Disease relevance of Norpregneninolone

• Letter: Jaundice associated with norethisterone-acetate treatment of breast cancer [1].
• Two courses of 21 days of 5 mg norethisterone daily caused reversion to normal in all 57 cases of cystic hyperplasia and 6 of the 8 cases of atypical hyperplasia [2].
• METHODS: Seventy-two noncirrhotic patients bleeding from gastrointestinal angiodysplasia confirmed by endoscopy or angiography were randomized to receive in double-blind conditions treatment with ethinylestradiol (0.01 mg) plus norethisterone (2 mg) (1 tablet/d), or placebo (1 tablet/d) for a minimum period of 1 year (range: 1-2 years) [3].
• Forty women aged 64.7 +/- 5.1 yr with established postmenopausal osteoporosis were blindly allocated to 1 yr's treatment with either continuous combined estrogen/progestogen therapy (2 mg estradiol + 1 mg norethisterone acetate + 500 mg calcium daily) or placebo + 500 mg calcium daily [4].
• In the present study 17 women with endometriosis were treated with 400 mg nafarelin combined with 1.2 mg norethisterone (NET) for 6 months, followed by 6 months with only 1.2 mg NET [5].

Psychiatry related information on Norpregneninolone

• Disease risk is higher in patients with malignancies, hepatitis C virus infection, those who present late, when norethisterone is used to prevent menstruation, and when broad-spectrum antibiotics and antifungals are used during and after the conditioning therapy [6].
• Low dose, transdermal norethisterone acetate caused few adverse symptomatic or psychological side-effects and appeared well tolerated [7].

High impact information on Norpregneninolone

• The effects of transdermal norethisterone acetate on symptoms, lipid metabolism, and psychological status were determined by comparing features in the oestrogen-only phase and in the combined phase; the effects were very mild [8].
• In 28 women on 50 microgram preparations containing 3 mg or 4 mg norethisterone, mean values of factor VII, fibrinogen, fibrinolytic activity, cholesterol, fasting triglycerides, and systolic blood-pressure were higher than in 15 women whose preparations contained only 1 mg of norethisterone [9].
• Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation [10].
• In a randomized, double blind, clinical prospective trial comprising 35 women treated with either hormone replacement therapy (HRT) (cyclic estradiol/norethisterone acetate) or placebo we performed histomorphometric studies on paired bone biopsies obtained before and after 2 years of treatment [11].
• OBJECTIVES: To determine the single- and multiple-dose pharmacokinetics of oral thalidomide (200 mg/day, administered for 21 days) and to assess the effects of steady-state plasma concentrations of thalidomide on the single-dose pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone) [12].

Chemical compound and disease context of Norpregneninolone

• In the current study, we investigated the effect of tibolone in comparison with that of estradiol and norethisterone acetate on atherogenesis in 140 ovariectomized New Zealand White rabbits that had been induced by an atherogenic diet (0.4% cholesterol, 20 weeks) [13].
• OBJECTIVE: To compare the efficacy and acceptability of the levonorgestrel intrauterine system and norethisterone for the treatment of idiopathic menorrhagia [14].
• Comparative study of tranexamic acid and norethisterone in the treatment of ovulatory menorrhagia [15].
• In the postmenopausal group, following treatment with sequential mestranol and norethisterone, significant reductions were recorded in the concentrations of sodium, urea, calcium, albumin, alkaline phosphatase and glucose and significant increases were recorded in the concentration of globulin and in body weight [16].
• The effects of danazol, mefenamic acid, norethisterone and a progesterone-impregnated coil on endometrial prostaglandin concentrations in women with menorrhagia [17].

Biological context of Norpregneninolone

• OBJECTIVE: To evaluate the effect of thalidomide on the plasma pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone) [18].
• We have examined the effects of transdermal estradiol and oral norethisterone on insulin sensitivity using the hyperinsulinemic euglycemic clamp method by performing a randomized, double blind, placebo-controlled study in 22 healthy women after a surgically induced menopause [19].
• Double bond hydrogenation decreased the transcriptional potency of norethisterone and Gestodene through both PR isoforms with a 100- to 1,000-fold difference, respectively [20].
• DESIGN: Forty women complaining of climacteric symptoms were randomized to receive either transdermal estradiol patches (50 microg daily) in combination with an intrauterine system releasing 20 microg of levonorgestrel daily or an established regimen of an oral dose of 2 mg of estradiol and 1 mg of norethisterone acetate daily for 1 year [21].
• Norethisterone 2.5 mg/day was administered to 26 postmenopausal women (aged 54-79 years) with varying degrees of osteoporosis and with a forearm bone mineral density value more than 2 SD below the young normal mean [22].

