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Hershel Jick - One of the best experts on this subject based on the ideXlab platform.
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further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing Norgestimate and 35 μg of ethinyl estradiol
Contraception, 2007Co-Authors: Susan S Jick, James A Kaye, Hershel JickAbstract:Abstract Context In 2006, we published a study that indicated that the new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin did not increase the risk for venous thromboembolism (VTE) compared to oral contraceptive containing Norgestimate and 35 μg of EE. Objective This report updates information on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using oral contraceptives containing Norgestimate (either monophasic or triphasic) and 35 μg of EE (Norgestimate-35) using an additional 17months of data. Design, Setting and Participants Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women, aged 15 to 44 years, who started either the contraceptive patch or Norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE) who were not in the earlier study. Up to four controls were matched to each case by age and calendar time. Main Outcome Measures Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives. Results We identified 56 new cases of newly diagnosed, idiopathic VTE in the updated study population. The OR comparing the contraceptive patch to Norgestimate-35 was 1.1 (95% CI 0.6–2.1). Conclusions After evaluating an additional 17 months of data, the results indicate that the risk of nonfatal VTE for the contraceptive patch is closely similar to the risk for oral contraceptives containing 35 μg of EE and Norgestimate.
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Original research article Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing Norgestimate and 35 μg of ethinyl estradiol
2007Co-Authors: Susan S Jick, James A Kaye, Hershel JickAbstract:Context: In 2006, we published a study that indicated that the new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin did not increase the risk for venous thromboembolism (VTE) compared to oral contraceptive containing Norgestimate and 35 μg of EE. Objective: This report updates information on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using oral contraceptives containing Norgestimate (either monophasic or triphasic) and 35 μg of EE (Norgestimate-35) using an additional 17 months of data. Design, Setting and Participants: Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women, aged 15 to 44 years, who started either the contraceptive patch or Norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE) who were not in the earlier study. Up to four controls were matched to each case by age and calendar time. Main Outcome Measures: Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives. Results: We identified 56 new cases of newly diagnosed, idiopathic VTE in the updated study population. The OR comparing the contraceptive patch to Norgestimate-35 was 1.1 (95% CI 0.6–2.1). Conclusions: After evaluating an additional 17 months of data, the results indicate that the risk of nonfatal VTE for the contraceptive patch is closely similar to the risk for oral contraceptives containing 35 μg of EE and Norgestimate.
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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.
Contraception, 2006Co-Authors: Susan S Jick, Hershel JickAbstract:Abstract Background It has been suggested that the risk for cerebral venous sinus thrombosis (CVST) may be greater among users of the contraceptive patch than among users of oral contraceptives (OCs). Methods From the PharMetrics database, we identified women aged 15–44 years who filled at least one prescription for either the contraceptive patch or desogestrel-containing, Norgestimate-containing or levonorgestrel-containing OCs to assess the risk of CVST. The person-time of current exposure to each study drug, as well as the incidence rates (IRs) and incidence rate ratios (IRRs) of CVST, was calculated. Results We identified over 1 million users of the four study drugs. There were five cases of CVST among current users of desogestrel, seven cases among current users of Norgestimate, two cases among current users of levonorgestrel and none among current users of the contraceptive patch. The IRs per 100,000 woman-years were 2.7 [95% confidence interval (95% CI)=0.9–6.3], 1.6 (95% CI=0.7–3.3), 0.7 (95% CI=0.1–2.4) and 0.0 (95% CI=0.0–4.8), respectively, in users of desogestrel, Norgestimate, levonorgestrel and the contraceptive patch. There were two women who had CVST while not currently taking a hormonal contraceptive (IR=0.4 per 100,000 woman-years; 95% CI=0.1–1.3). The IRRs were 4.0 (95% CI=0.7–42.4) for desogestrel-containing versus levonorgestrel-containing OCs, and 2.4 (95% CI=0.5–24.0) for Norgestimate-containing versus levonorgestrel-containing OCs. The IRR for the patch could not be calculated. Conclusions There is no evidence of an increased risk of CVST in users of the contraceptive patch compared to users of levonorgestrel-containing OCs.
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Risk of nonfatal venous thromboembolism with oral contraceptives containing Norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel.
