Lynestrenol

284.44

284.44

200-151-4

N2Z8ALG4U5

73879|37725

DTXSID4021478

Solid

G - Genito urinary system and sex hormones

2937230000

20.2

4.75 (est)

1.1±0.1 g/cm3

159 °C

399.6±42.0 °C at 760 mmHg

176.9±20.9 °C

1.568

In water, 0.768 mg/L at 25 deg C (est)

6.91X10-8 mm Hg at 25 deg C (est)

D -13° (chloroform)

Henry's Law constant = 2.85X10-6 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 1.24X10-10 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

RC8964300

P201, P202, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P308+P313, P312, P322, P330, P363, P405, P501

H302

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.

|Danger|H302 (94.44%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P308+P313, P312, P322, P330, P363, P405, and P501|Aggregated GHS information provided by 18 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Lynestrenol, given 48 hr beforehand, enhances the elimination of phenobarbital and phenytoin from mouse plasma and consequently diminishes their anticonvulsant effect. The hexobarbital sleeping time is shortened and the in vitro metabolism of hexobarbital is accelerated by the same pretreatment. The increase of the rate of phenobarbital and phenytoin elimination may be due to acceleration of their metabolism by lynestrenol.

Oral contraceptives which owe their effectiveness to hormonal preparations. (See all compounds classified as Contraceptives, Oral, Hormonal.)|Oral contraceptives which owe their effectiveness to synthetic preparations. (See all compounds classified as Contraceptives, Oral, Synthetic.)

The tissue distribution of 4-14C-lynestrenol (17 alpha-ethynyl-oestr-4-en-17 beta-ol) following oral administration to pregnant rats was studied by whole body autoradiography and liquid scintillation counting. Pregnant females were sacrificed on days 10, 12, 14 and 19 of gestation, in each case 5 hours after oral administration of 43 uCi 4-14C-lynestrenol per animal. The isotopelabelled compound was distributed throughout most tissues, including the fetuses. The highest concentrations were found in the liver, while there was lower activity in the fatty tissues and the activity in the fetuses was comparable with that in the brain. The placental transfer was verified by the results of liquid scintillation counting. The concentration of labelled substance in the fetuses increased with the duration of pregnancy.|... The evaluation of plasma norethindrone levels in subjects receiving lynestrenol has not yet been reported. After the administration of norethindrone, the peak level of norethindrone in the plasma was obtained within 2 hours, and the peak concentration in the plasma was about 3.5 ng/mL/mg norethindrone. During a period of 2-6 hours after the administration of norethindrone, the half-life of norethindrone in the plasma was approximately 1.8 hours, and during the period of 6-24 hours, half-life was variable. On the other hand, after lynestrenol administration, the peak level of norethindrone in the plasma was obtained within 4 hours, and the peak concentration of norethindrone was about 1.9 ng/mL/mg lynestrenol. During a period of 4-12 hours, the half-life of norethindrone was about 2.5 hours. The peak of norethindrone level after lynestrenol administration was lower and appeared later than that after administration of the same dose of norethindrone. Norethindrone in plasma in subjects receiving lynestrenol could be measured for a longer period than in those receiving the same dose of norethindrone. These results suggest that lynestrenol is stored in fat tissue and is slowly metabolized to norethindrone.|The peak concentration, peak time, the area under the serum concentration time curve (AUC) and half-life of serum norethisterone (NET) after a single application of lynestrenol (LYN) to female volunteers demonstrated that 0.7 mg NET is bioequivalent to 1 mg LYN which is rapidly converted to NET. There was a decrease of the peak values and an increase of half-life of NET during the periovulatory and luteal phase which was, however, not significant due to the great individual differences. The shift of the peak time to longer intervals and the increase of half-life of NET after ingestion of higher LYN doses indicate a certain limitation of the metabolic capacity of the liver. ...|... Eleven normal males were administer either 1 capsule containing 2.5 mg lynestrenol and 0.05 mg ethynylestradiol or tablets containing the same dose of steroids. Blood samples were taken just before and 1,2,4,8, and 24 hours after the drugs were administered. 8 days later the subjects were given the opposite formulations and blood samples were again obtained at the same time intervals. Radioimmunoassay was used to assess levels of free and conjugated ethynylestradiol and norethisterone in the serum samples. Biovailability assessments were made by calculating the areas under the time-concentration curves. Results demonstrated that the conversion of lynestrenol to norethisterone in vivo was complete. Unconjugated ethynylestradiol mean values, 2 and 4 hours after administration of the drugs, were higher for capsules than for tablets. For blood samples taken at other time periods the mean values of unconjugated ethynylestradiol were similar for both capsules and tablets. For conjugated ethynylestradiol the mean values and the areas under the curve, for blood samples obtained at each time interval, showed no significant difference for tablets and capsules.|167 women were treated with 0.5 mg lynestrenol/day for a period of 8-32 weeks immediately postpartum. The lactation periods of 67 of the women were observed during the stay in hospital (maximum 7 days) in comparison with a control group (n = 20) of untreated women in the puerperium. There was no quantitative difference in milk production between the lynestrenol-treated women and the control group. ...

