Estrogens Research Papers - Academia.edu (original) (raw)

This article presents an up-to-date review of the literature on hormone augmentation in the elderly to help primary care physicians better evaluate and utilize hormone replacement and optimization strategies to benefit their patients. The scientific literature suggests that hormone supplementation with estrogen, progesterone, testosterone, growth hormone, and thyroid hormone has the potential to improve quality of life and to prevent, or reverse, the many symptoms and conditions associated with aging, including fatigue, depression, weight gain,frailty, osteoporosis, loss of libido, and heart disease. Possible long-term side effects are also considered.

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- Geriatrics, Aging, Clinical Practice, Progesterone

Atrazine, a chlorotriazine herbicide, is used to control annual grasses and broadleaf weeds. In this review, we summarize our laboratory's work evaluating the neuroendocrine toxicity of atrazine (and related chlorotriazines) from an historic perspective. We provide the rationale for our work as we have endeavored to determine: 1) the underlying reproductive changes leading to the development of mammary gland tumors in the atrazine-exposed female rat; 2) the cascade of physiological events that are responsible for these changes (i.e., the mode of action for mammary tumors); 3) the potential cellular mechanisms involving adverse effects of atrazine; and 4) the range of reproductive alterations associated with this pesticide.

- by Michael G Narotsky
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- Reproduction, Aging, Biology, Pregnancy

The reluctance of physicians to use estrogens in women with hormone responsive disorders is a tragic result of the 2002 WHI study. Although their hostility to estrogen therapy antedated these studies, the flawed data is now used as justification for the denial of estrogens for treatment of low bone density and various types of hormone responsive depression in women. Estrogens

- by David Reid
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- Depression, Menopause, England, Postmenopausal Women
- by Atsuo Yanagisawa
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- Menstruation, Electrocardiography, Sudden Death, Progesterone

This mini-review focuses on sexual differentiation of the reproductive organs and the brain in birds and the effects of endocrine modulators on these processes. Sex determination in birds is genetically controlled, but the genetic events implicated are largely unknown. Female birds have one Z and one W sex chromosome, while males have two Z sex chromosomes. It is not clear whether it is the presence of the W chromosome in females, the double dose of the Z chromosome in males vis-aÁ-vis females, or both of these characteristics that are crucial for the determination of sex in birds. Oestradiol directs sexual differentiation in birds during critical periods of development. Consequently, exogenous compounds that interfere with the endogenous oestrogen balance can disrupt sexual differentiation of the reproductive organs and the brain. Therefore, sexual differentiation in birds provides a good model for studying the effects of endocrine modulators at various biological levels from gene expression to behaviour. Some compounds known to be present in the environment can alter endocrine function and have adverse effects when administered during development, resulting in alterations in gonads, accessory sexual organs, and behaviour. Data reviewed in this paper are mostly from laboratory studies on endocrine modulators with oestrogenic activity, whereas evidence for adverse effects of pollutants on sexual differentiation in avian wildlife is scarce.

- by Jeanette Axelsson
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- Genetics, Ecotoxicology, Gene expression, Biological Sciences

Following a lead obtained from stem-bark extract of Butea monosperma, two structurally related methoxyisoflavones; cajanin and isoformononetin were studied for their effects in osteoblasts. Cajanin had strong mitogenic as well as differentiation-promoting effects on osteoblasts that involved subsequent activation of MEK-Erk and Akt pathways. On the other hand, isoformononetin exhibited potent anti-apoptotic effect in addition to promoting osteoblast differentiation that involved parallel activation of MEK-Erk and Akt pathways. Unlike genistein or daidzein, none of these two compounds appear to act via estrogen receptors in osteoblast. Once daily oral (by gavage) treatment for 30 consecutive days was given to recently weaned female Sprague–Dawley rats with each of these compounds at 10.0 mg kg−1 day−1 dose. Cajanin increased bone mineral density (BMD) at all skeletal sites studied, bone biomechanical strength, mineral apposition rate (MAR) and bone formation rate (BFR), compared with control. BMD levels at various anatomic positions were also increased with isoformononetin compared with control however, its effect was less potent than cajanin. Isoformononetin had no effect on the parameters of bone biomechanical strength although it enhanced MAR and BFR compared with control. Isoformononetin had very mild uterotrophic effect, whereas cajanin was devoid of any such effect. Our data suggest that cajanin is more potent than isoformononetin in accelerating peak bone mass achievement. To the best of our knowledge, this work represents the first attempt to elucidate structure-activity relationship between the two methoxylated isoflavones regarding their effects in osteoblasts and bone formation. J. Cell. Biochem. 108: 388–399, 2009. © 2009 Wiley-Liss, Inc.

- by divya singh
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- Aging, Enzyme Inhibitors, Apoptosis, Cell Differentiation

Background: Alzhcimcr's disease (AD) is the most common cause of cognitive impairment in older patients and is expected to increase greatly in prevalence. Interventions that could delay disease onset would have a major public health impact. Objective: The objective of this article is to review evidence from epidemiologic studies and controlled trials addressing whether AD can be prevented. Methods: Data were gathered through a comprehensive, systematic search of MEDLINE using focused search criteria and spanning a 6-year period from January 1998 through January 2004; a hand search of reference lists from these studies and reviews; a review of the Cochrane Database of Systematic Reviews; and a hand search of relevant journals. Selection of articles was based on the clinical focus. Additional inclusion criteria were used to select key articles that contained higher-level evidence in accordance with explicit, validated criteria. Results: Preventive interventions for AD include vitamins, nonsteroidal anti-inflammatory drugs, and agents that protect the endothelium (eg, statins). Good control of hypertension with angiotensinconverting enzyme inhibitors and long-acting dihydropyridines also confers neuroprotective benefits. Conclusions: The paradigm that AD is pharmacologically unresponsive is shifting as more effective pharmacotherapies for prevention and treatment rapidly emerge. Our understanding of the molecular mechanisms of neurodegeneration will soon allow us to more specifically target and interrupt the processes that contribute to this progressive dementia.