Contraception, 2006Co-Authors: Susan S Jick, James A Kaye, Stefan Russmann, Hershel JickAbstract:Abstract Context Previous studies have reported that users of the “third-generation” oral contraceptives (OCs) containing the progestins gestodene and desogestrel have about twice the risk for venous thromboembolism (VTE) compared to users of older OCs containing levonorgestrel. Estimates of the risk for VTE among users of Norgestimate-containing OCs compared to other OCs, however, are lacking. Objective The purpose of this study is to obtain quantitative information on the risk of nonfatal VTE in women using OCs containing either Norgestimate or desogestrel in comparison with women taking OCs containing levonorgestrel. Design, Setting and Participants Based on information from PharMetrics, a United States-based company that collects and records information on claims paid by managed care plans, we used a nested case-control study design to estimate relative risks of nonfatal VTE among 15- to 39-year-old current users of OCs containing Norgestimate with 35 μg of ethinyl estradiol (EE), desogestrel with 30 μg of EE or levonorgestrel with 30 μg of EE, both monophasic and triphasic preparations, during the period January 2000 to March 2005. Cases were women with a well-documented VTE of uncertain origin that was diagnosed in current users of a study drug. Up to four controls were closely matched to each case by age and calendar time, and odds ratios (ORs) were calculated using conditional logistic regression comparing the risk of VTE among users of the three contraceptives. We also estimated and compared the incidence rates for all three OCs. Results Based on 281 newly diagnosed idiopathic cases of VTE and 1055 controls, we found that the adjusted ORs for nonfatal VTE comparing Norgestimate- or desogestrel-containing OC users to users of levonorgestrel-containing OCs were 1.1 [95% confidence interval (CI), 0.8–1.6] and 1.7 (95% CI, 1.1–2.4), respectively. The incidence rates of VTE were 30.6 (95% CI, 25.5–36.5), 53.5 (95% CI, 42.9–66.0) and 27.1 (95% CI, 21.1–34.3) per 100,000 woman-years for users of Norgestimate-, desogestrel- and levonorgestrel-containing OCs, respectively. The incidence rate ratios for Norgestimate-containing OCs compared to levonorgestrel-containing OCs and desogestrel-containing OCs compared to levonorgestrel-containing OCs were 1.1 (95% CI, 0.8–1.5) and 2.0 (95% CI, 1.4–2.7), respectively. Conclusions The risk of nonfatal VTE among users of desogestrel-containing OCs is significantly elevated compared to that of levonorgestrel-containing OCs. The risk of VTE in users of Norgestimate-containing OCs was closely similar to that of users of levonorgestrel-containing OCs.
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risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing Norgestimate and 35 μg of ethinyl estradiol
Contraception, 2006Co-Authors: Susan S Jick, James A Kaye, Stefan Russmann, Hershel JickAbstract:Abstract Context There is concern that a new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin increases the risk for venous thromboembolism (VTE) compared to previously marketed oral contraceptives (OCs). Objective Quantitative information was obtained on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using OCs, Norgestimate (either monophasic or triphasic) and 35 μg EE (Norgestimate-35), an OC that has been marketed for over a decade. Design, Setting and Participants Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women aged 15 to 44, who started either the contraceptive patch or Norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE). Up to four controls were matched to each case by age and calendar time. Main Outcome Measures Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives and incidence rates of nonfatal VTE for new users of each of the study contraceptives. Results We identified 68 newly diagnosed, idiopathic cases of VTE in the study population. In the case-control analysis, the OR comparing the contraceptive patch to Norgestimate-35 was 0.9 (95% CI 0.5–1.6). The overall incidence rate for VTE was 52.8 per 100,000 women-years (95% CI 35.8–74.9) among users of the contraceptive patch and 41.8 per 100,000 women-years among users of Norgestimate-35 (95% CI 29.4–57.6), and the age-adjusted VTE incidence rate ratio (IRR) for current use of the contraceptive patch vs. Norgestimate-35 was 1.1 (95% CI 0.7–1.8). Conclusions The risk of nonfatal VTE for the contraceptive patch is similar to the risk for OCs containing 35 μg ethinylestradiol and Norgestimate.