The concentration of norethindrone in plasma samples from subjects receiving norethindrone (norethisterone) and lynestrenol orally was measured by high pressure liquid chromatography (HPLC). Norethindrone is a synthetic gestagen widely used in contraceptive formulations, and lynestrenol is also a synthetic gestagen which is metabolized to norethindrone in humans.|Although /little/ is known about the transformation of lynestrenol and norethynodrel, it appears that lynestrenol first undergoes hydroxylation at carbon 3 and then oxidation of the hydroxyl group to form norethisterone.|There is limited information on the metabolism of levonorgestrel, norethindrone and structurally related contraceptive steroids. Both levonorgestrel and norethindrone undergo extensive reduction of the alpha, beta-unsaturated ketone in ring A. Levonorgestrel also undergoes hydroxylation at carbons 2 and 16. The metabolites of both compounds circulate predominantly as sulfates. In urine, levonorgestrel metabolites are found primarily in the glucuronide form, whereas norethindrone metabolites are present in approximately equal amounts as sulfates and glucuronides. Of the progestogens structurally related to norethindrone, norethindrone acetate, ethynodiol diacetate, norethindrone enanthate, and perhaps lynestrenol, undergo rapid hydrolysis and are converted to the parent compound and its metabolites. There is no convincing evidence that norethynodrel is converted to norethindrone. Of the progestogens structurally related to levonorgestrel, it appears that neither desogestrel nor gestodene are transformed to the parent compound. However, there is evidence that norgestimate can be, at least partly, converted to levonorgestrel. ...

