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Objectives: This study aimed to compare contraceptive efficacy and safety of drospirenone 4 mg in a 24/4-day regimen in nonobese and obese users and describe pharmacokinetics according to bodyweight., Study Design: We analyzed data from three drospirenone 4 mg trials (2 European and 1 United States) to report outcomes in nonobese (body mass index <30 kg/m 2 ) and obese (body mass index ≥30 kg/m 2 ) users. We used data from the US trial to calculate the Pearl Index (pregnancies per 100 woman-years) in nonbreastfeeding participants aged ≤35 years at enrollment for confirmed pregnancies. We assessed safety outcomes from all trials based on reported treatment-emergent adverse events. We evaluated pharmacokinetics by bodyweight in the US trial., Results: The three trials combined comprised 2152 nonobese and 425 obese participants, including 590 nonobese and 325 obese participants in the US trial. Eight nonobese and four obese participants had confirmed pregnancies in the US trial, resulting in Pearl Indices of 3.0 (95% CI: 1.3-5.8) and 2.9 (95% CI: 0.8-7.3), respectively. Two-hundred forty-four (11.3%) nonobese and 39 (9.2%) obese participants discontinued due to a treatment-emergent adverse event. The pharmacokinetic analysis included 814 participants with a median weight of 73 (interquartile range 61-89) kg and median plasma drospirenone exposure (AUC 0-24ss ) of 661.3 (interquartile range 522-828) ng∙h/mL. Changing bodyweight from the median to the fifth percentile (51 kg) or 95th percentile (118 kg) changed drospirenone exposure (AUC 0-24,ss ) by 22.2% and -23.6%, respectively., Conclusions: Drospirenone 4 mg demonstrated similar contraceptive efficacy for both nonobese and obese users despite a difference in exposure based on bodyweight., Implications: Our limited comparison between obese and nonobese users of drospirenone-only oral contraception demonstrated no evidence that efficacy or discontinuation for adverse events differs between groups. Serum drospirenone levels vary by bodyweight and may correlate with bleeding outcomes., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: To evaluate tolerability and safety of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg oral contraceptive using pooled data from two, multicenter, phase 3 trials., Study Design: The two trials enrolled participants aged 16-50 years with a body mass index ≤35.0 kg/m 2 to use E4/DRSP in a 24/4-day regimen for up to 13 cycles. We pooled data from participants who used at least one E4/DRSP dose and had a follow-up assessment to analyze adverse events (AEs), vital signs, and laboratory parameters, including serum lipids, glucose, glycated hemoglobin, and potassium. We consolidated similar Medical Dictionary for Regulatory Activities preferred terms into groupings., Results: Of 3725 participants enrolled, we included 3417 in the analyses of whom 1786 (52.3%) reported ≥1 AE. Most participants with reported AEs had AEs that investigators rated as mild or moderate (n = 1665, 93.2%); of participants reporting AEs, 1105 (61.9%) did so during cycles 1 to 3. In total, 981 (28.7%) participants experienced ≥1 treatment-related AE, most frequently related to bleeding complaints (n = 323, 9.5%), breast pain or tenderness (n = 136, 4.0%), acne (n = 113, 3.3%), and mood disturbance (n = 111, 3.2%). Discontinuation due to treatment-related AEs occurred in 272 participants (8.0%), with only bleeding complaints (n = 97, 2.8%) and mood disturbance (n = 38, 1.1%) at rates exceeding 1%. Three participants experienced serious AEs, which the site investigators considered treatment-related: one venous thromboembolism, one worsening of depression, and one ectopic pregnancy. We found no clinically relevant changes in weight, blood pressure, heart rate, or laboratory parameters during treatment., Conclusions: E4/DRSP is associated with a favorable tolerability and safety profile., Implications Statement: Pooling data allowed for a robust assessment of tolerability and safety, including relatively infrequent events. Other than bleeding complaints and mood disturbance, no adverse event resulted in E4/DRSP discontinuation at rates >1%. Post-marketing surveillance studies are needed to evaluate long-term safety of the E4/DRSP COC and population-based venous thromboembolism risks., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen., Study Design: We pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcategorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors., Results: Analyses included 3027 participants, of whom 451 (14.9%) had a BMI ≥30 kg/m 2 . The pooled PI was 1.52 (95% confidence interval 1.04-2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%-1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94-2.57) and 1.43 (0.78-2.40), respectively; in new starters and switchers of 1.88 (1.09-3.00) and 1.24 (0.68-2.08), respectively; and by BMI <25 kg/m 2 , 25 to 29.9 kg/m 2 , and ≥30 kg/m 2 of 1.14 (0.64-1.88), 2.19 (1.05-4.03), and 2.27 (0.83-4.94), respectively. In multivariable analysis, we found associations of prior pregnancy (hazard ratio [HR] 3.61[1.56-8.38]), Black race (HR 4.61[1.97-10.80]), age 16 