Increased Estradiol Levels Research Articles

Women with an avoidant attachment style show attenuated estradiol responses to emotionally intimate stimuli

The current study examined neuroendocrine processes associated with emotional intimacy in humans. Despite the importance of this aspect of close relationships, emotional intimacy has received much less attention in neuroendocrine research compared to other aspects of close relationships. In this study, participants viewed movie clips depicting an emotionally intimate parent–child interaction or other, non-intimate themes, and we assessed whether depictions of emotional intimacy increased levels of estradiol, a steroid hormone associated with attachment and caregiving processes. We also examined whether estradiol responses were moderated by individual differences in attachment avoidance, or people's discomfort with closeness and intimacy. Our findings revealed that, among single participants, estradiol levels increased in response to the emotionally intimate clip, but this effect was not observed among currently partnered participants. Moreover, the effects of emotional intimacy were moderated by gender and attachment avoidance, such that highly avoidant women showed smaller increases in estradiol after watching the emotionally intimate clip. Women's avoidance was unrelated to estradiol responses in the non-intimate control conditions, however, suggesting that the effects of avoidance were specific to intimate contexts. Taken together, the current findings contribute to our understanding of the biological bases of attachment and caregiving processes. They also highlight the potential role of estradiol in avoidant individuals' regulation of closeness and intimacy.

Influence of estradiol on functional brain organization for working memory

Working memory is a cognitive function that is affected by aging and disease. To better understand the neural substrates for working memory, the present study examined the influence of estradiol on working memory using functional magnetic resonance imaging. Pre-menopausal women were tested on a verbal n-back task during the early (EF) and late follicular (LF) phases of the menstrual cycle. Although brain activation patterns were similar across the two phases, the most striking pattern that emerged was that estradiol had different associations with the two hemispheres. Increased activation in left frontal circuitry in the LF phase was associated with increased estradiol levels and decrements in working memory performance. In contrast, increased activation in right hemisphere regions in the LF phase was associated with improved task performance. The present study showed that better performance in the LF than the EF phase was associated with a pattern of reduced recruitment of the left-hemisphere and increased recruitment of the right-hemisphere in the LF compared to EF phase. We speculate that estradiol interferes with left-hemisphere working-memory processing in the LF phase, but that recruitment of the right hemisphere can compensate for left-hemisphere interference. This may be related to the proposal that estradiol can reduce cerebral asymmetries by modulating transcallosal communication (Hausmann, 2005).

Does a fall in serum estradiol levels after hCG administration correlate with lower pregnancy rates in patients undergoing fresh art cycles?

Numerous factors have been proposed to correlate with (predict) the success of an ART cycle. One such factor is a rise in estradiol level following hCG. Our objective was to determine whether a fall in serum estradiol levels the day after hCG administration correlated with lower pregnancy rates in fresh, non-donor ART cycles. Retrospective cohort study. Patients undergoing fresh, non-donor embryo transfer cycles between January 1st, 2003 and January 31st, 2010 were included in the study. The primary outcome variable was a post-transfer positive serum hCG. Serum estradiol measurements were drawn the morning after hCG administration (6-11 hours post injection) and compared to the estradiol levels drawn 24 hours earlier. Pregnancy rates of women with falling serum estradiol levels were compared with patients with stable or rising estradiol levels using the chi-square test. Age, baseline FSH, type of pituitary down-regulation, number of days of ovarian stimulation, total ampules of gonadotropin administered, number of oocytes retrieved, and oocyte maturity rate were also compared between the two groups using t-test or chi-square, as appropriate. A total of 1970 cycles met inclusion criteria of which 1877 had the same or increasing serum estradiol levels and 93 had decreasing estradiol levels on the morning after hCG trigger administration. There were no statistically significant differences in demographics between the groups. The pregnancy rate in women with declining estradiol levels after hCG trigger administration did not differ from patients with the same or rising estradiol levels (54% vs 55%, P=0.89). This large cohort study demonstrated that patients with decreasing estradiol levels after hCG trigger administration had similar pregnancy rates as patients with the same or increasing estradiol levels. Obtaining estradiol levels after hCG trigger administration is not useful in predicting pregnancy rates.