- by BRIDGETT STANDRIDGE
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- Public Health, Folic acid, Prevention, Molecular Mechanics

Background and aim. Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. The aim of this study was to examine the putative protective role of estradiol against sepsis-induced oxidative organ damage. Materials and methods. Sepsis was induced by cecal ligation and puncture method in Wistar albino rats. Sham-operated (control) and sepsis groups received saline or estradiol propionate (10 mg/kg) intraperitoneally immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde, glutathione levels, and myeloperoxidase activity were determined in the liver and ileum, while oxidant-induced tissue fibrosis was determined by collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels, and lactate dehydrogenase were measured for the evaluation of liver functions and tissue damage, respectively. Tumor necrosis factor-␣ was also assayed in serum samples. Results. In the saline-treated sepsis group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity, and collagen content were increased in the tissues (P < 0.01 to P < 0.001), suggesting oxidative organ damage, which was also verified histologically. In the estradioltreated sepsis group, all of these oxidant responses were reversed significantly (P < 0.05 to P < 0.01). Liver function tests and tumor necrosis factor-␣ levels, which were increased significantly (P < 0.001) following sepsis, were decreased (P < 0.05 to P < 0.001) with estradiol treatment. Conclusion. The results demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage, and estradiol, by its antioxidant properties, ameliorates oxidative organ injury, implicating that treatment with estrogens might be applicable in clinical situations to ameliorate multiple organ damage induced by sepsis.

- by Berrak Yegen
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- Oxidative Stress, Liver diseases, Liver, Glutathione

Although passive sampling has been previously used for the monitoring of volatile and semi-volatile contaminants in air, there are limited data on the use of this technique coupled with bioassays based on specific biological responses. Biological responses including those mediated by the aryl hydrocarbon (AhR) receptor as well as (anti-)estrogenicity and (anti-)androgenicity of samples from four Eastern European countries (Lithuania, Slovakia, Romania, and Serbia) were determined. To address the potential differences of specific toxic potencies of pollutant mixtures in ambient air in Eastern Europe, each country was characterized by a single more remote location that served to determine regional background conditions and one location in more urbanized and industrialized locations, which were defined as "impacted" areas. Besides samples from Lithuania, a significant gradient in concentrations of AhR-mediated potency from background and impacted localities was observed. Greatest potencies were measured in samples from impacted locations in Romania and Slovakia. Concentrations of polycyclic aromatic hydrocarbons (PAHs) that were quantified accounted for 3-33 % of the 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents determined by use of the bioassay. No significant estrogenic potency was detected but anti-estrogenic effects were produced by air from two background locations (Lithuania, Slovakia) and three impacted locations (Lithuania, Romania, and Serbia). Anti-androgenic potency was observed in all samples. The greatest antiestrogenic potency was observed at the background location in Slovakia. Anti-estrogenic and anti-androgenic potencies of studied air samples were probably associated with compounds that are not routinely monitored. The study documents suitability of passive air sampling for the assessment of specific toxic potencies of ambient air pollutants.

- by Anita Érseková
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- Eastern Europe, Environmental Monitoring, Air pollution, Multidisciplinary
- by Rupert Leong
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- Epidemiology, Molecular Biology, Gastroenterology, Cancer
- by Martina Pasillas
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- Genetics, Functional Analysis, Technology, Cytokines

Resveratrol (Resv), a natural occurring phytolexin present in grapes and other foods, possesses chemopreventive effects revealed by its striking modulation of diverse cellular events associated with tumor initiation, promotion and progression. Catechol estrogens generated in the metabolism of estrogens are oxidized to catechol quinones that react with DNA to form predominantly depurinating estrogen-DNA adducts. This event can generate the mutations responsible for cancer initiation. In this regard, Resv acts as both an antioxidant and an inducer of the phase II enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1). In this report, we present the effects of Resv on the metabolism of estrogens in normal breast epithelial cells (MCF-10F) treated with 4-hydroxyestradiol (4-OHE2) or estradiol-3,4-quinone (E2-3,4-Q). Resv induced NQO1 in a dose- and time-dependent manner, but did not affect the expression of catechol-O-methyltransferase. Ultraperformance liquid chromatography/tandem mass spectrometry was used to determine the effects of Resv on estrogen metabolism. Preincubation of the cells with Resv for 48 h decreased the formation of depurinating estrogen-DNA adducts from 4-OHE2 or E2-3,4-Q and increased formation of methoxycatechol estrogens. When Resv was also present with the 4-OHE2 or E2-3,4-Q, even greater increases in methoxycatechol estrogens were observed, and the DNA adducts were undetectable. We conclude that Resv can protect breast cells from carcinogenic estrogen metabolites, suggesting that it could be used in breast cancer prevention.

- by Eleanor Rogan
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- Chemistry, Breast Cancer, Medicine, Antioxidants

In recent years there has been a growing body of clinical and laboratory evidence demonstrating the neuroprotective effects of estrogen and progesterone after traumatic brain injury (TBI) and spinal cord injury (SCI). In humans, women have been shown to have a lower incidence of morbidity and mortality after TBI compared with age-matched men. Similarly, numerous laboratory studies have demonstrated that estrogen and progesterone administration is associated with a mortality reduction, improvement in neurological outcomes, and a reduction in neuronal apoptosis after TBI and SCI. Here, we review the evidence that supports hormone-related neuroprotection and discuss possible underlying mechanisms. Estrogen and progesterone-mediated neuroprotection are thought to be related to their effects on hormone receptors, signaling systems, direct antioxidant effects, effects on astrocytes and microglia, modulation of the inflammatory response, effects on cerebral blood flow and metabolism, and effects on mediating glutamate excitotoxicity. Future laboratory research is needed to better determine the mechanisms underlying the hormones' neuroprotective effects, which will allow for more clinical studies. Furthermore, large randomized clinical control trials are needed to better assess their role in human neurodegenerative conditions.

