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Julia Grunert - One of the best experts on this subject based on the ideXlab platform.
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effects of an ethinyl estradiol Gestodene transdermal contraceptive patch on the endometrium a single center uncontrolled study
Women's Health, 2014Co-Authors: Martin Merz, Julia GrunertAbstract:Aim: This study aims to investigate the effect of a transdermal contraceptive patch containing ethinyl estradiol and Gestodene on endometrial proliferation over 1 year. Materials & methods: In this open-label, uncontrolled, Phase IIb study, women (aged 18–35 years) used the patch for 13 cycles of 28 days. The primary variable was histologic endometrial effects at cycle 13. Secondary objectives included contraceptive efficacy and safety. Results: Overall, 89 women were treated. At all visits, endometrial biopsies were devoid of any abnormalities. One woman became pregnant. The patch was well tolerated, with no safety concerns. Conclusion: The ethinyl estradiol and Gestodene patch had an endometrial effect consistent with suppression of endometrial proliferation in most patients. No endometrial abnormalities or other concerns were reported; compliance was good.
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Effects of an ethinyl estradiol/Gestodene transdermal contraceptive patch on the endometrium: a single-center, uncontrolled study
Women's Health, 2014Co-Authors: Martin Merz, Julia GrunertAbstract:Aim: This study aims to investigate the effect of a transdermal contraceptive patch containing ethinyl estradiol and Gestodene on endometrial proliferation over 1 year. Materials & methods: In this open-label, uncontrolled, Phase IIb study, women (aged 18–35 years) used the patch for 13 cycles of 28 days. The primary variable was histologic endometrial effects at cycle 13. Secondary objectives included contraceptive efficacy and safety. Results: Overall, 89 women were treated. At all visits, endometrial biopsies were devoid of any abnormalities. One woman became pregnant. The patch was well tolerated, with no safety concerns. Conclusion: The ethinyl estradiol and Gestodene patch had an endometrial effect consistent with suppression of endometrial proliferation in most patients. No endometrial abnormalities or other concerns were reported; compliance was good.
Martin Merz - One of the best experts on this subject based on the ideXlab platform.
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effects of an ethinyl estradiol Gestodene transdermal contraceptive patch on the endometrium a single center uncontrolled study
Women's Health, 2014Co-Authors: Martin Merz, Julia GrunertAbstract:Aim: This study aims to investigate the effect of a transdermal contraceptive patch containing ethinyl estradiol and Gestodene on endometrial proliferation over 1 year. Materials & methods: In this open-label, uncontrolled, Phase IIb study, women (aged 18–35 years) used the patch for 13 cycles of 28 days. The primary variable was histologic endometrial effects at cycle 13. Secondary objectives included contraceptive efficacy and safety. Results: Overall, 89 women were treated. At all visits, endometrial biopsies were devoid of any abnormalities. One woman became pregnant. The patch was well tolerated, with no safety concerns. Conclusion: The ethinyl estradiol and Gestodene patch had an endometrial effect consistent with suppression of endometrial proliferation in most patients. No endometrial abnormalities or other concerns were reported; compliance was good.
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Effects of an ethinyl estradiol/Gestodene transdermal contraceptive patch on the endometrium: a single-center, uncontrolled study
Women's Health, 2014Co-Authors: Martin Merz, Julia GrunertAbstract:Aim: This study aims to investigate the effect of a transdermal contraceptive patch containing ethinyl estradiol and Gestodene on endometrial proliferation over 1 year. Materials & methods: In this open-label, uncontrolled, Phase IIb study, women (aged 18–35 years) used the patch for 13 cycles of 28 days. The primary variable was histologic endometrial effects at cycle 13. Secondary objectives included contraceptive efficacy and safety. Results: Overall, 89 women were treated. At all visits, endometrial biopsies were devoid of any abnormalities. One woman became pregnant. The patch was well tolerated, with no safety concerns. Conclusion: The ethinyl estradiol and Gestodene patch had an endometrial effect consistent with suppression of endometrial proliferation in most patients. No endometrial abnormalities or other concerns were reported; compliance was good.
C Christiansen - One of the best experts on this subject based on the ideXlab platform.
