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Actas Dermo-sifiliograficas Jun 2020Oral contraceptives combine estrogen and progesterone to suppress ovulation. Synthetic forms are usually used. In dermatology, oral contraceptives are prescribed for 2... (Review)
Review
Oral contraceptives combine estrogen and progesterone to suppress ovulation. Synthetic forms are usually used. In dermatology, oral contraceptives are prescribed for 2 main reasons: to prevent pregnancy when teratogenic drugs must be taken and to treat skin manifestations of hyperandrogenism. Most oral contraceptives improve both acne and hirsutism, but the androgenic effect of progestogens - particularly if the contraceptive contains first- or second-generation progestogens- can trigger or exacerbate acne. One of the most serious side effects of oral contraceptives, thrombosis, is mainly caused by the estrogen component and its dose. If we mainly consider a contraceptive's thrombotic profile when prescribing, the choice would be to have 30μg or less of ethinyl estradiol combined with levonorgestrel. On the other hand, if our main objective is to treat signs of androgenization, we would prefer contraceptives containing progestogens with antiandrogenic effects.
Topics: Contraceptives, Oral; Dermatology; Ethinyl Estradiol; Female; Humans; Levonorgestrel; Pregnancy; Progesterone
PubMed: 32404240
DOI: 10.1016/j.ad.2019.06.006 -
Contraception Sep 2018The recent Danish cohort study reported a 20% increased risk of breast cancer among current and recent hormonal contraception users. These results are largely consistent...
The recent Danish cohort study reported a 20% increased risk of breast cancer among current and recent hormonal contraception users. These results are largely consistent with previous studies. This study did not report on stage of disease at diagnosis, and it is not clear to what extent the apparent increased risk may be due to a small advance in the timing of diagnosis. This study did not report on the risk associated with the use of a 20-mcg ethinyl estradiol pill. They did find an increasing risk in current users of longer duration and an increased risk with use of the levonorgestrel intrauterine system-both of these potentially important findings have not been consistently found in previous studies and require further investigation. The breast cancer effects described now in multiple studies wane with time, and in the long term, hormonal contraception use has been found not to be associated with any increased total cancer risk.
Topics: Breast Neoplasms; Cohort Studies; Contraception; Ethinyl Estradiol; Humans; Levonorgestrel
PubMed: 30193687
DOI: 10.1016/j.contraception.2018.05.002 -
Women's Health (London, England) 2023The spironolactone derivative drospirenone is combined with ethinylestradiol or estetrol in combined oral contraceptives. Formulations with 17-β-estradiol are used to... (Review)
Review
The spironolactone derivative drospirenone is combined with ethinylestradiol or estetrol in combined oral contraceptives. Formulations with 17-β-estradiol are used to treat climacteric symptoms. A drospirenone-only formulation has been introduced for contraception. Here, the pharmacological properties of drospirenone, the impact of the different formulations on metabolic and laboratory parameters, and the resulting clinical implications are reviewed. Ethinylestradiol, an inhibitor of CYP metabolic enzymes, changes the pharmacokinetics of drospirenone, leading to a higher drospirenone exposure with ethinylestradiol/drospirenone compared to the drospirenone-only preparation. In addition, several metabolic alterations have been described. The impact of estetrol is less pronounced, and for 17-β-estradiol/drospirenone and drospirenone-only, decreased triglyceride and cholesterol levels were observed. Ethinylestradiol induces various pro-coagulatory factors, leading to hypercoagulability. The effect is significantly reduced with estetrol, and no influence was observed with the drospirenone-only preparation. The anti-mineralocorticoid activity of drospirenone seems to positively counteract the renin-angiotensin-aldosterone-system-activating action of ethinylestradiol. There is no influence on blood pressure with ethinylestradiol/drospirenone and estetrol/drospirenone formulations, while in clinical trials, a reduction has been observed with 17-β-estradiol/drospirenone and drospirenone-only. Anti-aldosterone activity via non-renal mineralocorticoid receptors is associated with cardiovascular health, while interactions with parathyroid hormone signaling impact bone structure and vascular calcification. Though the clinical relevance is unclear for drospirenone, data in this context are reviewed. To sum up, the advantages of drospirenone in hormonal contraception and treatment of menopausal symptoms have been demonstrated for all the formulations described here. Combination with estrogen confers benefits and risks, which must be considered.
