ISSN:0001-6349    

DOI:10.3109/00016349009156499

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

No single pharmacologic agent has been more widely studied than the oral contraceptive (OC). Scientific efforts have been directed primarily toward maximizing the benefits of OCs—which remain the most effective, reversible form of birth control—while minimizing their potential risks, specifically thromboembolic disorders and cardiovascular disease.Decreases in the dose of estrogen from the 100 μg—150 μg levels of the 1960s to the 30 μg—50 μg formulations of today have been accompanied by dramatic reductions in the risk of thromboembolic events. In healthy women not predisposed to these conditions, the risk of thromboembolism is now considered very small. Similar reductions in the doses of progestin have also resulted in decreases in the incidence of stroke and myocardial infarction.Evidence suggests that not only dose but androgenic activity of a progestin may negatively impact on risk of cardiovascular disease. Thus development of OCs containing a progestin with the least potential for androgenically mediated side effects appears to b

ISSN:0001-6349    

DOI:10.3109/00016349009156500

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Cardiovascular disease is the leading cause of death in American women, accounting for nearly half a million deaths annually. While most of these women are postmenopausal, data from the Bogalusa Heart Study have shown that fatty streak formation begins early in life, perhaps even in childhood. Successful risk intervention is best initiated early in the process, before the clinical manifestations of disease become apparent.Several major risk factors for cardiovascular disease—elevated cholesterol, elevated blood pressure, and cigarette smoking—are amenable to intervention. The critical role of cholesterol in the pathogenesis of cardiovascular disease, and the impact of even small fluctuations of important subfractions on CV risk have been demonstrated in numerous epidemiologic and clinical studies.A sensitive predictor of cardiovascular risk appears to be the high‐density lipoprotein (HDL) cholesterol fraction, which is considered cardioprotective if elevated and a significant independent risk factor if decreased. Reductions in HDL have been documented following the use of even low‐dose oral contraceptives containing progestins of high androgenic activity. Elevated LDL cholesterol may be an independent risk factor for CV disease in women. Hence, changes in the LDL/HDL ratio may be more sensitive predictors of change in CV risk. Major risk factors for CV disease in women are outlined with specific reference to the effects of oral contraceptives on lipop

ISSN:0001-6349    

DOI:10.3109/00016349009156501

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Norgestimate is a new progestin developed for use with ethinyl estradiol as a combination oral contraceptive. It binds to rabbit uterine progestational receptors and in the oral form stimulates a progestational endometrial effect in rabbits. Norgestimate also exerts a direct effect on target organs, stimulating the endometrium in rabbits when injected directly into the uterine horn and inhibiting luteinizing hormone release from rat pituitary cells in culture. Like other progestins, norgestimate inhibits ovulation in several species and estrogen‐induced vaginal cornification in ovariectomized rats, but it is not estrogenic. Unlike other progestins, including levonorgestrel and gestodene, norgestimate is relatively free of androgenic activity. Norgestimate's affinity for the androgen receptor is very poor (0.003 × dihydrotestosterone [DHT]), even poorer than that of progesterone (0.005 × DHT). In sharp contrast are the marked affinities of levonorgestrel (0.220 × DHT) and gestodene (0.154 × DHT) for that receptor. The selectivity of norgestimate at receptor level is demonstrated clearly by its highly favorable androgen‐to‐progestin binding ratio.Norgestimate is similar to progesterone in not significantly stimulating ventral prostate growth in immature rats, whereas levonorgestrel, gestodene, and desogestrel are significantly androgenic in this model.Further evidence of norgestimate's minimal androgenicity is its lack of affinity for human sex hormone binding globulin in vitro. In conclusion, these preclinical studies, consistent with clinical studies, demonstrate the progestational efficacy and selectivity of nor

ISSN:0001-6349    

DOI:10.3109/00016349009156502

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The search for a highly selective progestin that exerts a potent and targeted progestational response with minimal or absent androgenic effect has paralleled investigation into the possible impact of these agents on cardiovascular disease in women.Such a progestin, norgestimate (NGM), in a dose of 250 μg, has been combined with ethinyl estradiol (EE) 35 μg in a new oral contraceptive (OC), Ortho‐Cyclen or Cilest. Results of two long‐term, multicentric clinical trials demonstrate that this formulation is comparable in efficacy to the norgestrel‐containing OC Lo/Ovral. There were no statistically significant differences in pregnancy rate, and both OCs were well‐tolerated in a large and diverse study population.In several areas, however, the inherently lower androgenicity of the norgestimate OC produced clinical changes compared with the norgestrel formulation. These changes were primarily evident in the more natural menstrual patterns with the norgestimate OC, its less severe impact on the endometrium, and, most important, its positive impact on lipoprotein metabolism. NGM/EE consistently produced statistically significant increases in high density lipoprotein (HDL) and concomitant improvement in the ratio of low density lipoprotein (LDL) to HDL. By cycle 24, this highly predictive parameter of atherosclerotic risk had decreased 7.7% in the NGM/EE group. Conversely, the norgestrel‐containing formulation resulted in statistically significant decreases in HDL and increases in the LDL/HDL ratio: by cycle 24, these patients showed an 18.5% increase in the LDL/HDL ratio. All between regimen comparisons of mean changes in the LDL/HDL ratio were statistically significant, from baseline through cycles 3, 6

ISSN:0001-6349    

DOI:10.3109/00016349009156503

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Several European studies have been conducted to confirm the efficacy, tolerability, and safety of a new oral contraceptive (OC) combining 250 μg norgestimate with 35 μg ethinyl estradiol (Ortho‐Cyclen or Cilest). In a 12‐month multicenter German study of 147 women, treatment with this formulation resulted in no pregnancies, a low incidence of side effects, and excellent cycle control. The drug had no effect on estrogen‐mediated fibrin formation nor on the activity of coagulation inhibiting or promoting factors. Similarly, the documented low androgenicity of the highly selective progestational agent norgestimate results in a more positive metabolic profile. Glucose, insulin, and hemoglobin A1cconcentrations measured before and after glucose loading were not adversely affected by treatment with the norgestimate‐containing OC, and all changes were reversible on its discontinuation. In addition, lipid metabolism was positively influenced by the drug. Low‐density lipoprotein cholesterol, a known risk factor for cardiovascular disease, was reduced while the cardioprotective lipid fraction, high‐density lipoprotein cholesterol, was increased.Clinical trials to determine the OC's effects on coagulation, endocrine function, and carbohydrate and lipid metabolism are reviewed. Also discussed are several studies demonstrating the formulation's unique endometrial effects, which may possibly be related to its low androgenic activity and consequent low incidence of breakthrough bleeding a

ISSN:0001-6349    

DOI:10.3109/00016349009156504

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0001-6349    

DOI:10.3109/00016349009156505

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0001-6349    

DOI:10.3109/00016349009156506

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY