Gestodene

Gestodene (GES) is widely used in human therapy and animal husbandry and is frequently detected in aquatic environments. Although GES adversely affects aquatic organisms at trace levels, its effects on the reproductive biology of fish remain inconclusive. In this study, female zebrafish (Danio rerio) were exposed to environmentally relevant levels of GES for the evaluation of the effects of GES on the reproductive system by using endpoints including gene expression, plasma steroid concentrations, histological and morphological analyses, copulatory behavior, and reproductive output...

BACKGROUND: Gestodene (GEST) is widely used in female contraception. It is currently being used as an oral contraceptive. However, unfortunately, oral contraceptives are often associated with several bothersome side effects and poor compliance. Therefore, a sustained delivery system for GEST to overcome these shortcomings is highly desirable. OBJECTIVES: The present study successfully developed a kind of novel dissolving microneedles (DMNs) with a potential for sustained release and a minimally invasive intradermal treatment of GEST...

Gestodene (GES) is a common synthetic progesterone frequently detected in aquatic environments. Chronic exposure to GES can cause masculinization of a variety of fish; however, whether metabolism is closely related to the masculinization has yet to be explored. Hence, the ovary metabolome of adult female western mosquitofish (Gambusia affinis) after exposing to GES (0.0, 5.0, 50.0, and 500.0 ng/L) for 40 days was analyzed by using high-performance liquid chromatography ionization with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS)...

Ultra-low-dose hormonal pills have become the preferred treatment option for polycystic ovary syndrome (PCOS). Existing literature shows marked heterogeneity in the metabolic effects of pills with different compositions. This may have been due to the improper choice of outcome variables for comparison. Total cholesterol-high-density lipoprotein ratio (TC/HDL) discordance with low-density lipoprotein cholesterol (LDL-C) was a better marker of the future risk of atherosclerotic cardiovascular disease and was stable to variations...

BACKGROUND: Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE). OBJECTIVE: The aim of this study was to investigate the association between oral contraceptive use and natural anticoagulants, that is, protein C (PC), protein S (PS), and antithrombin in pregnant women with deep vein thrombosis (DVT). MATERIALS AND METHODS: This case-control study was conducted on 330 pregnant women, that is, cases 165 (who used oral contraceptives) and controls 165 (who did not use oral contraceptives)...

Synthetic progestins are micropollutants of special concern, due to their growing use in human and veterinary therapies and their risks to aquatic life. Currently, there is a lack of environmental information on these compounds, worldwide. The main objective of this work was to characterize the levels of the most consumed progestins in Portugal. For that, Ria de Aveiro, Tagus estuary and Ria Formosa were sampled in a temporal perspective to evaluate levels of drospirenone (DRO), desogestrel (DSG), gestodene (GST) and levonorgestrel (LNG)...

BACKGROUND: SERPINC1 is a glycoprotein that regulates blood coagulation. SERPINC1 congenital or acquired deficiencies represent a significant risk factor for thromboembolic disease. SERPINC1 acquired defects are observed in very few cases and can occur in many clinical conditions such as treatment with L-asparaginase or oral contraceptive (particularly estrogen derivatives), but these conditions are not routinely investigated. CASE PRESENTATION: A 50-year-old Caucasian woman who took gestodene 75 µg/ethinylestradiol 20 µg as oral contraceptive, was sent to our thrombophilia clinic because, on thrombophilia testing, a reduction of SERPINC1 (74%) and a slight increase in circulating D-dimer and homocysteine were found...

We developed and validated use of ultra-high performance liquid chromatography-heated electrospray ionization-tandem triple quadrupole mass spectrometry (LC-MS/MS) to simultaneously analyze serum concentrations of ethinylestradiol (EE), dienogest (DNG), norelgestromin (NGMN), norethindrone (NET), gestodene (GSD), levonorgestrel (LNG), etonogestrel (ENG), segesterone acetate (NES), medroxyprogesterone acetate (MPA), and drospirenone (DRSP). The calibration range for all targets was 0.009 to 10 ng/ml, with lower limit of quantification of 0...

Estrogenic endocrine disruptors are one of the biggest ecotoxicological threats in water that pose a significant ecological burden and health-risk for humans due to their high biological activity and proven additive effects. Therefore, we have developed and validated the most comprehensive and ultra-sensitive analytical method published to date, for reliable quantification of 25 high-risk endocrine disruptors at their ecologically relevant concentrations: naturally excreted hormones (estradiol, estrone, estriol, testosterone, corticosterone, and progesterone), synthetic hormones used for contraception and menopausal symptoms (ethinylestradiol, drospirenone, chlormadinone acetate, norgestrel, gestodene, tibolone, norethindrone, dienogest, and cyproterone) and bisphenols (BPS, BPA, BPF, BPE, BPAF, BPB, BPC, and BPZ)...

PURPOSE: The contraceptive gestodene is a potent synthetic progestin used in several low-dose contraceptive formulations. Clinical studies reported a relationship between long-term use of combined oral contraceptives containing gestodene (GDN) and profound alterations in glucose metabolism in women. The observation that contraceptive synthetic progestins exert hormone-like effects other than their progestational activities, prompted us to investigate whether GDN may induce estrogen-like effects, even though GDN does not interact with estrogen receptors...

