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Abstract Objective To compare the impact on thrombin generation of the new combined oral contraceptive containing 15 mg estetrol and 3 mg drospirenone with ethinylestradiol (30 or 20 mcg) associated either with 150 mcg levonorgestrel or with 3 mg drospirenone. Methods Data were collected from the “E4/DRSP Endocrine Function, Metabolic Control and Hemostasis Study” (NCT02957630). Overall, the per-protocol set population included 24 subjects in the ethinylestradiol/levonorgestrel arm, 28 subjects in the ethinylestradiol/drospirenone arm, and 34 subjects in the estetrol/drospirenone arm. Thrombograms and thrombin generation parameters (lag time, peak, time to peak, endogenous thrombin potential, and mean velocity rate index) were extracted for each subject at baseline and after 6 cycles of treatment. Results After 6 cycles of treatment, ethinylestradiol-containing products arms show a mean thrombogram outside the upper limit of the reference range, that is the 97.5th percentile of all baseline thrombograms. On the other hand, the mean thrombogram of estetrol/drospirenone is within this reference interval. After 6 cycles of treatment, all thrombin generation parameters are statistically less affected by estetrol/drospirenone than ethinylestradiol-containing products. Conclusions In conclusion, an association of 15 mg estetrol with 3 mg drospirenone does not have an impact on thrombin generation compared with ethinylestradiol-containing products that, either associated with levonorgestrel or drospirenone, are able to increase the production of procoagulant factors and decrease the production of anticoagulant ones, shifting the patient to a prothrombotic state. Ethinylestradiol-containing products thus generate prothrombotic environments contrary to estetrol which demonstrates a neutral profile on hemostasis.

The estrogens estrone (E1), 17α-estradiol (E2α), 17β-estradiol (E2β), and estriol (E3) are natural sex hormones produced by humans and animals. In addition, there are some synthetic estrogens, such as 17α-ethinylestradiol (EE2), used for contraception purposes. These compounds are able to produce endocrine disruption in living organisms at nanogram-per-liter levels. In both humans and animals, estrogens are excreted in urine and feces, reaching the natural environment through discharge from sewage treatment plants (STP) and manure disposal units. In STPs, hormone removal depends on the type of treatment process and on different parameters such as the hydraulic and sludge retention times. Thus, hormone elimination rates vary from 0% to 90% in different STPs. Animals are also an important source of estrogens in the environment. Indeed, animals produce high concentrations of hormones which will end up in manure which is typically spread on land. Hence, waste-borne animal hormones may transfer these pollutants to the soil. The purpose of this review is to highlight the significance for both health and the environment of pollution by estrogens and critically review the existing knowledge on their fate and removal in different treatment processes. Relevant information on the microbial degradation of hormones and metabolic pathways is also included.

Among several types of emerging contaminants, the endocrine disruptors 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) are particularly notable. These compounds are discharged into sewage systems and subsequently into water bodies, as conventional wastewater treatment processes are unable to effectively eliminate such pollutants. Therefore, the present study aimed to evaluate the possibility of removing the endocrine disruptors 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) from water using the photocatalytic activity of the compound Ag3AsO4. Silver arsenate was synthesized and characterized, the quantification of the hormones E2 and EE2 was achieved by high-performance liquid chromatography with a fluorescence detector, and a validation process and some preliminary tests were performed on the photodegradation of the hormones using the Ag3AsO4 catalyst. Validation was performed, and satisfactory results were achieved: r = 0.9987 (E2), r = 0.9984 (EE2), a detection limit of 5.01 (E2) and 0.51 (EE2), a quantification limit of 15.19 (E2) and 1.54 (EE2), coefficients of variation for precision intraday and interday lower than 10.9725% and 11.3393%, respectively, and a recovery of 100.15% (E2) and 100.31% (EE2). In photodegradation studies, Ag3AsO4 showed different behavior in the presence of light for each hormone. In solution with E2, it reached a removal rate of 35% of the hormone under LED light, acting as a photocatalyst, while with EE2, it reached a removal rate of 96%; both results were obtained after 30 min of exposure to visible light. When this study is compared with other processes and materials, the high efficiency of the Ag3AsO4 photocatalyst in removing E2 and EE2, persistent emerging contaminants, becomes evident. This advancement has significant implications for wastewater treatment, offering a promising solution that can mitigate environmental impacts caused by endocrine disruptors.

