Disease relevance of norethynodrel

• Enovid-induced exacerbation of high blood pressure in stroke-prone rats (SHR) [1].
• All steroids and combinations, except norethynodrel administered alone (154 mug/kg/day), reduced body weight gain [2].
• Female guinea pigs were given daily doses of a combination of oral contraceptive (OC) agents, consisting of mestranol and norethynodrel suspended in sesame oil or distilled H2O, and were infected in the genital tract with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC) [3].
• Fifty patients with endometriosis were treated with hormones: 27 with danazol and 23 with Enavid (mestranol 75 micrograms and norethynodrel 5 mg) [4].
• Two oral contraceptive steroids, mestranol and norethynodrel, were evaluated for mutagenicity in the Salmonella histidine reversion assay [5].

High impact information on norethynodrel

• Norethindrone and its isomer norethynodrel exclusively caused Ag-NORs to scatter in the nuclear matrix, from the nucleolus [6].
• This effect was also observed in C3H mice treated with either 17beta-estradiol or the oral contraceptive Enovid [7].
• The blood pressure of the Enovid-treated SP/SHR rose most acutely [8].
• After 48 days, the Enovid-treated animals developed acute and lethal strokes characterized by massive thrombonecrogenic lesions of the parietal lobe [8].
• Response of heart rate to acute administration of isoproterenol in rats treated chronically with norethynodrel, ethinyl estradiol, and both combined [9].

Chemical compound and disease context of norethynodrel

• Subsequently, other rats were pretreated with Enovid or corn oil for 5 weeks before hypertension was induced by implanting deoxycorticosterone acetate (Doca) [10].
• The combination of a progestogen and an estrogen (Enovid, Enovid E) has been used successfully in the management of nine patients with hereditary hemorrhagic telangiectasia (HHT) and severe epistaxis: Such therapy was instituted when epistaxis was severe and only after other therapeutic measures had failed [11].
• These results indicated that, in the steroid combination found in the oral contraceptive Enovid, it is the estrogenic component that results in hypertension in this rat model [12].

Biological context of norethynodrel

• The groups receiving ethinyl estradiol alone, and in combination with norethynodrel, but not norethynodrel alone, showed a reduced water intake compared with untreated controls [13].
• Chronic treatment with ethynyl estradiol alone (48-50 mug/kg/day) and in combination with several doses of norethynodrel either attenuated or prevented the increase in tail skin temperature accompanying sC. administration of isoproterenol (200 mug/kg b.wt.) to male and female rats [2].
• The era of oral contraception began in May 1960, when Enovid was approved by the Food and Drug Administration for ovulation inhibition, and was immediately thereafter introduced for such use [14].
• This substance, a combination of the progestin norethynodrel and the estrogen mestranol was first approved in 1957 for the treatment of a variety of disorders associated with the menstrual cycle [14].
• The binding of 7,12-dimethylbenz[a]anthracene to mammary gland macromolecules in the hamster:effects of Enovid feeding or transplacental exposure to diethylstilboestrol [15].

Anatomical context of norethynodrel

• Histochemical and ultrastructural effects of enovid E on the endometrium of the baboon [16].
• Progesterone and norethynodrel depressed the respiration, glycolytic metabolism and the motility of washed spermatozoa [17].
• The effects of norethynodrel on the visual cortex of rats exposed to differential environments: a preliminary study of electrolytes and water [18].
• Progesterone and norethynodrel appeared to act on the plasma membrane of human spermatozoa to increase its permeability and hence to facilitate the loss of essential cofactors required for the glycolytic and oxidative processes [17].
• When autonomic ganglia were subsequently blocked with mecamylamine, the ensuing blood pressure fall was invariably larger in Enovid-treated than in corn oil-treated rats [19].

Associations of norethynodrel with other chemical compounds

• Mestranol and norethynodrel inhibit metabolic cooperation in V-79 Chinese hamster cells [20].
• The contraceptive 17 alpha-ethynyl-substituted 19-nor steroids, norethisterone (Ki = 48 microM) and norethynodrel (Ki = 38 microM), were evaluated and found not to inactivate aromatase, suggesting that the potential conversion of either compound to SCH 10015 did not occur to a significant extent in these microsomal incubations [21].
• The plasma concentrations of the two pharmacologically active 3-hydroxyl metabolites of tibolone, 3alpha-hydroxyl-7-methyl- norethynodrel (3alpha-HMN) and 3beta-hydroxyl-7-methyl- norethynodrel (3beta-HMN) in plasma were determined by using a validated liquid chromatography-mass spectrometry (LC-MS) method [22].
• In comparison with norethinodrel and norethindrone, lynestrenol and oestrenol appeared in vitro to be stronger competitors for oestradiol than in vivo (Part I; Van Kordelaar et al. 1975) [23].
• Female CD1 mice given the contraceptive steroids mestranol and norethynodrel (1:10) in the diet (0.0033%) for 4 months had a growth reduction of 20% when compared with mice fed a normal diet, and had lower convulsive thresholds when tested with the vitamin B6 antagonists 2,4-dimethyl-5-methyl-hydroxypyrimidine and thiosemicarbazide [24].

Analytical, diagnostic and therapeutic context of norethynodrel

• Weanling, male and female, stroke-prone, spontaneously hypertensive rats (SP/SHR) were fed either a regular diet, a low protein diet derived from fish tissue + 1% saline drinking water, or the fish diet + 1% saline + daily injections of 0.1 mg Enovid/100 g bw/sc [8].
• This pressure difference was later verified by direct measurement of phasic aortic pressures from indwelling catheters and by the postmortem finding that Enovid-treated rats had larger hearts than corn oil-treated ones [10].
• One group received 2 mg./kg./day of norethynodrel in subcutaneous injections, and the other group received nothing [25].
• Hormones affected by hypophysectomy or castration do not appear to interfere with sensory effects, though a progestogen norethynodrel does appear to interact with them [26].
• In the mid-1950s it was shown that ovulation can be inhibited by oral administration of progesterone or of synthetic progestogens such as norethynodrel [27].

References