化工社化工社 化学情報印刷レポート · 研究参考用
ノルエチステロン
ノルエチステロン · ノルエチンドロン · ゲステスト · ミクロノル · ノルゲスチン · ノレチステロン · ノルプレグネニノロン · 17β-ヒドロキシ-17-エチニルエストラ-4-エン-3-オン
識別子と物理属性
| CAS No. | 68-22-4 |
|---|---|
| 分子式 | C20H26O2 |
| 平均分子量 | 298.4 g/mol |
| 単同位体質量 | 298.19328007 g/mol |
| SMILES | C#C[C@]1(O)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@@]21C |
| InChIKey | VIKNJXKGJWUCNN-XGXHKTLJSA-N |
| PubChem CID | 6230 |
| ChEMBL | CHEMBL1162 |
| ChEBI | CHEBI:7627 |
| EC No. | 200-681-6 |
| DTXSID | DTXSID9023380 |
| 現地名 | ノルエチステロン |
化学・物理的性質
| XLogP | 3 |
|---|---|
| 極性表面積 | 37.3 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 2 |
| 回転可能結合数 | 1 |
| 重原子数 | 22 |
| 形式電荷 | 0 |
| 複雑度 | 594 |
| 物質分類 | Pharmaceutical and(or) hormone |
| 医薬品 | Pharmaceuticals -> Listed in ZINC15 |
| 脂質 | Lipids -> Sterol Lipids [ST] -> Steroids [ST02] -> C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives [ST0203] |
| LogP（分配係数） | log Kow = 2.973.2 |
| 臭い | ODORLESS |
| 味 | Slightly bitter taste |
| Color/Form | White crystalline powderCrystals from ethyl acetate |
| 溶解度 | PRACTICALLY INSOL IN WATERSOL IN CHLOROFORM, ETHER, DIOXANESOL @ 25 °C: 1 IN 12.5 PARTS 95% ETHANOL, 1 IN 4 PARTS ACETONE /ACETATE/Solubility in double-distilled water, 0.98 mg/L /Norethindrone acetate/SLIGHTLY SOL IN VEGETABLE OILSOL @ 25 °C: 1 IN 150 PARTS 95% ETHANOL, 1 IN 5 PARTS PYRIDINE, 1 IN 80 PARTS ACETONE, 1 IN 30 PARTS CHLOROFORMSparingly soluble in alcoholsoluble in chloroform and dioxaneslightly soluble in ether.In double-distilled water, 1.44 mg/LIn water, 7.04 mg/L water at 25 °Cクロロホルム：50mg/mL 無色透明7.043mg/L(25℃) |
| Human Drugs | Breast FeedingLactationMilk, HumanContraceptive Agents, FemaleContraceptives, Oral, SyntheticFDA approved drugs -> Active ingredientPharmaceuticalsOral hormonal contraceptives |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| Decomposition | When heated to decomposition, it emits acrid smoke and fumes. |
| 融点 | 202-208C204 °CCrystals from methylene chloride and hexanemax absorption: 240 nm (e = 18,690)MP: 161-162 °C /Norethindrone acetate/203.5 °C397.4 °F205-206 °C (lit.) |
| 沸点 | 379.83°C (rough estimate) |
| 比旋光度 | D20 -31.7° (chloroform)D20 -25° (chloroform) |
| 密度 | 1.0766 (rough estimate) |
| 屈折率 | 1.4800 (estimate) |
| 貯蔵条件 | 2-8°C |
| 外観・状態 | 粉 |
| pKa（酸解離定数） | 13.09±0.40(Predicted) |
| 色 | ホワイトからオフホワイト |
| 由来生物 | rabbit |
| Merck | 6697 |
| BRN | 1915671 |
| Specific Activity | 122-165nmol/min·mg |
| ヘンリー定数 | 1.7×104 mol/(m3Pa) at 25℃, HSDB (2015) |
| BCS Class | 1 |
| 主な用途 | 医薬品（低分子化合物） |
| InChI | 1S/C20H26O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,12,15-18,22H,4-11H2,2H3/t15-,16+,17+,18-,19-,20-/m0/s1 |
| InChIKey | VIKNJXKGJWUCNN-XGXHKTLJSA-N |
| SMILES | O[C@@]1([C@@]2([C@H]([C@H]3[C@@H]([C@H]4CCC(=O)C=C4CC3)CC2)CC1)C)C#C |
| CAS データベース | 68-22-4(CAS DataBase Reference) |
| NISTの化学物質情報 | Norethindrone(68-22-4) |
| EPAの化学物質情報 | Norethisterone (68-22-4) |
化学的特性
Off-White to Pale Yellow Solid
安全性と法規制
| GHS 分類 | DangerH312 (28.4%): Harmful in contact with skin [Warning Acute toxicity, dermal]P203, P261, P271, P280, P302+P352, P304+P340, P317, P318, P321, P362+P364, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 67 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 規制情報 | Hazard Traits - CarcinogenicityDevelopmental ToxicityStatus: Active Update: 27-07-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/21038Norethindrone: Does not have an individual approval but may be used under an appropriate group standard |
| その他の安全情報 | IMAP assessments - 19-Norpregn-4-en-20-yn-3-one, 17-hydroxy-, (17.alpha.)-: Human health tier I assessment |
| FDA 要件 | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including norethindrone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including norethindrone acetate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Norethindrone acetate/ |
| Special Reports | National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Norethisterone (68-22-4) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s139nore.pdf] |
| Hazard Classes and Categories | Acute Tox. 4 (28.4%) |
| 保管条件 | Norethindrone acetate tablets should be stored in well-closed containers at room temperature (approximately 25 °C). |
| 処分方法 | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash. |