Sewage sludge, a byproduct of wastewater treatment, can be converted into biochar, offering a sustainable solution for waste management and water treatment. Although biochars from biomass have been widely studied, sewage sludge-derived biochars remain underexplored. This study investigated the use of alkaline-treated sewage sludge-derived biochar (AlBC) as an adsorbent for three water pollutants: caffeine (CAF), carbamazepine (CBZ), and 17α-ethinyl estradiol (EE2). A comprehensive analysis was conducted to explore the kinetic and thermodynamic behaviors of these pollutants under varying conditions, such as different adsorbent dosage, temperature, and water matrix values. The AlBCSS showed enhanced surface area and improved adsorption capacity, with EE2 being preferentially adsorbed (qe: 9.51 mg g−1), followed by CAF (6.12 mg g−1) and CBZ (4.58 mg g−1). Adsorption followed the Langmuir isotherm for CAF and CBZ, and the Freundlich isotherm for EE2, while kinetics were best described by the pseudo-second-order and Elovich models. Thermodynamic analysis revealed that the adsorption process was spontaneous, primarily driven by physical interactions. Factors such as dosage, temperature, and pollutant concentration influenced adsorption, with no saturation observed at higher concentrations. The natural water matrix had a minimal effect on removal efficiency (40–100%), whereas AlBC exhibited promising results after four adsorption cycles. These results highlight the potential of sewage sludge-derived biochar as a sustainable adsorbent for emerging water pollutants, supporting circular economy practices in wastewater management.

Oral contraceptive (OC) use is associated with increased intrarenal renin–angiotensin–aldosterone system (RAA System) activity and risk of nephropathy, though the contribution of progestins contained in the OC in the regulation of angiotensin-dependent control of the renal circulation has not been elucidated. A total of 18 OC users (8 non-diabetic, 10 Type 1 diabetic) were studied in high salt balance, a state of maximal RAA System suppression. Progestational and androgenic activity of the progestin in each OC was standardized to that of the reference progestin norethindrone. Renal plasma flow (RPF) was measured by para-aminohippurate clearance at baseline and in response to angiotensin-converting enzyme (ACE) inhibition. There was a positive correlation between OC progestational activity and the RPF response to ACE inhibition ( r =0.52, P =0.03). Similar results were noted with OC androgenic activity ( r =0.54, P =0.02). On subgroup analysis, only non-diabetic subjects showed an association between progestational activity and angiotensin-dependent control of the renal circulation ( r =0.71, P =0.05 non-diabetic; r =0.14, P =0.7 diabetic; P =0.07 between groups). Similar results were noted with respect to androgenic activity ( r =0.88, P =0.005 non-diabetic; r =−0.33, P =0.3 diabetic; P =0.002 between groups). Our results suggest that the OC progestin component is a significant influence on the degree of angiotensin-dependent control of the renal circulation, though these findings may not apply to women with diabetes.

Endocrine-disrupting chemicals (EDCs) in municipal effluents directly affect the sexual development and reproductive success of fishes, but indirect effects on invertebrate prey or fish predators through reduced predation or prey availability, respectively, are unknown. At the Experimental Lakes Area in northwestern Ontario, Canada, a long-term, whole-lake experiment was conducted using a before-after-control-impact design to determine both direct and indirect effects of the synthetic oestrogen used in the birth control pill, 17α-ethynyloestradiol (EE2). Algal, microbial, zooplankton and benthic invertebrate communities showed no declines in abundance during three summers of EE2 additions (5–6 ng l−1), indicating no direct toxic effects. Recruitment of fathead minnow (Pimephales promelas) failed, leading to a near-extirpation of this species both 2 years during (young-of-year, YOY) and 2 years following (adults and YOY) EE2 additions. Body condition of male lake trout (Salvelinus namaycush) and male and female white sucker (Catostomus commersonii) declined before changes in prey abundance, suggesting direct effects of EE2 on this endpoint. Evidence of indirect effects of EE2 was also observed. Increases in zooplankton, Chaoborus, and emerging insects were observed after 2 or 3 years of EE2 additions, strongly suggesting indirect effects mediated through the reduced abundance of several small-bodied fishes. Biomass of top predator lake trout declined by 23–42% during and after EE2 additions, most probably an indirect effect from the loss of its prey species, the fathead minnow and slimy sculpin (Cottus cognatus). Our results demonstrate that small-scale studies focusing solely on direct effects are likely to underestimate the true environmental impacts of oestrogens in municipal wastewaters and provide further evidence of the value of whole-ecosystem experiments for understanding indirect effects of EDCs and other aquatic stressors.

Background Endometriosis is currently considered a systemic inflammatory disease and different non-invasive inflammatory markers, such as cell-free DNA (cfDNA), have recently been evaluated. Hormonal treatments are frequently prescribed as first-line treatments to improve symptoms, reduce lesions and improve the quality of life of patients with endometriosis. The most frequently used hormonal treatments are estroprogestins and progestins due to their effectiveness and well-tolerated clinical profile. However, the impact these hormonal treatments may have on these markers has yet to be determined. The aim of this study was to assess whether cfDNA levels are modified under the two main first-line hormonal treatments in patients with deep endometriosis (DE). Methods Ninety patients diagnosed with DE were analyzed in this prospective, observational study. Forty-five received daily oral treatment with dienogest 2 mg, and 45 with 2 mg dienogest/30 μg ethinylestradiol. Plasma cfDNA levels were evaluated by fluorescent assay prior to initiation of treatment and at 6 and 12 months of treatment. Results An increase in cfDNA levels was observed during the follow-up at 6 and 12 months. However, these higher levels were only statistically significant at 12 months of treatment. The increase of cfDNA levels was similar with both treatments. Conclusion Higher cfDNA levels were observed in DE patients at 12 months of oral hormonal treatment showing similar results with dienogest or dienogest/ethinylestradiol. This increase could be explained by apoptosis of the endometriosis foci due to the treatment.

