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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.

/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.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Pregnant Belted Dutch rabbits were administered lynestrenol (17-alpha-ethynyl-oestr-4-en-17-beta-ol) orally on days 6-18 of gestation at a dose of 0.5 mg/kg/day. The dose littered on term and the surviving offspring were observed until four weeks old. Neurological disturbances characterized by behavioral abnormalities and locomotor disabilities were observed. About 40% of the offspring died within four weeks, and more than 70% of these had congenital malformations.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Pregnant Belted Dutch rabbits were administered lynestrenol 17-alpha-ethynyl-oestr-4-en-17-beta-ol) orally on days 6-18 of gestation at doses of 0.1, 0.5, and 2.5 mg/kg/day. On day 29 of gestation the does were killed and autopsied and the fetuses were examined for external, visceral and skeletal abnormalities. Lynestrenol administration produced a statistically significant increase in the number of post-implantation loss (p = 0.05) and in the average per cent of abnormal fetuses per dose group (63%, 66%, and 87% for the medicated group, versus 12% for the placebo group, p = 0.05). None of the doses tested was lethal to the does, but the average weight gain was decreased for the medium and the high dose groups. Abnormalities of the central nervous system and skeletal variants were the most frequent findings in the fetuses.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ 2 experiments on virgin female rats (average weight 200 g) were performed to study the effects of small doses of lynestrenol on the early pregnancy of the rat. In both experiments, the rats were caged with a mate overnight and if, on the following morning, spermatozoa were found on the vaginal smear, that day became Day 1 of pregnancy. In Experiment 1, the test group (15) received .1 mg lynestrenol sc and the control group (14) 1 mL propyleneglycol on Days 2, 3, 4, and 5 of pregnancy. Experiment 2 differed in that the rats received 1 mg dosages of lynestrenol. On Day 7 of pregnancy, Experiment 1 rats were killed and their ovaries and genital tracts were examined. In Experiment 2, the rats were permitted to live until Day 23 to see if they would achieve full-term pregnancy. If delivery did not occur, they were killed (Day 25) and examined for fetuses. In Experiment 1, the dose did not significantly increase the number of lost ova (20% in controls), as indicated by the implanted embryos/recent corpora lutea ratio counted on Day 7. There was an increase in the number of ciliated cells in the epithelium and a diminution of the deciduoid tissue of the stroma. No histological changes were seen in the ovaries, embyros, or uteri. The 1 mg dosage of lynestrenol prevented pregnancy in all of the rats. Doses were smaller than those needed to inhibit ovulation, and the time of administration of the doses excluded any action on sperm transport, capacitation, or penetration. Lynestrenol would appear to act on the pregnant rat's genital tract, as oviducts displayed evidence of estrogen stimulation.

/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/