| 体内負荷 | Five women with well-established lactation (exact time postpartum not stated) were given an oral dose of 350 ug of norethindrone daily. Breastmilk levels were measured several times on the first day of treatment. Peak milk levels occurred at 2 or 4 hours after the dose in various individuals. Average milk levels were 0.747 ug/L at 2 hours after the dose0.747 mcg/L at 4 hours0.396 ug/L at 8 hours0.253 ug/L at 12 hoursand, 0.174 ug/L at 12 hours after the dose. ... Milk norethindone levels were measured in 4 women after daily ingestion of oral norethindrone 350 ug started after 3 months postpartum. Peak milk norethindrone levels in the range of 0.4 to 0.5 ug/L occurred between 1 and 3 hours after the dose and dropped slowly over the 6-hour study interval to about 0.15 to 0.4 ug/L. ... At 6 to 20 weeks postpartum, 15 women received a single tablet of a combination oral contraceptive containing a dose of 3 mg of norethindrone. At 2 to 2.5 hours after the dose, a foremilk sample was taken. The mothers breastfed their infants and then a hindmilk sample was taken. The two samples were pooled for assay. Milk levels averaged 2.4 ug/L (range 0.9 to 5.5 ug/L) ...At 6 to 20 weeks postpartum, 15 women received a single tablet of a combination oral contraceptive containing a dose of 3 mg of norethindrone. At 2 to 2.5 hours after the dose the mothers breastfed their infantsinfant serum samples were taken 1.5 to 2 hours later at about 4 hours after the maternal dose. Infant serum levels averaged 0.19 ug/L which was 0.8% of peak maternal serum levels drawn at 2 to 2.5 hours after the dose. |
| 相互作用 | The concomitant use of antibiotics and oral contraceptives should be included in the assessment of contraceptive failure. A case of unwanted adolescent pregnancy in an 18-year-old female who had a severe staphylococcal skin infection and an underlying chronic granulomatous disease is presented and discussed. She had been receiving semisynthetic penicillin (500 mg. of oxacillin sodium every 6 hours) for 6 weeks and reported not having a menstrual period for 40 days. She was also on an oral contraceptive (1 mg. norethindrone/0.035 mg. estradiol). Results of a beta subunit human chorionic gonadotropin in serum test confirmed that she was pregnant. Careful review of her contraceptive package and antibiotic prescription suggests that indeed she had faithfully followed directions with both medicines. She and her boyfriend and the family received counselinga therapeutic abortion was done. Advising a different contraceptive method or an additional contraceptive modality may be indicated in adolescents taking longterm antibiotic medication.... In a randomized, 2-way crossover study, 20 healthy female subjects received Treatments A and B. Treatment A consisted of a single dose of OrthoNovum containing 1 mg norethisterone (norethindrone) and 35 microg ethinyl estradiol. Treatment B consisted of bosentan, 125 mg b.i.d. for 7 days plus concomitant norethisterone and ethinyl estradiol on Day 7. Plasma concentrations of norethisterone and ethinyl estradiol were measured on days of oral contraceptive administration. In the absence of bosentan, the pharmacokinetics of norethisterone and ethinyl estradiol were characterized by Cmax and AUC0-infinity values (95% CI) of 9.8 (8.1, 11.9) ng/mL and 72.9 (57.0, 93.1) ng x hr/mL, and 53.0 (47.0, 59.9) pg/mL and 758 (655, 878) pg x hr/mL, respectively. Concomitant bosentan did not affect the Cmax but significantly decreased the AUC of norethisterone and ethinyl estradiol by 13.7% (-23.5, -2.6) and 31.0% (-40.5,-20.2), respectively. The maximum decrease in AUC of norethisterone and ethinyl estradiol in an individual subject was 56% and 66%, respectively. Bosentan decreases the AUC of norethisterone and ethinyl estradiol in healthy female subjects. In patients treated with bosentan, reduced efficacy of hormonal contraceptives should be considered.The effects of phenytoin treatment on plasma concentrations of norethisterone (NET) was studied in 7 healthy female rhesus monkeys. Before phenytoin treatment was started each monkey received an oral dose of 0.5 mg NET and 2 weeks later the same dose was given intravenously. On both occasions, plasma concentrations of NET were measured