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This pooled analysis compared the risk of venous thromboembolism (VTE) associated with combined oral contraceptives (COCs) containing estradiol (E2) valerate-dienogest with those containing ethinyl E2-levonorgestrel. Data were retrieved from two large, prospective, observational cohort studies. Propensity score subclassification was applied to balance baseline parameters between the COC user cohorts. Crude and adjusted hazard ratios (HRs) were calculated based on the extended Cox model. The pooled data set included 11,616 E2 valerate-dienogest users and 18,681 ethinyl E2-levonorgestrel users, contributing 17,932 and 29,140 women-years of observation, respectively. A significantly decreased VTE risk in E2 valerate-dienogest COCs compared with ethinyl E2-levonorgestrel COCs was observed (propensity score-stratified HR 0.46, 95% CI, 0.22-0.98). This pooled analysis expands data from a previous postauthorization safety study and provides valuable real-world safety information on the relative safety of current COCs., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To estimate the real-use contraceptive effectiveness of the combined oral contraceptive (COC) containing dienogest and oestradiol valerate (DNG/oEV) compared to other combined oral contraceptives (oCOC) and particularly, levonorgestrel-containing OCs (LNG). Methods: Prospective, non-interventional cohort study with two main exposure groups and one exposure subgroup: new users of DNG/oEV and oCOC, with the subgroup, LNG. In a planned secondary analysis, pregnancy outcomes were investigated, including contraceptive failure. The influence of age, parity and OC-type were assessed. Results: 30,098 COC users were followed for a total oral contraceptive exposure time of 68,362 woman-years (WY) and 287 unintended pregnancies were reported. The overall contraceptive failure rate in the European population was 0.4 events/100 WY (95% CI, 0.4-0.5). DNG/oEV showed lower contraceptive failure rates compared to the comparators. This difference was maintained when the study population was restricted to women aged 18-35 years; the pearl index (PI) for this demographic for DNG/oEV was 0.37 (95% CI 0.24-0.54) and 0.76 (95% CI 0.56-1.01) for LNG. The hazard ratios (HRs) adjusted for age, parity, smoking and BMI were 0.7 (95% CI, 0.5-0.98, p  = .04) and 0.5 (95% CI, 0.3-0.8, p  < .01) for DNG/oEV versus oCOC and LNG, respectively. The corresponding adjusted HRs in women aged 25 years or younger were 0.6 (95% CI 0.4-1.1) and 0.4 (95% CI, 0.2-0.8), respectively. Conclusions/discussion: DNG/oEV showed improved contraceptive effectiveness compared with oCOC and particularly LNG-COC when adjusted for age, parity, user status and smoking.

Objectives: The International Active Surveillance study "Safety of Contraceptives: Role of Estrogens" (INAS-SCORE) investigated the cardiovascular risks associated with the use of a combined oral contraceptive (COC) containing dienogest and estradiol valerate (DNG/EV) compared to established COCs in a routine clinical setting., Study Design: Transatlantic, prospective, noninterventional cohort study conducted in the United States and seven European countries with two main exposure groups and one exposure subgroup: new users of DNG/EV and other COC (oCOC), particularly levonorgestrel-containing COCs (LNG). All self-reported clinical outcomes of interest (OoI) were validated via attending physicians and relevant source documents. Main OoI were serious cardiovascular events (SCE), particularly venous thromboembolic (VTEs) events. Comprehensive follow-up procedures were implemented. Statistical analyses were based on Cox regression models., Results: A total of 50,203 new COC users were followed up for up to 5.5years (mean value, 2.1years). Overall 20.3% and 79.7% of these women used DNG/EV and oCOC (including 11.5% LNG users), respectively. A low loss to follow-up of 3.1% was achieved. Based on 47 (VTE) and 233 (SCE) events, the primary analysis (European data set) yielded adjusted hazard ratios for DNG/EV vs. oCOC of 0.4 and 0.5, respectively. The upper bounds of the 95% confidence intervals were 0.98 (VTE) and 0.96 (SCE). The corresponding hazard ratios for DNG/EV vs. LNG showed similar point estimates but the confidence intervals included unity., Conclusion: DNG/EV is associated with similar or even lower cardiovascular risk compared to oCOC and LNG., Implication Statement: A COC containing DNG and EV is associated with similar or even lower cardiovascular risk compared to COCs containing levonorgestrel or other progestogens., (Copyright © 2016 Elsevier Inc. All rights reserved.)

To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COCLNG) in users over 40. In this large, observational study, new users1 of NOMAC-E2 and COCLNG were recruited in Europe, Australia, and Latin America and followed-up via questionnaires. Incidence of venous thromboembolism (VTE) was expressed as incidence rate (IR; events/104 women-years [WY]). Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 WY). Mood and weight changes were defined as mean changes in mood score and percentage of body weight. Overall, 7,762 NOMAC-E2 and 6,059 COCLNG users over 40 were followed-up. NOMAC-E2 showed no increased VTE risk compared to COCLNG; confirmed events: 5 NOMAC-E2 (IR 5.9; 95% CI, 1.9–13.7) vs 4 COCLNG (IR 5.9; 95% CI, 1.6–15.1). Unintended pregnancy did not differ substantially between cohorts; confirmed events: 4 NOMAC-E2 (PI 0.05; 95% CI, 0.01–0.13) vs 5 COCLNG (PI 0.08; 95% CI, 0.03–0.18). No differential effect on mood and weight was observed between cohorts. NOMAC-E2 can be considered a valid alternative to COCLNG in perimenopausal women. [ABSTRACT FROM AUTHOR]