to 25 years (HR 2.37[1.09-5.15]) and compliance <99% of expected pills (HR 4.21[2.04-8.66]) with conception., Conclusion: E4/DRSP is an effective oral contraceptive overall and across subgroups stratified by age, contraceptive history, and BMI. Other than compliance, predictors of contraceptive failure are nonmodifiable., Implications Statement: Pooled results from two phase 3 trials demonstrate high contraceptive efficacy of the novel estetrol-drospirenone oral contraceptive. Several non-modifiable risk factors, including prior pregnancy, race, and age, are associated with higher pregnancy risk. Additional research is needed to better understand predictors of combined oral contraceptive failure., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate the bleeding patterns of a new combined oral contraceptive containing estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg in a 24/4-day regimen., Study Design: We pooled bleeding data from two parallel, open-label, 13-cycle phase 3 trials that enrolled participants 16 to 50 years old with body mass index (BMI) ≤35 kg/m 2 . Participants reported vaginal bleeding/spotting in daily diaries. For this bleeding analysis, we included participants with at least one evaluable cycle. We calculated mean frequencies of scheduled and unscheduled bleeding/spotting episodes and median duration of bleeding/spotting episodes, and assessed associations between treatment compliance, BMI and recent hormonal contraceptive use on bleeding/spotting outcomes., Results: We included 3409 participants with 33,815 cycles. Scheduled bleeding/spotting occurred in 87.2% to 90.4% of participants/cycle, with a median duration of 4 to 5 days. Unscheduled bleeding/spotting decreased from 27.1% in Cycle 1 to 20.6% in Cycle 2 to ≤17.5% from Cycle 5 onwards. Most (66.5%) unscheduled bleeding/spotting episodes were spotting-only. Between 5.8% and 7.8% of users/cycle experienced absence of any scheduled or unscheduled bleeding/spotting. Missing one or more active pills resulted in a higher occurrence of unscheduled bleeding/spotting (adjusted odds ratio [aOR] 2.13 [95% confidence interval 1.68-2.70]) and absence of scheduled bleeding/spotting (aOR 2.36 [1.82-3.07]). Participants with a BMI ≥30 kg/m 2 reported more absence of scheduled bleeding/spotting (aOR 1.68 [1.37-2.05]). Switchers and starters reported similar frequencies of unscheduled bleeding/spotting (aOR 0.94 [0.83-1.07]) and absence of scheduled bleeding/spotting (aOR 1.00 [0.85-1.19]). Three percent of participants discontinued for a bleeding-related adverse event., Conclusion: E4/DRSP use results in a predictable bleeding pattern with limited unscheduled bleeding/spotting. Noncompliance and BMI affect bleeding patterns., Implications Statement: Most estetrol/drospirenone users experience a predictable and regular bleeding pattern. Providers can educate patients about the expected bleeding patterns and should advise users that they may infrequently experience no scheduled bleeding/spotting. This information may improve user acceptability and continuation of this new oral contraceptive., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To assess efficacy, cycle control, and safety of an oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg., Study Design: Women aged 16 to 50 years with a body mass index ≤35 kg/m 2 enrolled in this multicenter, open-label, 13-cycle, phase 3 trial evaluating E4/DRSP in a 24-active/4-placebo regimen. Follow-up was scheduled at Cycles 2, 4, 7, and 10 and within 3 weeks of completing Cycle 13. Participants used daily diaries to record pill use and vaginal bleeding. We evaluated efficacy outcomes in women 16 to 35 years and bleeding patterns and safety (adverse events [AEs]) in all participants. We assessed overall and method-failure pregnancy rates using the Pearl index (PI) and life-table analysis. Scheduled bleeding included spotting or bleeding starting during the 4-day placebo period or first 3 days of the next cycle., Results: We enrolled 1864 women of whom 1674 were 16 to 35 years. Women 16 to 35 years had a PI of 2.65 (95% CI 1.73-3.88), method-failure PI of 1.43 (95% CI 0.7-2.39) and 13-cycle life-table pregnancy rate of 2.1%. Scheduled bleeding occurred in 82.9% to 87.0% of women per cycle; median duration was 4.5 days. Unscheduled bleeding decreased from 30.3% in Cycle 1 to 21.3% to 22.1% during Cycles 2 to 4 and remained stable (15.5% to 19.2%) thereafter. The most frequently reported AEs were headache (5.0%) and metrorrhagia (4.6%). One-hundred thirty-two (7.1%) women discontinued the study early for an AE, most commonly for metrorrhagia (0.9%) and menorrhagia (0.8%). No thromboembolic events occurred., Conclusion: E4/DRSP is an effective oral contraceptive with a predictable bleeding pattern for most women and low AE rates., Implications Statement: A new oral contraceptive with a novel estrogen, estetrol, combined with drospirenone has efficacy and safety within the range of other available oral contraceptives. Large phase 4 studies will be needed to confirm if this combination is associated with an improved adverse event profile or lower thrombosis risk., (Copyright © 2021. Published by Elsevier Inc.)