at frequent intervals during 24 hours. The monkeys were given phenytoin daily orally for more than 4 weeks. The absorption of phenytoin was confirmed by plasma determinations of phenytoin. While still on phenytoin treatment, the monkeys were again given 0.5 mg NET orally and 2 weeks later i.v. and blood sampling was repeated. During phenytoin treatment, plasma NET concentrations were always below those found before treatment. Both at iv and oral administration, the areas under the plasma concentration vs time curve (AUC) were reduced to 55% of the pretreatment AUCs. No difference in plasma half-life was found during phenytoin treatment. The results of this study may suggest that women on antiepileptic treatment with phenytoin should be given an oral contraceptive with a comparatively high dose of the steroids to provide contraceptive efficacy.The pharmacokinetics of norethisterone have been studied in 8 women during and one month after treatment with rifampicin (450--600 mg/day). Rifampicin caused a significant reduction in the AUC of a single dose of 1 mg norethisterone from 37.8 +/- 13.1 to 21.9 +/- 5.9 ng/mL X hr (p less than 0.01). The plasma norethisterone half life (beta-phase) was also reduced from 6.2 +/- 1.7 to 3.2 +/- 1.0 hr (p less than 0.0025). In one additional woman on long term oral contraceptive therapy the 12 hour plasma norethisterone concentration was reduced by rifampicin from 12.3 ng/mL to 2.3 ng/mL. Rifampicin caused a significant increase in antipyrine clearance, 6 beta-hydroxycortisol excretion and plasma gamma-glutamyltranspeptidase activity but there was no significant correlations between changes in these indices of liver microsomal enzyme induction. There was a significant correlation between the percentage increase in antipyrine clearance and the percentage decrease in norethisterone AUC during rifampicin. The changes in norethisterone pharmacokinetics during rifampicin therapy are compatible with the known enzyme inducing effect of rifampicin.For more Interactions (Complete) data for NORETHINDRONE (8 total), please visit the HSDB record page. |
| 生態毒性値 | LC50Species: Daphnia magna (Water flea, age <24 hr neonate)Conditions: freshwater, static, 20 °CConcentration: 6410 ug/L for 48 hr /100% purity/ |
| 環境中動態 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 220(SRC), determined from a log Kow of 2.97(2) and a regression-derived equation(3), indicates that norethindrone is expected to have moderate mobility in soil(SRC). Volatilization of norethindrone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.8X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Norethindrone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.1X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Biodegradation data in soil were not available(SRC, 2011).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 220(SRC), determined from a log Kow of 2.97(2) and a regression-derived equation(3), indicates that norethindrone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 5.8X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(5), an estimated BCF of 42(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data in water were not available(SRC, 2011).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), norethindrone, which has an estimated vapor pressure of 3.1X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase norethindrone is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 1.1 hours(SRC), calculated from its rate constant of 1.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase norethindrone may be removed from the air by wet or dry deposition(SRC). Norethindrone contains chromophores that absorb at wavelengths >290 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC). |
| 暴露経路 | Norethindrone acetate is completely and rapidly deacetylated to norethindrone (NET) after oral administration, and the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone is rapidly absorbed from norethindrone acetate, in which maximum plasma concentration occur 2 hours post-dose (Tmax). When a single dose is given to healthy women, the Cmax is 26.19 Њ± 6.19 hours. The AUC (0-inf) is 166.90 Њ± 56.28 ng/mL*h. Absolute oral bioavailability is approximately 64%. The effect of food on the pharmacokinetics of norethindrone acetate is unknown. |