Anatomical context of Norpregneninolone

• Oestrogen injection resulted in cytosol receptor depletion and a 'deficit' in receptor content extending for 6 h, whereas norethisterone acetate-induced translocation was quantitative [23].
• There is no new information of major significance about the pharmacokinetics of levonorgestrel, norethisterone (norethindrone) or ethinylestradiol, although it has been shown that the concentrations of these hormones secreted in breast milk are small and mothers taking combined oral contraceptive steroids may breast-feed safely [24].
• The 3 beta,5 alpha-tetrahydro derivatives of both norethisterone and Gestodene were active in other cells in addition to HeLa cells and activated reporter expression through the oxytocin promoter [20].
• OBJECTIVE: To evaluate the short- and long-term effect on the uterus, endometrium, and vascular reactivity of uterine arteries of sequential transdermal estradiol (50 microg/day) and norethisterone (0.25 mg/day in the last 14 days of each cycle) [25].
• Norethisterone does not inhibit rat testis delta 5-3 beta-hydroxysteroid dehydrogenase [26].

Associations of Norpregneninolone with other chemical compounds

• Specific binding in vitro of [3H]oestradiol-17 beta in liver cytosols was inhibited by (+)-norgestrel and norethisterone acetate, but not progesterone, at concentrations of 10--100 microM [23].
• The blood pressure level and the renin-angiotensin system were investigated in 24 menopausal women (12 normotensive and 12 hypertensive) before, during and after six months of treatment with either oestradiol or trisekvens (sequential preparation containing oestradiol, oestriol and norethisterone acetate) [27].
• Antipyrine pharmacokinetics were studied in 6 healthy women before and 2, 8 and 12 weeks after administering the injectable progestagen (progestin), norethisterone (norethindrone) enanthate 200mg intramuscularly [28].
• Effect of medroxyprogesterone acetate and norethisterone on serum-stimulated and estradiol-inhibited proliferation of human coronary artery smooth muscle cells [29].
• 3 In phenobarbitone-treated rabbits, following intravenous administration of norethisterone there was no significant change in the area under the curve (AUC) compared to controls [30].

Gene context of Norpregneninolone

• However, when samples with detectable norethisterone were excluded IGFBP-1 increased by 46% (P < 0.01) during oral therapy [31].
• MEASUREMENTS: IGF-I, IGF-II, IGFBP-1, IGFBP-3, oestradiol and norethisterone were analysed by radioimmuno-assays [31].
• In women taking 35 micrograms EE with either 600 micrograms or 1000 micrograms norethisterone, increases in CP were similar but SHBG increased more with the lower dose [32].
• In this study, we have examined both ER- and PR-mediated transcriptional activity of a number of A-ring chemically reduced derivatives of norethisterone and Gestodene [20].
• In this study, AR- and progesterone receptor (PR)-dependent transcriptional activation induced by norethisterone (NET), levonorgestrel (LNG) and gestodene (GSD), and their 5alpha-reduced derivatives, including limited trypsin digestion of AR in the presence of natural and synthetic progestins were investigated [33].

Analytical, diagnostic and therapeutic context of Norpregneninolone

• Virgin rats received whole-body irradiation with 2.6 Gy gamma-rays 1 month after the administration of low- or high-dose pellets of contraceptive steroids, such as 17alpha-ethinylestradiol (EE(2)) combined with 19-norethisterone (NET) [34].
• In contrast, following oral administration of norethisterone to treated rabbits, the AUC was 20% and the peak plasma concentration 17% of that in controls [30].
• One hundred post-menopausal patients with locally advanced cervical cancer were systematically allocated by rotation to the four treatment groups: (1) control group receiving no treatment; (2) ethinyl oestradiol 50 micrograms: (3) norethisterone 5 mg: (4) a combination of ethinyl oestradiol and norethisterone [35].
• Microcapsules made from a biocompatible, biodegradable polymeric excipient, poly(DL-lactide-co-glycolide) (DL-PLGA) that contained 22 weight percent (wt %) norethisterone (NET), were prepared by a solvent-evaporation microencapsulation process [36].
• A rapid and sensitive radioimmunoassay for norethisterone [37].

References