- by moti klein
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- Neuroprotection, Progesterone, Estrogens, Current Neuropharmacology

Clinical trials have shown that 3-hydoxy-3- methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, known as statins, significantly reduce the risk of both primary and secondary coronary heart disease events. Although these trials have included few women, the evidence suggests that statins are as effective in women as in men. The addition of hormone replacement therapy to statin therapy augments lowering of low- density lipoprotein cholesterol, but may not increase the favorable effects on clinical events achieved with statins alone. Finally, new data suggest that statins may also reduce the risk of osteoporotic fractures, a provocative finding still in need of verification by clinical trials.

- by david herrington
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- Osteoporosis, Bone Density, Risk factors, LDL-cholesterol
- by Janet Adolphson
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- Aging, Atherosclerosis, Japan, Norway
- by Brian Hampton
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- Cancer, Breast Cancer, Fetal development, Cell line

Aims: Postpartum blues is thought to be related to hormonal events accompanying delivery. We investigated whether blues-like symptoms depend on the rate of the decline of hormones, by comparing the behavioral consequences of an abrupt versus a gradual decline of gonadal hormones in an animal model. Methods: Female rats were treated with estrogen and progesterone for 23 days, administered either by injections or by subcutaneously implanted tubes filled with hormones. A gradual hormone decline was achieved by discontinuation of the injections; and rapid decline by removal of the tubes. Control groups received either a continued treatment or no hormones. In the period following the decline the stressreactivity was tested with an acoustic startle test on 3 consecutive days, and anxiety behavior with an openfield test on the 2nd day. The Hypothalamus-, Pituitary-, Adrenal-axis (HPA-axis) response to stress was measured by assessing the corticosterone levels and hypothalamic c-fos expression stress-response at the 4th day. Key findings: The rapid decline of hormones induced an increased startle response lasting for two days, and increased anxiety-like behavior in the open field. This was not found in the gradual-decline and control groups. The HPA-axis response to stress was decreased in all hormone-treated animals. Significance: This animal study suggests that: 1) abrupt rather than gradual hormonal changes induce increased stress-reactivity and anxiety-like behavior; 2) postpartum blues may result from differences in the capacity to adapt to the changes of gonadal hormones; 3) Recovery of pregnancy-induced diminished HPAaxis response is independent of the postpartum hormone kinetics.

- by Dirk Fokkema and +1
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- Life Sciences, Anxiety, Startle Reflex, Progesterone

Astroglia and steroid hormones such as estrogen and progesterone regulate cell growth, function, and protection in the central nervous system (CNS). It appears that astrocytes and steroids act in concert to promote cell survival under pathological conditions. With respect to the role of mitochondrial fusion and fission in energy metabolism, apoptosis, and proliferation, astrocyte mitochondria resemble a perfect intracellular target for steroids to modulate these processes, thereby promoting cell vitality after damage. We have studied the effects of estrogen and progesterone on cell viability in comparison with mitochondrial fusion and fission gene transcription in primary cortical astrocytes from female and male mouse brains. Estrogen-and progesterone-treated female astrocytes demonstrated an increase in cell number and proliferation marker accompanied by an upregulation of fusion and fission gene transcription, which were apparently balancing pro-and anti-apoptotic processes. On the other hand, male astrocytes exhibited no change in cell number after estrogen treatment, but a decrease after progesterone administration. This could be the consequence of stimulated apoptosis in male astrocytes by both steroids, which was counterbalanced by an increased proliferation in the presence of estrogen, whereas it was strengthened in the presence of progesterone. Supportively, estrogen promoted and progesterone decreased the transcription of fusion and fission genes. We suggest that estrogen and progesterone affect mitochondrial fusion and fission gene transcription in cortical astrocytes in a gender-specific way, thereby influencing mitochondrial function differently in both genders. Thus, interaction of sex steroids with mitochondria may represent one possible cause for gender differences in cellular pathology in the CNS.

- by Cordian Beyer
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- Mitochondria, Molecular endocrinology, Energy Metabolism, Progesterone

OBJECTIVES To investigate the efficacy and tolerability of the oral hormone replacement therapy (HRT) containing 1 mg estradiol (E2) plus 2 mg drospirenone (DRSP) in Thai women with postmenopausal symptoms. MATERIAL AND METHOD Fifty-five Thai women with postmenopausal symptoms participated in this multicenter, open-label, non-comparative Phase IV study. The primary endpoint was the reduction of hot flushes after 12 weeks of treatment. Secondary endpoints included changes infrequency and intensity of menopausal symptoms as well as safety assessments after 4, 8, and 12 weeks of treatment. RESULTS Treatment with 1 mg E2 plus 2 mg DRSP reduced the frequency of hot flushes in 94.6% of women at the end of the 12-week treatment period. In 60% of women, the frequency of hot flushes was reduced to 10% or less, compared to baseline findings and 49.1% of women had no remaining hot flushes. Other postmenopausal symptoms such as vaginal dryness, urinary incontinence, dysuria, and dyspareunia imp...

- by Sukanya Chaikittisilpa
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- Thailand, Treatment Outcome, Medicine, Aged

The steroidal hormonal proWles of two sympatric species of desert snails, Sphincterochila zonata and Sphincterochila prophetarium were determined at three ecophysiological-behavior stages, i.e., aestivation, cryptobiosis, and active-feeding phases. Live snails were collected in their natural habitat every month for 13 months, the corpi removed and extracted with organic solvents and the progesterone, testosterone, and estrogen concentrations determined by radioimmunoassay. In both these hermaphroditic species during aestivation, a peak of testosterone followed by a peak of estrogen was observed. During the brief active intervals, minor peaks of estrogen were also observed but these were much lower than seen during aestivation. Although the two species have diVerent microhabitats during aestivation, there was little diVerence in the hormonal proWle, although S. prophetarum had about two fold higher progesterone concentration than S. zonata.

