Abstract The need to seek improved combined oral contraceptive (COC) efficacy, with fewer health risks and better acceptability, has been ongoing since the introduction of COCs more than 50 years ...ago. New progestin formulations combined with lower doses of ethinyl estradiol (EE), the predominant estrogenic component of COCs, have reduced the incidence of venous thromboembolism and other negative outcomes of COC treatment. Previous attempts to use endogenous 17β-estradiol (E2 ) instead of EE were limited primarily by poor cycle control. The recent introduction of E2 -based formulations has renewed interest to determine if there are potential benefits of using E2 in COCs. These formulations have been shown to have similar efficacy and cycle control as EE-based COCs. This review provides a brief summary of the pharmacology of EE and E2 , including metabolism, pharmacokinetics and pharmacodynamics, as well as adverse effects of these estrogens.
Natural estrogens such as estrone (E1), 17β-estradiol (E2), estriol (E3), and the synthetic one, 17α-ethinylestradiol (EE2), are excreted by humans and animals and enter into environment through ...discharge of domestic sewage effluents and disposal of animal waste. The occurrence of these substances in aquatic ecosystems may affect the endocrine system of humans and wildlife so it has emerged as a major concern for water quality. Extensive research has being carried out during the last decades on the efficiency of the degradation and/or removal of these hormones in sewage treatment plants (STPs). Conventional and advanced treatments have been investigated by different authors for the elimination of estrogens from water. This paper aims to review the different processes and treatments that have been applied for the elimination of E1, E2, E3 and EE2 from water. With this purpose, physical, biological and advanced oxidation processes (AOP) have been addressed.
Reviewing the estrogens' removal processes from waters is essential to understand how to reduce/eliminate them in the environment and how research on this topic should be carried on in the near future.
Celebrating 75 years of oestradiol Simpson, Evan; Santen, Richard J
Journal of molecular endocrinology,
12/2015, Volume:
55, Issue:
3
Journal Article
Peer reviewed
Open access
Oestrogens exert important effects on the reproductive as well as many other organ systems in both men and women. The history of the discovery of oestrogens, the mechanisms of their synthesis, and ...their therapeutic applications are very important components of the fabric of endocrinology. These aspects provide the rationale for highlighting several key components of this story. Two investigators, Edward Doisy and Alfred Butenandt, purified and crystalized oestrone nearly simultaneously in 1929, and Doisy later discovered oestriol and oestradiol. Butenandt won the Nobel Prize for this work and Doisy's had to await his purification of vitamin K. Early investigators quickly recognized that oestrogens must be synthesized from androgens and later investigators called this process aromatization. The aromatase enzyme was then characterized, its mechanism determined, and its structure identified after successful crystallization. With the development of knock-out methodology, the precise effects of oestrogen in males and females were defined and clinical syndromes of deficiency and excess described. Their discovery ultimately led to the development of oral contraceptives, treatment of menopausal symptoms, therapies for breast cancer, and induction of fertility, among others. The history of the use of oestrogens for postmenopausal women to relieve symptoms has been characterized by cyclic periods of enthusiasm and concern. The individuals involved in these studies, the innovative thinking required, and the detailed understanding made possible by evolving biologic and molecular techniques provide many lessons for current endocrinologists.
A database of human dermatopharmacokinetic parameters of 12 transdermal patches is established. The effect of system design, application site, and metabolism on pharmacokinetic data is discussed, and ...interindividual variability of data and its possible sources evaluated. Using multiple regression analysis, two equations based on drugs physicochemical characteristics are suggested for partial prediction of peak plasma concentration (
C
max) after patch application. Patch application presumably decreases variance as rub-off, wash and exfoliation steps are diminished.
The results showed that interindividual variation, in terms of coefficient of variation (CV) of
C
max, is inversely correlated with drugs molecular weight and lipophilicity in the range of 200
<
MW
<
400 and 1.6
<
log
K
oct
<
4.3. Multiple regression analysis of
C
max against physichochemical parameters demonstrated the prominent contribution of hydrogen bonding acceptability of the molecules on their maximal plasma concentration after patch administration.
The findings suggest that the serum concentration profile for transdermal therapeutic systems (TTS) is a net result of the system performance, drug absorption and elimination. Thus, the variability in serum concentration is a function of variability of each process involved. This should be noted in explanation of effect of molecular features of drugs on their plasma concentration profile.
In genetically heterogeneous mice produced by the CByB6F1 x C3D2F1 cross, the “non‐feminizing” estrogen, 17‐α‐estradiol (17aE2), extended median male lifespan by 19% (p < 0.0001, log‐rank test) and ...11% (p = 0.007) when fed at 14.4 ppm starting at 16 and 20 months, respectively. 90th percentile lifespans were extended 7% (p = 0.004, Wang–Allison test) and 5% (p = 0.17). Body weights were reduced about 20% after starting the 17aE2 diets. Four other interventions were tested in males and females: nicotinamide riboside, candesartan cilexetil, geranylgeranylacetone, and MIF098. Despite some data suggesting that nicotinamide riboside would be effective, neither it nor the other three increased lifespans significantly at the doses tested. The 17aE2 results confirm and extend our original reports, with very similar results when started at 16 months compared with mice started at 10 months of age in a prior study. The consistently large lifespan benefit in males, even when treatment is started late in life, may provide information on sex‐specific aspects of aging.