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low doses of estradiol in combination with Gestodene to prevent early postmenopausal bone loss
American Journal of Obstetrics and Gynecology, 2000Co-Authors: Nina Hannover Bjarnason, I Byrjalsen, Christian Hassager, Jens Haarbo, C ChristiansenAbstract:Abstract Objective: Our purpose was to study combinations of estradiol and Gestodene for prevention of bone loss in early postmenopausal women. Study Design: We randomly assigned 278 healthy, early postmenopausal women to receive either 2 mg 17β-estradiol sequentially combined with 25 μg Gestodene (group 2/25s), 2 mg estradiol sequentially combined with 50 μg Gestodene (group 2/50s), 1 mg estradiol sequentially combined with 25 μg Gestodene (group 1/25s), 1 mg estradiol continuously combined with 25 mg Gestodene (group 1/25c), or placebo. Results: After 3 years the changes in bone mineral density of the spine were as follows (mean ± SEM): group 2/25s, 7.41% ± 0.72%; group 2/50s, 8.53% ± 0.90%; group 1.25s, 6.67% ± 0.88%; group 1/25c, 4.44% ± 0.59%; and placebo group, –2.03% ± 0.64%. The changes in bone mineral density were mirrored in the biochemical bone markers. The average responses for the urinary C-terminal telopeptide fragments of type I collagen corrected for creatinine excretion were as follows (mean of baseline ± SEM): group 2/25s, –68.8% ± 0.03%; group 2/50s, –72.8% ± 0.02%; group 1/25s, –60.7% ± 0.03%; group 1/25c, –52.28% ± 0.04%; and placebo group, 6.5% ± 0.09%. Beneficial lipid effects were found in all active groups. The decreases in low-density lipoprotein were as follows (mean ± SEM): group 2/25s, –13.7% ± 3.0%; group 2/50s, –14.6% ± 3.2%; group 1/25s, –9.28% ± 2.2%; group 1/25c, –9.92% ± 2.4%; and placebo group, 1.53% ± 1.9%. Conclusion: These results demonstrate that estradiol therapy with 1 mg estradiol is fully protective against early postmenopausal bone loss. (Am J Obstet Gynecol 2000;183:550-60.)
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Progestational effects of combinations of Gestodene on the postmenopausal endometrium during hormone replacement therapy.
American journal of obstetrics and gynecology, 1999Co-Authors: I Byrjalsen, N H Bjarnason, C ChristiansenAbstract:The aim of the study was to assess the dose-response effects on the postmenopausal endometrium of 3 sequential combined hormone replacement regimens and 1 continuous combined hormone replacement regimen of estradiol and Gestodene. In this 2-year double-blind, placebo-controlled study, 278 healthy postmenopausal women received either 2 mg estradiol sequentially combined with 50 microg or 25 microg Gestodene, 1 mg estradiol sequentially or continuously combined with 25 microg Gestodene, or placebo. All 4 hormone treatment regimens produced a safe endometrial histologic appearance. The regimens that were based on the lower dose of 1 mg estradiol was associated with less uterine bleeding than were those that were based on 2 mg estradiol. For sequentially opposing the 2 mg dose of estradiol, the dose of 25 microg Gestodene was less efficient in producing secretory activity than was the dose of 50 microg Gestodene. The measurement of placental protein 14 in serum reflected the secretory transformation of the endometrial buildup. The reduction in bleeding episodes associated with regimens with lower estradiol doses may lead to improved long-term therapy compliance by menopausal women. The potency of progestogens can be assessed by measuring the serum concentration of placental protein 14.
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progestational effects of combinations of Gestodene on the postmenopausal endometrium during hormone replacement therapy
American Journal of Obstetrics and Gynecology, 1999Co-Authors: I Byrjalsen, N H Bjarnason, C ChristiansenAbstract:Abstract Objective: The aim of the study was to assess the dose-response effects on the postmenopausal endometrium of 3 sequential combined hormone replacement regimens and 1 continuous combined hormone replacement regimen of estradiol and Gestodene. Study Design: In this 2-year double-blind, placebo-controlled study, 278 healthy postmenopausal women received either 2 mg estradiol sequentially combined with 50 μg or 25 μg Gestodene, 1 mg estradiol sequentially or continuously combined with 25 μg Gestodene, or placebo. Results: All 4 hormone treatment regimens produced a safe endometrial histologic appearance. The regimens that were based on the lower dose of 1 mg estradiol was associated with less uterine bleeding than were those that were based on 2 mg estradiol. For sequentially opposing the 2 mg dose of estradiol, the dose of 25 μg Gestodene was less efficient in producing secretory activity than was the dose of 50 μg Gestodene. The measurement of placental protein 14 in serum reflected the secretory transformation of the endometrial buildup. Conclusion: The reduction in bleeding episodes associated with regimens with lower estradiol doses may lead to improved long-term therapy compliance by menopausal women. The potency of progestogens can be assessed by measuring the serum concentration of placental protein 14. (Am J Obstet Gynecol 1999;180:539-49.)