- by laurence shore
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- Physiology, Zoology, Israel, Progesterone

Eight botanical preparations that are commonly used for the treatment of menopausal symptoms were tested for estrogenic activity. Methanol extracts of red clover (Trifolium pratense L.), chasteberry (Vitex agnus-castus L.), and hops (Humulus lupulus L.) showed significant competitive binding to estrogen receptors R (ERR) and (ER ). With cultured Ishikawa (endometrial) cells, red clover and hops exhibited estrogenic activity as indicated by induction of alkaline phosphatase (AP) activity and up-regulation of progesterone receptor (PR) mRNA. Chasteberry also stimulated PR expression, but no induction of AP activity was observed. In S30 breast cancer cells, pS2 (presenelin-2), another estrogen-inducible gene, was up-regulated in the presence of red clover, hops, and chasteberry. Interestingly, extracts of Asian ginseng (Panax ginseng C.A. Meyer) and North American ginseng (Panax quinquefolius L.) induced pS2 mRNA expression in S30 cells, but no significant ER binding affinity, AP induction, or PR expression was noted in Ishikawa cells. Dong quai [Angelica sinensis (Oliv.) Diels] and licorice (Glycyrrhiza glabra L.) showed only weak ER binding and PR and pS2 mRNA induction. Black cohosh [Cimicifuga racemosa (L.) Nutt.] showed no activity in any of the above in vitro assays. Bioassay-guided isolation utilizing ER competitive binding as a monitor and screening using ultrafiltration LC-MS revealed that genistein was the most active component of red clover. Consistent with this observation, genistein was found to be the most effective of four red clover isoflavones tested in the above in vitro assays. Therefore, estrogenic components of plant extracts can be identified using assays for estrogenic activity along with screening and identification of the active components using ultrafiltration LC-MS. These data suggest a potential use for some dietary supplements, ingested by human beings, in the treatment of menopausal symptoms.

- by Joanna xu
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- Engineering, Menopause, Dietary Supplements, Agricultural
- by Franck Mauvais-Jarvis
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- Genetics, Obesity, Risk assessment, Transgenic Mice

Background: In animals, fetal testosterone (fT) plays a central role in organizing the brain and in later social behavior. In humans, exposure to atypical levels of prenatal androgens may result in masculine behavior and ability patterns.... more

- by Simon Baron-Cohen
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- Theory of Mind, Intention, Empathy, Biological Sciences

A case-control study was carried out in Mexico City during 19951997 among women with epithelial ovarian cancer (84 cases) and endometrial cancer (85 cases). The control group consisted of 668 healthy women, matched according to age... more

- by Eduardo Salazar-martínez
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- Cancer, Menopause, Ovarian Cancer, Multivariate Analysis

The abundant production of testicular estrogens and the presence of both ESR1 and ESR2 within boar testes are consistent with a role for estrogen in testicular development and/or function in this species. This study was aimed at determining the role of endogenous estrogen in the regulation of testicular development and function, including the effects on testis weight, histology, sperm production (detergent-resistant spermatid numbers), Sertoli cell numbers, and Leydig cell volume in the boar. Twenty-eight littermate pairs of boars were assigned to groups as follows: 1 boar from each pair was assigned to the control group (vehicle) and the other was assigned to treatment and received 0.1 mg/kg body weight of an aromatase enzyme inhibitor (letrozole) orally each week beginning at 1 week of age until castration at 2, 3, 4, 5, 6, 7, or 8 months of age. Testes were weighed and testicular parenchyma was recovered for determination of histology and detergent-resistant spermatid num-bers, and for determination of Sertoli cell number and Leydig cell volume by staining for GATA-4 and 17-a hydroxylase/17-20 lyase respectively. Testes of aromatase-inhibited boars initially exhibited delayed lumen formation, lower testicular weight, fewer detergentresistant spermatids, and fewer Sertoli cells, but by 7 to 8 months, these boars had recovered and had larger testes, more detergentresistant spermatids per testis, and more Sertoli cells. Total Leydig cell volume increased in proportion to testis size. Reducing endogenous estrogen is consistent with a delay in testicular maturation/puberty that allows for a longer window for the proliferation of Sertoli cells and maturation of Leydig cells, resulting in larger testes and higher spermatid production.

- by Eeman At-taras and +3
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- Andrology, Nitriles, tESTIS, Sertoli cells

This study examined the effects of long-term estrogen treatment (sc 17␤-estradiol minipellets) on learning in C57BL/6J female and male mice using a position discrimination task in the T-maze and a win-stay task (1/8 arms baited) in the radial arm maze (RAM). In addition, hippocampal monoamines and ChAT activity were measured at the end of the study and correlated to task performance. Female sham-operated (gonadally intact) and ovariectomized (OVX) mice were treated with estrogen either for 7 or 40 days before the behavioral tests and intact male mice for 7 days before the behavioral tests. In sham-operated mice the 40-day estrogen treatment improved RAM performance and in OVX mice both the 7-and 40-day estrogen treatments improved the performance in both maze tasks. The estrogen treatment also improved RAM performance in males. The hippocampal ChAT, NA, 5-HIAA, and DOPAC levels were decreased in OVX mice. Furthermore, the effects of estrogen treatment on the levels of hippocampal 5-HT and its metabolite 5-HIAA were different in sham-operated than in OVX mice. We could find no correlation between cognitive measures and neurochemical variables. This study gives new information about the effects of estrogen on learning and hippocampal neurotransmitters in mice. © 2002 Elsevier Science (USA)

- by Jukka Puoliväli
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- Memory, Biological Sciences, Serotonin, Dopamine