Topics: Female; Humans; Progestins; Estetrol; Estrogens; Ethinyl Estradiol; Contraceptives, Oral, Combined; Estradiol
PubMed: 36744531
DOI: 10.1177/17455057221147388 -
Frontiers in Endocrinology 2021Previous toxicokinetic studies have shown that mussels ( spp.) can readily absorb the three main mammalian sex steroids, estradiol (E), testosterone (T) and progesterone...
Previous toxicokinetic studies have shown that mussels ( spp.) can readily absorb the three main mammalian sex steroids, estradiol (E), testosterone (T) and progesterone (P) from water. They also have a strong ability to store E and the 5α-reduced metabolites of T and P in the form of fatty acid esters. These esters were shown to have half-lives that were measured in weeks (i.e. they were not subject to fast depuration). The present study looked at the toxicokinetic profile of two other common steroids that are found in water, the potent synthetic oestrogen, (ethinyl-estradiol) (EE one of the two components of 'the pill'), and cortisol, a natural stress steroid in vertebrates. In the first three hours of uptake, tritiated EE was found to be taken up at a similar rate to tritiated E. However, the levels in the water plateaued sooner than E. The ability of the animals to both esterify and sulphate EE was found to be much lower than E, but nevertheless did still take place. After 24 h of exposure, the majority of radiolabelled EE in the animals was present in the form of free steroid, contrary to E which was esterified. This metabolism was reflected in a much lower half-life (of only 15 h for EE in the mussels as opposed to 8 days for E and >10 days for T and P). Intriguingly, hardly any cortisol (in fact none at all in one of the experiments) was absorbed by the mussels. The implications of this finding in both toxicokinetic profiling and evolutionary significance (why cortisol might have evolved as a stress steroid in bony fishes) are discussed.
Topics: Animals; Estrogens; Ethinyl Estradiol; Hydrocortisone; Metabolic Clearance Rate; Mytilus; Water; Water Pollutants, Chemical
PubMed: 34975764
DOI: 10.3389/fendo.2021.794623 -
American Family Physician May 2020
Review
Topics: Contraceptive Devices, Female; Drug Combinations; Ethinyl Estradiol; Female; Humans; Pregnenediones
PubMed: 32412221
DOI: No ID Found -
Contraception Mar 2021To assess the contraceptive efficacy, safety, and tolerability of a contraceptive transdermal delivery system, (TDS; TWIRLA) containing levonorgestrel (LNG) and ethinyl...
OBJECTIVE
To assess the contraceptive efficacy, safety, and tolerability of a contraceptive transdermal delivery system, (TDS; TWIRLA) containing levonorgestrel (LNG) and ethinyl estradiol (EE).
STUDY DESIGN
This single-arm, open-label, multicenter, 1-year (13 cycle), phase 3 study enrolled sexually active women ≥18 years old at risk for pregnancy irrespective of body mass index (BMI). Women used patches in 28-day cycles (3 consecutive administrations of 7-day patches followed by 7 days off-treatment/patch-free week). We assessed contraceptive efficacy by the Pearl Index (PI) in women 18 to 35 years, excluding cycles without intercourse or when other contraceptive methods were used.
RESULTS
The study enrolled 2032 demographically diverse women in the US, of which 35.3% had a BMI ≥30 kg/m. In the primary efficacy analysis, the PI (95% confidence interval) was 5.8 (4.5-7.2) pregnancies per 100 woman-years. PIs trended higher as BMI increased; the PI was 4.3 (2.9-5.8) in women with BMI <30 kg/m and 8.6 (5.8-11.5) in women with BMI ≥30 kg/m. Hormone-related treatment-emergent adverse events included nausea (4.1%) and headache (3.6%); 11% of women discontinued due to adverse events. Four women (all with BMIs ≥30 kg/m) reported thromboembolic events considered related to treatment.
CONCLUSIONS
The low-dose LNG/EE TDS was effective in preventing pregnancy in a population of women representative of US demographics. Efficacy was reduced in women with BMI ≥30 kg/m. The TDS safety and tolerability profile was consistent with other similar dose combined hormonal contraceptives. Results of this phase 3 study supported the US Food and Drug Administration approval of TWIRLA for prevention of pregnancy in women with BMI <30 kg/m.
IMPLICATIONS
TDS (120 µg/day levonorgestrel and 30 µg/day ethinyl estradiol) is an effective, low-dose transdermal contraceptive patch with favorable tolerability profile approved for prevention of pregnancy in women with BMI <30 kg/m. TDS has reduced effectiveness in women with BMI ≥30 kg/m.
Topics: Adolescent; Body Mass Index; Contraceptives, Oral, Combined; Estradiol; Ethinyl Estradiol; Female; Humans; Levonorgestrel; Pregnancy
PubMed: 33259782
DOI: 10.1016/j.contraception.2020.11.011 -
BMJ (Clinical Research Ed.) Sep 1990
Topics: Cyproterone; Drug Therapy, Combination; Ethinyl Estradiol; Female; Hirsutism; Humans; Polycystic Ovary Syndrome
PubMed: 2224213
DOI: 10.1136/bmj.301.6753.619 -
Scientific Reports Feb 2018Primodos was a hormone pregnancy test used between 1958-1978 that has been implicated with causing a range of birth defects ever since. Though Primodos is no longer...
Primodos was a hormone pregnancy test used between 1958-1978 that has been implicated with causing a range of birth defects ever since. Though Primodos is no longer used, it's components, Norethisterone acetate and Ethinyl estradiol, are used in other medications today including treatments for endometriosis and contraceptives. However, whether Primodos caused birth defects or not remains controversial, and has been little investigated. Here we used the developing zebrafish embryo, a human cell-line and mouse retinal explants to investigate the actions of the components of Primodos upon embryonic and tissue development. We show that Norethisterone acetate and Ethinyl estradiol cause embryonic damage in a dose and time responsive manner. The damage occurs rapidly after drug exposure, affecting multiple organ systems. Moreover, we found that the Norethisterone acetate and Ethinyl estradiol mixture can affect nerve outgrowth and blood vessel patterning directly and accumulates in the forming embryo for at least 24 hrs. These data demonstrate that Norethisterone acetate and Ethinyl estradiol are potentially teratogenic, depending on dose and embryonic stage of development in the zebrafish. Further work in mammalian model species are now required to build on these findings and determine if placental embryos also are affected by synthetic sex hormones and their mechanisms of action.