W. Kuhnz - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics and serum protein binding of Gestodene and 3-keto-desogestrel in women after single oral administration of two different contraceptive formulations
Drug Research, 1992Co-Authors: W. Kuhnz, B. Schütt, J. Power, David BackAbstract:In Berlin Germany and Liverpool England health workers took blood samples from 18 24-34 year old women who took either a single oral contraceptive pill (Femovan) with 75 mcg Gestodene and 30 mcg ethinyl and 30 mcg ethinyl estradiol or a single oral contraceptive pill with 150 mcg desogestrel and 30 mcg ethinyl estradiol followed 7 days later by a single pill with 75 mcg Gestodene and 30 mcg ethinyl estradiol. Researchers aimed to determine the serum protein binding traits of both progestins and their pharmacokinetics. They used specific radioimmunoassays and ultrafiltration to measure levels and serum protein binding of Gestodene and the active metabolite of desogestrel 3-keto-desogestrel (KDG). The free faction of both progestins was the same 91.9% for Gestodene and 1.7% for KDG). The percent Gestodene bound to albumin was not significantly different from that of KDG (47.8% vs. 63.7%). Similarly there was no significant difference between the percent Gestodene and percent KDG bound to sex hormone binding globulin (SHBG) while Gestodene tended to bind more with SHBG than albumin. The SHBG binding of Gestodene was not as strong as that of albumin binding of KDG however. After pill administration KDG reached maximum levels later than did Gestodene (1.5 hours vs. 7 hours). Mean maximum level of Gestodene was 4.9 ng/ml. Post maximum levels of Gestodene fell biphasically with half lives at a mean of 0.13 hours and 14.7 hours respectively. The area under the cure of Gestodene was 32.9 ng x ml-1 x h. Mean maximum level of KDg was 1.7 ng/ml. Post-maximum levels of Gestodene fell biphasically with half lives at a mean of 0.5 and 17 hours respectively. The area under the curve of Gestodene was 15.2 ng x ml-1 x h. Lower bioavailability of KDG (60-80% vs. 100% for Gestodene) may have accounted for the slightly greater interindividual variation of drug levels for KDG than Gestodene.
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pharmacokinetics and protein binding of Gestodene under treatment with a low dose combination oral contraceptive for three months
Drug Research, 1992Co-Authors: L Dibbelt, W. Kuhnz, R Knuppen, G JuttingAbstract:In Germany health workers drew serum samples from 40 healthy young women who used a low dose oral contraceptive (OC) (Femovan Femodene) with 30 mcg ethinyl estradiol and 75 mcg Gestodene for 3 treatment cycles to measure Gestodene levels the free fraction of Gestodene and its distribution over the binding proteins in serum pools from all women. Mean maximum Gestodene levels occurred .8 to .9 hours after taking the pill. The mean maximum Gestodene level on test day 1 was 4.3 ng ml-1 during the first treatment cycle. This figure increased significantly to 7.4 ng ml-1 during the third cycle. Both day 1 levels were significantly lower than the levels obtained on day 10 (10.4 and 13.1 ng ml-1 respectively) and day 21 (12.1 and 13.4 ng ml-1 respectively). The area under the curve zero to 4 hours after pill intake was 9.3 ng ml-1. These figures rose 250-400% and 300-500% respectively on days 10 and 21. During the third treatment cycle figures for days 10 and 21 were somewhat lower than those during the first cycle. 78% of total Gestodene was bound to sex hormone binding globulin (SHBG) and 21% was bound to albumin on day 1 of the first treatment cycle. Just 1% of Gestodene continued to be free. ON day 21 the fraction of Gestodene bound to SHBG rose to 87% that bound to albumin was 13% and 0.5% remained free. Gestodene was not redistributed over its binding proteins during the third treatment cycle. These results indicated that pharmacokinetic accumulation and the increase in serum SHBG concentration and binding capacity for Gestodene allows researchers to understand changes in Gestodene levels during longterm treatment with a low dose OC containing Gestodene.