Objective: To investigate unintended pregnancy and changes in mood, acne, and weight in NOMAC-E2 vs levonorgestrel-containing COC (COCLNG) users under 25 years. Methods: In this large, observational study, new users (first-ever users of an eligible COC or restarting with the same or a new eligible COC after a break of at least 2 months) of NOMAC-E2 and COCLNG were recruited in 12 countries in Europe, Australia, and Latin America and followed up via questionnaires for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 women-years). Crude (HRcrude) and adjusted hazard ratios (HRadj) were calculated. Mood and acne changes were defined as change of score from baseline. Weight change was defined as percent change of body weight. Results: Overall, 12,829 NOMAC-E2 users and 17,095 COCLNG users under 25 were followed-up. The risk of unintended pregnancy was statistically significantly lower in the NOMAC-E2 cohort; confirmed events: 30 NOMAC-E2 (PI 0.24; 95% CI, 0.16–0.35) vs 94 COCLNG (PI 0.51; 95% CI, 0.41–0.62). The HRcrude for unintended pregnancy comparing NOMAC-E2 to COCLNG was 0.47 (95% CI, 0.31–0.71) and the HRadj was 0.52 (95% CI, 0.34–0.78). No differential effect on acne, mood, and weight was observed between cohorts. Conclusions: NOMAC-E2 shows a significantly better contraceptive effectiveness in young women and has no differential effect on acne, mood, and weight compared to COCLNG. [ABSTRACT FROM AUTHOR]

Background: Several promising new medications containing low-dose estradiol (E2) in combination with a progestin and an additional component, such as gonadotropin-releasing hormone antagonists, are currently being developed for use in pre-menopausal women. Objective: This pooled analysis was designed to estimate the thromboembolic safety profile of E2 and its ester, estradiol valerate (E2Val), when used in combined hormonal treatments in a pre-menopausal population. Methods: Data regarding users of combined oral contraceptives (COCs) and combined menopausal hormonal therapy (MHT) containing either E2/E2Val or ethinylestradiol (EE) ⩽ 30 µg were retrieved from five large prospective, non-interventional, cohort studies in Europe, US, and Canada with similar study design but differing medication cohorts. Propensity score sub-classification was applied to balance baseline parameters between cohorts and time-to-event analysis of venous thromboembolic events (VTE) was carried out based on the extended Cox model to calculate crude and adjusted hazard ratios (HR). Results: (1) Crude incidence rates of VTE were higher in MHT users compared to pre-menopausal COC users, (2) the VTE risk in menopausal users of E2/E2Val-norethindrone acetate was not higher than that in menopausal users of E2/E2Val-progestin (adjusted HR 0.71; 95% confidence interval, 0.41-1.26) and (3) the VTE risk in pre-menopausal users of E2/E2Val-progestin was similar, or lower, than pre-menopausal users of EE⩽30µg-progestin (adjusted HR 0.49; 95% confidence interval, 0.28–0.84). Conclusion: Our data presents a solid safety assessment of combined hormonal preparations containing E2/E2Val. We conclude that the risk of E2/E2Val-norethindrone acetate in pre-menopausal users is unlikely to be higher than the known risk of COCs containing EE ⩽ 30 µg-progestin. [ABSTRACT FROM AUTHOR]

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Objectives: The "Long-term Active Surveillance Study for Oral Contraceptives" investigated the risks of long-term use of a 21-day regimen of drospirenone and ethinylestradiol (DRSP) compared to established oral contraceptives (OCs) in a routine clinical setting.Study Design: Prospective, controlled, non-interventional cohort study conducted in seven European countries with three main exposure groups: new users of DRSP, levonorgestrel-containing OCs (LNG), and OCs containing other progestogens (Other OCs). All self-reported clinical outcomes of interest (OoI) were validated via attending physicians and relevant source documents. Main OoI were serious clinical outcomes, in particular cardiovascular events. Comprehensive follow-up procedures were implemented. Statistical analyses were based on Cox regression models.Results: A total of 1,113 study centers enrolled 59,510 women. Overall 28%, 26% and 45% of these women used DRSP, LNG and Other OCs, respectively. Study participants were followed for up to ten years (mean value, 5.4years), which generated 318,784 woman-years (WY) of observation. Low loss to follow-up and drop-out rates of 2.9% and 16.8% were achieved. DRSP, LNG, and Other OCs showed similar incidence rates of venous thromboembolism. Corresponding hazard ratios (HRs) were close to unity. For arterial thromboembolic events (ATE) and initiation of antihypertensive treatment statistically significant lower risks were found for DRSP compared to LNG and Other OCs.Conclusion: DRSP use was associated with similar general health risks and a low risk of ATE compared to OCs containing other progestogens.Implication Statement: The 21-day regimen of drospirenone-containing combined oral contraceptives is associated with similar risk of VTE compared to other combined oral contraceptives as well as potentially with a lower risk of ATE. [ABSTRACT FROM AUTHOR]