Ann J. Davis - One of the best experts on this subject based on the ideXlab platform.
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triphasic Norgestimate ethinyl estradiol oral contraceptive for the treatment of dysfunctional uterine bleeding
Obstetrics & Gynecology, 2000Co-Authors: Ann J. DavisAbstract:Abstract Objective: To compare the efficacy of a triphasic combination oral contraceptive (OC) containing Norgestimate and ethinyl estradiol (Ortho Tri-Cyclen) and placebo in the treatment of metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding (DUB). To our knowledge, this study is the first report of a placebo-controlled study of an OC in the treatment of DUB. Methods: In this double-blind, placebo-controlled, multicenter trial, 201 women with DUB were randomized to Norgestimate/ethinyl estradiol (NGM/EE) or placebo for 3 cycles. Efficacy was determined by evaluating investigator and subject assessments of DUB resolution, abnormal uterine bleeding patterns during an 84-day reference period, and change from baseline in quality-of-life (SF-36). Results: Subjects were on average 29.6 years of age, 72.6 kg, and had a 6.1 year history of DUB. The most frequently reported type of DUB was oligomenorrhea. Higher percentages of both investigators and subjects in the NGM/EE group (81.4% and 87.1%) compared with the placebo group (35.8% and 45.3%) assessed the subject’s condition as “improved.” These findings were similar in each of the four DUB-type subgroups. Significantly fewer subjects receiving NGM/EE than subjects receiving placebo reported abnormal bleeding patterns ( P P Conclusion: The triphasic OC containing Norgestimate and ethinyl estradiol is an effective treatment for DUB.
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Triphasic Norgestimate-ethinyl estradiol for treating dysfunctional uterine bleeding.
Obstetrics and gynecology, 2000Co-Authors: Ann J. Davis, Amy Godwin, Joel Lippman, William Olson, Michael E. KafrissenAbstract:Objective: To compare the efficacy of a triphasic combination oral contraceptive (OC) containing Norgestimate and ethinyl estradiol (E2) and placebo in the treatment of metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding (DUB). Methods: In this multicenter, randomized, double-masked study, 201 women (15–50 years of age) with DUB received triphasic Norgestimate-ethinyl E2 or placebo, for three consecutive 28-day treatment cycles. Efficacy was determined by evaluating investigator and subject assessments of DUB resolution, abnormal uterine bleeding patterns during an 84-day reference period, and change from baseline in subjects’ quality of life. The sample size was based on the assumption that the proportions of subjects exhibiting treatment success (percentage of subjects with investigator and subject overall assessments of DUB resolution of “improved”) were 65% for the active group and 40% for the placebo group (α = 0.05, 1 − β = 0.80). Results: More than 80% of subjects receiving triphasic Norgestimate-ethinyl E2 had improvements in their abnormal bleeding patterns as assessed by investigators, and the subjects themselves compared with fewer than 50% of subjects in the placebo treatment group (P < .001). Abnormal bleeding patterns were reported by significantly fewer subjects receiving triphasic Norgestimate-ethinyl E2 than in the placebo treatment group (P < .001). Change from baseline in physical functioning (eg, self-care, walking, lifting, exercising) was significantly more improved in the triphasic Norgestimate-ethinyl E2 group than in the placebo group. Conclusion: The triphasic combination of Norgestimate and ethinyl E2 is an effective treatment for metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding.
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Triphasic Norgestimate/ethinyl estradiol oral contraceptive for the treatment of dysfunctional uterine bleeding∗
Obstetrics & Gynecology, 2000Co-Authors: Ann J. DavisAbstract:Abstract Objective: To compare the efficacy of a triphasic combination oral contraceptive (OC) containing Norgestimate and ethinyl estradiol (Ortho Tri-Cyclen) and placebo in the treatment of metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding (DUB). To our knowledge, this study is the first report of a placebo-controlled study of an OC in the treatment of DUB. Methods: In this double-blind, placebo-controlled, multicenter trial, 201 women with DUB were randomized to Norgestimate/ethinyl estradiol (NGM/EE) or placebo for 3 cycles. Efficacy was determined by evaluating investigator and subject assessments of DUB resolution, abnormal uterine bleeding patterns during an 84-day reference period, and change from baseline in quality-of-life (SF-36). Results: Subjects were on average 29.6 years of age, 72.6 kg, and had a 6.1 year history of DUB. The most frequently reported type of DUB was oligomenorrhea. Higher percentages of both investigators and subjects in the NGM/EE group (81.4% and 87.1%) compared with the placebo group (35.8% and 45.3%) assessed the subject’s condition as “improved.” These findings were similar in each of the four DUB-type subgroups. Significantly fewer subjects receiving NGM/EE than subjects receiving placebo reported abnormal bleeding patterns ( P P Conclusion: The triphasic OC containing Norgestimate and ethinyl estradiol is an effective treatment for DUB.