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pharmacokinetics of the contraceptive steroids levonorgestrel and Gestodene after single and multiple oral administration to women
American Journal of Obstetrics and Gynecology, 1990Co-Authors: W. KuhnzAbstract:Abstract Little is known about the pharmacokinetics of the two progestins levonorgestrel and Gestodene during long-term administration compared with single-dose pharmacokinetics. The predictive value of single-dose administration for the pharmacokinetic behavior of a progestin during long-term treatment was investigated for two triphasic oral contraceptives. One contained levonorgestrel and the other Gestodene, each in combination with ethinyl estradiol. In eight Japanese women who received the levonorgestrel-containing formulation over a treatment cycle, steady-state trough levels of levonorgestrel were higher than those obtained by computer simulation based on single-dose administration. An analogous observation was made in a group of 10 white women who received the Gestodene-containing formulation. A close correlation between Gestodene and sex hormone-binding globulin concentrations was demonstrated for eight subjects; the other two patients already had initially high sex hormone-binding globulin levels. Ethinyl estradiol-induced production of sex hormone-binding globulin seems to be a major factor that contributes to the accumulation of the two progestins in the plasma. Computer simulation, based on single-dose pharmacokinetics, allows an estimation of this contribution.
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Pharmacokinetics of Gestodene and ethinyl estradiol after oral administration of a monophasic contraceptive
American Journal of Obstetrics and Gynecology, 1990Co-Authors: Ulrich Täuber, W. Kuhnz, M. HümpelAbstract:The pharmacokinetic and protein-binding properties of Gestodene and ethinyl estradiol have been investigated after single and multiple dosing in several studies in 83 healthy, young women. After oral administration, Gestodene is completely absorbed and bioavailable and exhibits dose-linear pharmacokinetics. During long-term pill use, serum levels of Gestodene were four to five times higher than after single administration, showing a periodic increase from day 1 to day 10 during each cycle. Ultrafiltration studies revealed that 75.3% of total serum Gestodene is bound to sex hormone-binding globulin, 24.1% is bound to albumin, and only 0.6% is not protein bound. Thus Gestodene levels during steady state are explained by an increase in sex hormone binding-globulin as a result of concomitant administered ethinyl estradiol and a specific binding of Gestodene to this protein. Serum levels of ethinyl estradiol during single and multiple administration were identical and were not different from those observed with another preparation containing 30 μg of ethinyl estradiol.
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protein binding of active ingredients and comparison of serum ethinyl estradiol sex hormone binding globulin corticosteroid binding globulin and cortisol levels in women using a combination of Gestodene ethinyl estradiol femovan or a combination of d
American Journal of Obstetrics and Gynecology, 1990Co-Authors: M. Hümpel, W. Kuhnz, Ulrich Täuber, Michael Pfeffer, K Brill, R Heithecker, Thomas Louton, Bernd Steinberg, Wolfgang Seifert, Barbara SchuttAbstract:Abstract Results from two clinical pharmacokinetic studies are given. The first study was an observational study in oral contraceptive users who took either a combination of Gestodene and ethinyl estradiol (pill A, Femovan) or desogestrel and ethinyl estradiol (pill β, Marvelon). A total of 69 women (39 receiving pill A and 30 receiving pill B) were evaluated to determine serum ethinyl estradiol, sex hormone-binding globulin, corticosteroid-binding globulin, and cortisol levels. Samples were obtained on 1 day during the tenth to twenty-first days of pill intake. All women received the respective oral contraceptive for at least 3 months. The test power was such that an 80% difference of 1 standard deviation of each target variable would have been detected (α = 0.05; β = 0.1). No statistically significant differences were found in sex hormone-binding globulin, corticosteroid-binding globulin, or cortisol serum levels between both groups. Time and height of maximum ethinyl estradiol levels were identical as was the area under the curves. Ex vivo protein-binding analysis of the progestins revealed a free portion of 0.6% for Gestodene and 2.5% for 3-ketodesogestrel as the active metabolite of desogestrel. Sex hormone—binding globUlin-bound portions were much higher for Gestodene (75.3% ± 9.1%) than for 3-ketodesogestrel (31.6% ± 12%). The remaining fractions were bound to albumin. In a second study, ethinyl estradiol-bioequivalence from pills A and B was investigated in 18 women in a controlled, single-dose, randomized, crossover design. The area under the ethinyl estradiol serum levels were identical up to 4 hours after pill intake between both treatments. According to the relatively low variation in data in this group of women, a 10% difference in ethinyl estradiol-availability could have been detected. Both studies indicate that the pharmacokinetics of ethinyl estradiol were independent of the concomitantly administered progestin, that is, desogestel and Gestodene. (Am J Obstet Gynecol 1990;163:329-333.)