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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the effect on endocrine and metabolic parameters of a new combined oral contraceptive (COC) containing estetrol (E4) and drospirenone (DRSP)., Study Design: Randomized, open-label, controlled, 3-arm, parallel study. Healthy subjects received either E4 15 mg/DRSP 3 mg (E4/DRSP) (n = 38), or ethinylestradiol (EE) 30 µg/levonorgestrel (LNG) 150 µg (n = 29), or EE 20 µg/DRSP 3 mg (n = 31) for 6 treatment cycles. Median percentage change from baseline to cycle 3 and to cycle 6 were evaluated for endocrine parameters, liver proteins, lipid profile, and carbohydrate metabolism., Results: At cycle 6, E4/DRSP treatment had less effect on gonadotropins (follicle stimulating hormone [FSH] +30.5%, luteinizing hormone [LH] -7.5%) compared to EE/LNG (FSH -84.0%, LH -92.0%) and EE/DRSP (FSH -64.0%, LH -90.0%). With E4/DRSP increases in total cortisol (+26.0%) and cortisol binding globulin ([CBG] (+40.0%) were less compared to EE/LNG (cortisol +109.0%, CBG +152.0%) and EE/DRSP (cortisol +107.0%, CBG +140.0%). Liver proteins, except CRP, increased, but the effect was less pronounced with E4/DRSP for angiotensinogen (+75.0%) compared to EE/LNG (+170.0%) and EE/DRSP (+206.5%) and for sex hormone binding globulin ([SHBG] +55.0%), compared to EE/LNG (+74.0%) and EE/DRSP (+251.0%). E4/DRSP had minimal impact on lipid parameters; the largest effect was observed for triglycerides (+24.0%), which was less compared to EE/LNG (+28.0%) and EE/DRSP (+65.5%). E4/DRSP had no effect on carbohydrate metabolism., Conclusions: E4/DRSP treatment has limited effects on endocrine and metabolic parameters. The effects on gonadotropins, cortisol, CBG, angiotensinogen, SHBG and triglycerides were less pronounced compared to EE-containing products., Implications Statement: Combining E4 15 mg with DRSP 3 mg resulted in a COC with a different metabolic profile in comparison to EE-containing products. The clinical relevance of these findings needs to be further assessed, using clinical endpoints to establish the safety profile of this new COC., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To assess the effect on hemostasis parameters of a new combined oral contraceptive (COC)., Study Design: In this randomized, single centre, open-label, exploratory study, healthy women received either 15 mg estetrol/3 mg drospirenone (E4/DRSP) (n = 39), 30 mcg ethinylestradiol/150 mcg levonorgestrel (EE/LNG) (n = 30), or 20 mcg ethinylestradiol/3 mg drospirenone (EE/DRSP) (n = 32) for six 28-day cycles. Blood was collected at baseline, cycle 3, and cycle 6. Median change from baseline was evaluated for procoagulant, anticoagulant, and fibrinolytic parameters, and for sex hormone-binding globulin (SHBG)., Results: Median change of endogenous thrombin potential (ETP) based activated protein C sensitivity resistance (APCr) at cycle 6 was +30% for E4/DRSP, +165% for EE/LNG (p-value <0.05 vs E4/DRSP), and +219% for EE/DRSP (p-value <0.05 vs E4/DRSP). Changes to prothrombin fragment 1 + 2 and SHBG for E4/DRSP, EE/LNG, and EE/DRSP were +23%, +71%, and +64% (p-value <0.05 vs E4/DRSP); and +55%, +74% and +251% (p-value <0.05 vs E4/DRSP), respectively. At cycle 6, changes to other hemostasis parameters for E4/DRSP were similar or smaller than for EE/LNG or EE/DRSP., Conclusions: In this study, changes in hemostasis parameters after treatment with 6 cycles of E4/DRSP were smaller or similar to those observed for EE/LNG. Similar, but more pronounced changes were also observed versus EE/DRSP, which supports the hypothesis that the effect of COCs on hemostasis parameters is mainly mediated by the estrogenic component. Further studies are needed to provide more insight into the venous thromboembolic risk of E4/DRSP., Implications Statement: This study reports that the effects on hemostasis parameters of a COC containing 15 mg E4/3 mg DRSP are less or similar to those for EE/LNG or EE/DRSP. It also demonstrates that the choice of estrogen modulates the effects of COCs on hemostasis parameters., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess the safety, tolerability and bleeding