Genitourinary syndrome of menopause is a condition comprising the atrophic symptoms and signs women may experience in the vulvovaginal and bladder-urethral areas as a result of the loss of sex steroids that occurs with menopause. It is a progressive condition that does not resolve without treatment and can adversely affect a woman's quality of life. For a variety of reasons, many symptomatic women do not seek treatment and, of those who do, many are unhappy with their options. Additionally, many healthcare providers do not actively screen their menopausal patients for the symptoms of genitourinary syndrome of menopause. In this review, we discuss the clinical presentation of genitourinary syndrome of menopause as well as the treatment guidelines recommended by the major societies engaged in women's health. This is followed by a review of available treatment options that includes both hormonal and non-hormonal therapies. We discuss both the systemic and vaginal estrogen products that have been available for decades and remain important treatment options for patients; however, a major intent of the review is to provide information on the newer, non-estrogen pharmacologic treatment options, in particular oral ospemifene and vaginal prasterone. A discussion of adjunctive therapies such as moisturizers, lubricants, physical therapy/dilators, hyaluronic acid, and laser therapy is included. We also address some of the available data on both the patient and healthcare providers perspectives on treatment, including cost, and touch briefly on the topic of treating women with a history of, or at high risk for, breast cancer.

- by Velja Mijatovic
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- Sexuality, Quality of life, Menopause, Complementary Therapies

Social attachment is vital for human health and welfare. Recent experimental evidence in humans has identified the role of neuroactive hormones, especially the peptide oxytocin, in mediating trusting behaviors. Herein, we test if the endocrinological basis for trust between humans scales up to the country level. Trust pervades nearly every aspect of our daily lives, yet survey data on trust show substantial variation across countries. Using 31 measures of biological, social, and environmental factors associated with hormone levels for a sample of 41 countries, we find that two classes of factors are related to trust: consumption of plant-based estrogens (phytoestrogens), and the presence of environmental conditions that include measures of estrogen-like molecules. Our findings provide preliminary evidence that interpersonal trust at the country level may be related to the intake of neuroactive hormones. #

- by Paul Zak
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- Neuroeconomics, Trust, Economics and Human Biology, Global Health

The occurrence of 28 pharmaceuticals and 10 estrogens has been investigated in waters from the lower part of the Llobregat River basin, where the main intakes for production of drinking water for Barcelona (Spain) are located. Sampling was programmed to monitor the same mass of water on its way down the river to reflect inputs from discharges, contribution from subsidiaries plus persistence of the compounds in the surface water. Analysis of pharmaceuticals was performed by off-line solid phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry with a triple quadrupole analyzer (LC-QqQ-MS/MS). Further analysis by ultra performance liquid chromatography-mass spectrometry with a time-of-flight analyzer (UPLC-TOF-MS) has been proposed and applied for confirmation of several of these target compounds. Estrogens have been analysed by on-line SPE-LC-QqQ-MS/MS. Within the class of pharmaceuticals, 23 out of the 28 compounds investigated, were detected in at least one sample. The highest concentrations were observed for the b-blockers metoprolol (8042 ng L À1 ) and sotalol (788 ng L À1 ), the antibiotic ofloxacin (1904 ng L À1 ), and the lipid regulator gemfibrozil (1014 ng L À1 ). Within the group of estrogens, only estrone and estrone-3-sulfate were positively identified, with concentrations for the former (0.82-5.81 ng L À1 ) close in some locations to those considered sufficient to induce estrogenic effects in aquatic organisms (1-10 ng L À1 ). As a general pattern, concentration of target compounds increases along the river flow as expected.

- by Miren López de Alda
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- Mass Spectrometry, Environmental Monitoring, Rivers, Multidisciplinary

123 unlit PIUSCILLUU wlLil imusca iutjtuwcu uy w4lcly umimuctt -j—t times a day. After a week a stool was collected. While results were pending, she was started on co-trimoxazole (160/800 mg twice a day). All symptoms, including diarrhoea, ceased within a day. The stool contained numerous C cayetanensis oocytes. A second stool taken 2 days after treatment was negative. 4 children (1 with diarrhoea) who had C cayetanensis oocytes identified in their stools were asked to undergo treatment with co-trimoxazole (5/25 mg/kg) for 3 days. All stopped excreting the organism within 3-8 (13) days. This mean is probably skewed high because 1 child did not have stool samples collected over a 4 day period, after which the samples were negative. In a group of similar patients studied during the past 6 months, but who were untreated, the mean duration of oocyst excretion was 14 (9) days.

- by Susan Jobling
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- Pregnancy, tESTIS, Milk, Lancet

Summary. Background: The metabolism of estrogen contained within hormone replacement therapy (HRT) is influenced by the route of administration, and this may affect the risk of venous thromboembolism. Thrombin generation, a global coagulation assay, is a marker of hypercoagulability and is of potential use in determining the thrombotic risk associated with particular HRT administration routes. Objectives: To determine whether any effect of oral and transdermal HRT on thrombin generation is related to the plasma estrogen profile. Methods: We investigated the effects of oral, transdermal and no HRT (controls) in 52, 39 and 52 postmenopausal women, respectively, on thrombin generation, standard markers of thrombophilia, estradiol level and estrone level. Results: All parameters of thrombin generation were altered in women using oral HRT as compared with controls (P < 0.001 for all comparisons). No such differences were found in women using transdermal HRT. Estrone levels correlated with peak thrombin generation (R = 0.451, P < 0.001) in women using oral HRT, but there was no correlation in women using the transdermal route. Conclusions: Thrombin generation is significantly increased in women who use HRT administered by the oral route. This is probably mediated by the hepatic first-pass metabolism of estrone, the main metabolite of oral estradiol, which is avoided by the transdermal route. The effect of estrone on thrombin generation may provide the explanation for the higher thrombotic risk seen in women using oral rather than transdermal HRT.