Interventions that increase lifespan when started late in life are most likely to be useful in the clinic. Testing genetically diverse mice, the “non‐feminizing” estrogen, 17‐α‐estradiol, extended median male lifespan by 19% (p < 0.0001, log‐rank test) and 11% (p = 0.007) when fed at 14.4 ppm starting at 16 and 20 months, respectively. Nicotinamide riboside and three other drugs did not affect lifespan in either sex.
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.
The occurrence, removal and bioaccumulation of steroid estrogens such as the natural estrone (E1), 17β-estradiol (E2) and estriol (E3), as well as the synthetic 17α-ethynylestradiol (EE2) were ...investigated in Dianchi Lake catchment, China. The results show that traditional secondary treatment processes in eight sewage treatment plants (STPs) of Kunming were not efficient enough to completely remove steroid estrogens, but ultraviolet (UV) photodegradation in advanced treatment displayed more effectively for the removal of the residual compounds. The amount of total steroid estrogens (∑SEs) discharged to Dianchi Lake catchment by the eight STPs was 35.8g/day, in which STP-3 was the dominant source, accounting for 50.8%. Because of the pollution input from treated and untreated sewages, estrogens were widely detected in surface water and sediment samples collected from 21 inflow rivers of Dianchi Lake, 10 National Surface Water Quality Monitoring Sites of the lake itself and its unique outflow river, with the mean concentration of ∑SEs in the range of 5.3–798.2ng/L (water) and 3.7–202.4ng/g (dry weight, sediment), 1.5–39.2ng/L (water) and 2.7–20.9ng/g (sediment), and 4.2ng/L (water) and 6.6ng/g (sediment), respectively. Due to the continuous input of estrogens to Dianchi Lake from STPs and inflow rivers, present estrogen levels in various tissues of wild fish species sampled from the lake (2013) were higher than the values detected in the previous years (2009 and 2010). The bioaccumulation of steroid estrogens in wild fish species from different sampling sites was in the order of STP-5>Dianchi Lake (2013)>Dianchi Lake (2010)≈Dianchi Lake (2009)≫field control>laboratory control, which is mainly affected by exposure concentrations. By employing risk quotient (RQ), it is found that eco-toxicological risk of steroid estrogens in Dianchi Lake catchment was in a sequence of 22 rivers>effluents of eight STPs>Dianchi Lake (2013)>Dianchi Lake (2010), and high RQs were found in EE2, which should be controlled preferentially in this catchment.
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•Estrogens were widely detected in sewage, surface water, sediment and organism.•Mass input of estrogens to Dianchi Lake from sewage treatment plant was 35.8g/day.•Present estrogen levels in Dianchi Lake were higher than in previous years.•Bioaccumulation of estrogens in wild fish was affected by exposure concentrations.•High eco-toxicological risk was found in Dianchi Lake catchment by employing RQs.
Current approaches to diagnosing testosterone deficiency do not consider the physiological consequences of various testosterone levels or whether deficiencies of testosterone, estradiol, or both ...account for clinical manifestations.
We provided 198 healthy men 20 to 50 years of age with goserelin acetate (to suppress endogenous testosterone and estradiol) and randomly assigned them to receive a placebo gel or 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel daily for 16 weeks. Another 202 healthy men received goserelin acetate, placebo gel or testosterone gel, and anastrozole (to suppress the conversion of testosterone to estradiol). Changes in the percentage of body fat and in lean mass were the primary outcomes. Subcutaneous- and intraabdominal-fat areas, thigh-muscle area and strength, and sexual function were also assessed.
The percentage of body fat increased in groups receiving placebo or 1.25 g or 2.5 g of testosterone daily without anastrozole (mean testosterone level, 44±13 ng per deciliter, 191±78 ng per deciliter, and 337±173 ng per deciliter, respectively). Lean mass and thigh-muscle area decreased in men receiving placebo and in those receiving 1.25 g of testosterone daily without anastrozole. Leg-press strength fell only with placebo administration. In general, sexual desire declined as the testosterone dose was reduced.
The amount of testosterone required to maintain lean mass, fat mass, strength, and sexual function varied widely in men. Androgen deficiency accounted for decreases in lean mass, muscle size, and strength; estrogen deficiency primarily accounted for increases in body fat; and both contributed to the decline in sexual function. Our findings support changes in the approach to evaluation and management of hypogonadism in men. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00114114.).
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