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Ingrid Duijkers - One of the best experts on this subject based on the ideXlab platform.
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the effect of estetrol drospirenone on ovarian function is similar to a well established combined oral contraceptive results from a phase 2 study
Journal of the Endocrine Society, 2021Co-Authors: Ingrid Duijkers, Christine Klipping, Maud Jost, Adriana Bastidas, Jeanmichel FoidartAbstract:Background: Combined oral contraceptives (COCs) often contain ethinylestradiol (EE), an estrogen known to be associated with several side effects including venous thromboembolism. Estetrol (E4) is a native estrogen synthesized by the human fetal liver during pregnancy. Results from a phase 2 dose-finding study showed that E4 15 mg in combination with drospirenone 3 mg (E4/DRSP) resulted in a good bleeding profile and cycle control. Here, we present phase 2 results showing the effect of E4/DRSP on ovarian function. Study Design: A single-center, randomized, open-label, parallel study was conducted in healthy young volunteers with proven ovulatory cycles. Study subjects received either E4 15 mg/DRSP 3 mg (n=41) or EE 20 µg/DRSP 3 mg (n=41) in a 24/4-day regimen for three consecutive cycles. Both in cycle 1 and 3, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH), estradiol and progesterone levels were determined, and follicular size and endometrial thickness were measured every three days using transvaginal ultrasound. Ovarian function was assessed using the Hoogland score, which considers follicular size and estradiol/progesterone levels. Return of Ovulation was determined after treatment cessation. Safety and tolerability were assessed by monitoring adverse events (AEs), vital signs, physical and gynecological examination, clinical laboratory parameters, 12-lead electrocardiogram and echocardiogram. Results: No Ovulations were reported during the use of E4/DRSP, while three Ovulations occurred in two subjects in the EE/DRSP group. In both groups, most participants had no ovarian activity according to the Hoogland score. In cycle 1, Hoogland scores and follicular diameters were similar in both groups. In cycle 3, these parameters were slightly less suppressed in the E4/DRSP group when compared to EE/DRSP. While mean FSH and LH concentrations were less inhibited by E4/DRSP, mean estradiol and progesterone concentrations and endometrial thickness were similarly suppressed in both groups. Return of Ovulation occurred on average 15.5 days after discontinuation of E4/DRSP intake. The number of frequently reported AEs considered to be related to study medication was similar for both treatment groups except for breast pain (11 subjects in the E4/DRSP group versus 4 subjects with EE/DRSP). Most related AEs were of mild or moderate intensity. Three subjects discontinued due to an AE, one with E4/DRSP (severe stress, emotional lability), and two with EE/DRSP (emotional lability, depressed mood). Other safety assessments did not show significant abnormalities. No serious AEs were reported. Conclusions: The combination of E4 15 mg and DRSP 3 mg results in adequate Ovulation Inhibition and ovarian function suppression, which is similar to a well-established COC containing EE/DRSP. E4/DRSP is considered safe and well-tolerated.
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effects of an oral contraceptive containing estetrol and drospirenone on ovarian function
Contraception, 2021Co-Authors: Ingrid Duijkers, Christine Klipping, Maud Jost, Virginie Kinet, Adriana Bastidas, Jeanmichel FoidartAbstract:Abstract Objective To evaluate the effects of estetrol 15 mg/drospirenone 3 mg on ovarian function. Study design Single-center, randomized, open-label, parallel study in healthy young women with proven ovulatory cycles. Participants received either estetrol 15 mg/drospirenone 3 mg (E4/DRSP) (n = 41) or ethinylestradiol 20 µg/drospirenone 3 mg (EE/DRSP) (n = 41) in a 24/4-day regimen for 3 consecutive cycles. Follicular size and endometrial thickness were measured by transvaginal ultrasound every 3 days in cycles 1 and 3. Blood was sampled for hormone analysis. Ovarian function expressed as Hoogland score was based on follicular size, serum estradiol (E2) and progesterone (P) concentrations. Ovulation was defined as a ruptured follicle-like structure >13 mm with serum E2 concentrations >100 pmol/L and serum P concentrations >5 nmol/L. We assessed return of Ovulation after treatment cessation, and safety throughout the study. Results None of the participants ovulated with E4/DRSP use, while one participant ovulated once and one participant ovulated twice during EE/DRSP treatment. Most participants had a Hoogland score of 1 (no ovarian activity) in cycle 1 (85.0% and 82.9% of participants on E4/DRSP and EE/DRSP, respectively) and in cycle 3 (65.8% and 83.8%, respectively). E4/DRSP suppressed follicle-stimulating hormone and luteinizing hormone to a lesser extent than EE/DRSP, whereas both treatments comparably suppressed E2 and P and endometrial thickness. Return of Ovulation occurred, on average, 15.5 days after E4/DRSP treatment discontinuation. E4/DRSP was safe and well-tolerated. Conclusions E4 15 mg/DRSP 3 mg results in adequate Ovulation Inhibition and ovarian function suppression, comparable to a marketed combined oral contraceptive containing EE/DRSP. Implications statement Treatment with E4 15 mg/DRSP 3 mg showed complete Ovulation Inhibition, despite less suppression of follicle-stimulating hormone and luteinizing hormone compared to EE/DRSP. If it becomes commercially available, E4/DRSP, containing a naturally occurring estrogen, should be as effective as EE/DRSP.