Susan S Jick - One of the best experts on this subject based on the ideXlab platform.
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further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing Norgestimate and 35 μg of ethinyl estradiol
Contraception, 2007Co-Authors: Susan S Jick, James A Kaye, Hershel JickAbstract:Abstract Context In 2006, we published a study that indicated that the new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin did not increase the risk for venous thromboembolism (VTE) compared to oral contraceptive containing Norgestimate and 35 μg of EE. Objective This report updates information on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using oral contraceptives containing Norgestimate (either monophasic or triphasic) and 35 μg of EE (Norgestimate-35) using an additional 17months of data. Design, Setting and Participants Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women, aged 15 to 44 years, who started either the contraceptive patch or Norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE) who were not in the earlier study. Up to four controls were matched to each case by age and calendar time. Main Outcome Measures Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives. Results We identified 56 new cases of newly diagnosed, idiopathic VTE in the updated study population. The OR comparing the contraceptive patch to Norgestimate-35 was 1.1 (95% CI 0.6–2.1). Conclusions After evaluating an additional 17 months of data, the results indicate that the risk of nonfatal VTE for the contraceptive patch is closely similar to the risk for oral contraceptives containing 35 μg of EE and Norgestimate.
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Original research article Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing Norgestimate and 35 μg of ethinyl estradiol
2007Co-Authors: Susan S Jick, James A Kaye, Hershel JickAbstract:Context: In 2006, we published a study that indicated that the new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin did not increase the risk for venous thromboembolism (VTE) compared to oral contraceptive containing Norgestimate and 35 μg of EE. Objective: This report updates information on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using oral contraceptives containing Norgestimate (either monophasic or triphasic) and 35 μg of EE (Norgestimate-35) using an additional 17 months of data. Design, Setting and Participants: Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women, aged 15 to 44 years, who started either the contraceptive patch or Norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE) who were not in the earlier study. Up to four controls were matched to each case by age and calendar time. Main Outcome Measures: Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives. Results: We identified 56 new cases of newly diagnosed, idiopathic VTE in the updated study population. The OR comparing the contraceptive patch to Norgestimate-35 was 1.1 (95% CI 0.6–2.1). Conclusions: After evaluating an additional 17 months of data, the results indicate that the risk of nonfatal VTE for the contraceptive patch is closely similar to the risk for oral contraceptives containing 35 μg of EE and Norgestimate.
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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.
Contraception, 2006Co-Authors: Susan S Jick, Hershel JickAbstract:Abstract Background It has been suggested that the risk for cerebral venous sinus thrombosis (CVST) may be greater among users of the contraceptive patch than among users of oral contraceptives (OCs). Methods From the PharMetrics database, we identified women aged 15–44 years who filled at least one prescription for either the contraceptive patch or desogestrel-containing, Norgestimate-containing or levonorgestrel-containing OCs to assess the risk of CVST. The person-time of current exposure to each study drug, as well as the incidence rates (IRs) and incidence rate ratios (IRRs) of CVST, was calculated. Results We identified over 1 million users of the four study drugs. There were five cases of CVST among current users of desogestrel, seven cases among current users of Norgestimate, two cases among current users of levonorgestrel and none among current users of the contraceptive patch. The IRs per 100,000 woman-years were 2.7 [95% confidence interval (95% CI)=0.9–6.3], 1.6 (95% CI=0.7–3.3), 0.7 (95% CI=0.1–2.4) and 0.0 (95% CI=0.0–4.8), respectively, in users of desogestrel, Norgestimate, levonorgestrel and the contraceptive patch. There were two women who had CVST while not currently taking a hormonal contraceptive (IR=0.4 per 100,000 woman-years; 95% CI=0.1–1.3). The IRRs were 4.0 (95% CI=0.7–42.4) for desogestrel-containing versus levonorgestrel-containing OCs, and 2.4 (95% CI=0.5–24.0) for Norgestimate-containing versus levonorgestrel-containing OCs. The IRR for the patch could not be calculated. Conclusions There is no evidence of an increased risk of CVST in users of the contraceptive patch compared to users of levonorgestrel-containing OCs.