| Milk Concentrations | EXPERIMENTAL: Five women with well-established lactation (exact time postpartum not stated) were given an oral dose of 350 ug of norethindrone daily. Breastmilk levels were measured several times on the first day of treatment. Peak milk levels occurred at 2 or 4 hours after the dose in various individuals. Average milk levels were 0.747 ug/L at 2 hours after the dose0.747 ug/L at 4 hours0.396 ug/L at 8 hours0.253 ug/L at 12 hoursand, 0.174 ug/L at 12 hours after the dose.EXPERIMENTAL: Milk norethindone levels were measured in 4 women after daily ingestion of oral norethindrone 350 ug started after 3 months postpartum. Peak milk norethindrone levels in the range of 0.4 to 0.5 ug/L occurred between 1 and 3 hours after the dose and dropped slowly over the 6-hour study interval to about 0.15 to 0.4 ug/L.EXPERIMENTAL: At 6 to 20 weeks postpartum, 15 women received a single tablet of a combination oral contraceptive containing a dose of 3 mg of norethindrone. At 2 to 2.5 hours after the dose, a foremilk sample was taken. The mothers breastfed their infants and then a hindmilk sample was taken. The two samples were pooled for assay. Milk levels averaged 2.4 ug/L (range 0.9 to 5.5 ug/L). |
| 毒性の概要 | Progestins diffuse freely into target cells and bind to the progesterone receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge. |
| Effluent Concentrations | For norethindrone, a concentration range of 0.45 to 1.20 ug/L was reported as a result of analysis of raw sewage entering 14 representative sewage plants within a 50-mile radius of Cincinnati, OHthe average concentration was 0.83 ug/L. The treated effluent concentration range was 0.28 to 1.01 ug/L, average 0.60 ug/L(1). Norethindrone was detected in effluent collected from an unspecified sedimentation tank at concentrations ranging from 8 to 20 ng/L(2). The compound was detected in effluent from the Eysines Sewage Treatment Plant (northern suburbs, Bordeaux, France) at mean concentrations of <5.0, <1.0, and <2.0 ng/L in July 2003, September 2003, and February 2004, respectively (detection limit = 5.0, 1.0, and 2.0 ng/L respectively)(3). Norethindrone was tested for but not detected (detection limit = 2-100 ng/L) in effluent samples from sewage treatment plants in the vicinity of Barcelona, Spain, sampled from April to June, 1999(4). |
| Soil Adsorption/Mobility | The Koc of norethindrone is estimated as 220(SRC), using a log Kow of 2.97(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that norethindrone is expected to have moderate mobility in soil. |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ 12 normal female volunteers were recruited to examine the effects of capsules containing 35 mcg ethinyl estradiol (EE) and 500 mcg norethisterone (NET) and suspended in an oily medium of polyethylene glycol 400 surrounded by a soft gelatin capsule on the pituitary-ovarian axis. These women were studied for 2 cyclesin the 1st cycle no capsules were taken and daily blood samples were drawn from days 5-21. FSH, LH, estradiol, and progesterone were assayed. In the next cycle, 35 mcg EE and 500 mcg NET were taken on days 5-21 with daily blood samples drawn. Capsules were taken 2 hours before blood sampling and FSH, LH, estradiol, and progesterone as well as EE and NET were assayed. ...Ten of 12 volunteers showed a control cycle suggestive of ovulation (serum progesterone levels greater than 30 nmol/L and a significant midcycle LH surge). During the pill cycle, these same 10 patients experienced suppression of ovulation as demonstrated by low progesterone levels in the second 1/2 of the cycle. NET and EE levels varied to the extent that they indicate a resonably physiologic variation. Results indicate that ovulation was suppressed in 11 of 12 subjects and cervical mucus studies showed that the local sperm blocking mechanism of the progestogen was operating whenever this parameter was assessed. This capsule formulation did suppress pituitary-ovarian function satisfactorily and the capsule is mainly acting by suppressing the positive feedback of estradiol on LH and not as strongly by suppressing follicular activity. .../SIGNS AND SYMPTOMS/ Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females./CASE