Instruct: Given a question, retrieve documents that can help answer the question.
Query: What can we do with xenoestrogens?
Xenoestrogens are a type of xenohormone that imitates estrogen. They can be either synthetic or natural chemical compounds. Synthetic xenoestrogens include some widely used industrial compounds, such as PCBs, BPA, and phthalates, which have estrogenic effects on a living organism even though they differ chemically from the estrogenic substances produced internally by the endocrine system of any organism. Natural xenoestrogens include phytoestrogens which are plant-derived xenoestrogens. Because the primary route of exposure to these compounds is by consumption of phytoestrogenic plants, they are sometimes called "dietary estrogens". Mycoestrogens, estrogenic substances from fungi, are another type of xenoestrogen that are also considered mycotoxins.
, estradiol is available in the United States in the following forms:Oral estradiol valerate (Progynova) and other esters of estradiol that are used by injection like estradiol benzoate, estradiol enantate, and estradiol undecylate all are not marketed in the U.S. Polyestradiol phosphate (Estradurin) was marketed in the U.S. previously but is no longer available.
Estradiol is available in a variety of different formulations, including oral, intranasal, transdermal/topical, vaginal, injectable, and implantable preparations. An ester may be attached to one or both of the hydroxyl groups of estradiol to improve its oral bioavailability and/or duration of action with injection. Such modifications give rise to forms such as estradiol acetate (oral and vaginal), estradiol valerate (oral and injectable), estradiol cypionate (injectable), estradiol benzoate (injectable), estradiol undecylate (injectable), and polyestradiol phosphate (injectable; a polymerized ester of estradiol), which are all prodrugs of estradiol.
In the absence of hormone, estrogen receptors are largely located in the cytosol. Hormone binding to the receptor triggers a number of events starting with migration of the receptor from the cytosol into the nucleus, dimerization of the receptor, and subsequent binding of the receptor dimer to specific sequences of DNA known as hormone response elements. The DNA/receptor complex then recruits other proteins that are responsible for the transcription of downstream DNA into mRNA and finally protein that results in a change in cell function. Estrogen receptors also occur within the cell nucleus, and both estrogen receptor subtypes have a DNA-binding domain and can function as transcription factors to regulate the production of proteins.
Estradiol enantate, sold under the brand names Perlutal and Topasel among others, is an estrogen medication which is used in hormonal birth control. It is formulated in combination with dihydroxyprogesterone acetophenide (DHPA; algestone acetophenide), a progestin, and is used as a combined injectable contraceptive. Estradiol enantate is not available alone. The medication is given by injection into muscle once a month.
Side effects of estradiol enantate include breast tenderness, breast enlargement, nausea, headache, and fluid retention. The drug is a synthetic estrogen and hence is an agonist of the estrogen receptor (ER), the biological target of estrogens like estradiol. Estradiol enantate is an estrogen ester and a long-lasting prodrug of estradiol in the body. Because of this, it is considered to be a natural and bioidentical form of estrogen.
Estradiol enantate was first described by 1954, and was first studied in combination with DHPA as a combined injectable contraceptive in 1964. The combination was introduced for clinical use by the mid-1970s. Estradiol enantate is not available as a standalone medication (i.e., by itself without DHPA). The combination is available in Latin America and Hong Kong, and was also previously marketed in Spain and Portugal.
In addition to single-drug formulations, oral estradiol valerate is available in combination with the progestin dienogest as a combined oral contraceptive and intramuscular estradiol valerate is marketed in combination with the progestins hydroxyprogesterone caproate and norethisterone enantate as combined injectable contraceptives. Intramuscular estradiol valerate has also been marketed in combination with testosterone enantate, but this formulation has been discontinued. The availability of estradiol valerate-containing products varies throughout the world.
As indicated in their individual Wikipedia pages, 5-hydroxyeicosatetraenoic acid (which, like 5-oxo-eicosatetraenoic acid, acts through the OXER1 receptor), 5-oxo-eicosatetraenoic acid, 12-Hydroxyeicosatetraenoic acid, 15-Hydroxyeicosatetraenoic acid, and 20-Hydroxyeicosatetraenoic acid show numerous activities in animal and human cells as well as in animal models that are related to, for example, inflammation, allergic reactions, cancer cell growth, blood flow to tissues, and/or blood pressure. However, their function and relevancy to human physiology and pathology have not as yet been shown.
As the sodium salt, sodium estradiol sulfate, E2S is present as a minor constituent (0.9%) of conjugated equine estrogens (CEEs), or Premarin. It effectively functions as a prodrug to estradiol in this preparation, similarly to E1S. E2S is also formed as a metabolite of estradiol, as well as of estrone and E1S. Aside from its presence in CEEs, E2S is not available as a commercial pharmaceutical drug.