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Risk of nonfatal venous thromboembolism with oral contraceptives containing Norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel.
Contraception, 2006Co-Authors: Susan S Jick, James A Kaye, Stefan Russmann, Hershel JickAbstract:Abstract Context Previous studies have reported that users of the “third-generation” oral contraceptives (OCs) containing the progestins gestodene and desogestrel have about twice the risk for venous thromboembolism (VTE) compared to users of older OCs containing levonorgestrel. Estimates of the risk for VTE among users of Norgestimate-containing OCs compared to other OCs, however, are lacking. Objective The purpose of this study is to obtain quantitative information on the risk of nonfatal VTE in women using OCs containing either Norgestimate or desogestrel in comparison with women taking OCs containing levonorgestrel. Design, Setting and Participants Based on information from PharMetrics, a United States-based company that collects and records information on claims paid by managed care plans, we used a nested case-control study design to estimate relative risks of nonfatal VTE among 15- to 39-year-old current users of OCs containing Norgestimate with 35 μg of ethinyl estradiol (EE), desogestrel with 30 μg of EE or levonorgestrel with 30 μg of EE, both monophasic and triphasic preparations, during the period January 2000 to March 2005. Cases were women with a well-documented VTE of uncertain origin that was diagnosed in current users of a study drug. Up to four controls were closely matched to each case by age and calendar time, and odds ratios (ORs) were calculated using conditional logistic regression comparing the risk of VTE among users of the three contraceptives. We also estimated and compared the incidence rates for all three OCs. Results Based on 281 newly diagnosed idiopathic cases of VTE and 1055 controls, we found that the adjusted ORs for nonfatal VTE comparing Norgestimate- or desogestrel-containing OC users to users of levonorgestrel-containing OCs were 1.1 [95% confidence interval (CI), 0.8–1.6] and 1.7 (95% CI, 1.1–2.4), respectively. The incidence rates of VTE were 30.6 (95% CI, 25.5–36.5), 53.5 (95% CI, 42.9–66.0) and 27.1 (95% CI, 21.1–34.3) per 100,000 woman-years for users of Norgestimate-, desogestrel- and levonorgestrel-containing OCs, respectively. The incidence rate ratios for Norgestimate-containing OCs compared to levonorgestrel-containing OCs and desogestrel-containing OCs compared to levonorgestrel-containing OCs were 1.1 (95% CI, 0.8–1.5) and 2.0 (95% CI, 1.4–2.7), respectively. Conclusions The risk of nonfatal VTE among users of desogestrel-containing OCs is significantly elevated compared to that of levonorgestrel-containing OCs. The risk of VTE in users of Norgestimate-containing OCs was closely similar to that of users of levonorgestrel-containing OCs.