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maintenance of Ovulation Inhibition with a new progestogen only pill containing drospirenone after scheduled 24 h delays in pill intake
Contraception, 2016Co-Authors: Ingrid Duijkers, Doris Hegermahn, Dominique Drouin, Enrico Colli, Sven O SkoubyAbstract:Abstract Objectives Traditional progestogen-only pills (POPs) have stringent daily timing and missed pill rules that might affect contraceptive reliability. A new-generation oestrogen-free pill has been developed, containing 4-mg drospirenone with a unique regimen of 24 active treatment days followed by four placebo tablets. A previous study showed that this new drospirenone-only pill effectively inhibited Ovulation. Clinical efficacy, however, can be affected by compliance, and delayed or forgotten pill intake often occurs in daily life. The aim of this study was to investigate if Inhibition of Ovulation was maintained after four scheduled 24-h delays in tablet intake. Study design One hundred thirty healthy women with proven ovulatory cycles were randomized, and 127 were treated with the drospirenone-only pill during two cycles. In treatment Group A ( n =62), 24-h delays in tablet intake were scheduled on days 3, 6, 11 and 22 during Cycle 2 and, in treatment Group B ( n =65) during Cycle 1, respectively. Ovulation was defined as disappearance or persistence of a large follicle and progesterone levels higher than 5ng/mL for at least 5 consecutive days. Results The overall Ovulation rate was 0.8%; only one subject in Group A fulfilled the Ovulation criteria in Cycle 2. Follicular diameters in the regular-intake and the delayed-intake cycles were similar. Conclusion Despite the 4-day hormone-free period and multiple intentional 24-h delays in tablet intake, Ovulation Inhibition was maintained. This property distinguishes this new-generation oestrogen-free pill from traditional POPs by allowing the same "safety window" or flexibility in intake as combined oral contraceptives without compromising contraceptive reliability. Implications Delayed or forgotten pill intake is very common. Ovulation Inhibition by the new-generation oestrogen-free pill, containing 4-mg drospirenone for 24days followed by a 4-day treatment-free period, was maintained despite four 24-h delays in tablet intake, so the impact of delayed intake on contraceptive reliability will be low.
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original research article maintenance of Ovulation Inhibition with a new progestogen only pill containing drospirenone after scheduled 24 h delays in pill intake
2016Co-Authors: Ingrid Duijkers, Doris Hegermahn, Dominique Drouin, Enrico Colli, Sven O SkoubyAbstract:Objectives: Traditional progestogen-only pills (POPs) have stringent daily timing and missed pill rules that might affect contraceptive reliability. A new-generation oestrogen-free pill has been developed, containing 4-mg drospirenone with a unique regimen of 24 active treatment days followed by four placebo tablets. A previous study showed that this new drospirenone-only pill effectively inhibited Ovulation. Clinical efficacy, however, can be affected by compliance, and delayed or forgotten pill intake often occurs in daily life. The aim of this study was to investigate if Inhibition of Ovulation was maintained after four scheduled 24-h delays in tablet intake. Study design: One hundred thirty healthy women with proven ovulatory cycles were randomized, and 127 were treated with the drospirenone-only pill during two cycles. In treatment Group A (n=62), 24-h delays in tablet intake were scheduled on days 3, 6, 11 and 22 during Cycle 2 and, in treatment Group B (n=65) during Cycle 1, respectively. Ovulation was defined as disappearance or persistence of a large follicle and progesterone levels higher than 5 ng/mL for at least 5 consecutive days. Results: The overall Ovulation rate was 0.8%; only one subject in Group A fulfilled the Ovulation criteria in Cycle 2. Follicular diameters in the regular-intake and the delayed-intake cycles were similar. Conclusion: Despite the 4-day hormone-free period and multiple intentional 24-h delays in tablet intake, Ovulation Inhibition was maintained. This property distinguishes this new-generation oestrogen-free pill from traditional POPs by allowing the same “safety window” or flexibility in intake as combined oral contraceptives without compromising contraceptive reliability. Implications: Delayed or forgotten pill intake is very common. OvulationInhibitionbythenew-generationoestrogen-freepill,containing4-mg drospirenone for 24 days followed by a 4-day treatment-free period, was maintained despite four 24-h delays in tablet intake, so the impact of delayed intake on contraceptive reliability will be low.
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a two centre open label randomised study of Ovulation Inhibition with three transdermal contraceptive patches each containing different amounts of ethinyl estradiol and gestodene in healthy young women
Journal of Obstetrics and Gynaecology, 2016Co-Authors: K Waellnitz, Christine Klipping, Ingrid Duijkers, T Rautenberg, B Rohde, Christian ZurthAbstract:Here we report the findings of a two-centre, open-label, randomised, Phase IIa study designed to investigate whether an ethinyl estradiol (EE)/gestodene (GSD) patch that has been developed (referred to herein as the ‘EE/GSD patch’) reliably inhibits Ovulation in comparison with patches delivering lower doses of these hormones. The study rationale was to provide justification of the doses of EE and GSD selected for the EE/GSD patch. Healthy women, aged 18–35 years, were randomised to receive treatment with either the EE/GSD patch, a ‘reduced-GSD patch’ (delivering similar amounts of EE and approximately half the amount of GSD) or a ‘reduced-EE/GSD patch’ (delivering half the amount of EE and GSD). Treatment was administered for three 28-day cycles (three × 7 patch-wearing days, plus a 7-day patch-free interval). The primary pharmacodynamic variable was the percentage of women with Ovulation in at least one of Cycles 2 and/or 3, as indicated by Hoogland score. Pharmacokinetic parameters for EE and GSD were ...