- by Raj Arya
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- Risk, Thrombin, Haemostasis and Thrombosis, Clinical Sciences

In several animal studies, prolactin has been found to be essential for mammary epithelial development, and its administration has been consistently shown to increase the rate of mammary tumours. High levels of steroid hormones have also been suggested to enhance mammary cancer development. The present study investigates the levels of the following hormones in serum and in tissue homogenates in dogs bearing canine mammary tumours: prolactin (PRL), progesterone (P4), dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T), 17␤-estradiol (17␤-E2) and estrone sulfate (S04E1). Eighty mammary tumours (40 dysplasias and benign and 40 malignant tumours) from 32 female dogs, and 10 normal mammary glands from eight female dogs without history of mammary tumours, were analysed. Prolactin and steroid hormones in serum and tissue homogenates, were analysed by enzyme immunoassays (EIA) techniques, previously validated for this animal species. Levels of prolactin in tissue homogenates were significantly different between malignant and benign mammary tumours (p < 0.01). Serum prolactin concentrations were lower in the control group as compared with the group of dogs with benign tumours and in dogs with malignant tumours (p = 0.01). Serum prolactin levels in dogs with benign lesions were not significantly different than those obtained from dogs with malignant tumours. Levels of steroid hormones were significantly higher in malignant tumours compared with the benign tumours and normal mammary glands (p < 0.01) both in serum and homogenate determinations.

- by Felisbina Queiroga
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- Animal Studies, Dogs, Prolactin, Androgens

To better understand factors contributing to behavioral development, we studied patients with Turner syndrome (TS), a disorder typically marked by prenatal onset of ovarian dysfunction. We compared girls and women (ages 12 and up) with TS (n = 21) to matched controls (n = 21) in cognitive and motor skills, as well as sex-typed personality characteristics and activity preferences. Measures were categorized (based on prior studies) as showing an average male advantage (male-superior measures), female advantage (female-superior measures), or no sex difference (sex-neutral measures). It was hypothesized that, if gonadal function contributes to behavioral development, effects of this deficiency would be more prominent on sexually differentiated than sex-neutral measures and thus that patient-control differences would be most marked for measures that show sex differences. Our findings indicated that TS patients and controls differed more on cognitive and motor domains that show sex differences than on sex-neutral domains. Patients also had more &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;undifferentiated&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; personalities and showed reduced sex-typed interests and activities. Differing experiences, as indexed by interests and activities, did not explain the observed cognitive and motor differences. These results are consistent with a role for ovarian hormones acting on the brain to influence cognitive and behavioral development, although they do not rule out other possible interpretations.

- by Mitchell Geffner and +1
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- Personality, Cognition, Behavior, Adolescent

Introduction. A significant number of postmenopausal women suffer from distressing problems because of urogenital atrophy secondary to the decline in circulating estrogen levels. Treatment with topical hormones may provide relief in such women when used judiciously.Aim. To study the effects of local estrogen with or without local testosterone on urogenital and sexual health in postmenopausal women.Methods. Seventy-five postmenopausal women symptomatic for urogenital atrophy and sexual dysfunction were randomly divided into two study groups and one control group. The women in study group 1 received local estrogen cream; study group 2 received local estrogen and testosterone cream; the control group received nonhormonal lubricant KY gel for 12 weeks. The urogenital and sexuality score, along with the vaginal health index and the vaginal maturation index (VMI), was calculated at the beginning of therapy and 12 weeks later.Main Outcome Measures. Changes in the urogenital and sexuality score along with vaginal health index and VMI.Results. After 12 weeks of therapy, there was a significant improvement in all the four study parameters, which correlated well with the improvement in symptoms of urogenital atrophy and sexual dysfunction in both the study groups as compared with the control group. Improvement in sexuality score was greatest with combined estrogen–androgen therapy. There were no adverse effects and the therapies were well accepted without any compliance issue.Conclusion. Local estrogen either alone or with androgen is highly effective in relieving symptoms of urogenital atrophy and in improving sexual function in symptomatic postmenopausal women. Raghunandan C, Agrawal S, Dubey P, Choudhury M, and Jain A. A comparative study of the effects of local estrogen with or without local testosterone on vulvovaginal and sexual dysfunction in postmenopausal women. J Sex Med 2010;7:1284–1290.

- by Priyanka Dubey
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- Sexual Dysfunction, Postmenopausal Women, Testosterone, Sexual Medicine

We tested the hypothesis that estrogen promotes improvement in urethral function and nerve regeneration following bilateral pudendal nerve crush in ovariectomized female rats. Materials and Methods: A total of 52 female rats underwent ovariectomy 6 days before bilateral pudendal nerve crush. Estrogen and sham capsules were subcutaneously implanted at the time of nerve crush in 16 and 14 of these rats, respectively, while 22 served as unoperated controls. Seven days following nerve crush urethral LPP testing was performed using urethane anesthesia. Spinal cord sections containing motoneurons of Onufrowicz's nucleus were subjected to in situ hybridization to detect the expression of ␤ II tubulin mRNA, a marker of the neuroregenerative response. Results: Mean LPP Ϯ SEM was significantly decreased after pudendal nerve crush in sham treated animals compared to unoperated controls (32.1 Ϯ 6.8 vs 54.4 Ϯ 11.6 cm H 2 O). Rats with an estrogen implant had an LPP of 42.5 Ϯ 16.8 cm H 2 O, which was significantly greater than rats given sham implants and significantly less than unoperated controls. Rats that received an estrogen implant had increased ␤ II tubulin mRNA expression compared to those that received a sham implant.