Gestodene (GES), altrenogest (ALT), and medroxyprogesterone acetate (MPA) are three potent synthetic progestins detected in agricultural soils; however, their biotransformation outcomes in soils remain unclear. This study explored the biotransformation of these progestins in five agricultural soils with different physicochemical properties. The biotransformation data were well-described by a first-order decay model (R2 = 0.83-0.99), with estimated half-lives ranging between 12.1 and 188 h. Amplicon sequencing indicated that the presence of progestins changed the bacterial richness and community structure in the soils...

The frequent detection of progestins in various aquatic environments and their potential endocrine disruptive effects in fish have attracted increasing attention worldwide. However, data on their effects on thyroid function and neurotoxicity in fish are limited, and the underlying mechanisms remain unclear. Here, the effects of gestodene (GES, a common progestin) on the thyroid endocrine and nervous systems of mosquitofish (Gambusia affinis) were studied. Adult female fish were exposed to GES at environmentally relevant concentrations (4...

Studies directly comparing the efficacies and potencies of multiple progestins used in contraception and menopausal hormone therapy (MHT) in parallel via human progesterone receptor isoform A (PR-A) in the same model system are limited, and how these parameters are influenced by the density of PR-A are unclear. This is surprising as it is known that the expression levels of PR-A vary in different tissues and diseases. We thus determined for the first time the relative efficacies and potencies for transactivation of the natural PR ligand, progesterone (P4 ), the PR-specific agonist promegestone (R5020), and selected progestins from all four generations in parallel via different densities of PR-A overexpressed in the MDA-MB-231 breast cancer cell line...

OBJECTIVE: To compare the risk of venous thromboembolism (VTE) among young women for nine combined oral contraceptives (COCs), including progestogens with an as yet unclear risk of VTE such as chlormadinone and nomegestrol, using COCs containing levonorgestrel with low ethinylestradiol (<50 μg) as a reference. DESIGN: Case-control study nested in a cohort of new users of COCs. SETTING: German claims data. POPULATION: A total of 1166 cases of VTE matched to 11 660 controls nested in a cohort of 677 331 girls and young women aged 10-19 years with one or more COCs dispensed between 2005 and 2017 after a 1-year period without any COCs...

INTRODUCTION: The increased risk of venous thromboembolism associated with the use of hormonal contraception is well recognized, but evidence regarding hormonal contraception containing natural estradiol is limited. This study aimed to assess the associations between the patterns of use of different systemic hormonal contraceptives and the risk of venous thromboembolism during 2017-2019. MATERIAL AND METHODS: All fertile-aged women (15-49 years) living in Finland in 2017 and using hormonal contraception in 2017 and their 1:1 age- and residence-matched controls not using hormonal contraception in 2017 (altogether 587 559 women) were selected from the Prescription Centre...

Many factors must be considered and discussed with women when initiating a contraceptive method and the risk of venous thromboembolism (VTE) is one of them. In this review, we discuss the numerous strategies that have been implemented to reduce the thrombotic risk associated with combined oral contraceptives (COCs) from their arrival on the market until today. Evidences suggesting that COCs were associated with an increased risk of VTE appeared rapidly after their marketing. Identified as the main contributor of this risk, the dosage of the estrogen, i...

Progestins and estrogens are widespread in various aquatic environments and their potential endocrine disruption effects to aquatic organisms have drawn growing concern. However, their combined effects in aquatic organisms remain elusive. The aim of the present study was to assess the effects of the binary mixtures of gestodene (GES) and 17α-ethinylestradiol (EE2) on the hypothalamic-pituitary-thyroid (HPT) axis of zebrafish (Danio rerio) using the eleuthero-embryos. Embryos were exposed to GES and EE2 alone or in combination at concentrations ranging from 41 to 5329 ng L-1 (nominal ones from 50 to 5000 ng L-1 ) for 48 h, 96 h and 144 h post fertilization (hpf)...

OBJECTIVES: To detect the signals for drospirenone-containing oral contraceptives (DCOCs) and describe the reporting pattern of adverse events (AEs) caused by DCOCs compared with levonorgestrel/desogestrel/gestodene-containing (second/third generation) oral contraceptives. DESIGN: A descriptive analysis of claims data. SETTING: The Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database from 1 February 2008 to 31 December 2017...

Hormonal contraception exposes women to synthetic progesterone receptor (PR) agonists, progestins, and transiently increases breast cancer risk. How progesterone and progestins affect the breast epithelium is poorly understood because we lack adequate models to study this. We hypothesized that individual progestins differentially affect breast epithelial cell proliferation and hence breast cancer risk. Using mouse mammary tissue ex vivo, we show that testosterone-related progestins induce the PR target and mediator of PR signaling-induced cell proliferation receptor activator of NF-κB ligand (Rankl), whereas progestins with anti-androgenic properties in reporter assays do not...

The presence of sex steroid hormones in aquatic ecosystems is of rapidly growing concern worldwide since they can affect the different non-target species including cladocerans. Although data are available on the effects of estrogens on the well-established ecotoxicological model organism Daphnia magna, the molecular or behavioural alterations induced by environmentally relevant concentrations (from a few ng L-1 to a few hundred ng L-1 in average) of progestogens have not been investigated on this species. In the present study, we exposed neonates of D...