patterns of drospirenone 4.0 mg., Study Design: A multicenter, open-label, safety trial in sexually-active adolescents aged 12-17 years for six 28-day treatment cycles (Core Phase) and an optional 7-13 cycle extension with administration of drospirenone 4.0 mg in a regimen of 24 active/4 placebo tablets., Results: We enrolled 111 subjects, and after eight failed Screening and one withdrew consent, 102 remained evaluable; 89 (87.3%) completed the Core Phase. Overall, treatment with drospirenone 4.0 mg was well tolerated. Possibly-related TEAEs were reported for 23 subjects (22.5% of the 102 evaluable); two serious adverse events were reported during the Extension Phase (pharyngitis and joint dislocation), neither related to treatment. The number of subjects reporting dysmenorrhea decreased from 47 prior to Screening, to 14 at the end of Cycle 6, to 8 at the end of Cycle 13. Assessments of vital signs and gynecological and physical examinations were unremarkable. We observed a trend towards less bleeding and/or spotting over the first cycles with the use of drospirenone: the proportion of subjects with both scheduled and unscheduled bleeding and spotting decreased, while the proportion with absence of bleeding or spotting increased. Only five subjects (4.9% of 102 evaluable) prematurely terminated the trial due to irregular bleeding. At the end of 6 months, 85.3% rated the tolerability of drospirenone as "excellent" or "good"., Conclusions: The results indicate that 4.0 mg drospirenone over 13 treatment cycles was well tolerated, safe and acceptable for the majority of adolescents., Implications: Drospirenone 4.0 mg oral pills provide a well-tolerated, safe and acceptable contraceptive choice for adolescents., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To determine the pharmacokinetics (PK) of drospirenone (DRSP), alone versus in combination with ethinyl estradiol (EE), after single and repeated administration., Study Design: We conducted a single-centre, open-label, crossover, 2-treatment, 2-period, 2-sequence study in which non-micronized DRSP 4 mg or a combination of DRSP 3 mg and EE 0.02 mg were administered to healthy female subjects on day 1 to obtain a single-dose kinetic profile, and from day 4 to day 15 to obtain a repeated-dose kinetic profile. The maximum observed concentration (C max ) and area under the concentration/time curve (AUC) were determined in a model-independent way using non dose corrected data. Statistical analysis was based on a parametric method (ANOVA-log)., Results: A total of 24 healthy female subjects were randomized 1:1 into the study. The mean relative, non-dose-corrected PK estimates after single-dose administration for the endpoints AUC (0-72h) , AUC (0-24h) and C max were 543.5 ng*h/mL, 296.1 ng*h/mL and 27.3 ng/mL for DRSP alone, and 442.0 ng*h/mL, 264.7 ng*h/mL and 37.5 ng/mL for the DRSP/EE combination; p < 0.001. The mean relative, non-dose-corrected PK estimates after repeated dose administration for the endpoints AUC (0-72h) , AUC (0-24h) and C max were 1066.8 ng*h/ml, 570.2 ng*h/mL and 41.0 ng/mL for DRSP alone, and 1394.5 ng*h/mL, 732.8 ng*h/mL and 61.4 ng/mL for the DRSP/EE combination; p < 0.001., Conclusions: DRSP alone exhibits a lower accumulation ratio than together with EE. The extent of systemic exposure at steady-state is about 32% less with the new formulation (AUC (0-24h) , steady-state geometric mean ratio: 77.8%; 90% confidence interval: 74.6%-81.1%). This PK profile may be caused by EE., Implications: Our results suggest that metabolic pathways of DRSP can be inhibited by EE resulting in higher DRSP plasma concentrations in DRSP/EE formulations than in a DRSP-alone formulation. The enzymes CYP3A4 and SULT1A1 may play a role. Additional drug-drug-interaction studies are needed to better understand these metabolic pathways and their future clinical implications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The effects of estetrol (E4), a natural fetal estrogen, combined with drospirenone (DRSP) were evaluated on plasma levels of sex hormone-binding globulin (SHBG), angiotensinogen and 12 hemostasis markers., Study Design: Combinations of 3 mg DRSP with 