Christine Klipping - One of the best experts on this subject based on the ideXlab platform.
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the effect of estetrol drospirenone on ovarian function is similar to a well established combined oral contraceptive results from a phase 2 study
Journal of the Endocrine Society, 2021Co-Authors: Ingrid Duijkers, Christine Klipping, Maud Jost, Adriana Bastidas, Jeanmichel FoidartAbstract:Background: Combined oral contraceptives (COCs) often contain ethinylestradiol (EE), an estrogen known to be associated with several side effects including venous thromboembolism. Estetrol (E4) is a native estrogen synthesized by the human fetal liver during pregnancy. Results from a phase 2 dose-finding study showed that E4 15 mg in combination with drospirenone 3 mg (E4/DRSP) resulted in a good bleeding profile and cycle control. Here, we present phase 2 results showing the effect of E4/DRSP on ovarian function. Study Design: A single-center, randomized, open-label, parallel study was conducted in healthy young volunteers with proven ovulatory cycles. Study subjects received either E4 15 mg/DRSP 3 mg (n=41) or EE 20 µg/DRSP 3 mg (n=41) in a 24/4-day regimen for three consecutive cycles. Both in cycle 1 and 3, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH), estradiol and progesterone levels were determined, and follicular size and endometrial thickness were measured every three days using transvaginal ultrasound. Ovarian function was assessed using the Hoogland score, which considers follicular size and estradiol/progesterone levels. Return of Ovulation was determined after treatment cessation. Safety and tolerability were assessed by monitoring adverse events (AEs), vital signs, physical and gynecological examination, clinical laboratory parameters, 12-lead electrocardiogram and echocardiogram. Results: No Ovulations were reported during the use of E4/DRSP, while three Ovulations occurred in two subjects in the EE/DRSP group. In both groups, most participants had no ovarian activity according to the Hoogland score. In cycle 1, Hoogland scores and follicular diameters were similar in both groups. In cycle 3, these parameters were slightly less suppressed in the E4/DRSP group when compared to EE/DRSP. While mean FSH and LH concentrations were less inhibited by E4/DRSP, mean estradiol and progesterone concentrations and endometrial thickness were similarly suppressed in both groups. Return of Ovulation occurred on average 15.5 days after discontinuation of E4/DRSP intake. The number of frequently reported AEs considered to be related to study medication was similar for both treatment groups except for breast pain (11 subjects in the E4/DRSP group versus 4 subjects with EE/DRSP). Most related AEs were of mild or moderate intensity. Three subjects discontinued due to an AE, one with E4/DRSP (severe stress, emotional lability), and two with EE/DRSP (emotional lability, depressed mood). Other safety assessments did not show significant abnormalities. No serious AEs were reported. Conclusions: The combination of E4 15 mg and DRSP 3 mg results in adequate Ovulation Inhibition and ovarian function suppression, which is similar to a well-established COC containing EE/DRSP. E4/DRSP is considered safe and well-tolerated.
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effects of an oral contraceptive containing estetrol and drospirenone on ovarian function
Contraception, 2021Co-Authors: Ingrid Duijkers, Christine Klipping, Maud Jost, Virginie Kinet, Adriana Bastidas, Jeanmichel FoidartAbstract:Abstract Objective To evaluate the effects of estetrol 15 mg/drospirenone 3 mg on ovarian function. Study design Single-center, randomized, open-label, parallel study in healthy young women with proven ovulatory cycles. Participants received either estetrol 15 mg/drospirenone 3 mg (E4/DRSP) (n = 41) or ethinylestradiol 20 µg/drospirenone 3 mg (EE/DRSP) (n = 41) in a 24/4-day regimen for 3 consecutive cycles. Follicular size and endometrial thickness were measured by transvaginal ultrasound every 3 days in cycles 1 and 3. Blood was sampled for hormone analysis. Ovarian function expressed as Hoogland score was based on follicular size, serum estradiol (E2) and progesterone (P) concentrations. Ovulation was defined as a ruptured follicle-like structure >13 mm with serum E2 concentrations >100 pmol/L and serum P concentrations >5 nmol/L. We assessed return of Ovulation after treatment cessation, and safety throughout the study. Results None of the participants ovulated with E4/DRSP use, while one participant ovulated once and one participant ovulated twice during EE/DRSP treatment. Most participants had a Hoogland score of 1 (no ovarian activity) in cycle 1 (85.0% and 82.9% of participants on E4/DRSP and EE/DRSP, respectively) and in cycle 3 (65.8% and 83.8%, respectively). E4/DRSP suppressed follicle-stimulating hormone and luteinizing hormone to a lesser extent than EE/DRSP, whereas both treatments comparably suppressed E2 and P and endometrial thickness. Return of Ovulation occurred, on average, 15.5 days after E4/DRSP treatment discontinuation. E4/DRSP was safe and well-tolerated. Conclusions E4 15 mg/DRSP 3 mg results in adequate Ovulation Inhibition and ovarian function suppression, comparable to a marketed combined oral contraceptive containing EE/DRSP. Implications statement Treatment with E4 15 mg/DRSP 3 mg showed complete Ovulation Inhibition, despite less suppression of follicle-stimulating hormone and luteinizing hormone compared to EE/DRSP. If it becomes commercially available, E4/DRSP, containing a naturally occurring estrogen, should be as effective as EE/DRSP.