REPORTS/ 2 cases of thromboembolism in young women with no risk factors except use of triphasic oral contraceptives are reported. A 21-year old White woman, Gravida I Para I, presented to the emergency room with a painful, blue, mottled right lower leg after pain in the hip and buttock for 1 week. She had taken a triphasic oral contraceptive containing 35 ug ethinyl estradiol and 0.5, 0.75, 1 mg norethindrone for 1 month, and had no other related history. Doppler and venogram tests showed thrombosis of the ileal, femoral, popliteal and infrapopliteal veins. She was treated with heparin, streptokinase, and urokinase without success and recovered after ileal, femoral and popliteal thrombectomy. The 2nd case was a 30-year-old Gravida III Para I Black woman who had taken a pill containing 50 ug ethinyl estradiol and 500 ug norgestrel for 13 years and had recently switched to the triphasic pill described above. She had dull midepigastric pain, nausea, vomiting, diarrhea and chills, for 1 week. Physical exam was negative except for abdominal tenderness and a heart murmur. Abdominal ultrasound revealed portal venous thrombosis extending to the splenic and superior mesenteric veins. She was treated with transhepatic urokinase without effect and celiotomy was performed. She was discharged with an occluded right branch of the portal vein./CASE REPORTS/ A 23-year-old woman presented with severe headache, followed by hemiparesis, seizures, and altered sensorium. She had been prescribed norethindrone acetate for the management of dysfunctional uterine bleeding secondary to polycystic ovary syndrome. Investigations revealed acquired hyperhomocysteinemia, presumably due to nutritional deficiencies, and evidence of CVST on MRI and magnetic resonance venography. Investigations showed no evidence of inherited thrombophilia. The patient was treated with low molecular weight heparin, followed by warfarin, vitamin B12, vitamin B6, and folic acid, and recovered successfully. Although venous thrombosis is usually linked to the ingestion of estrogen, rather than progestogen, this case illustrates that patients who are prescribed progestogen-only pills for gynaecological disorders may develop thrombosis, especially if they have predisposing metabolic disorders.For more Human Toxicity Excerpts (Complete) data for NORETHINDRONE (40 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Norethindrone's production and use in combination with other drugs as a contraceptive(1) may result in its release to the environment through various waste streams(SRC). |
| Carcinogen Classification | 2B, possibly carcinogenic to humans. (L135) |
| 水環境危害等級（WGK） | 3 |
| RTECS 番号 | RC8975000 |
| 輸送番号（UN） | UN 3077 9 / PGIII |
| 毒性 | LD50 oral in mouse: 6gm/kg |
| 税関コード | 29144000 |
| 危険文句（R） | 40-36/37/38-20/21/22 |
| 化審法 | (9)-2147 |
| 危険表示 | Xn |
| 安全措置（S） | 22-36/37/39-45-37/39-26 |
| 危険等級 | Aquatic Acute 1Aquatic Chronic 1Carc. 2Lact.Repr. 1A |
| 貯蔵分類 | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| 有害物質データ | 68-22-4(Hazardous Substances Data) |
用途
説明
Norethindrone is a progestin (a synthetic substance with properties similar to progesterone) that is best known as the first female oral contraceptive, or the “pill.”Norethindrone’s global impact on society and culture has made it one of the most important inventions in history.
来歴
The development of norethindrone as a female oral contraceptive took place indirectly over 30 years as a result of steroid research.This research accelerated in the 1930s when structures and medical applications of steroidal compounds were determined.Steroids are lipids, which include cholesterol, bile salts,and sex hormones,that are characterized by a structure of three fused six-carbon rings and a five-carbon ring. In 1957, both norethindrone and norethynodrel were approved by the Food and Drug Administration (FDA) for treating menstrual problems and infertility. In 1960, the FDA approved Searle's norethynodrel under the trade name Enovid. Norethindrone was approved as an oral contraceptive in 1962 under the trade name Ortho-Novum.
使用
Progesteron. Norethindrone and acetate in combination with estrogen as contraceptive (oral). It is reasonably anticipated to be a human carcinogen