Topics: Animals; Cell Line; Cell Proliferation; Dose-Response Relationship, Drug; Drug Interactions; Embryo, Nonmammalian; Embryonic Development; Ethinyl Estradiol; Hormones; Humans; Mice; Nervous System; Norethindrone Acetate; Pregnancy Tests; Time Factors; Toxicity Tests; Zebrafish
PubMed: 29440757
DOI: 10.1038/s41598-018-21318-9 -
The AAPS Journal Mar 2014Interest in pharmaceuticals in the environment has increased substantially in recent years. Several studies in particular have assessed human and ecological risks from... (Review)
Review
Interest in pharmaceuticals in the environment has increased substantially in recent years. Several studies in particular have assessed human and ecological risks from human pharmaceutical estrogens, such as 17α-ethinyl estradiol (EE2). Regulatory action also has increased, with the USA and other countries developing rules to address estrogens and other pharmaceuticals in the environment. Accordingly, the Center for Drug Evaluation and Research at the US Food and Drug Administration has conducted a review and analysis of current data on the long-term ecological exposure and effects of EE2 and other estrogens. The results indicate that mean-flow long-term predicted environmental concentrations (PECs) of EE2 in approximately 99% or more of US surface water segments downstream of wastewater treatment plants are lower than a predicted no-effect concentration (PNEC) for aquatic chronic toxicity of 0.1 ng/L. Exceedances are expected to be primarily in localized, effluent-dominated water segments. The median mean-flow PEC is more than two orders of magnitude lower than this PNEC. Similar results exist for other pharmaceutical estrogens. Data also suggest that the contribution of EE2 more broadly to total estrogenic load in the environment from all sources (including other human pharmaceutical estrogens, endogenous estrogens, natural environmental estrogens, and industrial chemicals), while highly uncertain and variable, appears to be relatively low overall. Additional data and a more comprehensive approach for data collection and analysis for estrogenic substances in the environment, especially in effluent-dominated water segments in sensitive environments, would more fully characterize the risks.
Topics: Ecology; Estrogens; Ethinyl Estradiol; Humans; Pharmaceutical Preparations; Risk Assessment; Water Pollutants, Chemical
PubMed: 24470211
DOI: 10.1208/s12248-014-9561-3 -
General and Comparative Endocrinology Jan 2020In aquatic toxicology, perhaps no pharmaceutical has been investigated more intensely than 17alpha-ethinylestradiol (EE2), the active ingredient of the birth control... (Review)
Review
In aquatic toxicology, perhaps no pharmaceutical has been investigated more intensely than 17alpha-ethinylestradiol (EE2), the active ingredient of the birth control pill. At the turn of the century, the fields of comparative endocrinology and endocrine disruption research witnessed the emergence of omics technologies, which were rapidly adapted to characterize potential hazards associated with exposures to environmental estrogens, such as EE2. Since then, significant advances have been made by the scientific community, and as a result, much has been learned about estrogen receptor signaling in fish from environmental xenoestrogens. Vitellogenin, the egg yolk precursor protein, was identified as a major estrogen-responsive gene, establishing itself as the premier biomarker for estrogenic exposures. Omics studies have identified a plethora of estrogen responsive genes, contributing to a wealth of knowledge on estrogen-mediated regulatory networks in teleosts. There have been ~40 studies that report on transcriptome responses to EE2 in a variety of fish species (e.g., zebrafish, fathead minnows, rainbow trout, pipefish, mummichog, stickleback, cod, and others). Data on the liver and testis transcriptomes dominate in the literature and have been the subject of many EE2 studies, yet there remain knowledge gaps for other tissues, such as the spleen, kidney, and pituitary. Inter-laboratory genomics studies have revealed transcriptional networks altered by EE2 treatment in the liver; networks related to amino acid activation and protein folding are increased by EE2 while those related to xenobiotic metabolism, immune system, circulation, and triglyceride storage are suppressed. EE2-responsive networks in other tissues are not as comprehensively defined which is a knowledge gap as regulated networks are expected to be tissue-specific. On the horizon, omics studies for estrogen-mediated effects in fish include: (1) Establishing conceptual frameworks for incorporating estrogen-responsive networks into environmental monitoring programs; (2) Leveraging in vitro and computational toxicology approaches to identify chemicals associated with estrogen receptor-mediated effects in fish (e.g., male vitellogenin production); (3) Discovering new tissue-specific estrogen receptor signaling pathways in fish; and (4) Developing quantitative adverse outcome pathway predictive models for estrogen signaling. As we look ahead, research into EE2 over the past several decades can serve as a template for the array of hormones and endocrine active substances yet to be fully characterized or discovered.
Topics: Animals; Endocrine Disruptors; Ethinyl Estradiol; Fishes; Male; Time Factors; Transcriptome
PubMed: 31733209
DOI: 10.1016/j.ygcen.2019.113325