
^RCOG Faculty of Sexual; Reproductive Healthcare; Clinical Effectiveness Unit (January 2012). "Clinical guidance: emergency contraception"(PDF). Clinical Guidance. London: Royal College of Obstetricians and Gynaecologists. ISSN1755-103X. Archived from the original(PDF) on 2012-05-26. Retrieved 2012-04-30. p.3:
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
^Speroff L, Darney PD (2011). "Special uses of oral contraception: emergency contraception, the progestin-only minipill". A clinical guide for contraception (5th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 153–166. ISBN978-1-60831-610-6. p. 155:
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.
^Glasier A, Cameron ST, Blithe D, Scherrer B, Mathe H, Levy D, Gainer E, Ulmann A (October 2011). "Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel". Contraception. 84 (4): 363–7. doi:10.1016/j.contraception.2011.02.009. PMID21920190.
^Endrikat J, Gerlinger C, Richard S, Rosenbaum P, Düsterberg B (December 2011). "Ovulation inhibition doses of progestins: a systematic review of the available literature and of marketed preparations worldwide". Contraception. 84 (6): 549–57. doi:10.1016/j.contraception.2011.04.009. PMID22078182.
^ abcdeMeriggiola MC, Farley TM, Mbizvo MT (2003). "A review of androgen-progestin regimens for male contraception". Journal of Andrology. 24 (4): 466–83. doi:10.1002/j.1939-4640.2003.tb02695.x. PMID12826683. 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).
^ abNeubauer H, Ma Q, Zhou J, Yu Q, Ruan X, Seeger H, Fehm T, Mueck AO (October 2013). "Possible role of PGRMC1 in breast cancer development". Climacteric. 16 (5): 509–13. doi:10.3109/13697137.2013.800038. PMID23758160. S2CID29808177.
^ abRuan X, Neubauer H, Yang Y, Schneck H, Schultz S, Fehm T, Cahill MA, Seeger H, Mueck AO (October 2012). "Progestogens and membrane-initiated effects on the proliferation of human breast cancer cells". Climacteric. 15 (5): 467–72. doi:10.3109/13697137.2011.648232. PMID22335423. S2CID11302554.
^ abPopulation Reports: Injectables and implants. Department of Medical and Public Affairs, George Washington University. 1987. Archived from the original on 2021-04-20. Retrieved 2018-04-15. 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).
^ abCrabbé P, Archer S, Benagiano G, Diczfalusy E, Djerassi C, Fried J, Higuchi T (March 1983). "Long-acting contraceptive agents: design of the WHO Chemical Synthesis Programme". Steroids. 41 (3): 243–53. doi:10.1016/0039-128X(83)90095-8. PMID6658872. S2CID12896179.
^Meikle AW (1 June 1999). Hormone Replacement Therapy. Springer Science & Business Media. pp. 383–. ISBN978-1-59259-700-0. Archived from the original on 1 August 2020. Retrieved 15 April 2018. 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.
^ abcFilshie M, Guillebaud J (22 October 2013). Contraception: Science and Practice. Elsevier Science. pp. 12–. ISBN978-1-4831-6366-6. 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.
^ abcdMarks L (2010). Sexual Chemistry: A History of the Contraceptive Pill. Yale University Press. pp. 73, 76. ISBN978-0-300-16791-7. 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.
^ abOrtiz-Gómez T, Santesmases MJ (22 April 2016). Gendered Drugs and Medicine: Historical and Socio-Cultural Perspectives. Taylor & Francis. pp. 175–. ISBN978-1-317-12981-3. Archived from the original on 6 October 2021. Retrieved 18 April 2018. 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. [...]
^Albach H (1993). Culture and Technical Innovation: A Cross-Cultural Analysis and Policy Recommendations. Walter de Gruyter. p. 952. ISBN978-3-11-013947-1. Archived from the original on August 28, 2021. Retrieved August 5, 2020. [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.]
^Apelo R, Veloso I (1970). "Results of a controlled study employing d-norgestrel and ethinyl estradiol". Contraception. 2 (6): 391–400. doi:10.1016/S0010-7824(70)80002-6. ISSN0010-7824. 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).
^Brosens I, Van Assche A, Wijnants P (1971). "Comparative clinical and morphological studies on 2 oral contraceptives which contain DL-norgestrel and D-norgestrel respectively". Geburtshilfe und Frauenheilkunde. 31 (3): 251–257. Archived from the original on 2018-04-15. Retrieved 2018-04-15. 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.
^Schneider W, Spona J, Matt K (1974). "Inhibition of ovulation by means of a combined preparation with reduced amounts of active substance". Contraception. 9 (1): 81–92. doi:10.1016/0010-7824(74)90096-1. ISSN0010-7824.
^Brat T (1974). "Clinical trial with a new low oestrogen combined oral contraceptive". Current Medical Research and Opinion. 2 (8): 465–470. doi:10.1185/03007997409115244. PMID4614952.
^Balaji (19 November 2009). Textbook of Oral and Maxillofacial Surgery. Elsevier India. p. 569. ISBN978-81-312-0300-2. Archived from the original on 28 August 2021. Retrieved 15 April 2018. 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%).
^Yuzpe AA, Thurlow HJ, Ramzy I, Leyshon JI (August 1974). "Post coital contraception--A pilot study". The Journal of Reproductive Medicine. 13 (2): 53–8. PMID4844513.
^Ho PC, Kwan MS (March 1993). "A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception". Human Reproduction. 8 (3): 389–92. doi:10.1093/oxfordjournals.humrep.a138057. PMID8473453.