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risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing Norgestimate and 35 μg of ethinyl estradiol
Contraception, 2006Co-Authors: Susan S Jick, James A Kaye, Stefan Russmann, Hershel JickAbstract:Abstract Context There is concern that a new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin increases the risk for venous thromboembolism (VTE) compared to previously marketed oral contraceptives (OCs). Objective Quantitative information was obtained on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using OCs, Norgestimate (either monophasic or triphasic) and 35 μg EE (Norgestimate-35), an OC that has been marketed for over a decade. Design, Setting and Participants Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women aged 15 to 44, who started either the contraceptive patch or Norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE). Up to four controls were matched to each case by age and calendar time. Main Outcome Measures Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives and incidence rates of nonfatal VTE for new users of each of the study contraceptives. Results We identified 68 newly diagnosed, idiopathic cases of VTE in the study population. In the case-control analysis, the OR comparing the contraceptive patch to Norgestimate-35 was 0.9 (95% CI 0.5–1.6). The overall incidence rate for VTE was 52.8 per 100,000 women-years (95% CI 35.8–74.9) among users of the contraceptive patch and 41.8 per 100,000 women-years among users of Norgestimate-35 (95% CI 29.4–57.6), and the age-adjusted VTE incidence rate ratio (IRR) for current use of the contraceptive patch vs. Norgestimate-35 was 1.1 (95% CI 0.7–1.8). Conclusions The risk of nonfatal VTE for the contraceptive patch is similar to the risk for OCs containing 35 μg ethinylestradiol and Norgestimate.
Michael E. Kafrissen - One of the best experts on this subject based on the ideXlab platform.
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Triphasic Norgestimate-ethinyl estradiol for treating dysfunctional uterine bleeding.
Obstetrics and gynecology, 2000Co-Authors: Ann J. Davis, Amy Godwin, Joel Lippman, William Olson, Michael E. KafrissenAbstract:Objective: To compare the efficacy of a triphasic combination oral contraceptive (OC) containing Norgestimate and ethinyl estradiol (E2) and placebo in the treatment of metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding (DUB). Methods: In this multicenter, randomized, double-masked study, 201 women (15–50 years of age) with DUB received triphasic Norgestimate-ethinyl E2 or placebo, for three consecutive 28-day treatment cycles. Efficacy was determined by evaluating investigator and subject assessments of DUB resolution, abnormal uterine bleeding patterns during an 84-day reference period, and change from baseline in subjects’ quality of life. The sample size was based on the assumption that the proportions of subjects exhibiting treatment success (percentage of subjects with investigator and subject overall assessments of DUB resolution of “improved”) were 65% for the active group and 40% for the placebo group (α = 0.05, 1 − β = 0.80). Results: More than 80% of subjects receiving triphasic Norgestimate-ethinyl E2 had improvements in their abnormal bleeding patterns as assessed by investigators, and the subjects themselves compared with fewer than 50% of subjects in the placebo treatment group (P < .001). Abnormal bleeding patterns were reported by significantly fewer subjects receiving triphasic Norgestimate-ethinyl E2 than in the placebo treatment group (P < .001). Change from baseline in physical functioning (eg, self-care, walking, lifting, exercising) was significantly more improved in the triphasic Norgestimate-ethinyl E2 group than in the placebo group. Conclusion: The triphasic combination of Norgestimate and ethinyl E2 is an effective treatment for metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding.
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Norgestimate and ethinyl estradiol in the treatment of acne vulgaris: a randomized, placebo-controlled trial.
Obstetrics and gynecology, 1997Co-Authors: Geoffrey P. Redmond, Michael E. Kafrissen, Joel Lippman, William Olson, Terry M. Jones, Joseph L. JorizzoAbstract:Objective To evaluate the efficacy of a triphasic, combination oral contraceptive (OC), (Norgestimate-ethinyl estradiol), in comparison with placebo in the treatment of moderate acne vulgaris. Methods Two hundred fifty women were enrolled in a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the effectiveness of Norgestimate-ethinyl estradiol in the treatment of acne vulgaris. Subjects were 15–49 years old and had moderate acne vulgaris. Each month for 6 months, subjects received either 3 consecutive weeks of active OC treatment followed by 1 week of inactive drug, or 4 consecutive weeks of color-matched placebo tablets. Efficacy was assessed by facial acne lesion counts, the investigator's global assessment, and the subject's self-assessment. Hormone levels were also measured. Results Despite the large placebo effect inherent in an acne trial (due to, for example, careful skin care, frequent office visits, regression to the mean), of the 164 subjects who completed the study without major protocol deviations, the OC group was significantly better than the placebo group for all primary efficacy measures: inflammatory lesions (mean reduction, 51.4% compared to 34.6%; P = .01), total lesions (mean reduction, 46.4% compared to 33.9%; P = .001); investigator's global assessment (83.3% compared to 62.5%; P = .001). Free testosterone decreased significantly and sex hormone-binding globulin increased significantly in the OC group, but remained unchanged in the placebo group. Conclusion A triphasic combination of Norgestimate and ethinyl estradiol is an effective treatment for moderate acne vulgaris in women with no known contraindication to OC therapy.