PurposeMidostaurin, approved for treating FLT-3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is metabolized by cytochrome P450 (CYP) 3A4 to two major metabolites, and may inhibit and/or induce CYP3A, CYP2B6, and CYP2C8. Two studies investigated the impact of midostaurin on CYP substrate drugs and oral contraceptives in healthy participants.MethodsUsing sentinel dosing for participants’ safety, the effects of midostaurin at steady state following 25-day (Study 1) or 24-day (Study 2) dosing with 50 mg twice daily were evaluated on CYP substrates, midazolam (CYP3A4), bupropion (CYP2B6), and pioglitazone (CYP2C8) in Study 1; and monophasic oral contraceptives (containing ethinylestradiol [EES] and levonorgestrel [LVG]) in Study 2.ResultsIn Study 1, midostaurin resulted in a 10% increase in midazolam peak plasma concentrations (Cmax), and 3–4% decrease in total exposures (AUC). Bupropion showed a 55% decrease in Cmax and 48–49% decrease in AUCs. Pioglitazone showed a 10% decrease in Cmax and 6% decrease in AUC. In Study 2, midostaurin resulted in a 26% increase in Cmax and 7–10% increase in AUC of EES; and a 19% increase in Cmax and 29–42% increase in AUC of LVG. Midostaurin 50 mg twice daily for 28 days ensured that steady-state concentrations of midostaurin and the active metabolites were achieved by the time of CYP substrate drugs or oral contraceptive dosing. No safety concerns were reported.ConclusionMidostaurin neither inhibits nor induces CYP3A4 and CYP2C8, and weakly induces CYP2B6. Midostaurin at steady state has no clinically relevant PK interaction on hormonal contraceptives. All treatments were well tolerated.

Estrogens in aquatic environments pose significant ecological and health risks due to their cumulative effects rather than individual impacts. This study investigates the voltammetric behavior of estrone (E1), 17β-estradiol (E2), estriol (E3), and 17α-ethinylestradiol (EE2), presenting a cost-effective and straightforward method for their simultaneous determination. Using differential pulse voltammetry (DPV) with a boron-doped diamond electrode, the method demonstrates high precision (deviations under 4%) and a linear dynamic range of 15.35–134.55 µmol·L−1. Integration of a vacuum evaporation step reduced detection limits to 10−8 mol·L−1, enabling effective analysis of real water samples. This optimized approach ensures practical applicability for monitoring total estrogen content in aquatic systems, providing an accessible and reliable alternative to conventional methods.

Norgestimate (NGM) is a progestin with negligible androgenic activity that is available in combination with ethinyl estradiol (EE) as a monophasic combined oral contraceptive (COC). It has been more than 30 years since a clinical study evaluated the effects of monophasic NGM/EE on menstrual cycle characteristics in healthy women, and in the interim, there has been growing recognition that clinical trials of contraceptives should evaluate a wide range of potential positive and negative impacts for users. The aim of this study is to investigate menstrual cycle control during the use of a monophasic COC formulation containing NGM 0.25 mg and EE 0.035 mg (Effimia; Italfarmaco SpA), using established methodologies as well as patient-reported outcomes. This is a prospective observational study being undertaken in a target population of 228 healthy Italian women aged 18-35 years who are starting oral contraception for the first time or switching from another COC. The participants are asked to complete a diary for 6 cycles recording information about their menstrual cycles (frequency, duration, regularity, estimated flow volume, and breakthrough bleeding), any unscheduled bleeding, and an evaluation of dysmenorrhea, using a 100-mm visual analog scale from 0=no pain to 100=very severe pain, and any adverse events. Compliance is assessed after 3 and 6 months via returned medication. The primary end point is the change from baseline in the rate of intermenstrual bleeding during the sixth cycle. At baseline, 3 months, and 6 months, acne will also be assessed using the Global Acne Grading Scale, and participants will complete a Profile of Mood State to assess premenstrual syndrome and the Female Sexual Function Index to evaluate the quality of their sex life. A subgroup of 28 participants at 1 site (Genoa) is also providing a blood sample for the assessment of metabolic, endocrine, and coagulation parameters. Study enrollment began in July 2023 and is expected to be complete by December 2024. Data analysis is expected to be complete by October 2025. This study into the effects of monophasic NGM/EE 0.25/0.035 mg on menstrual characteristics in healthy Italian women will provide up-to-date data on these effects and includes assessments of a range of other parameters, such as acne severity and patient-reported outcomes, in line with recent international consensus recommendations. ClinicalTrials.gov NCT06067256; https://clinicaltrials.gov/study/NCT06067256 and EudraCT 2021-003027-15; https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003027-15/IT. DERR1-10.2196/63683.