Disease relevance of NORGESTIMATE

• Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea [1].
• There was a more than two-fold increase in the venous thromboembolism rate (incidence rate ratio 2.2, 95% confidence interval [CI] 1.3-3.8) among transdermal contraceptive system users (20 cases, 40.8 per 100,000 woman-years) compared with norgestimate-containing oral contraceptives users (37 cases, 18.3 per 100,000 woman-years) [2].
• Acute myocardial infarction occurred in three transdermal contraceptive system users compared with seven among norgestimate-containing oral contraceptives users (incidence rate ratio 1.8, 95% CI 0.5-6.8) [2].
• CONCLUSION: The triphasic combination of norgestimate and ethinyl E2 is an effective treatment for metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding [3].
• Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris [4].

Psychiatry related information on NORGESTIMATE

• Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in adolescent females with anorexia nervosa: a double-blind, placebo-controlled study [5].

High impact information on NORGESTIMATE

• The isomers of norgestimate (levonorgestrel 17-acetate oxime) and other Delta(4)-3-ketosteroid oximes have been separated by a new normal phase HPLC method [6].
• In common with oral contraceptives containing desogestrel or norgestimate, and in contrast with those containing levonorgestrel, gestodene-containing preparations are associated with neutral or positive changes in lipid and carbohydrate metabolism [7].
• OBJECTIVE: To estimate the incidence of venous thromboembolism, acute myocardial infarction, and ischemic stroke among transdermal contraceptive system users compared with users of norgestimate-containing oral contraceptives with 35 mcg ethinyl estradiol [2].
• This open-label, randomized, 2-way crossover study characterized the pharmacokinetics and pharmacodynamics of a transdermal contraceptive patch and a norgestimate-containing oral contraceptive [8].
• In vitro evidence suggested that at least norgestimate might also inhibit other transporters like the multidrug resistance-associated protein 2 (MRP2) [9].

Chemical compound and disease context of NORGESTIMATE

• Lower doses and newer progestins, such as norgestimate, gestodene, and desogestrel, have demonstrated a decreased potential to reverse the positive cardiovascular effects of estrogen while still eradicating persisting or de novo endometrial hyperplasia [10].
• Metabolism of the oral contraceptive steroids ethynylestradiol, norgestimate and 3-ketodesogestrel by a human endometrial cancer cell line (HEC-1A) and endometrial tissue in vitro [11].
• Cerebral venous sinus thrombosis in users of four hormonal contraceptives: levonorgestrel-containing oral contraceptives, norgestimate-containing oral contraceptives, desogestrel-containing oral contraceptives and the contraceptive patch [12].

Biological context of NORGESTIMATE

• Biotransformation, pharmacologic, and pharmacokinetic studies of norgestimate and its metabolites indicate that 17-deacetyl norgestimate, along with the parent drug, contributes to the biologic response [13].
• Because of the minimal androgenicity of norgestimate, norgestimate/ethinyl estradiol has a low impact on carbohydrate and lipid metabolism [14].
• Weight gain and elevated blood pressure were insignificant in clinical trials with both fixed-dose and phasic ethinyl estradiol/norgestimate formulations [15].
• The data arising from these studies were used to fit approximate functions relating the amount of norgestimate and ethinyl estradiol to the rate of spotting and breakthrough bleeding, gastrointestinal disturbance, and pregnancies [16].
• According to data from randomised, comparative trials of 1 year's duration, continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day relieves climacteric symptoms (vasomotor symptoms and vulvovaginal atrophy) in postmenopausal women [17].

Anatomical context of NORGESTIMATE

• Effects of 180 micrograms and 250 micrograms norgestimate on pituitary-ovarian function and cervical mucus [18].
• Metabolism of norgestimate by human gastrointestinal mucosa and liver microsomes in vitro [19].
• The aim of using new synthetic progestogens (gestodene and norgestimate) in oral hormonal contraceptives is to find a combination that has a more beneficial effect on metabolism and endometrium than presently available formulations [20].
• The metabolism of the progestogen oral contraceptive norgestimate has been studied in vitro using human intestinal mucosa and human liver microsomes [19].
• The affinity of norgestimate for uterine progestogen receptors and its direct action on the uterus [21].

Associations of NORGESTIMATE with other chemical compounds

• To date clinical trials have shown that both formulations of ethinyl estradiol/norgestimate offer contraceptive efficacy equivalent to that of other oral contraceptives [15].
• Although direct comparative trials are lacking, available data suggest that the new, continuous 17beta-estradiol/intermittent norgestimate hormone replacement therapy formulation may offer advantages over regimens that contain older progestins with metabolic disadvantages [22].
• Progestins used in oral contraceptive formulations available in the United States include norgestimate, desogestrel, norethindrone, norethindrone acetate, and levonorgestrel [23].
• Effect of the progestogens, gestodene, 3-keto desogestrel, levonorgestrel, norethisterone and norgestimate on the oxidation of ethinyloestradiol and other substrates by human liver microsomes [24].
• CONCLUSIONS: The norgestimate-containing COC significantly decreased androgen production and concentrations of free androgens, without reducing insulin sensitivity in non-obese PCOS subjects [25].

Gene context of NORGESTIMATE

• Matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression is not regulated by norgestimate or norelgestromin [26].
• The relative binding affinity of norgestimate for human sex hormone-binding globulin was compared with that of its metabolites and other progestins by measuring their abilities to displace [3H]testosterone from this carrier protein in vitro [27].
• In the presence of NADPH, after 5 h incubation only 30.5 +/- 14.6% (mean +/- SD) of steroid present was norgestimate [19].
• The competition experiments suggest that norgestimate is a prodrug and that the metabolites, levonorgestrel and levonorgestrel-17-acetate, which actively bind to the progesterone receptor, must first be formed from the parent drug via metabolic processes in vivo [28].
• The LDL/HDL ratio did not change significantly except with the use of the triphasic norgestimate preparation, in which case it decreased slightly [29].

Analytical, diagnostic and therapeutic context of NORGESTIMATE

• Determination of circular dichroism and ultraviolet spectral parameters of norgestimate- and other Delta(4)-3-ketosteroid oxime isomers via normal phase HPLC method [6].
• Disposition of norgestimate in the presence and absence of ethinyl estradiol after oral administration to humans [30].
• Determination of norgestimate and ethinyl estradiol in tablets by high-performance liquid chromatography [31].
• Hyperinsulinaemic euglycaemic clamp techniques were performed before and after 6 months of treatment with a monophasic COC containing norgestimate [25].
• The efficacy and tolerability of norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol): results of an open, multicenter study of 59,701 women [32].

References