5 or 10 mg E4 were compared with YAZ® (20 mcg ethinyl estradiol and 3 mg DRSP; EE/DRSP) in parallel groups of 15-18 healthy young women. Main outcome was the relative change from pretreatment to the end (day 24±1) of the third treatment cycle., Results: All E4 combinations showed low estrogen impact compared to EE/DRSP. Effects on SHBG and angiotensinogen of 10 mg E4 combined with DRSP were 15%-20% that of EE/DRSP. Both E4/DRSP combinations reduced D-dimer level and the 5 mg E4/DRSP combination also decreased fragment 1+2., Conclusions: The reduction in coagulation markers suggests an anticoagulant effect from DRSP. The indications of a low thrombosis risk for E4 preparations should be validated in larger studies. IMPLICATION STATEMENT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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. Ovulation inhibition by the new-generation oestrogen-free pill, containing 4-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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: This study was performed to assess the contraceptive efficacy of the drospirenone (DRSP)-only pill and to provide information regarding its safety and cycle-control profile., Study Design: This prospective, multicenter, noncomparative study was conducted at 41 European sites in healthy women at risk of pregnancy, aged 18 to 45 years. The study medication was DRSP 4.0mg daily for 24 days followed by a placebo for 4 days (DRSP 4 mg 24/4, Exeltis, Spain) for thirteen 28-day treatment cycles. The primary efficacy endpoint was the overall Pearl Index (PI). Bleeding patterns, changes in vital signs and changes in laboratory values were also analyzed., Results: A total of 713 participants with 7638 DRSP treatment cycles were analyzed. The overall PI was 0.51 (95% confidence interval, 0.1053-1.4922). The proportion of participants with any bleeding decreased from 72.7% in Cycle 1 to 40% in Cycle 6 and 32.1% in Cycle 13. Unscheduled bleeding decreased from 49.1% in Cycle 1 to 27.8% in Cycle 6 and to 22.8% in Cycle 13. Prolonged bleeding was reported by 6.5% during Cycles 2 to 4 decreasing to 4.2% during Cycles 11 to 13. There were no reports of deep vein thrombosis, pulmonary embolism or hyperkalemia. No relevant changes were observed for laboratory parameters, body weight, body mass index, blood pressure or heart rate. Study drug acceptability was considered as "excellent/good" by over 82% of subjects., Conclusion: This new DRSP-only oral contraceptive provides clinical contraceptive efficacy similar to that of the currently marketed Combination estrogen plus progestin Oral Contraceptive, with a good safety profile, and favorable cycle control., Implications: A novel 4-mg DRSP-only pill taken daily for 24 days followed by a placebo for 4 days demonstrated contraceptive efficacy similar to that of currently marketed Combination estrogen plus progestin Oral Contraceptive, with a good safety profile, and favorable cycle control., (Copyright © 2015. Published by Elsevier Inc.)

Background: Hypertension is a primary cardiovascular risk factor. Oral contraceptives (OCs) may increase blood pressure and cardiovascular events. We evaluated whether an OC containing ethynylestradiol (EE) in association with the spironolactone-derived progestin drospirenone (DRSP) influences 24-h ambulatory blood pressure of normotensive women., Study Design: Twenty-four-hour blood pressure was measured every 30 min by an ambulatory blood pressure device in 18 normotensive healthy women prior to and after 6 months of use of an OC containing 30 mcg EE and 3 mg DRSP., Results: OC induced no modification in 24-h, nighttime and daytime blood pressure. Heart rate increased about 4 beats/min in the 24-h (p<.05) and daytime (p<.02) measurements., Conclusions: In normotensive women, an OC containing 30 mcg EE plus 3 mg DRSP does not modify blood pressure, and significantly increases 24-h and daytime heart rate. These data suggest a neutral effect on hypertension-associated cardiovascular risk and point out an unreported effect on heart rate of which cause and effect require further evaluation., (Copyright © 2013 Elsevier Inc. All rights reserved.)