- by Margot Damaser
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- Urology, Urinary incontinence, The, Nerve Regeneration

In this review we focused on steroid metabolomics in human fetuses and newborns and its role in the physiology and pathophysiology of human pregnancy and subsequent stages of human life, and on the physiological relevance of steroids influencing the nervous systems with regards to their concentrations in the fetus. Steroid profiling provides valuable data for the diagnostics of diseases related to altered steroidogenesis in the fetal and maternal compartments and placenta. We outlined a potential use of steroid metabolomics for the prediction of reproductive disorders, misbalance of hypothalamic-pituitary-adrenal axis, and impaired insulin sensitivity in subsequent stages of human life. A possible role of steroids exhibiting a non-genomic effect in the development of gestational diabetes and in the neuroprotection via negative modulation of AMPA/kainate receptors was also indicated. Increasing progesterone synthesis and catabolism, declining production of tocolytic 5␤-pregnane steroids, and rising activities of steroid sulfotransferases with the approaching term may be of importance in sustaining pregnancy. An increasing trend was demonstrated with advancing gestation toward the production of ketones (and 3␤-hydroxyl groups in the case of 3␣-hydroxy-steroids) was demonstrated in the fetus on the expense of 3␣-hydroxy-, 17␤-hydroxy-, and 20␣-hydroxy-groups weakening in the sequence C17, C3, and C20. There was higher production of active progestogen but lower production of active estrogen and GABAergic steroids with the approaching term. Rising activities of placental CYP19A1 and oxidative isoforms of HSD17B, and of fetal CYP3A7 with advancing gestation may protect the fetus from hyperestrogenization. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

- by Martin Hill
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- Biology, Medicine, Fetal development, Brain
- by Bethanee Schlosser
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- Dermatology, Medicine, Clinical Sciences, Estrogens

Whiteside et al. [S.P. Whiteside, A. Hanson, P.E. Cowell, Hormones and temporal components of speech: sex differences and effects of menstrual cyclicity on speech, Neurosci. Lett. 367 (2004) 44-47] documented effects of menstrual cycle phase and sex on voice onset time (VOT) in naturally timed speech using whole words. VOT is a temporal component of speech that plays an important role in production and perception [L.L. Koenig, Laryngeal factors in voiceless consonant production in men, women, and 5-year-olds, J. Speech Lang. Hear. Res. 43 (2000) 1211-1228; A. Löfqvist, L.L. Koenig, R.S. McGowan, Vocal tract aerodynamics in /aCa/ utterances: measurements, Speech Commun. 16 (1995) 49-66; T.M. Nearey, B. Rochet, Effects of place of articulation and vowel context in VOT production and perception for French and English Stops, J. Int. Phon. Assoc. 24 (1994) 1-18; L.M. Rimol, T. Eichele, K. Hugdahl, The effect of voice-onset-time on dichotic listening with consonant-vowel syllables, Neuropsychologia 44 (2006) 191-196; P.G. Simos, R.L. Diehl, J.I. Breier, M.R. Molis, G. Zouridakis, A.C. Papanicolaou, MEG correlates of categorical perception of a voice onset time continuum in humans, Cogn. Brain Res. 7 (1998) 215-219; S.P. Whiteside, J. Marshall, Developmental trends in voice onset time: some evidence for sex differences, Phonetica 58 (2001) 196-210]. The present study was designed to replicate and expand upon Whiteside et al. [S.P. Whiteside, A. Hanson, P.E. Cowell, Hormones and temporal components of speech: sex differences and effects of menstrual cyclicity on speech, Neurosci. Lett. 367 (2004) 44-47] using a speeded syllable repetition paradigm. VOT measurements for 6 English plosives (/p b t d k g/) were obtained from speech samples of 15 women and 20 men (age 20-25 years). Women were tested across two points in the menstrual cycle (Days 2-5: low estrogen and progesterone/low-EP; Days 18-25: high estrogen and progesterone/high-EP) and men were tested once. Results indicated significant interaction between menstrual cycle phase and voicing (F(1,14)=8.239, P&amp;amp;amp;amp;amp;lt;0.02), whereby the voiced plosives (b, g) displayed shorter VOT values and the voiceless plosives (p, k) displayed longer values at the high-EP phase. Thus, the distinction between the voiced and voiceless plosive was enhanced at high-EP. Significant sex effects (F(1,33)=10.080, P&amp;amp;amp;amp;amp;lt;0.005) were seen with women at high-EP but not the low-EP phase having longer VOT values than men for voiceless plosives. Sex differences between the voiced and voiceless plosives were enhanced at the high-EP phase. This study indicates a role for activational ovarian hormones in regulating temporal features of speech in both whole words and speeded syllable repetition.

- by Sandra Whiteside
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- Psychology, Cognitive Science, Speech Communication, Speech

Study Objective: To compare use of the weekly transdermal contraceptive patch (patch) with daily combined hormonal contraceptive pills (pills) in adolescents. Design: Prospective longitudinal study of adolescents' self-selected (non-randomized) use of the patch or pills. Setting: Urban, university hospital-affiliated, adolescent outpatient clinic. Participants: 13e22-year-old female adolescents seeking hormonal contraception, 40 who chose the patch and 40 who chose pills. Interventions: Data were collected via self-report on paper questionnaires at three-cycle intervals for a total of up to nine cycles. Main Outcome Measures: Method continuation, perfect use, method satisfaction, quality of life, and side effects, including menstrual changes and perceived mood changes. Results: After nine cycles, 38% of patch users and 60% of pill users were still using the method they had chosen at enrollment. There were no significant differences between the groups in self-reported perfect use. No differences were found in quality of life or side effects. Both patch and pill users noted menses became lighter and more predictable and reported decreased depression prior to their menses; only the pill group reported improvement in premenstrual anger. Method satisfaction was similar in both groups except patch users were more likely to report that their contraceptive method improved normal daily activities. Conclusions: Despite apparent advantages of the patch over the pill, adolescents using both methods continue to face challenges achieving perfect and sustained contraceptive use.