15-Hydroxyeicosatetraenoic acid (also termed 15-HETE, 15("S")-HETE, and 15"S"-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. Various cell types metabolize arachidonic acid to 15("S")-hydroperoxyeicosatetraenoic acid (15("S")-HpETE). This initial hydroperoxide product is extremely short-lived in cells: if not otherwise metabolized, it is rapidly reduced to 15"(S)"-HETE. Both of these metabolites, depending on the cell type which forms them, can be further metabolized to 15-oxo-eicosatetraenoic acid (15-oxo-ETE), 5"S",15"S"-dihydroxy-eicosatetraenoic acid (5("S"),15("S")-diHETE), 5-oxo-15("S")-hydroxyeicosatetraenoic acid (5-oxo-15("S")-HETE, a subset of specialized pro-resolving mediators viz., the lipoxins, a class of pro-inflammatory mediators, the eoxins, and other products that have less well-defined activities and functions. Thus, 15("S")-HETE and 15("S")-HpETE, in addition to having intrinsic biological activities, are key precursors to numerous biologically active derivatives.
Although the goal of the program is to prevent pregnancies of women who take the drug, male patients must also participate in anti-pregnancy restrictions, primarily due to fears that male isotretinoin users might share their prescriptions with females without their physicians' knowledge. There has been no link to birth defects from Accutane associated with males using the drug, though male sexual dysfunction has been suggested by one study. As this has not been conclusively proven, this is not acknowledged as a side effect in the official literature accompanying the medication.
Xenic acid is a noble gas compound formed by the dissolution of xenon trioxide in water. Its chemical formula is HXeO. It is a very powerful oxidizing agent, and its decomposition is dangerous as it liberates a large amount of gaseous products: xenon, oxygen, and ozone. However, this feature is also what makes xenic acid practically useful in syntheses: there is no chance of introducing impurities to the oxidation products, as all the byproducts can be trivially evaporated.
Isotretinoin is a teratogen; there is about a 20–35% risk for congenital defects in infants exposed to the drug "in utero", and about 30–60% of children exposed to isotretinoin prenatally have been reported to show neurocognitive impairment. Because of this, there are strict controls on prescribing isotretinoin to women who may become pregnant and women who become pregnant while taking isotretinoin are strongly advised to terminate their pregnancies.
Contraception has many benefits beyond preventing pregnancy. Combination estrogen-progestin contraceptives can successfully treat dysmenorrhea (painful periods), provide symptom relief from endometriosis, reduce heavy menstrual bleeding and improve anemia related to menstrual blood loss, reduce symptoms of premenstrual syndrome and premenstrual dysphoric disorder, reduce ovarian and colon cancer risk, reduce moderate acne, prevent of menstrual migraines, and reduce hirsutism (abnormal hair growth). The progestin containing intrauterine device can reduce heavy menstrual bleeding and protect against pre-cancerous changes or cancer in the uterus. Condoms (male or female) are the only contraceptive method which protects against acquisition of sexually transmitted infections.
It has been shown that oxytocin differentially affects males and females. Females who are administered oxytocin are overall faster in responding to socially relevant stimuli than males who received oxytocin. Additionally, after the administration of oxytocin, females show increased amygdala activity in response to threatening scenes; however, males do not show increased amygdala activation. This phenomenon can be explained by looking at the role of gonadal hormones, specifically estrogen, which modulate the enhanced threat processing seen in females. Estrogen has been shown to stimulate the release of oxytocin from the hypothalamus and promote receptor binding in the amygdala.
The effect on sexual desire is varied, with increase or decrease in some but with no effect in most. Combined oral contraceptives reduce the risk of ovarian cancer and endometrial cancer and do not change the risk of breast cancer. They often reduce menstrual bleeding and painful menstruation cramps. The lower doses of estrogen released from the vaginal ring may reduce the risk of breast tenderness, nausea, and headache associated with higher dose estrogen products.
Progestin-only pills, injections and intrauterine devices are not associated with an increased risk of blood clots and may be used by women with a history of blood clots in their veins. In those with a history of arterial blood clots, non-hormonal birth control or a progestin-only method other than the injectable version should be used. Progestin-only pills may improve menstrual symptoms and can be used by breastfeeding women as they do not affect milk production. Irregular bleeding may occur with progestin-only methods, with some users reporting no periods. The progestins drospirenone and desogestrel minimize the androgenic side effects but increase the risks of blood clots and are thus not first line. The perfect use first-year failure rate of injectable progestin is 0.2%; the typical use first failure rate is 6%.
The term "endocrine disruptor" was coined at the Wingspread Conference Centre in Wisconsin, in 1991. One of the early papers on the phenomenon was by Theo Colborn in 1993. In this paper, she stated that environmental chemicals disrupt the development of the endocrine system, and that effects of exposure during development are often permanent.
