drospirenone (Slinda / LPRICF113 / LF111)

THE Environmental Impact of Contraceptive Methods - A Systematic Review.

van der Heide E E R EER, Cohen E S ES, Pieters L I LI, van Heel D A M DAM et al.

Contraception contributes to healthcare's global environmental footprint through pharmaceutical emissions and disposable waste. Steroid hormones used in hormonal contraception are widely detected in aquatic environments, raising concerns regarding their ecotoxicological risks. This review synthesizes environmental impacts of registered (non-)hormonal contraceptives, aiming to compare their environmental sustainability and estimate comparative ecotoxicological risk profiles of hormonal methods. A systematic literature search of Medline, Embase, Web of Science Core Collection, and Scopus was conducted through January 8, 2026, covering life cycle assessments, carbon footprint studies, water monitoring studies, chronic ecotoxicological effect studies, and environmental risk assessments. Of 3,409 records retrieved, 78 studies met predefined inclusion criteria. Extracted data were organised by study type, contraceptive method, environmental impact categories, and ecotoxicological endpoints. Available life cycle assessments were limited to condoms and showed that natural rubber condoms were associated with lower production-related environmental burden than polyisoprene condoms. The total waste associated with the use of long-acting hormonal contraceptives was lower compared to short-acting methods and non-hormonal intrauterine devices. Environmental risk assessments revealed global occurrence of estrogens and progestins in surface waters, with some posing risks to aquatic ecosystems. Comparative ecotoxicological profiles suggested lower relative ecotoxicity for drospirenone- and desogestrel-containing oral contraceptives per daily dose compared with other hormonal methods, and potentially lower ecotoxicity for levonorgestrel intrauterine devices compared to levonorgestrel containing oral formulations. Overall, the included studies reported on only a limited range of environmental impacts, such as waste production, carbon footprint and ecotoxicity, while overlooking other aspects of environmental sustainability. Because of this no definitive conclusions or comparisons could be made based on the full environmental sustainability. However, by extending the focus beyond direct environmental impacts towards overall sustainability, different contraceptive groups were ranked according to their overall sustainability. This led to the conclusion that long-acting reversible contraceptives are relatively more sustainable then short-acting reversible methods.

RETRACTION: Combined Contraceptive Ring Versus Combined Oral Contraceptive (30-μg Ethinylestradiol and 3-mg Drospirenone.

A.M.M. Mohamed, W.S.M. El-Sherbiny, and W.A.I. Mostafa, "Combined Contraceptive Ring Versus Combined Oral Contraceptive (30-μg Ethinylestradiol and 3-mg Drospirenone," International Journal of Gynecology & Obstetrics 114, no. 2 (2011): 145-148, https://doi.org/10.1016/j.ijgo.2011.03.008. The above article, published online on 12 June 2011 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the journal Editor-in-Chief, Michael Geary; and John Wiley & Sons Ltd. Concerns were raised on PubPeer [1] of the viability of the study, which measured several features every three months for a year, including a 12 month follow up, but with only three authors and no listed funding. An unusual pattern involving the last digit of the standard deviations reported in Table 5 was also noted. A review by the editorial team, which included re-calculation of the statistical data, identified further statistical anomalies in Tables 1, 2, and 4 that are incompatible with the reported results. When reached for clarification and access to the full set of study data, the authors were unable to provide the data as the study was conducted more than 10 years ago. They did provide a response to the editorial team's assessment. Lacking the study data for further analysis, along with the inconsistencies present in several places in the article, the Editor-in-Chief considers the data and conclusions to be unreliable. Therefore, a retraction is warranted. [1] B. Mol, "Combined Contraceptive Ring Versus Combined Oral Contraceptive (30-μg Ethinylestradiol and 3-mg Drospirenone," PubPeer 2026, https://pubpeer.com/publications/60212B830C0D42151398B9384FDD6A.

A Novel Polarity Switching LC-MS/MS Method for Simultaneous Quantification of Drospirenone and Estetrol: Application to Pharmacokinetic Studies in Human Plasma.

Singh Pravesh P, Dar Sajad Khaliq SK, Khan Faisal Hamid FH, Sherwani Asjad Nabi Khan ANK et al.

A sensitive, selective, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using a polarity switch technique was developed and validated for the simultaneous determination of drospirenone (DSP) and estetrol (E4) in human plasma for the first time. Solid phase extraction (SPE) with Bond Elut PLEXA cartridges was performed. Chromatographic separation was obtained on Eclipse XDB-C8 (150 mm × 4.6 mm, 3.5 μm) column using 2-mM ammonium bicarbonate solution:methanol (30:70, v/v) as the mobile phase at a flow rate of 0.750 mL/min. A polarity switching method was performed in a triple quadrupole mass spectrometer using multiple reaction monitoring (MRM). MRM was performed in positive mode for DSP transitions m/z 367.2 → 171.1 and DSP-D4 transitions m/z 371.2 → 171.1, and in negative mode for E4 transitions m/z 303.1 → 241.2, 273.0 and E4-d3 transitions m/z 306.2 → 243.2, 275.0. Calibration curves were linear over the concentration ranges of 0.351-100.446 and 0.351-50.134 ng/mL for DSP and E4, respectively. The accuracy measured for both analytes ranged from -2.74% to 4.21%. Both the analytes showed consistent recoveries ranged from 77.25% to 81.34% with no significant matrix effect. The method was successfully applied in a pharmacokinetic study of DSP and E4 tablets (3 mg + 14.2 mg).

Effects of estetrol/drospirenone vs drospirenone-only on thrombin generation in women with polycystic ovary syndrome: a randomized, double-blind, controlled trial.

Chantrapanichkul Panicha P, Wiwatboworn Paveenutch P, Rattanachaiyanont Manee M, Tanmahasamut Prasong P et al.

Combined oral contraceptives are first-line treatment for polycystic ovary syndrome (PCOS); however, venous thromboembolism risk remains a concern. Estetrol/drospirenone (E4/DRSP) has a more favorable thrombin generation assay (TGA) profile than ethinyl estradiol-based combined oral contraceptives, but direct comparison with progestin-only pills is lacking. This study aimed to compare the effects of E4/DRSP and DRSP-only on TGA parameters, hyperandrogenic symptoms, and vaginal bleeding patterns in women with PCOS. In a randomized, double-blind, controlled trial, women with PCOS aged 18 to 40 years at Siriraj Hospital, Thailand (May-December 2025) were assigned in a 1:1 ratio to E4/DRSP or DRSP-only for 12 weeks. The primary outcome was change in TGA parameters measured with and without thrombomodulin (TM). Secondary outcomes were vaginal bleeding patterns, modified Ferriman-Gallwey score, acne severity, and treatment satisfaction. Both regimens increased endogenous thrombin potential and peak height on TGA, without TM (E4/DRSP: 1699 to 1888; DRSP-only: 1836 to 2085 nM·min; within-group P ≤ .017) and with TM (both P = .001), with no between-group differences (all P > .05). The endogenous thrombin potential-TM ratio rose in both groups, with no between-group difference (E4/DRSP: median +0.14; DRSP-only: +0.13; between-group P = .74). DRSP-only had fewer scheduled bleeding days across 3 cycles, whereas E4/DRSP reduced modified Ferriman-Gallwey score for hirsutism (P < .001). Waist-to-hip ratio, acne, and treatment satisfaction were comparable, with no serious adverse events. E4/DRSP and DRSP-only had comparable effects on thrombin generation and TM-mediated anticoagulation in women with PCOS. E4/DRSP reduced hirsutism, supporting its consideration as a treatment option for PCOS.