- by Pamela Murray
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- Quality of life, Medication Adherence, Menstruation, Adolescent

A huge amount of knowledge about sleep has accumulated during the last 5 decades following the discovery of rapid eye movement (REM) sleep. Nevertheless, there are numerous areas of considerable ignorance. One of these concerns the particularities of sleep in women. Most basic and clinical studies have been performed in male subjects, and only very recently research groups around the world have addressed women's sleep in health and disease. In this review, we summarize the present knowledge on the influence of oestrogens on the brain and on the distinctive changes of sleep across the menstrual cycle, during pregnancy and menopause. In addition, studies in female rodents are reviewed as well as the knowledge on female peculiarities regarding the interactions between sleep regulation and age-related changes in circadian rhythms. We also address specific aspects of sleep loss and sleep disorders in women. Finally, very recent studies on the sociology of sleep are summarized and future directions in the field are discussed.

- by Debra Skene
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- Menstruation, Menopause, Comparative Study, Social behavior

Morus nigra L. is a plant employed as a substitute for the conventional hormonal replacement therapy. This work analyzes the estrogenic effect of M. nigra on the reproductive system and embryonic development of Wistar rats. Female rats were orally treated with M. nigra hydroalcoholic extract (MnHE) at the dose levels of 25, 50, 75, 350 and 700 mg/kg of body weight over 15 days, and continued through mating until the 14th day of gestation. Vaginal smears were performed daily and the body weight of the females was recorded at 5 days intervals. On day 15 of gestation, the females were killed and their kidneys, liver, spleen and ovaries were removed and weighed. The number of implants, resorptions, and live and dead fetuses were evaluated. Histological sections of ovaries, measurement of the height of the uterine epithelium and vaginal smears were performed to assess the estrogenic activity. The results showed that the administration of MnHE did not significantly alter the analyzed variables. Therefore, considering the experimental model used in this study, the data obtained indicate that M. nigra did not exhibit any estrogenic activity nor did exert a toxic effect on the female reproductive system and on the embryonic development of rats.

- by Magda Narciso Leite
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- Reproduction, Embryonic Development, Plant extracts, Estrogens

Effects of ovariectomy and estrogen replacement on attractivity and receptivity in the red-sided garter snake (Thamnophis sirtalis parietalis) Abstract Activation of courtship behavior in male redsided garter snakes, Thamnophis sirtalis parietalis, is independent of the presence of sex steroids. The only consistent treatment that stimulates courtship behavior in males is prolonged exposure to low temperature followed by subsequent warming, mimicking the emergence from hibernation. We investigated whether attractivity and receptivity in female red-sided garter snakes is similarly steroid independent.

- by William Groat
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- Urology, Nonparametric Statistics, Turkey, Immunohistochemistry

Objective: To report the pregnancy outcome of a patient with congenital lipoid adrenal hyperplasia (CLAH) due to an 11-bp deletion of the steroidogenic acute regulatory protein (StAR) gene. Design: Case report. Setting: University-based pediatric endocrinology unit and private IVF clinic. Patient(s): A 24-year-old woman homozygous for a StAR gene deletion, married to a man heterozygous for the same molecular defect. Intervention(s): Ovarian stimulation, oocyte retrieval followed by IVF, blastomere biopsy, preimplantation genetic diagnosis, and additional estrogen support until placental function initiation. Main Outcome Measure(s): Normal pregnancy outcome and delivery of a healthy newborn. Result(s): A female patient with CLAH gave birth to a normal newborn after IVF and preimplantation genetic diagnosis. Conclusion(s): Pregnancy is feasible in patients with StAR gene mutations, provided that extra estrogens are offered until placental function ensues. (Fertil Steril Ò 2009;91:934.e15-e18.

- by Amalia Sertedaki and +2
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- Pregnancy, Fertility and Sterility, Ovulation Induction, Young Adult
- by Marie Budev
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- Adolescent, Clinical Sciences, Estrogens, Young Women

The impact of endocrine disrupting chemical (EDC) exposure on human health is receiving increasingly focused attention. The prototypical EDC bisphenol A (BPA) is an estrogenic highproduction chemical used primarily as a monomer for production of polycarbonate and epoxy resins. It is now well established that there is ubiquitous human exposure to BPA. In the general population exposure to BPA occurs mainly by consumption of contaminated foods and beverages that have contacted epoxy resins or polycarbonate plastics. To test the hypothesis that bioactive BPA was released from polycarbonate bottles used for consumption of water and other beverages, we evaluated whether BPA migrated into water stored in new or used high-quality polycarbonate bottles used by consumers. Using a sensitive and quantitative competitive enzyme-linked immunosorbent assay, BPA was found to migrate from polycarbonate water bottles at rates ranging from 0.20 to 0.79 ng per hour. At room temperature the migration of BPA was independent of whether or not the bottle had been previously used. Exposure to boiling water (100°C) increased the rate of BPA migration by up to 55-fold. The estrogenic bioactivity of the BPA-like immunoreactivity released into the water samples was confirmed using an in vitro assay of rapid estrogen-signaling and neurotoxicity in developing cerebellar neurons. The amounts of BPA found to migrate from polycarbonate drinking bottles should be considered as a contributing source to the total "EDC-burden" to which some individuals are exposed.

- by Jason Chua
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- Chemistry, Genomics, Cerebellum, HPLC

Uterine fibroids are the most common tumours presenting in women. The pathophysiology of fibroids is poorly understood, but disordered angiogenesis and altered smooth muscle cell proliferation are believed to play a role. In this review, current knowledge of both of these processes will be summarized. Differences between 'normal' adjacent myometrium and fibroid tumours within the same uterus are outlined. Exploiting these differences represents one of the best opportunities for the development of medical treatments that target fibroid tissue selectively.

- by Beverley Vollenhoven
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- Progesterone, Smooth muscle, Best practice, Estrogens
- by Jo Rayner
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- Adolescent, Pregnancy, Follow-up studies, Lancet