Clinical efficacy, safety and tolerability of recombinant human chorionic gonadotropin to restore spermatogenesis and androgen production of hypogonadotropic hypogonadal men

Gonadotropin therapy, in the form of human chorionic gonadotropin (hCG) and/or human menopausal gonadotropin (hMG), is indicated to restore spermatogenesis in hypogonadotropic hypogonadal (hypo-hypo) males. Recently, recombinant hCG (rec-hCG) become available, but data is limited on its effectiveness to treat men with hypo-hypo. We present the clinical efficacy, safety and tolerability of rec-hCG to restore spermatogenesis and androgenic status in a group of men with hypo-hypo seeking fertility. Case-series. Eleven men with adult-onset hypo-hypo seeking fertility restoration was treated with a single weekly subcutaneous (SC) injection of rec-hCG for a minimum of 12 weeks. All patients presented with clinical signs of hypoandrogenism and were azoospermic. Testis biopsy results revealed peritubular fibrosis and maturation arrest. Mean baseline FSH, LH and testosterone levels were 0.46 ± 0.28 mUI/mL, 0.39 ± 0.32 mUI/mL and 41.3 ± 26.9 ng/dL. All but one man restored spermatogenesis after a mean of 12 treatment weeks. Total motile sperm count at the completion of treatment was 39x106 (range 0.0-156.9x106). Testosterone levels at the 12th treatment weeks were 647.5 ± 219.0 ng/dL, respectively. A marked improvement in virilization, libido and erectile function was also observed. Mean combined testis volume increased from 24 mL before to 33 mL posttreatment. Headache, gynecomastia and increased estradiol levels were observed in one man who did not recover spermatogenesis. All patients reported hCG SC self-administration with mininmal or no local side effects and/or discomfort. In our series, a single weekly injection of rec-hCG was effective to restore spermatogenesis and androgen production in most adult-onset hypo-hypo males. In view of the favorable efficacy, safety and tolerability profile of rec-hCG, it may be considered as an alternative to intramuscular urinary-derived hCG administration to hypo-hypo men seeking fertility.

The effects of gonadal hormones on learning and memory in male mammals: A review

Abstract The primary role of the gonadal steroid hormones in mammals is to regulate reproduction and related behaviors; however, both androgens and estrogens are also integrally involved in mediating higher brain function and processes including cognition, neural development, and neural plasticity. In particular, a number of studies show that estradiol modulates dendritic spine growth and synapse density (synaptic plasticity) in the hippocampus of females, and that increased estradiol levels are generally associated with improvements on a variety of learning and memory tasks. While the majority of research has focused on the beneficial effects of estradiol in females, much less attention has been given to testosterone and its effects on learning and memory in males. Similar to estradiol titers in females, testosterone titers in males decline with age, albeit more gradually, and this decline has been correlated with impairment of certain cognitive tasks. Moreover, studies involving both humans and animals indicate that testosterone and its metabolites can augment responding on certain behavioral tasks, depending on the subject’s current hormonal state, the response required, and the stimuli involved (e.g., those involving spatial or nonspatial stimuli). While the exact mechanisms by which testosterone exerts its effects on learning and memory are not fully understood, recent findings suggest that testosterone modulates learning and memory in males through an interaction with the cholinergic system. The overall objective of this review is to discuss studies investigating the role of the gonadal hormones in mediating learning and memory processes in male mammals.

Inhibition of estradiol synthesis attenuates renal injury in male streptozotocin-induced diabetic rats

We previously showed that the male streptozotocin (STZ)-induced diabetic rat exhibits decreased circulating testosterone and increased estradiol levels. While supplementation with dihydrotestosterone is partially renoprotective, the aim of the present study was to examine whether inhibition of estradiol synthesis, by blocking the aromatization of testosterone to estradiol using an aromatase inhibitor, can also prevent diabetes-associated renal injury. The study was performed on male Sprague-Dawley nondiabetic, STZ-induced diabetic, and STZ-induced diabetic rats treated with 0.15 mg/kg of anastrozole, an aromatase inhibitor (Da) for 12 wk. Treatment with anastrozole reduced diabetes-associated increases in plasma estradiol by 39% and increased plasma testosterone levels by 187%. Anastrozole treatment also attenuated urine albumin excretion by 42%, glomerulosclerosis by 30%, tubulointerstitial fibrosis by 32%, along with a decrease in the density of renal cortical CD68-positive cells by 50%, and protein expression of transforming growth factor-β by 20%, collagen type IV by 29%, tumor necrosis factor-α by 28%, and interleukin-6 by 25%. Anastrozole also increased podocin protein expression by 18%. We conclude that blocking estradiol synthesis in male STZ-induced diabetic rats is renoprotective.