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a two centre open label randomised study of Ovulation Inhibition with three transdermal contraceptive patches each containing different amounts of ethinyl estradiol and gestodene in healthy young women
Journal of Obstetrics and Gynaecology, 2016Co-Authors: K Waellnitz, Christine Klipping, Ingrid Duijkers, T Rautenberg, B Rohde, Christian ZurthAbstract:Here we report the findings of a two-centre, open-label, randomised, Phase IIa study designed to investigate whether an ethinyl estradiol (EE)/gestodene (GSD) patch that has been developed (referred to herein as the ‘EE/GSD patch’) reliably inhibits Ovulation in comparison with patches delivering lower doses of these hormones. The study rationale was to provide justification of the doses of EE and GSD selected for the EE/GSD patch. Healthy women, aged 18–35 years, were randomised to receive treatment with either the EE/GSD patch, a ‘reduced-GSD patch’ (delivering similar amounts of EE and approximately half the amount of GSD) or a ‘reduced-EE/GSD patch’ (delivering half the amount of EE and GSD). Treatment was administered for three 28-day cycles (three × 7 patch-wearing days, plus a 7-day patch-free interval). The primary pharmacodynamic variable was the percentage of women with Ovulation in at least one of Cycles 2 and/or 3, as indicated by Hoogland score. Pharmacokinetic parameters for EE and GSD were ...
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Ovulation inhibiting effects of dienogest in a randomized dose controlled pharmacodynamic trial of healthy women
The Journal of Clinical Pharmacology, 2012Co-Authors: Christine Klipping, Ingrid Duijkers, Thomas Faustmann, Ageeth Remmers, Christian Zurth, Stefan Klein, Barbara SchuettAbstract:Dienogest offers pharmacological advantages for the effective treatment of endometriosis and for use in contraception and hormone replacement therapy. This pharmacodynamic study investigated the Ovulation-inhibiting effects of dienogest monotherapy in healthy women. Dienogest was administered at 0.5, 1, 2, or 3 mg daily for up to 72 days to women aged 18 to 35 years (n = 102). Ovarian activity was assessed pretreatment and during 2 treatment periods (days 0-36 and days 37-72) by the Hoogland score, based on follicle size and serum estradiol and progesterone levels. Additional hormonal parameters and endometrial thickness were assessed. Hoogland scoring indicated Ovulation in all women pretreatment, decreasing to 3 of 21, 1 of 23, 0 of 20, and 0 of 23 women in the 0.5-, 1-, 2-, and 3-mg groups, respectively (per-protocol set). Maximum serum estradiol concentrations were similar to pretreatment levels in the 0.5- or 1-mg group and decreased moderately (within physiologic levels) in the 2- or 3-mg group. Endometrial thickness was reduced by all dienogest doses. Hormonal changes during follow-up indicated resumption of Ovulation in most women, shortly after treatment cessation. Dienogest ≥2 mg daily provides moderate suppression of estradiol production and reliable Ovulation Inhibition, which reverses rapidly after treatment cessation.
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Ovulation Inhibition with four variations of a four phasic estradiol valerate dienogest combined oral contraceptive results of two prospective randomized open label studies
Contraception, 2008Co-Authors: Jan Endrikat, Ingrid Duijkers, W Schmidt, Susanne Parke, Dietmar Trummer, Christine KlippingAbstract:Abstract Background Attempts to improve the tolerability of combined oral contraceptives (COCs) have included the substitution of ethinylestradiol (EE) with 17β-estradiol (E2). However, this has proved unsatisfactory, specifically in terms of cycle control. To improve upon the poor cycle control seen previously, E2 [in the form of estradiol valerate (E2V); 1 mg of E2V contains 0.76 mg of E2] was combined with dienogest (DNG) in a novel four-phasic regimen. In the current studies, the Ovulation-Inhibition potency of four variations of this regimen was assessed. Study Design Two randomized, open-label, Phase II studies were performed. The first study compared two regimens (Regimens 1A and 2A) with similar dosages of DNG but different lengths of application. Having established in Study 1 that the length of application of Regimen 2A was most suitable, but that the dosages of DNG were too low for effective Ovulation Inhibition, a second study, which compared two regimens (Regimens 2B and 2C) with similar lengths of application but with increased dosages of DNG, was undertaken. The primary efficacy variable in both studies was the proportion of women with a Hoogland score of 5 or 6 during Cycle 2. Results The full analysis set comprised 192 and 203 women in Studies 1 and 2, respectively. In Study 1, 10 women (10.9%) in Regimen 1A and 6 women (6.4%) in Regimen 2A had a Hoogland score of 5 or 6. In Study 2, three women (3.1%) in Regimen 2B and one woman (1.0%) in Regimen 2C had a Hoogland score of 5 or 6. There were no safety concerns with any of the regimens. Conclusion The results of these studies identified a four-phasic COC preparation comprising E2V/DNG that provides efficient Ovulation Inhibition. It is expected that this regimen will lead to an innovative COC containing E2 instead of EE.