Herbert Kuhl - One of the best experts on this subject based on the ideXlab platform.
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Comparative Pharmacology of Newer Progestogens
Drugs, 1996Co-Authors: Herbert KuhlAbstract:The newer progestogens desogestrel, norgestimate, Gestodene, dienogest and nomegestrol share the common property of having weak or no androgenic effects, but there is great variation between agents in their pharmacokinetic properties and hormonal activities. Both desogestrel (acting as 3-keto-desogestrel) and norgestimate (acting mainly through levonorgestrel) are prodrugs. While nomegestrol is derived from 19-norprogesterone, the other compounds are 19-nortestosterone derivatives: desogestrel, norgestimate and Gestodene belong to the subgroup of 13-ethyl-gonanes with an ethinyl group at C_17α, and dienogest represents an estrane (13-methyl-gonane) with a cyanomethyl group at C_17α Both dienogest and nomegestrol have antiandrogenic properties. In proportion to the dose, the highest serum concentrations are observed after intake of Gestodene. When combined with ethinylestradiol, Gestodene and 3-keto-desogestrel accumulate in serum during daily treatment because of slowed-down elimination. This is probably caused both by binding to sex hormone-binding globulin (SHBG) and by inhibition of inactivating enzymes. Dienogest does not accumulate in serum, although at a dose of 2mg very high serum concentrations of dienogest are reached. The most potent progestogens are Gestodene and desogestrel, while the effect of dienogest and nomegestrol on endometrium and cervix is less, even though in a similar range. As the ovulation-inhibiting effect is brought about not only by receptor-mediated interactions but also by a direct inhibition of steroid biosynthesis, dienogest and nomegestrol are much less effective than Gestodene, desogestrel and norgestimate. Ethinylated progestogens, particularly Gestodene, have been demonstrated to inhibit cytochrome P450 enzymes. Both Gestodene and desogestrel may moderately reduce SHBG levels and counteract the stimulating effect of ethinylestradiol on hepatic serum proteins, while dienogest and nomegestrol have no influence. Compared with progestogens with androgenic properties which may restrict the stimulatory action of ethinylestradiol on haemostatic parameters, the newer progestogens do not seem to be superior with respect to haemostasis. There are no data on the direct effect of the compounds on the arterial and venous vessel wall. Due to the less pronounced antagonism on ethinylestradiol-induced changes in lipid metabolism, the newer progestogens appear to be beneficial rather than deleterious, although atherosclerosis was probably not promoted by the older formulations because of the direct effect of ethinylestradiol on the arterial wall. There is no evidence for a lesser impact of the newer progestogens on carbohydrate metabolism, which is mostly impaired by the estrogen component in oral contraceptives. Formulations containing the newer progestogens are, however, preferable in patients with hyperandrogenaemia, the symptoms of which may be improved by the suppression of total and free testosterone and an increase in SHBG; an additional beneficial effect of the antiandrogenic properties of dienogest or nomegestrol remains to be proven.
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Gestodene containing contraceptives
Clinical Obstetrics and Gynecology, 1995Co-Authors: Herbert Kuhl, C Junghoffmann, Inka WiegratzAbstract:Gestodene (GSD) is the most potent and therefore lowest dosed progestogen used in oral contraceptives. Pharmacokinetic studies have found serum levels of GSD to be considerably higher than those of comparable progestogens taken at higher doses. The monophasic and triphasic formulation suppress gonadotropin release and ovarian function profoundly and inhibit ovulation reliably with GSDs strong anti-estrogenic and progestogenic effectiveness based upon the high GSD serum concentrations achieved during daily intake. The authors describe the pharmacologic properties of GSD formulations containing GSD and ethinyl estradiol pharmacokinetics contraceptive effectiveness cycle control and side effects the effect on hormonal parameters the effect on lipid metabolism the effect on carbohydrate metabolism and the effect on hemostasis.