Increased Estradiol and Improved Sleep, But Not Hot Flashes, Predict Enhanced Mood during the Menopausal Transition

The antidepressant effect of estrogen in women undergoing the menopause transition is hypothesized to be mediated by central nervous system effects of increasing estradiol on mood or through a pathway involving suppression of hot flashes and associated sleep disturbance. Estrogen therapy (ET) and the hypnotic agent zolpidem were selected as interventions in a three-arm, double-blind, placebo-controlled trial to distinguish the effects of estradiol, sleep, and hot flashes on depression. Women with depressive disorders, hot flashes, and sleep disturbance were randomly assigned to transdermal 17β-estradiol 0.05 mg/d, zolpidem 10 mg/d, or placebo for 8 wk. Changes in serum estradiol, perceived sleep quality, objectively measured sleep, and hot flashes were examined as predictors of depression improvement [Montgomery-Åsberg Depression Rating Scale (MADRS)] using multivariate linear regression. Seventy-two peri/postmenopausal women with depression disorders were randomized to 17β-estradiol (n = 27), zolpidem (n = 31), or placebo (n = 14). There was no significant difference between groups in depression improvement (overall MADRS decrease 11.8 ± 8.6). Increasing estradiol (P = 0.009) and improved sleep quality (P < 0.001) predicted improved mood in adjusted models but reduced hot flashes (P = 0.99) did not. Post hoc subgroup analyses revealed that the therapeutic effect of increasing estradiol levels on mood was seen in perimenopausal (P = 0.009), but not postmenopausal, women. For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels. These results suggest that changes in estradiol and sleep quality, rather than hot flashes, mediate depression during the menopause transition. Therapies targeting insomnia may be valuable in treating menopause-associated depression.

The New Zealand obese mouse model of obesity insulin resistance and poor breeding performance: evaluation of ovarian structure and function

Infertility, associated with oligo/anovulation, increased ovarian volume, numerous follicular cysts, and metabolic disturbances such as obesity and insulin resistance (IR) are characteristics common to polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age. Here, we show that New Zealand obese (NZO) mice display similar metabolic characteristics such as obesity, leptin insensitivity, glucose intolerance, and IR. Importantly, NZO mice are poor breeders; however, the mechanism for this has not been investigated. The aim of this study was to assess the ovarian structure/morphology and sex hormone levels in female NZO and lean C57BL/6J control mice. Twenty-five NZO and twenty female control mice were studied at three different ages (young, adult, and aged). The animals were weighed, an insulin tolerance test was carried out, and blood was collected for measurement of hormone levels. The ovaries were removed for histological analysis. As expected, NZO mice presented higher body weights (P=0.001), increased basal plasma glucose (P=0.007), and insulin levels (P=0.001) as well as IR, compared with control mice. NZO mice showed an increased ovarian volume, reduced numbers of corpora lutea, and higher total follicle numbers (P=0.0001). The number of primordial follicles increased (P=0.02) at the young stage, as well as the amount of atretic follicles (P=0.03), in NZO compared with control mice. NZO mice also displayed reduced plasma LH and increased estradiol levels. In conclusion, NZO mice show a poor breeding performance due to decreased ovulation, increased number of primordial and atretic follicles, and ovarian size. Given that NZO mice are obese, hyperinsulinemic and insulin resistant, they are suitable for investigating pathophysiological mechanisms linking metabolic alterations with reproductive defects.

2295 DOES HEMODILUTION OR DECREASED CIRCULATING ANDROGENS EXPLAIN LOWER PSA CONCENTRATIONS AMONG OBESE MEN? - RESULTS FROM THE REDUCE TRIAL

You have accessJournal of UrologyProstate Cancer: Markers1 Apr 20112295 DOES HEMODILUTION OR DECREASED CIRCULATING ANDROGENS EXPLAIN LOWER PSA CONCENTRATIONS AMONG OBESE MEN? - RESULTS FROM THE REDUCE TRIAL Lionel L. Bañez, Leah Gerber, Daniel M. Moreira, Madeline G. McKeever, Roger Rittmaster, Gerald L. Andriole, and Stephen J. Freedland Lionel L. BañezLionel L. Bañez Durham, NC More articles by this author , Leah GerberLeah Gerber Durham, NC More articles by this author , Daniel M. MoreiraDaniel M. Moreira Durham, NC More articles by this author , Madeline G. McKeeverMadeline G. McKeever Durham, NC More articles by this author , Roger RittmasterRoger Rittmaster Research Triangle Park, NC More articles by this author , Gerald L. AndrioleGerald L. Andriole St. Louis, MO More articles by this author , and Stephen J. FreedlandStephen J. Freedland Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2540AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Lower serum PSA levels in men with increased body mass index (BMI) can potentially be explained by two distinct hypotheses: 1) As obese men have greater plasma volume and PSA levels are expressed as amount of PSA protein per volume of plasma, lower PSA levels among obese men may result from plasma hemodilution. 2) Because PSA production is androgen-driven, increased aromatase activity can lead to increased estradiol levels resulting in decreased circulating androgens and subsequent lower PSA levels. We determined whether PSA concentrations were lower in obese men in the REDUCE chemoprevention trial and whether hemodilution or decreased serum androgens contributed to lower PSA results among these men. METHODS We analyzed data from 7,572 men from the REDUCE trial with available anthropometric information. All participants had a negative prostate biopsy within six months prior to enrollment. Height and weight measurements at baseline were used to calculate BMI and estimate plasma volume. Mean-adjusted baseline PSA values for each BMI category (<25, 25–29.9, 30–34.9, ≥35 kg/m2) were calculated and tested for trend. Associations between PSA values at trial enrollment and plasma volume, serum testosterone, serum dihydrotestosterone (DHT) and BMI were assessed using linear regression models controlling for age, race, family history of CaP and prostate volume. RESULTS Median BMI was 26.9 kg/m2. Over 20% of the men were obese (n=1,547). Mean-adjusted PSA significantly decreased across increasing BMI categories (see table 1). After adjusting for demographic and clinical covariates, plasma volume was found to be inversely associated with PSA levels [β= −0.19; 95% CI (−0.31, −0.08); p=0.001]. Serum testosterone (p=0.89) and serum DHT levels (p=0.12) were not associated with PSA levels. When androgens but not plasma volume were controlled for, BMI was inversely associated with PSA [β= −0.09; 95% CI (−0.15, −0.03); p=0.002]. However, adding plasma volume to the model completely attenuated the association and BMI was no longer associated with PSA (p=0.53). Table 1. Mean-adjusted PSA (95% CI) by BMI Category⁎ less than 25 kg/m2 25-29.9 kg/m2 30-34.9 kg/m2 ≥35 kg/m2 p-trend PSA (ng/ml) 5.70 (5.62,5.79) 5.55 (5.49,5.61) 5.54 (5.44,5.65) 5.41 (5.20,5.62) 0.004 ⁎ adjusted for age, race, family history of prostate cancer, prostate volume, serum testosterone and serum DHT CONCLUSIONS In a large randomized CaP chemoprevention trial, obese men had lower PSA levels which appeared to be explained by hemodilution rather than decreased circulating androgen levels. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e920 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lionel L. Bañez Durham, NC More articles by this author Leah Gerber Durham, NC More articles by this author Daniel M. Moreira Durham, NC More articles by this author Madeline G. McKeever Durham, NC More articles by this author Roger Rittmaster Research Triangle Park, NC More articles by this author Gerald L. Andriole St. Louis, MO More articles by this author Stephen J. Freedland Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

In Vitro Maturation of Oocytes as a Strategy for Fertility Preservation

In vitro fertilization and embryo cryopreservation are regarded as the only established method for the preservation of fertility in female cancer patients. However, a possible delay in the treatment of cancer and exposure to supraphysiologic estrogen levels caused by ovarian stimulation raise concerns for patients and physicians. In vitro maturation avoids treatment delay or exposure to increased estradiol levels associated with in vitro fertilization. In vitro maturation combined with embryo or oocyte vitrification provides options that have been unavailable earlier, such as immature oocyte collection in the luteal phase, for some patients and improves the services provided by a fertility preservation program.

Developmental Programming: Gestational Testosterone Treatment Alters Fetal Ovarian Steroidogenic Gene Expression.

Gestational administration of testosterone increases ovarian androgen receptor protein expression in the fetus and culminates in hypersecretion of luteinizing hormone (LH), hyperestrogenism, persistent ovarian follicles, and oligo-/anovulation in adults. Since steroidogenic potential of the ovary gets established during fetal life, we hypothesized that maternal testosterone excess also alters steroidogenic enzyme expression within the fetal ovine ovary. Pregnant Suffolk ewes were treated with testosterone proprionate (T, 100 mg, twice weekly) or T + the androgen receptor antagonist, flutamide (15 mg/kg BW daily; T+F,) from days 30 to 90 of gestation. Fetal ovaries were collected on d65 (n=4, 5, and 5 for T, T+F, and control [C] groups, respectively) and d90 (n=5, 7, 4) of gestation and snap frozen. Ovarian RNA was subjected to quantitative RT-PCR to measure expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage (Cyp11A1), cytochrome P450 17α-hydroxylase (Cyp17), cytochrome P450 aromatase (Cyp19), 3-β-hydroxysteroid dehydrogenase (3βHSD), 5α-reductase, androgen receptor (AR), estrogen receptors (ER) α and β, and progesterone receptor (PR). Data were analyzed by 2-way ANOVA followed by Bonferroni post-hoc statistical tests. Maternal T had no effect on AR, PR, ERα and ERβ mRNA expression but levels of ERα and AR mRNA were higher in d90 than d65 ovaries. There was no age effect on steroidogenic enzyme expression in control ovaries. Gestational T excess increased (P<0.05) Cyp19 (3.9-fold) and 5α-reductase (1.8-fold) expression in fetal d65 ovaries but decreased (P<0.05) Cyp11A1 expression (3.7 fold) in d90 ovaries. Maternal T excess had no effect on mRNA expression of other steroidogenic enzymes. Co-treatment with the androgen antagonist, flutamide, prevented the T-induced decrease in Cyp11A1 mRNA seen at d90, but not the increase in Cyp19 and 5α-reductase seen in d65 ovaries. Co-treatment with T+F also increased (P<0.05) StAR (2.0-fold) and Cyp11A1 (3.0-fold) expression in d65 ovaries, compared to C and T-treated ovaries. Our findings suggest that the effects of gestational T treatment on Cyp11A1 is mediated by androgenic actions of T and the effects on Cyp19 and 5α-reductase likely via estrogenic actions stemming from aromatization of T to estrogen and that these changes are fetal age dependent. Increased StAR and Cyp11A1 mRNA expression at d65 in the T+F ovaries, but not the T-alone ovaries, indicates that AR is primarily repressing expression of these two transcripts. Additionally, the increased potential for estrogen metabolism (i.e., increased Cyp19) in the d65 T-alone but not T+F ovaries indicates that estrogenic effects can only be manifest if the AR is blocked. Evidence for estrogenic effect is consistent with our recent finding of increased estradiol levels in the fetal blood of day 65 and 90 T-treated fetuses. These studies demonstrate that maternal T treatment alters fetal ovarian steroidogenic gene expression and implicate direct actions of estrogens in addition to androgens in the reprogramming of fetal developmental trajectory leading up to adult reproductive pathologies. Supported by NIH P01 HD44232 (VP). (platform)

Proliferative, structural and molecular features of the Mdx mouse prostate

The prostate is fundamental to the male reproductive process, and the stroma-epithelium interaction has an important role in prostate maintenance. Studies suggest that dystroglycan (DG) plays a role in cancer development in various organs. Thus, the aims of this work were to characterize morphological and proliferative features of the prostatic stroma and epithelium of mdx mice; to verify the immunolocalization of the α and β DG, IGF-1 and laminin α3 receptors; and to relate those structural and molecular events to prostate pathogenesis and to verify the viability of this experimental model in prostate studies. Thirty male mice (mdx and C57BL10/Uni) were divided into control and mdx groups. Samples from the ventral prostate were collected for immunological, Western Blotting, transmission electron microscopy and morphometric analyses. Oestradiol and testosterone measurements were verified. The results showed diminished testosterone and increased oestradiol levels in the mdx group. Atrophied cells and hypertrophied stroma were seen in the mdx mice. Weak α and β DG and laminin α3 immunolocalization was demonstrated in the mdx group. Intense insulin-like growth factor receptor α-1 (IGFRα-1) localization was identified in the mdx animals. Thus, mdx animals showed changes in molecular and structural integrity and proliferation signals, leading to glandular homoeostasis imbalance, and compromise of prostate function. Also, the steroid hormone imbalance and the increased IGF-1 receptor level detected in mdx mice could be considered as a crucial factor in the pathogenesis of prostatic disorders.

Asian ethnicity in anonymous oocyte donors is associated with increased estradiol levels but comparable recipient pregnancy rates compared with Caucasians

To determine if differences exist in ovarian response and pregnancy rates between Asian and Caucasian donors. Retrospective cohort study. University-based clinic. Anonymous oocyte donors of self-reported Asian (n=63) or Caucasian (n=156) ethnicity who began ovarian stimulation between February 2000 and March 2008 and their matched recipients. None. Recipient pregnancy rates and oocyte donor ovarian responsiveness. Baseline characteristics were similar between Asian and Caucasian donors. Asian donors had peak serum estradiol levels that were 23% higher than their Caucasian counterparts (3715±220 vs. 3013±114 pg/mL). Adjusted estradiol levels per follicle measured and per oocyte retrieved were elevated in Asian donors (17% and 23% higher, respectively), and these differences were unchanged after adjusting for body mass index. No differences were noted in implantation rates (47.4% vs. 40.9%), clinical pregnancy rates (60.3% vs. 62.4%), or live-birth rates (55.5% vs. 59.9%) achieved using Asian vs. Caucasian oocyte donors. In contrast to autologous fresh in vitro fertilization cycles, Asian ethnicity is not associated with a lower pregnancy rate in recipient women using controlled hormone replacement when anonymous donor oocytes are used. Asian donors achieved statistically significantly higher serum estradiol levels during gonadotropin stimulation, suggesting an ethnic difference in steroid production and/or metabolism.

Legacy for Young Men: PFAAs and Human Sperm

Vol. 117, No. 6 EnvironewsOpen AccessLegacy for Young Men: PFAAs and Human Sperm Cynthia Washam Cynthia Washam Search for more papers by this author Published:1 June 2009https://doi.org/10.1289/ehp.117-a256bAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Recent studies suggest that men’s capacity for sperm production may be harmed by toxic exposures in both fetal and later life. Among the potential chemical culprits are the perfluoroalkyl acids (PFAAs), highly persistent degradation products of the polyfluorinated compounds used in products including nonstick cookware and water-resistant coatings for carpeting, clothing, and other textiles. Findings from a new Danish study suggest that exposure to PFAAs may help account for the otherwise unexplained poor semen quality observed in many young men today [EHP117:923–927; Joensen et al.].Studies in the 1990s found that PFAAs diminished testosterone levels and increased estradiol levels in male rats. In human studies, men have appeared to have higher serum PFAA concentrations than have even higher levels compared with those of older men. Young men may therefore be at higher risk for any potential adverse effects posed by these chemicals.Inspired by such observations, the Danish team designed what they believe is the first study of the effects of PFAAs on sperm quality in humans. They focused their investigation on perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) because of these compounds’ prevalence, their long half-lives, and existing evidence that they act as endocrine disruptors. The subjects included 105 young men from the general population who had provided semen samples in 2003 as part of Denmark’s compulsory military draft examination. These men had the highest and lowest testosterone counts of 546 potential subjects considered. Serum levels of PFOA and PFOS were combined to give each man a PFAA score. These scores were used to classify subjects into low-, intermediate-, and high-PFAA groups.Sperm quality varied markedly among all three groups. Compared with the low- and intermediate-PFAA groups, men in the high-PFAA group showed significantly poorer sperm quality in terms of both percentage and total numbers of morphologically normal sperm. Ejaculate from men in the low-PFAA group had a median count of 15.5 million normal sperm compared with 10 million and 6.2 million normal sperm in the intermediate- and high-PFAA groups, respectively. Average sperm concentration and motility also were lower in the high-PFAA group, but not significantly so. PFAAs were not inversely associated with testosterone levels, a finding that was contrary to expectations based on previous animal research.The researchers note that humans and wildlife will be exposed to persistent PFAAs for years to come. They speculate that high exposures to PFAAs may be contributing to low semen quality and subfertility reported in other studies. However, they caution, results from this preliminary study should be corroborated in larger studies.Men with the highest PFAA scores also had the highest percentages and numbers of morphologically abnormal sperm.FiguresReferencesRelatedDetails Vol. 117, No. 6 June 2009Metrics About Article Metrics Publication History Originally published1 June 2009Published in print1 June 2009 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Elevated Estradiol Plasma Levels in Women with Restless Legs during Pregnancy

Pregnant women have an increased risk of experiencing restless legs syndrome (RLS). Aim of this study was to elucidate the relationship between pregnancy-related hormonal and metabolic changes and RLS symptomatology. Blood measurements and overnight polysomnography were performed during the third trimester of pregnancy and again 3 months after delivery. We investigated blood hormonal levels (estradiol, prolactin, progesterone, testosterone, follicle-stimulating hormone [FSH], luteinizing hormone [LH], iron, ferritin, hemoglobin) and polysomnographic sleep parameters. Subjective sleep quality and RLS symptoms were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the International RLS study group (IRLSSG) rating scale. Sleep laboratory. Ten pregnant women fulfilling the IRLSSG criteria for RLS diagnosis and 9 pregnant healthy controls underwent the protocol. N/A. Women with RLS showed higher levels of estradiol during pregnancy compared to controls (34,211 +/- 6397 pg/mL vs. 25,475 +/- 7990 pg/mL, P<0.05). Patients also showed more periodic limb movements (PLMs) before and after delivery, particularly during sleep stage 1 and wakefulness (P<0.05). PLMs decreased postpartum in subjects with RLS only (P<0.05); sleep efficiency increased in women without RLS and remained unchanged in patients (P<0.05). No significant differences were found between groups before or after delivery in plasma concentrations of prolactin, progesterone, testosterone, FSH, LH, iron, ferritin or hemoglobin. RLS in pregnant women goes along with transiently increased estradiol levels and PLM indices suggesting that estrogens play a pathophysiological role for triggering RLS symptoms during pregnancy.

Estrogen-replacement therapy promotes angiogenesis after acute myocardial infarction by enhancing SDF-1 and estrogen receptor expression

Although observational data suggest that estrogen-replacement therapy (ERT) may confer cardioprotection, estrogen's putative protective role has been challenged. This study investigated the effect of estradiol on peripheral blood stem cells and angiogenesis after acute myocardial infarction and potential mechanisms of estrogen's pro-angiogenesis effect. An ovariectomized rat acute myocardial infarction (AMI) model was established by ligation of the left anterior descending coronary followed by delivery of varying doses of estradiol benzoate. Serum estradiol levels were assessed by radioimmunoassay. Expression levels of α and β estrogen receptor (ER) proteins in myocardium were determined by Western blotting. CD34 + cells in myocardium at 24 h and in peripheral blood 1, 3 and 7 days after AMI were measured by immunohistochemistry and flow cytometry, respectively. Stromal cell-derived factor (SDF-1) expression and capillary density in myocardium were detected by immunohistochemistry. In ovariectomized rats, ERT significantly increased estradiol levels and up-regulated ER-α and -β expression relative to untreated controls. Furthermore, ERT elevated the number of CD34 + cells in peripheral blood and myocardium, increased SDF-1 expression, and increased capillary density 4 weeks after AMI. Therefore, our data suggest that estrogen can promote the mobilization and homing of bone marrow stem cells into the myocardium and can increase capillary density in myocardium after AMI. The pro-angiogenesis effect of ERT is associated with enhanced SDF-1 and ER-α and -β expression in myocardium after AMI.

Surgical evaluation of endometriosis after IVF

Surgical evaluation of endometriosis after IVF

Oestradiol concentration as a predictor of ovarian response in FSH stimulated ewe-lambs

We investigated the prediction of ovarian response using oestradiol determination, in 37 gonadotrophin stimulated Karagouniko ewe-lambs. Ovarian stimulation was induced by serial FSH administrations, and laparoscopic follicular aspiration (OPU) was conducted 12 h after the last FSH injection. Oestradiol concentration was assessed in six blood samples collected prior to each FSH injection and in one sample collected prior to follicular aspiration. According to ovarian response, ewe-lambs were allotted in three groups: good, L1 ( n = 17); moderate, L2 ( n = 10); and poor, L3 ( n = 10). Based on the data obtained from 28 (75%) randomly selected animals, a statistical model was designed and tested on the remaining nine lambs for its ability to predict the probability of good ovarian response. From the 2nd sample, oestradiol concentration was constantly higher in group L1 in comparison with L3 lambs (all p-values for the contrasts were ≤0.02), while this difference between L1 and L2 lambs was significant only in the 6th and 7th sample (both p < 0.005). Using as criterion the oestradiol concentration of the 6th sample, the statistical model predicted all lambs that did not belong to group L1 and three of four lambs that belonged to group L1. Our results indicate that the moderate- and poor-donors could be safely predicted on the basis of oestradiol concentration 12 h prior to the scheduled follicular aspiration. Moreover, poor-donors could be identified—and rejected from further manipulations—on the basis of their inability to exhibit increased oestradiol levels in response to gonadotrophin stimulus.

P-105: Elevated serum progesterone/estradiol ratio and progesterone level during in vitro fertilization are negative predictors of cycle outcome

Premature luteinization, as determined by elevated progesterone (P) levels in the late follicular phase, has been associated with lower oocyte recovery, lower pregnancy rates, and increased miscarriage rates in IVF cycles. While some reports have demonstrated a decrease in pregnancy rates with P levels ≥ 0.9-1.0 ng/mL on the day of HCG administration, others have not confirmed this adverse effect. Like estradiol (E2), elevations of P might simply reflect a favorable ovarian response to gonadotropin stimulation. Thus, it has been postulated that progesterone/estradiol (P/E2) ratios might better reflect the existence of premature luteinization than P levels alone. This study evaluates the association of P levels and P/E2 ratios (measured on the day of hCG administration) with IVF cycle outcome. All IVF cycles performed at a university-affiliated institution between January 2002 and December 2003 were reviewed. The main outcome variables measured included the number of oocytes retrieved and fertilized, clinical pregnancy rates (PR) and live birth rates (LB). There were 348 IVF cycles among 261 patients. Standard gonadotropin stimulation was performed, with pituitary suppression achieved using GnRH agonist or antagonist. We tested the association of P levels and P/E2 ratios with outcome variables at different cut off values. P/E2 ratio was defined as [P (ng/mL) / E2 (pg/mL)] x 1000. χ2 and Student’s t test analyses were performed using SYSTAT software. There were 199 cycles which resulted in clinical pregnancies. The mean P level was equivalent in the pregnant and the non-pregnant group (1.4 vs 1.4 ng/mL, respectively, p=0.5). There were no differences in the age and basal FSH levels between groups with different P values and P/E2 ratios. When P > 1.5 ng/mL, there was a significantly higher peak E2 level, and greater number of oocytes retrieved and fertilized. However, a significant decrease in PR was seen in this group (50.4 % when P > 1.5 ng/mL vs. 61.7% when P ≤ 1.5 ng/mL, p=0.05), while the LBR remained similar (42.7% when P > 1.5 ng/mL vs 45.6% when P ≤ 1.5 ng/mL, p=0.6). With P/E2 ratio >1.0, significantly lower numbers of oocytes were retrieved and fertilized, and both the PR and LBR were significantly decreased. (Table 1, Figure 1).Tabled 1View Large Image Figure ViewerDownload (PPT) P/E2 ratio > 1.0 is associated with progressively lower clinical pregnancy and live birth rates. While progesterone level > 1.5 ng/mL is correlated with increased estradiol level and increased numbers of retrieved and fertilized oocytes, it is also associated with a decreased clinical pregnancy rate. These data in combination have potential utility in helping to select the day of HCG administration.

Effect of Hormone Replacement Therapy on Plasma Lipoproteins and Apolipoproteins, Endothelial Function and Myocardial Perfusion in Postmenopausal Women with Estrogen Receptor-α IVS1–397 C/C Genotype and Established Coronary Artery Disease

Effect of hormone replacement (HRT) therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-α (ER-α) IVS1–397 C/C genotype and established coronary artery disease. Background/Aims: Associations between various ER-α polymorphisms and clinical phenotypes have been studied, including lipid levels and coronary atherosclerosis. We studied 48 postmenopausal women to determine the effect of ER-α IVS1–397 polymorphism on the response to treatment with HRT. Methods: The study had a randomized, double-blind, placebo-controlled and crossover design. Patients were divided into two groups according to ER-α IVS1–397 polymorphism: CC genotype (n = 9); CT or TT genotype (n = 39). HRT was given continuously for 4 weeks, with 4-week washout periods between the treatment periods. Brachial artery Doppler and Tl-201 scintigraphy were performed at the end of each treatment period. Results: HRT lowered total cholesterol, LDL-c and Apo-B levels from baseline values (all p < 0.05) and to a similar degree in CC and CT/TT genotype patients. HRT increased estradiol, HDL-c and Apo A-1 levels relative to baseline values, but to a greater degree in CC patients (p = 0.04, 0.05 and 0.04 by ANOVA, respectively). HRT increased peak forearm blood flow, brachial artery diameter during reactive hyperemia and endothelium-dependent dilation in both groups, but to a greater degree in CC patients (p = 0.03, 0.03 and 0.04 by ANOVA, respectively). Summed stress and rest scores were also more markedly reduced in CC patients (p = 0.04 and 0.05, respectively). The increase in estradiol levels was strongly correlated with the improvement in endothelium-dependent dilation (r = 0.66, p < 0.01), which in turn showed negative correlation with summed stress (r = –0.62, p < 0.01) and rest scores (r = –0.52, p < 0.05) in the CC genotype group. Conclusion: These data suggest that the improvement in endothelium-dependent dilation and the reduction in perfusion abnormalities by increasing estradiol levels with HRT in postmenopausal women with coronary artery disease may differ with respect to different genotypes, the effect being more prominent in those patients with ER-α IVS1–397 CC genotype.