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A Norgestimate-containing oral contraceptive: review of clinical studies.
American Journal of Obstetrics and Gynecology, 1992Co-Authors: Michael E. KafrissenAbstract:Despite the well-documented efficacy and safety of low-dose oral contraceptives, the development of newer formulations containing highly selective progestins with minimal or no androgenic activity has been a goal of pharmaceutical research. The efficacy and safety of Norgestimate, a progestin with inherently low androgenicity, in combination with ethinyl estradiol, has been examined in several phase II and phase III clinical studies, and these are reviewed. Norgestimate/ethinyl estradiol has proved to be a low-dose oral contraceptive with high selectivity that provides the cycle control of older oral contraceptive formulations with comparable efficacy. Results of comparison studies between Norgestimate/ethinyl estradiol and formulations containing norgestrel, a progestin with relatively greater androgenic activity, in combination with ethinyl estradiol, are reported for effects on lipid and lipoprotein levels and carbohydrate metabolism. Norgestimate/ethinyl estradiol consistently produced statistically significant increases in high-density lipoprotein cholesterol and improvement in the ratio of low-density lipoprotein cholesterol to high-density lipoprotein. In contrast, norgestrel/ethinyl estradiol produced statistically significant decreases in high-density lipoprotein cholesterol and potentially adverse changes in the low-density/high-density lipoprotein ratio. Phase II studies have confirmed that Norgestimate/ethinyl estradiol has low androgenic activity and causes minimal effect on coagulation factors and carbohydrate metabolism.
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Inhibition of Diacylglycerol–Sensitive TRPC Channels by Synthetic and Natural Steroids
PloS one, 2012Co-Authors: Susanne Miehe, Peter Crause, Thorsten Schmidt, Matthias Löhn, Heinz-werner Kleemann, Thomas Licher, Werner Dittrich, Hartmut Rütten, Carsten StrübingAbstract:TRPC channels are a family of nonselective cation channels that regulate ion homeostasis and intracellular Ca2+ signaling in numerous cell types. Important physiological functions such as vasoregulation, neuronal growth, and pheromone recognition have been assigned to this class of ion channels. Despite their physiological relevance, few selective pharmacological tools are available to study TRPC channel function. We, therefore, screened a selection of pharmacologically active compounds for TRPC modulating activity. We found that the synthetic gestagen Norgestimate inhibited diacylglycerol-sensitive TRPC3 and TRPC6 with IC50s of 3–5 µM, while half-maximal inhibition of TRPC5 required significantly higher compound concentrations (>10 µM). Norgestimate blocked TRPC-mediated vasopressin-induced cation currents in A7r5 smooth muscle cells and caused vasorelaxation of isolated rat aorta, indicating that Norgestimate could be an interesting tool for the investigation of TRP channel function in native cells and tissues. The steroid hormone progesterone, which is structurally related to Norgestimate, also inhibited TRPC channel activity with IC50s ranging from 6 to 18 µM but showed little subtype selectivity. Thus, TRPC channel inhibition by high gestational levels of progesterone may contribute to the physiological decrease of uterine contractility and immunosuppression during pregnancy.