Martin Merz - One of the best experts on this subject based on the ideXlab platform.
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impact of body mass index on suppression of follicular development and Ovulation using a transdermal patch containing 0 55 mg ethinyl estradiol 2 1 mg gestodene a multicenter open label uncontrolled study over three treatment cycles
Contraception, 2014Co-Authors: Carolyn Westhoff, Keith Bangerter, Isabel Reinecke, Martin MerzAbstract:Abstract Background Body mass index (BMI) may influence Ovulation Inhibition resulting from transdermal hormone delivery. Investigation of this effect is important given the high prevalence of obesity in the US. Study Design This open-label, uncontrolled, Phase 2b trial stratified 173 women (18–35 years) according to three BMI groups (Group 1, n =56, ≤ 30 kg/m 2 ; Group 2, n =55, > 30 kg/m 2 and ≤ 35 kg/m 2 ; and Group 3, n =47, > 35 kg/m 2 ). Women used a contraceptive patch containing 0.55-mg ethinyl estradiol (EE) and 2.1-mg gestodene (GSD). The EE/GSD patch was used weekly for three 28-day cycles (one patch per week for 3 consecutive weeks followed by a 7-day, patch-free interval), and its effect on Ovulation was assessed by the Hoogland score, a composite score that comprises transvaginal ultrasound and estradiol (E 2 ) and progesterone levels every 3 days in Cycles 2 and 3. Evaluation of pharmacokinetic parameters was a secondary aim of the study, and blood samples for analytic determination of EE, GSD and sex hormone-binding globulin were taken during the pretreatment cycle, Cycle 2 and Cycle 3. Compliance was assessed using diary information and serum drug levels. Results In the per-protocol set, there were only six Ovulations during the study, and no participant ovulated in both study cycles. One Ovulation occurred in Group 1, three in Group 2 and two in Group 3. Ovulation Inhibition was unaffected by BMI; in all groups, most participants had Hoogland scores of 1 or 2 (i.e., follicle-like structures 2 , 80.0% in Cycle 2, 85.7% in Cycle 3; Group 2, > 30 kg/m 2 and ≤ 35 kg/m 2 , 61.4% in Cycle 2, 75.0% in Cycle 3; Group 3, > 35 kg/m 2 , 78.0% in Cycle 2, 72.5% in Cycle 3). Serum levels of follicle-stimulating hormone, luteinizing hormone, E 2 and progesterone were similar between groups. Body weight had a limited effect on EE clearance that was unlikely to be clinically relevant. Conclusion The EE/GSD patch provided effective Ovulation Inhibition, even in women with higher BMI. Implications This is the largest-to-date study of physiologic endpoints and found no clinically important differences in ovarian suppression among obese and normal-weight users of the EE/GSD contraceptive patch, thus providing reassurance that obese women can achieve the same high level of contraceptive protection as normal-weight users.
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original research article impact of body mass index on suppression of follicular development and Ovulation using a transdermal patch containing 0 55 mg ethinyl estradiol 2 1 mg gestodene a multicenter open label uncontrolled study over three treatmen
2014Co-Authors: Carolyn Westhoff, Keith Bangerter, Isabel Reinecke, Martin MerzAbstract:Background: Body mass index (BMI) may influence Ovulation Inhibition resulting from transdermal hormone delivery. Investigation of this effect is important given the high prevalence of obesity in the US. Study Design: This open-label, uncontrolled, Phase 2b trial stratified 173 women (18–35 years) according to three BMI groups (Group 1, n=56, ≤30 kg/m 2 ; Group 2, n=55, N30 kg/m 2 and ≤35 kg/m 2 ; and Group 3, n=47, N35 kg/m 2 ). Women used a contraceptive patch containing 0.55-mg ethinyl estradiol (EE) and 2.1-mg gestodene (GSD). The EE/GSD patch was used weekly for three 28-day cycles (one patch per week for 3 consecutive weeks followed by a 7-day, patch-free interval), and its effect on Ovulation was assessed by the Hoogland score, a composite score that comprises transvaginal ultrasound and estradiol (E2) and progesterone levels every 3 days in Cycles 2 and 3. Evaluation of pharmacokinetic parameters was a secondary aim of the study, and blood samples for analytic determination of EE, GSD and sex hormone-binding globulin were taken during the pretreatment cycle, Cycle 2 and Cycle 3. Compliance was assessed using diary information and serum drug levels. Results: In the per-protocol set, there were only six Ovulations during the study, and no participant ovulated in both study cycles. One Ovulation occurred in Group 1, three in Group 2 and two in Group 3. Ovulation Inhibition was unaffected by BMI; in all groups, most participants had Hoogland scores of 1 or 2 (i.e., follicle-like structures b13 mm: Group 1, ≤30 kg/m 2 , 80.0% in Cycle 2, 85.7% in Cycle 3; Group 2, N30 kg/m 2 and ≤35 kg/m 2 , 61.4% in Cycle 2, 75.0% in Cycle 3; Group 3, N35 kg/m 2 , 78.0% in Cycle 2, 72.5% in Cycle 3). Serum levels of follicle-stimulating hormone, luteinizing hormone, E2 and progesterone were similar between groups. Body weight had a limited effect on EE clearance that was unlikely to be clinically relevant. Conclusion: The EE/GSD patch provided effective Ovulation Inhibition, even in women with higher BMI. Implications: This is the largest-to-date study of physiologic endpoints and found no clinically important differences in ovarian suppression among obese and normal-weight users of the EE/GSD contraceptive patch, thus providing reassurance that obese women can achieve the same high level of contraceptive protection as normal-weight users.