Although the endocrine disruption has been disputed by some, work sessions from 1992 to 1999 have generated consensus statements from scientists regarding the hazard from endocrine disruptors, particularly in wildlife and also in humans.
A 2019 systematic review and meta-analysis found an incidence rate of VTE of 2.3 per 1000 person-years with feminizing hormone therapy in transgender women. For comparison, the rate in the general population has been found to be 1.0–1.8 per 1000 person-years and the rate in premenopausal women taking birth control pills has been found to be 3.5 per 1000 patient-years. As such, it appears that the risk of VTE with feminizing hormone therapy in transgender women is less than that with birth control pills. The risk of VTE with birth control pills in premenopausal women is considered to be an acceptable level of risk. There was significant heterogeneity in the rates of VTE across the included studied, and the meta-analysis was unable to perform subgroup analyses between estrogen type, estrogen route, estrogen dosage, concomitant antiandrogen or progestogen use, or patient characteristics (e.g., age, smoking status, weight) corresponding to known risk factors for VTE. Due to the inclusion of some studies using ethinylestradiol, which is more thrombotic and is no longer used in transgender women, the researchers noted that the VTE risk found in their study is likely to be an overestimate.
The 6-millimeter stent is placed through the trabecular meshwork, with one end of the stent sitting directly underneath the conjunctiva, past the outer wall of the sclera. The inner tip of the stent sits in the anterior chamber, allowing a direct connection for aqueous to flow into the subconjunctival space. The stent is made of a non-bioreactive material, which does not promote scarring of the conjunctiva. The XEN Gel Stent was FDA approved on Nov 22, 2016.
Progestins in birth control pills are sometimes grouped by generation. While the 19-nortestosterone progestins are consistently grouped into generations, the pregnane progestins that are or have been used in birth control pills are typically omitted from such classifications or are grouped simply as "miscellaneous" or "pregnanes". In any case, CPA has been described as a "first-generation" progestin similarly to closely related progestins like chlormadinone acetate, medroxyprogesterone acetate, and megestrol acetate.
In a series of relatively small studies of the combination of low-dose CPA and ethinylestradiol as a birth control pill, depression was reported to have occurred in 1.3 to 4% of cycles. This is similar to the rate of mood changes (<3.5%) observed with birth control pills containing other progestins. A pharmacoepidemiological study using data from the United Kingdom General Practice Research Database found that the incidence of depression with birth control pills containing CPA was identical to that of birth control pills containing other progestins ( = 0.99). In clinical studies of the combination of low-dose CPA and estradiol valerate for the treatment of menopausal symptoms, preexisting adverse mood symptoms have been found to be significantly improved.
Corticosteroids (cortisone), accutane (isotretinoin) and other vitamin A derivatives, barbiturates, certain antibiotics, propofol, volatile anesthetics, non-depolarizing muscle relaxants, some local anesthetics, statins, fibrates, glitazones, beta blockers, biguanides, amiodarone, some chemotherapies, some neuroleptics, nucleoside reverse transcriptase inhibitors and various other drugs.
Another potential effect of xenoestrogens is on oncogenes, specifically in relation to breast cancer. Some scientists doubt that xenoestrogens have any significant biological effect, in the concentrations found in the environment. However, there is substantial evidence in a variety of recent studies to indicate that xenoestrogens can increase breast cancer growth in tissue culture.
The ubiquitous presence of such estrogenic substances is a significant health concern, both individually and for a population. Life relies on the transmission of biochemical information to the next generation, and the presence of xenoestrogens may interfere with this transgenerational information process through "chemical confusion" (Vidaeff and Sever), who state: "The results do not support with certainty the view that environmental estrogens contribute to an increase in male reproductive disorders, neither do they provide sufficient grounds to reject such a hypothesis."
BPA (Bisphenol A) is the monomer used to manufacture polycarbonate plastic and epoxy resins used as a lining in most food and beverage cans. BPA global capacity is in excess of per year and thus is one of the highest-volume chemicals produced worldwide. The ester bonds in the BPA-based polycarbonates could be subject to hydrolysis and leaching of BPA. But in the case of epoxypolymers formed from bisphenol A, it is not possible to release bisphenol A by such a reaction. It is also noteworthy that, of the bisphenols, bisphenol A is a weak xenoestrogen. Other compounds, such as bisphenol Z, have been shown to have stronger estrogenic effects in rats.
The induction of CYP1A has been established to be a good bioindicator for xenoestrogen exposure. In addition, xenoestrogens stimulate vitellogenin (Vtg), which acts as a nutrient reserve, and Zona readiata proteins (Zrp), which forms eggshells. Therefore, Vtg and Zrp are biomarkers to exposure for fish.