Lynestrenol, a synthetic steroid progesterone-like substance, has been found to enhance the stimulation of normal human lymphocytes. It increases the phytohemagglutinin response and the mixed-lymphocyte cultures. This augmentation can, in some cases, be higher than 100% of the phytohemagglutinin or mixed lymphocyte reaction baseline. There is no significant effect on the pokeweed mitogen stimulation. It is concluded that lynestrenol can modulate, "in vitro", some T cell functions.|In 10 women taking 0.5 mg lynestrenol for oral contraception endometrium biopsies were carried out in several consecutive cycles between the 21st and 25th day of each cycle. In addition pregnandiol excretion in the urine was measured in one of the last three treatment cycles always on the 10th and 21st day of cycle. During treatment of a characteristic, monomorphic microscopical endometrium picture was observed with hardly distinct endometrium glands and only slight decidualike transformation of cellular elements of the stroma. From these histological pictures it is concluded that oral application of 0,5 mg lynestrenol produces endometrium changes characterized by insufficient transformation so that nidation of a blastocyte becomes impossible.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ 8 women, aged 22-28, with normal, ovulatory menstrual cycles, volunteered to take different doses of Lynestrenol to determine its effects on Luteineizing Hormone (LH) secretion, and on plasma progesterone levels. Blood samples were taken in the morning and plasma was immediately separated. Results showed that body temperature varied unpredictably during the cycle, and therefore could not be considered a reliable parameter of ovulation. 0.35 mg of Lynestrenol administered daily was enough to suppress ovulation, as evidenced by the absence of LH during midcycle. Although differences exists in individual reactions, administration of Lynestrenol beyond 0.6 mg. daily always suppresses ovulation because of hypothalamo-pituitary inhibition, while doses below 0.5mg. daily can bring about episodic peaks. It is still not clear how Lynestrenol influences gonadotropins, especially LH, while intermittent bleeding seems to be the only sure side effect.|/CASE REPORTS/ ... /The authors/ report the case of a 48-year-old woman with liver adenomatosis (LA), who had been taking an androgenic progestin therapy (lynestrenol) for 10 years. A major regression in the number and size of the lesions was observed 6 months after complete withdrawal of this therapy. Hepatocellular adenomas were studied by immunohistochemistry for estrogen, progesterone and androgen receptors (ER, PR and AR respectively), and for beta-catenin. Direct sequencing of the HNF-1alpha gene was also performed. ... /Investigators/ demonstrate significant immunostaining of AR in the hepatocellular adenomas. This staining was negative in the partially regressive adenoma. Immunostainings for ER and PR were negative. HNF-1alpha and the beta-catenin pathways were not involved in tumour pathogenesis. /This/ case suggests a role of androgenic progestin therapy in some cases of LA. Hormone therapy withdrawal may induce a significant regression in lesions.|/CASE REPORTS/ .../The authors/ present the case of a 32-year-old patient, who came for a check-up to /a/ gynaecology and obstetrics clinic ... because of irregular bleeding. The patient was subjected to hormonal linestrenol therapy, which she had administered herself, without further consultations with her gynecologist, during the previous 10 years. Complete diagnostic examinations were performed. Contrast sonohysterography enabled the visualization of multiple polyps inside the uterine cavity, which were confirmed by histopathological analysis of material obtained via explorative curettage. Histopathological material contained over 30 endometrial polyps. A control check-up after one month, as well as subsequent quarterly check-ups, resulted in normal findings. Analysis of the described case has indicated that the loss of sensitivity of progesterone receptors in endometrial cells is possible if there is a continuous presence of progesterone agonists in circulation, as is true of linestrenol in this case. The loss of sensitivity of progesterone receptors upsets normal hormonal activity during the secretory phase of the menstrual cycle, leading to copious, irregular bleeding. ...|/CASE REPORTS/ ... /Investigators/ report on a 24-year-old woman with variegate porphyria who, after intake of lynestrenol, developed typical cutaneous lesions but no viscero-neurological symptoms. The diagnosis was based on the characteristic urinary coproporphyrin and fecal protoporphyrin excretion patterns, and the specific peak of plasma fluorescence at 626 nm in spectrofluorometry. Biochemical analysis revealed that most of the family members, though free of clinical symptoms, excrete porphyrin metabolites in urine and stool similar to variegate porphyria, accompanied by a significant decrease of porphobilinogen deaminase activity of a range which is ordinarily found in patients with acute intermittent porphyria only (approximately 50%). These data first led to the assumption of two separate and independently inherited genetic defects, similar to the dual porphyria of Chester. Molecular analysis, however, revealed only a missense mutation of the protoporphyrinogen oxidase gene, but not of the porphobilinogen deaminase gene. Thus, in the family presented, porphobilinogen deaminase deficiency is likely to be a phenomenon secondary to the genetic defect of protoporphyrinogen oxidase.|For more Human Toxicity Excerpts (Complete) data for Lynestrenol (8 total), please visit the HSDB record page.

19-Norpregn-4-en-20-yn-17-ol, (17alpha)-

Lynestrenol is available commercially as a single-ingredient tablet and as a component of combination tablets that contain ethinylestradiol or mestranol.|Mixture wuth ethinyl estradiol. Fysionorm, Minilyn, Ovanon, Ovoresta, Yermonil.|Mixture with mestranol. Lyndiol.

... Infra-red absorption spectrophotometry with comparison to standards as the method for identifying lynoestrenol; potentiometric titration with sodium hydroxide is used to assay its purity.

Lipids -> Sterol Lipids [ST] -> Steroids [ST02] -> C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives [ST0203]