Sven O Skouby - One of the best experts on this subject based on the ideXlab platform.
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oestrogen free oral contraception with a 4 mg drospirenone only pill new data and a review of the literature
The European Journal of Contraception & Reproductive Health Care, 2020Co-Authors: Santiago Palacios, Pedro-antonio Regidor, Sven O Skouby, Enrico Colli, Dan Apter, Thomas Roemer, Christian Egarter, Rossella E Nappi, Ales SkřivanekAbstract:Purpose: The contraceptive pill is an effective and safe method of preventing pregnancy. The progestins used for contraception either are components of a combined hormonal contraceptive (tablets, patches or vaginal rings) or are used alone in progestin-only formulations. Progestin-only contraceptives are available as daily oral preparations, subcutaneous or intramuscular injectables (every 1-3 months), subdermal implants (every 3-5 years) and intrauterine systems (every 3-5 years). Long-acting progestins are highly effective in typical use and have a very low risk profile and few contraindications.Material and Methods: A new progestin-only, oestrogen-free contraceptive, drospirenone, in a dosage of 4 mg/day in a 24/4 regimen, has received regulatory approval in the USA and the EU. The molecule has antigonadotropic, antimineralocorticoid, antiestrogenic and antiandrogenic properties.Results: The regimen was chosen to improve the bleeding profile; maintain plasma oestradiol levels at those of the early follicular phase, to avoid hypoestrogenism; and preserve efficacy even with a missed pill, as drospirenone has a half-life of 30-34 h.Conclusions: Clinical studies have shown good efficacy, very low cardiovascular side effects and a favourable bleeding pattern, as well as maintenance of Ovulation Inhibition after scheduled 24 h delays in pill intake.
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maintenance of Ovulation Inhibition with a new progestogen only pill containing drospirenone after scheduled 24 h delays in pill intake
Contraception, 2016Co-Authors: Ingrid Duijkers, Doris Hegermahn, Dominique Drouin, Enrico Colli, Sven O SkoubyAbstract:Abstract Objectives Traditional progestogen-only pills (POPs) have stringent daily timing and missed pill rules that might affect contraceptive reliability. A new-generation oestrogen-free pill has been developed, containing 4-mg drospirenone with a unique regimen of 24 active treatment days followed by four placebo tablets. A previous study showed that this new drospirenone-only pill effectively inhibited Ovulation. Clinical efficacy, however, can be affected by compliance, and delayed or forgotten pill intake often occurs in daily life. The aim of this study was to investigate if Inhibition of Ovulation was maintained after four scheduled 24-h delays in tablet intake. Study design One hundred thirty healthy women with proven ovulatory cycles were randomized, and 127 were treated with the drospirenone-only pill during two cycles. In treatment Group A ( n =62), 24-h delays in tablet intake were scheduled on days 3, 6, 11 and 22 during Cycle 2 and, in treatment Group B ( n =65) during Cycle 1, respectively. Ovulation was defined as disappearance or persistence of a large follicle and progesterone levels higher than 5ng/mL for at least 5 consecutive days. Results The overall Ovulation rate was 0.8%; only one subject in Group A fulfilled the Ovulation criteria in Cycle 2. Follicular diameters in the regular-intake and the delayed-intake cycles were similar. Conclusion Despite the 4-day hormone-free period and multiple intentional 24-h delays in tablet intake, Ovulation Inhibition was maintained. This property distinguishes this new-generation oestrogen-free pill from traditional POPs by allowing the same "safety window" or flexibility in intake as combined oral contraceptives without compromising contraceptive reliability. Implications Delayed or forgotten pill intake is very common. Ovulation Inhibition by the new-generation oestrogen-free pill, containing 4-mg drospirenone for 24days followed by a 4-day treatment-free period, was maintained despite four 24-h delays in tablet intake, so the impact of delayed intake on contraceptive reliability will be low.
