Gestodene

Pharmacovigilance data analysis can accelerate the identification of drug-related safety signals or reassure on the safety profile. This study evaluates the venous thromboembolism (VTE) risk of newer combined oral contraceptive (COC) formulations with natural estrogens, such as estradiol (E2) and estetrol (E4), using data from the EudraVigilance database.

We conducted a disproportionality reporting rate analysis of VTE events associated with various COC formulations by extracting individual case reports from EudraVigilance database up to July 28, 2024. The study compared the proportionality reporting rate between natural estrogen-based COCs (E2 and E4) and conventional synthetic estrogen-based COCs (ethinylestradiol [EE]), with a comparison to EE-levonorgestrel.

The analysis revealed that COCs containing natural estrogens exhibited significantly lower proportionality reporting rates for thrombotic events compared to EE-based COCs. Specifically, E4-drospirenone (E4-DRSP) showed the lowest proportionality reporting rate (0.12), similar to progestin-only pills. EE-DRSP had the highest proportionality reporting rate (2.25), suggesting an increased thrombotic risk.

The study supports the safer thrombotic profile of natural estrogen-based COCs, particularly E2 and E4 formulations, over synthetic estrogen-based COCs containing EE. These findings support the hypothesis that E2- and E4-based pills are safer than EE-based pills, aligning with a shift toward safer contraceptive options in clinical practice.

Natural estrogens such as E2 and E4 may emerge as safer alternatives to synthetic estrogens like EE, particularly when combined with progestins like DRSP. This multilevel evidence underscores the importance of evidence-based prescribing practices to enhance patient safety and minimize thrombotic risks associated with COC use.

The occurrence of steroid hormones in small river ecosystems raises environmental alarms due to their limited dilution capacity, heightened susceptibility to diverse pollution sources, and their substantial contribution to the contamination of larger river systems. Here, we investigated the occurrence of 40 steroid hormones over 10 months in 10 first-order tributaries (n = 250) of Guangzhou City, China. The observed concentrations of Σsteroid hormones ranged from 30.5 to 450 ng/L (mean: 55.6 ± 35.4 ng/L). No substantial variation in steroid hormone concentrations was observed between the flood and dry seasons, reflecting an intricate balance of dilution dynamics, agricultural runoff, and wastewater releases. Further correlation analysis underscored wastewater discharge as a consistent source of steroid hormone occurrence, with spikes coinciding with concurrent fertilizer application and rainfall intervals. Steroid hormone concentrations displayed significant spatial variations. Correlation analyses connected steroid hormone levels to nutrients in tributaries and agricultural ditch water and land usage, highlighting the joint effect of runoff and various wastewater types on steroid hormone distribution. Interestingly, steroid hormone levels displayed minimal variation along the tributaries, suggesting uniform and continuous pollution sources. Source attribution analysis revealed that 51.7 % of steroid hormones originated from untreated domestic wastewater, followed by treated wastewater, livestock wastewater, and runoff. Notably, 92.0 % of the sampling sites registered at least one steroid hormone level exceeding the risk quotient threshold of 1, indicating widespread ecological hazards. Our research emphasizes the persistent and stable nature of steroid hormone-related risks across seasons and along the tributaries, highlighting the imperative for vigilant monitoring. We further advocate for intensified surveillance efforts during pivotal periods (e.g., fertilization periods and low rainfall intervals), to better address these environmental challenges.