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inhibition of diacylglycerol sensitive trpc channels by synthetic and natural steroids
PLOS ONE, 2012Co-Authors: Susanne Miehe, Peter Crause, Thorsten Schmidt, Matthias Löhn, Heinz-werner Kleemann, Thomas Licher, Werner Dittrich, Hartmut Rütten, Carsten StrübingAbstract:TRPC channels are a family of nonselective cation channels that regulate ion homeostasis and intracellular Ca2+ signaling in numerous cell types. Important physiological functions such as vasoregulation, neuronal growth, and pheromone recognition have been assigned to this class of ion channels. Despite their physiological relevance, few selective pharmacological tools are available to study TRPC channel function. We, therefore, screened a selection of pharmacologically active compounds for TRPC modulating activity. We found that the synthetic gestagen Norgestimate inhibited diacylglycerol-sensitive TRPC3 and TRPC6 with IC50s of 3–5 µM, while half-maximal inhibition of TRPC5 required significantly higher compound concentrations (>10 µM). Norgestimate blocked TRPC-mediated vasopressin-induced cation currents in A7r5 smooth muscle cells and caused vasorelaxation of isolated rat aorta, indicating that Norgestimate could be an interesting tool for the investigation of TRP channel function in native cells and tissues. The steroid hormone progesterone, which is structurally related to Norgestimate, also inhibited TRPC channel activity with IC50s ranging from 6 to 18 µM but showed little subtype selectivity. Thus, TRPC channel inhibition by high gestational levels of progesterone may contribute to the physiological decrease of uterine contractility and immunosuppression during pregnancy.
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Endothelium-independent relaxation of pre-contracted rat aortic rings by Norgestimate.
2012Co-Authors: Susanne Miehe, Peter Crause, Thorsten Schmidt, Matthias Löhn, Heinz-werner Kleemann, Thomas Licher, Werner Dittrich, Hartmut Rütten, Carsten StrübingAbstract:Representative wire myograph recording (A) illustrating the effect of Norgestimate on L-NAME treated intact aortic rings pre-contracted with phenylephrine. Compounds were applied as indicated in the perfusate. Acetylcholine (Ach) was applied to demonstrate the absence of endothelium-dependent vasorelaxation. Higher Norgestimate concentrations could not be tested due to the limited solubility of the compound. Concentration-response curve of Norgestimate-induced vasorelaxation (B). Norgestimate-induced relaxation was expressed as percentage of the phenylephrine-induced tension prior to Norgestimate application. The solid line represents the best fit of the data to the Hill model with: y0 = −4.26%, y1 = 84.8%, and n = 0.93. Data represent means ± SEM (n = 6).
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Norgestimate inhibits TRPC3- and TRPC6-mediated Ca2+ influx.
2012Co-Authors: Susanne Miehe, Peter Crause, Thorsten Schmidt, Matthias Löhn, Heinz-werner Kleemann, Thomas Licher, Werner Dittrich, Hartmut Rütten, Carsten StrübingAbstract:OAG-induced changes of [Ca2+]i in fluo-4-loaded TRPC3 CHO cells (A) and TRPC6 HEK-FITR cells (C) were measured in 96-well plates using a fluorometric imaging plate reader. Pre-incubation of cells with 30 µM Norgestimate (NG) significantly reduced TRPC3 and −6 mediated Ca2+ entry. Representative fluorescence traces are shown. Concentration-response curves for inhibition of TRPC3 (B) and TRPC6 (D) by Norgestimate were derived from the area under the fluorescence curves for each given concentration. The solid lines represent the best fit of the data to the Hill model with slopes of n = 1.67 (TRPC3) and n = 0.97 (TRPC6). Means ± SEM of 3 wells (B) or 4 wells (D) are shown. The chemical structure of Norgestimate is illustrated in B.
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Norgestimate blocks AVP-activated non-selective cation currents in A7r5 cells independent of vasopressin receptor function.
2012Co-Authors: Susanne Miehe, Peter Crause, Thorsten Schmidt, Matthias Löhn, Heinz-werner Kleemann, Thomas Licher, Werner Dittrich, Hartmut Rütten, Carsten StrübingAbstract:Effect of 10 µM Norgestimate (NG) on whole-cell currents evoked by 100 nM AVP in A7r5 cells (A). I–V relationships recorded at the indicated times (left panels) and time course of currents recorded at −60 mV (right panels) are shown. The I–V curves were obtained during voltage ramps from −100 to +80 mV. Voltage-gated L-type Ca2+ channels were blocked by 5 µM nimodipine during the whole experiment. Time-dependent changes of [Ca2+]i in fura-2-loaded A7r5 cells (B). Cells were pre-incubated with or without (control) 10 µM Norgestimate (NG) in calcium-free (1 mM EGTA) standard extracellular solution for 5 min before vasopressin receptor stimulation by application of 100 nM AVP. Data represent means ± SEM from 33 cells (control) and 36 cells (Norgestimate).