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original research article maintenance of Ovulation Inhibition with a new progestogen only pill containing drospirenone after scheduled 24 h delays in pill intake
2016Co-Authors: Ingrid Duijkers, Doris Hegermahn, Dominique Drouin, Enrico Colli, Sven O SkoubyAbstract:Objectives: Traditional progestogen-only pills (POPs) have stringent daily timing and missed pill rules that might affect contraceptive reliability. A new-generation oestrogen-free pill has been developed, containing 4-mg drospirenone with a unique regimen of 24 active treatment days followed by four placebo tablets. A previous study showed that this new drospirenone-only pill effectively inhibited Ovulation. Clinical efficacy, however, can be affected by compliance, and delayed or forgotten pill intake often occurs in daily life. The aim of this study was to investigate if Inhibition of Ovulation was maintained after four scheduled 24-h delays in tablet intake. Study design: One hundred thirty healthy women with proven ovulatory cycles were randomized, and 127 were treated with the drospirenone-only pill during two cycles. In treatment Group A (n=62), 24-h delays in tablet intake were scheduled on days 3, 6, 11 and 22 during Cycle 2 and, in treatment Group B (n=65) during Cycle 1, respectively. Ovulation was defined as disappearance or persistence of a large follicle and progesterone levels higher than 5 ng/mL for at least 5 consecutive days. Results: The overall Ovulation rate was 0.8%; only one subject in Group A fulfilled the Ovulation criteria in Cycle 2. Follicular diameters in the regular-intake and the delayed-intake cycles were similar. Conclusion: Despite the 4-day hormone-free period and multiple intentional 24-h delays in tablet intake, Ovulation Inhibition was maintained. This property distinguishes this new-generation oestrogen-free pill from traditional POPs by allowing the same “safety window” or flexibility in intake as combined oral contraceptives without compromising contraceptive reliability. Implications: Delayed or forgotten pill intake is very common. OvulationInhibitionbythenew-generationoestrogen-freepill,containing4-mg drospirenone for 24 days followed by a 4-day treatment-free period, was maintained despite four 24-h delays in tablet intake, so the impact of delayed intake on contraceptive reliability will be low.
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a randomised study comparing the effect on ovarian activity of a progestogen only pill pop containing desogestrel and a new pop containing drospirenone in a 24 4 regimen
The European Journal of Contraception & Reproductive Health Care, 2015Co-Authors: Ingrid Duijkers, Doris Hegermahn, Dominique Drouin, Sven O SkoubyAbstract:AbstractObjectives Progestogen-only pills (POPs) are safer with respect to cardiovascular risks than contraceptives containing estrogens. Despite the increased contraceptive efficacy of a desogestrel-only pill compared with a traditional POP, POPs are still not widely used due to an unpredictable bleeding pattern. A new POP containing 4 mg drospirenone has been developed with a 24/4 intake regimen which may improve the bleeding pattern. The objectives of this study were to investigate Ovulation Inhibition with the new drospirenone-only pill in comparison with the desogestrel-only pill and, in addition, to assess the effects on cervical mucus permeability and bleeding.Methods Sixty-four healthy volunteers with proven ovulatory cycles were randomised and treated with either the drospirenone-only or the desogestrel-only pill during two 28-day cycles. Follicular diameter, endometrial thickness, and serum estradiol (E2) and progesterone concentrations were measured and Hoogland scores were determined. Addition...
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Ovulation Inhibition by estetrol in an in vivo model
Contraception, 2008Co-Authors: Herjan Coelingh J T Bennink, Philippe Bouchard, Sven O Skouby, Christian F HolinkaAbstract:Abstract Background Currently, the synthetic steroid ethinylestradiol (EE) is the preferred estrogen in combined oral contraceptives. The aim of the present study was to evaluate the effectiveness of the natural steroid estetrol (E 4 ) as an Ovulation inhibitor in rats when compared to EE. Study Design Regularly cycling female rats were treated orally twice daily for four consecutive days, starting on the day of estrus, with E 4 (0.03, 0.1, 0.3, 1.0 or 3.0 mg/kg), EE (0.0003, 0.001, 0.003, 0.01 or 0.03 mg/kg) or vehicle control (eight animals per group). In a second experiment conducted under the same experimental protocol, 2.0 mg/kg of E 4 was administered as a single daily dose or as a dose of 1.0 mg/kg twice daily. In both studies, the primary end point was the number of ovulated oocytes in the genital tract. Results Estetrol at the twice daily dose of 0.3 mg/kg and above inhibited Ovulation. This effect was statistically significant (p The ED 50 for the EE and the E 4 dose response curves shows that EE is 18 times more potent than E 4 . Conclusion Twice daily administration of E 4 effectively inhibits Ovulation in cycling rats. The effect is dose-dependent. The relative potency of E 4 is about 18 times less compared to that of EE. We conclude that based on these data, combined with available pharmacological and clinical data on the safety and efficacy of E 4 , the human fetal estrogenic steroid estetrol is a potential candidate to replace EE in combined oral contraceptives.
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impact of body mass index on suppression of follicular development and Ovulation using a transdermal patch containing 0 55 mg ethinyl estradiol 2 1 mg gestodene a multicenter open label uncontrolled study over three treatment cycles
Contraception, 2014Co-Authors: Carolyn Westhoff, Keith Bangerter, Isabel Reinecke, Martin MerzAbstract:Abstract Background Body mass index (BMI) may influence Ovulation Inhibition resulting from transdermal hormone delivery. Investigation of this effect is important given the high prevalence of obesity in the US. Study Design This open-label, uncontrolled, Phase 2b trial stratified 173 women (18–35 years) according to three BMI groups (Group 1, n =56, ≤ 30 kg/m 2 ; Group 2, n =55, > 30 kg/m 2 and ≤ 35 kg/m 2 ; and Group 3, n =47, > 35 kg/m 2 ). Women used a contraceptive patch containing 0.55-mg ethinyl estradiol (EE) and 2.1-mg gestodene (GSD). The EE/GSD patch was used weekly for three 28-day cycles (one patch per week for 3 consecutive weeks followed by a 7-day, patch-free interval), and its effect on Ovulation was assessed by the Hoogland score, a composite score that comprises transvaginal ultrasound and estradiol (E 2 ) and progesterone levels every 3 days in Cycles 2 and 3. Evaluation of pharmacokinetic parameters was a secondary aim of the study, and blood samples for analytic determination of EE, GSD and sex hormone-binding globulin were taken during the pretreatment cycle, Cycle 2 and Cycle 3. Compliance was assessed using diary information and serum drug levels. Results In the per-protocol set, there were only six Ovulations during the study, and no participant ovulated in both study cycles. One Ovulation occurred in Group 1, three in Group 2 and two in Group 3. Ovulation Inhibition was unaffected by BMI; in all groups, most participants had Hoogland scores of 1 or 2 (i.e., follicle-like structures 2 , 80.0% in Cycle 2, 85.7% in Cycle 3; Group 2, > 30 kg/m 2 and ≤ 35 kg/m 2 , 61.4% in Cycle 2, 75.0% in Cycle 3; Group 3, > 35 kg/m 2 , 78.0% in Cycle 2, 72.5% in Cycle 3). Serum levels of follicle-stimulating hormone, luteinizing hormone, E 2 and progesterone were similar between groups. Body weight had a limited effect on EE clearance that was unlikely to be clinically relevant. Conclusion The EE/GSD patch provided effective Ovulation Inhibition, even in women with higher BMI. Implications This is the largest-to-date study of physiologic endpoints and found no clinically important differences in ovarian suppression among obese and normal-weight users of the EE/GSD contraceptive patch, thus providing reassurance that obese women can achieve the same high level of contraceptive protection as normal-weight users.
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original research article impact of body mass index on suppression of follicular development and Ovulation using a transdermal patch containing 0 55 mg ethinyl estradiol 2 1 mg gestodene a multicenter open label uncontrolled study over three treatmen
2014Co-Authors: Carolyn Westhoff, Keith Bangerter, Isabel Reinecke, Martin MerzAbstract:Background: Body mass index (BMI) may influence Ovulation Inhibition resulting from transdermal hormone delivery. Investigation of this effect is important given the high prevalence of obesity in the US. Study Design: This open-label, uncontrolled, Phase 2b trial stratified 173 women (18–35 years) according to three BMI groups (Group 1, n=56, ≤30 kg/m 2 ; Group 2, n=55, N30 kg/m 2 and ≤35 kg/m 2 ; and Group 3, n=47, N35 kg/m 2 ). Women used a contraceptive patch containing 0.55-mg ethinyl estradiol (EE) and 2.1-mg gestodene (GSD). The EE/GSD patch was used weekly for three 28-day cycles (one patch per week for 3 consecutive weeks followed by a 7-day, patch-free interval), and its effect on Ovulation was assessed by the Hoogland score, a composite score that comprises transvaginal ultrasound and estradiol (E2) and progesterone levels every 3 days in Cycles 2 and 3. Evaluation of pharmacokinetic parameters was a secondary aim of the study, and blood samples for analytic determination of EE, GSD and sex hormone-binding globulin were taken during the pretreatment cycle, Cycle 2 and Cycle 3. Compliance was assessed using diary information and serum drug levels. Results: In the per-protocol set, there were only six Ovulations during the study, and no participant ovulated in both study cycles. One Ovulation occurred in Group 1, three in Group 2 and two in Group 3. Ovulation Inhibition was unaffected by BMI; in all groups, most participants had Hoogland scores of 1 or 2 (i.e., follicle-like structures b13 mm: Group 1, ≤30 kg/m 2 , 80.0% in Cycle 2, 85.7% in Cycle 3; Group 2, N30 kg/m 2 and ≤35 kg/m 2 , 61.4% in Cycle 2, 75.0% in Cycle 3; Group 3, N35 kg/m 2 , 78.0% in Cycle 2, 72.5% in Cycle 3). Serum levels of follicle-stimulating hormone, luteinizing hormone, E2 and progesterone were similar between groups. Body weight had a limited effect on EE clearance that was unlikely to be clinically relevant. Conclusion: The EE/GSD patch provided effective Ovulation Inhibition, even in women with higher BMI. Implications: This is the largest-to-date study of physiologic endpoints and found no clinically important differences in ovarian suppression among obese and normal-weight users of the EE/GSD contraceptive patch, thus providing reassurance that obese women can achieve the same high level of contraceptive protection as normal-weight users.
