摘要:

Data arc reported from the combined results of two studies assessing the lipid and carbohydrate effects of a triphasic preparation of norgestimate and ethinyl estradiol (Ortho TriCyclen®, Tri‐Cilest®) over a 2‐year period in 1,783 healthy women. Mean values for serum levels of high‐density lipoprotein cholesterol (HDL‐C) were increased significantly. with a percent change at 24 months of 13.2. Values for the ratio of low‐density lipoprotein cholesterol to HDL‐C were reduced throughout the study period (mean change of −6.4%, at cycle 24). There were no clinically significant changes in fasting blood glucose levels or insulin levels or in values for glycosylated hemoglobin. These results are consistent with those of previous studies and indicate that the triphasic preparation of norgestimate and ethinyl estradiol is a selective and minimally androgenic oral contraceptive agent. Long‐term therapeutic benefit may accrue from the favorable influences on

ISSN:0001-6349    

DOI:10.3109/00016349209156508

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Norgestimate (NGM), a derivative of 19‐nortestosterone with very specific affinity for the progesterone receptor, has been used in combination with ethinyl estradiol (EE) at low doses in both monophasic and triphasic oral contraceptives (OCs). An open‐label comparative clinical trial was conducted with 4,234 healthy women using triphasic levonorgestrel (LNG)/EE and NGM/EE through a total of 22,312 menstrual cycles. Contraceptive efficacy was excellent with both preparations, with no statistically significant between‐regimen differences in pregnancy rates. The theoretical Pearl index was 0.12 for the NGM/EE triphasic, and 0.34 for the LNG/EE triphasic. Adverse experiences in both groups were typical of those that may occur among women taking low‐dose OC agents. The percentage of subjects discontinuing treatment because of use‐related adverse experiences was similar with the two preparations: 8.6% for the NGM/EE triphasic and 6.8% for the LNG/EE triphasic. In a separate mechanism of action study, specific endocrine parameters were investigated in 20 subjects using the NGM/EE triphasic for 4 cycles. Ovulation suppression was demonstrated in statistically significant decreases from pre‐treatment values in serum levels of luteinizing hormone, follicle‐stimulating hormone, progesterone, and estradiol. Significant on‐treatment increases in serum levels of sex hormone binding globulin evidenced minimal androgenicity. All hormonal values returned to or toward normal in the post‐treatment cycle. The study results support those obtained in large noncomparative studies of the NGM/EE triphasic. This phased‐dose combination suppresses ovulation and is a very effective, minimally androgenic contraceptive agent with a

ISSN:0001-6349    

DOI:10.3109/00016349209156509

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The contraceptive progestin norgestimate (NGM) has a high affinity for uterine progestin receptors and a lack of affinity for androgen receptors similar to that of natural progesterone. NGM's selectivity results in excellent efficacy, cycle control, and minimal androgenicity when it is combined with ethinyl estradiol (EE). Clinical studies of a monophasic regimen of NGM/EE indicate a positive impact on lipid metabolism, revealing an increase in serum levels of high‐density lipoprotein cholesterol with a concomitant and significant decrease in the low‐density lipoprotein/high‐density lipoprotein cholesterol ratio. Little impact on carbohydrate metabolism was noted. Serum levels of sex hormone binding globulin, an indicator of androgen‐estrogen balance, also increased significantly with NGM/EE in accordance with its low androgenic activity. A significant between‐regimen difference in SHBG was seen in a comparison study of NGM/EE and LNG/EE triphasic formulations (a mean rise of 68.6% with NGM/EE vs a decrease of 6.1% with LNG/EE). NGM's lack of estrogenicity was evidenced by unchanged prolactin levels and absence of effect on the coagulation system. In a large study of the monophasic formulation in 59.701 women, some improvement in acne was reported as well as minimal weight gain. An overview of clinical data is provided from United States and European trials as well as some preclinical data relevant to NGM's se

ISSN:0001-6349    

DOI:10.3109/00016349209156510

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Effective cycle control was demonstrated based on two multicenter, 2‐year studies of the triphasic oral contraceptive (OC) agent containing the new progestin norgestimate. The estrogen in this OC is ethinyl estradiol. These open‐label Phase III studies were conducted in the United States by 33 investigators at 33 sites who treated a total of 1,783 subjects, healthy women 17 to 38 years of age with menstrual cycle characteristics considered to be within the normal range. The norgestimate/ethinyl estradiol preparation was taken for up to 24 cycles. Follow‐up information was collected 3 to 4 months post‐treatment. Bleeding pattern analyses were based on 27,970 valid cycles. Normal cyclic bleeding patterns were experienced by most of the women during the study; only minimal and statistically and clinically insignificant variations in menstrual flow, dysmenorrhea, and premenstrual tension occurred. There was a low incidence of failed withdrawal bleeding in single cycles (<1.0% after cycle 6). There were no cases of amenorrhea, defined as two consecutive cycles of missed withdrawal flow. The incidence of breakthrough bleeding or spotting was highest during the initial treatment cycles and diminished with continued use of the formulation. The mean incidence of breakthrough bleeding was 2.36% in cycles 13 to 24. Apart from somewhat higher initial percentages among women new to oral contraception, the pattern of midcycle bleeding or spotting was similar to that of all women studied. Effective long‐term cycle control was demonstrated in women who used this

ISSN:0001-6349    

DOI:10.3109/00016349209156511

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The safety and efficacy of the triphasic oral contraceptive agent containing norgestimate and ethinyl estradiol were evaluated in a 12‐month study of 661 women. Excellent contraceptive efficacy was achieved, with two pregnancies ascribed to product failure in a total of 6,511 treatment cycles. The life‐table predicted pregnancy rate was 0.57 per 100 woman‐years of use. The overall and theoretical Pearl indexes were 0.5.5 and 0.37, respectively. Good cycle control was maintained in patterns similar to those noted in previous studies. The incidence of dysmenorrhea and premenstrual syndrome was sharply reduced. Side effects reported were typical of those associated with use of low‐dose oral contraceptive agents. Acceptability was high compared with agents used previously by the subjects. Total cholesterol did not change but high‐density lipoprotein cholesterol was significantly elevated at 3 and 12 months. There were no clinically significant changes in the parameters of hematology or blood chemist

ISSN:0001-6349    

DOI:10.3109/00016349209156512

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The effects of norgestimate triphasic (Ortho Tri‐Cyclen®, Tri‐Cilest®) and levonorgestrel triphasic (Triphasil®) formulations on lipid and androgen metabolism were assessed in a study of 66 healthy women treated through six menstrual cycles. Levels of the following were measured: cholesterol and its subfractions, triglycerides. carrier lipoproteins, estradiol, testosterone, and sex hormone binding globulin (SHBG). Comparison of baseline values with values after 3 and 6 months of treatment indicated that both regimens influenced lipid and androgen metabolism. There was a statistically significant between‐regimen difference in levels of high‐density lipoprotein, which were favorably increased with norgestimate triphasic hut reduced with levonorgestrel triphasic. Related data on SHBG showed that plasma levels of this marker of estrogen/androgen balance were increased significantly more in the norgestimate triphasic group, providing additional evidence of low androgenicity. Both regimens inhibited follicular growth to the same extent, as evidenced by low mean levels of estradiol in all on‐therapy cycles; and both decreased free testosterone. Side effects in both groups were minor and characteristic of those observed with low‐dose oral contraceptive agents. The results of the study support the reported safety and positive effects of norgestimate on lipid and androgen metabolism. in comparison with a levonorgestrel‐containing combined or

ISSN:0001-6349    

DOI:10.3109/00016349209156513

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY