Estradiol In Postmenopausal Women Research Articles

Abstract PS10-03: Impact of Baseline Oestradiol and Testosterone on the Preventive Effect of Anastrozole

Abstract It is well known that serum levels of oestradiol and testosterone, esp free hormone levels, influence the risk of developing breast cancer in postmenopausal women (Thomas et al 1997, Hankinson et al 1998, Kaaks et al 2005, Tin Tin et al 2021). However very little is known about how these hormone levels influence the effectiveness of aromatase inhibitors. In the IBIS-II Prevention Trial we compared anastrozole to placebo in 3864 women at high risk of breast cancer (Cuzick et al 2020). Of these women 3644 (94.3%) had a baseline blood sample. In those with a valid blood sample, 72 in the anastrozole arm and 142 in the placebo arm developed breast cancer (including DCIS) after 12.9 years of follow up (OR = 0.49, 95% CI 0.37–0.66 P< 0.0001). For each case two controls were selected, matched on age, treatment arm and follow up longer than the matching case. In these women oestradiol (E2), testosterone (Testo) and SHBG were measured by liquid chromatography – tandem mass spectroscopy, and E2/SHBG and Testo/SHBG ratios were computed to approximate free hormone levels, and analysed in quartiles. Hormone replacement therapy was not allowed during the trial, and women with use within 3 months prior to entry or outlier hormone values were excluded from these analyses. In the placebo arm higher levels of both of these ratios were associated with a higher breast cancer rate (OR per quartile 1.25 (1.04-1.59), P=0.018) for E2/SHBG and (OR per quartile 1.22 (1.02-1.47), P = 0.032) for Testo/SHBG), whereas no significant effect was seen in the anastrozole arm (OR = 1.05 (0.81-1.37), and 1.16 (0.90-1.49), resp) (Table). Neither treatment interaction was significant. Absolute numbers of cases were similar between the anastrozole and placebo arms in the lowest quartile of E2/SHBG (18 anastrozole, 22 placebo), but higher numbers were seen in the placebo arm for the other quartiles. Similar results were seen for testo/SHBG, and supportive, but weaker results were seen for these two hormones without an SHBG adjustment, SHBG and BMI at entry. Adjusting for other risk factors had no influence on these findings. Effect sizes were similar during the 5 year treatment period and thereafter. There were too few ER negative cases to compare results by receptor status. Vasomotor side effects were higher with increasing E2/SHBG levels in both arms, but no other hormone showed an effect, and no hormone level was significantly associated with gynaecologic or musculoskeletal side effects. As aromatase inhibitors effectively eliminate the production of oestradiol in postmenopausal women, these results suggest they may be more effective in postmenopausal women with high oestradiol or testosterone levels, and raise questions about their value in women in the lower quartile of serum levels for these hormones for prevention and possibly adjuvant treatment. Table: Risk of breast cancer by quartiles of the oestradiol/SHBG in ratio high risk women treated with anastrozole or placebo. Citation Format: Jack Cuzick, Kim Chu, Brian Keevil, Antony Howell, Bernardo Bonanni, Evans Gareth, Kaija Holli, Sibylle Loibl, Nicholas Zdenkowski, Steven Cummings, Mitch Dowsett. Impact of Baseline Oestradiol and Testosterone on the Preventive Effect of Anastrozole [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-03.

Alternative dosing regimen of exemestane in a randomized presurgical trial: the role of obesity in biomarker modulation

In a 3-arm presurgical trial, four-six weeks exemestane 25 mg three times/week (TIW) was non-inferior to 25 mg/day (QD) in suppressing circulating estradiol in postmenopausal women with ER-positive breast cancer. Since obesity may decrease exemestane efficacy, we analyzed changes in sex steroids, adipokines, Ki-67, and drug levels in relation to obesity. Postmenopausal women with early-stage ER-positive breast cancer were randomized to either exemestane 25 mg QD (n = 57), 25 mg TIW (n = 57), or 25 mg/week (QW, n = 62) for 4–6 weeks before breast surgery. Serum and tissue pre- and post-treatment biomarkers were stratified by body mass index (BMI)< or ≥30 kg/m2. Post-treatment median exemestane and 17-OH exemestane levels were 5–6 times higher in the QD arm compared to the TIW arm. For obese women, TIW maintained comparable reductions to QD in systemic estradiol levels, although the reduction in estrone was less with the TIW regimen. There was less suppression of SHBG with the TIW versus the QD dose schedule in obese women which should result in less systemic bioavailable estrogens. Metabolically, the effect of the TIW regimen was similar to the QD regimen for obese women in terms of leptin suppression and increase in the adiponectin-leptin ratio. Reduction in tissue Ki-67 was less for obese women on the TIW regimen than QD, although changes were similar for non-obese women. Our findings suggest that TIW exemestane should be explored further for primary cancer prevention in both normal weight and obese cohorts.

SAT015 Improving The Quality Of Disease Biomarker Measurements In Patient Care And Research-CDC's Clinical Standardization Programs

Abstract Disclosure: O. Sugahara: None. T. Buchannan: None. U. Danilenko: None. A. Ribera: None. L. Collins: None. N. Vasquez: None. K. Dahya: None. F. Pokuah: None. H. Zhou: None. L. Zhang: None. A.N. Lyle: None. H.W. Vesper: None. High-quality disease biomarker tests are critical for the correct diagnosis and treatment of patients, accurate interpretation of research data, and effective use of research findings in health care. CDC’s Clinical Standardization Programs (CDC CSP) assist researchers and laboratories with assessing and improving the analytical performance of biomarker tests performed in patient care, public health, and research. CDC CSP develops and applies reference methods, materials, and protocols to consistently calibrate biomarker tests across instruments and laboratories and to assess and improve other analytical performance characteristics, such as analytical specificity. CDC CSP works with test manufacturers and laboratories operating in-house developed tests to correctly calibrate tests. Additional programs help clinical and research laboratories monitor the accuracy and reliability of tests over time. Furthermore, CDC CSP collaborates with researchers on the development of reference intervals and on using new and emerging biomarkers in patient care and public health. CDC CSP provides comprehensive programs for traditional blood lipids, testosterone, estradiol, vitamin D, and free thyroxine. Programs for free testosterone, parathyroid hormones, apolipoproteins, and angiotensin peptides will be available soon. CDC CSP collaborated with members of the Partnership for the Accurate Testing of Hormones (PATH) and established reference intervals for testosterone in men. CDC CSP is currently working to develop reference intervals for testosterone in women and for estradiol in postmenopausal women. A CDC CSP interlaboratory study on free thyroxine measurements showed high variability in calibration accuracy among free thyroxine assays. CDC CSP is using its reference methods and materials to minimize this variability. It is anticipated that assay recalibration may change measurement values for some tests by up to 50%. CDC CSP is working with PATH and the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) to educate stakeholders about the upcoming change in free thyroxine measurements. Presentation: Saturday, June 17, 2023

The Efficacy of Nigella sativa L. and Curcumin Nanomicelle Alone or Together on Lipid Profile, Glycemic Control Indices, and Serum 17-Β Estradiol in Postmenopausal Women.

Menopause is a condition for metabolic disorders. This study aimed to evaluate the effect of Nigella sativa (NS), curcumin nanomicelle (CN), lipid profile, glycemic status and 17-β estradiol (ES) levels in postmenopausal women. Triple-blind randomized clinical trial was conducted on 120 postmenopausal women. Participants were randomly assigned to four groups: 1) NS capsule 1000 mg and CN placebo, 2) 80 mg CN capsule and NS placebo, 3) both NS and CN capsules and 4) NS and CN placebo. Participants received a single dose daily for 6 months. The serum lipid profile, glycemic control biomarkers, and ES were measured pre-and post-intervention using biochemical methods. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, fasting blood sugar (FBS), fasting insulin (FI), insulin resistance (IR), and ES showed significant improvement in NS group. CN significantly reduced TC, FI, and IR, and significantly increased ES. The combination of NS-CN significantly decreased TC, LDL, FI, and IR, and increased HDL and ES. The comparison of the studied with the placebo groups showed that these changes were significant in glycemic indices and NS significantly increased estrogen. NS, CN and NS-CN improved lipid profiles, blood sugar, and hormone levels. However, this improvement was significant in glycemic indices and estrogen levels compared to the placebo group. No superiority of combined NS-CN over NS or CN was found in this trial.

Efficacy of Alternative Dose Regimens of Exemestane in Postmenopausal Women With Stage 0 to II Estrogen Receptor–Positive Breast Cancer

Successful therapeutic cancer prevention requires definition of the minimal effective dose. Aromatase inhibitors decrease breast cancer incidence in high-risk women, but use in prevention and compliance in adjuvant settings are hampered by adverse events. To compare the noninferiority percentage change of estradiol in postmenopausal women with estrogen receptor-positive breast cancer given exemestane, 25 mg, 3 times weekly or once weekly vs a standard daily dose with a noninferiority margin of -6%. This multicenter, presurgical, double-blind phase 2b randomized clinical trial evaluated 2 alternative dosing schedules of exemestane. Postmenopausal women with estrogen receptor-positive breast cancer who were candidates for breast surgery were screened from February 1, 2017, to August 31, 2019. Blood samples were collected at baseline and final visit; tissue biomarker changes were assessed from diagnostic biopsy and surgical specimen. Biomarkers were measured in different laboratories between April 2020 and December 2021. Exemestane, 25 mg, once daily, 3 times weekly, or once weekly for 4 to 6 weeks before surgery. Serum estradiol concentrations were measured by solid-phase extraction followed by liquid chromatography-tandem mass spectrometry detection. Toxic effects were evaluated using the National Cancer Institute terminology criteria, and Ki-67 was assessed by immunohistochemistry. A total of 180 women were randomized into 1 of the 3 arms; median (IQR) age was 66 (60-71) years, 63 (60-69) years, and 65 (61-70) years in the once-daily, 3-times-weekly, and once-weekly arms, respectively. In the intention-to-treat population (n = 171), the least square mean percentage change of serum estradiol was -89%, -85%, and -60% for exemestane once daily (n = 55), 3 times weekly (n = 56), and once weekly (n = 60), respectively. The difference in estradiol percentage change between the once-daily and 3-times-weekly arms was -3.6% (P for noninferiority = .37), whereas in compliant participants (n = 153), it was 2.0% (97.5% lower confidence limit, -5.6%; P for noninferiority = .02). Among secondary end points, Ki-67 and progesterone receptor were reduced in all arms, with median absolute percentage changes of -7.5%, -5.0%, and -4.0% for Ki-67 in the once-daily, 3-times-weekly, and once-weekly arms, respectively (once daily vs 3 times weekly, P = .31; once daily vs once weekly, P = .06), and -17.0%, -9.0%, and -7.0% for progesterone receptor, respectively. Sex hormone-binding globulin and high-density lipoprotein cholesterol had a better profile among participants in the 3-times-weekly arm compared with once-daily arm. Adverse events were similar in all arms. In this randomized clinical trial, exemestane, 25 mg, given 3 times weekly in compliant patients was noninferior to the once-daily dosage in decreasing serum estradiol. This new schedule should be further studied in prevention studies and in women who do not tolerate the daily dose in the adjuvant setting. ClinicalTrials.gov Identifier: NCT02598557; EudraCT: 2015-005063-16.

Association between aldehyde exposure and sex steroid hormones among adults.

Exogenous and endogenous exposure to aldehydes is seen worldwide. Aldehydes are closely associated with human diseases, especially reproductive toxicity. However, the effect of aldehyde exposure on sex steroid hormones among adults remains uninvestigated. A total of 851 participants aged over 18years were included in this cross-sectional analysis based on data from National Health and Nutrition Examination Survey (NHANES) 2013-2014. Serum aldehyde concentrations were quantified following an automated analytical method. Sex steroid hormones including total testosterone, estradiol, and sex hormone binding globulin (SHBG) were detected. Multivariate linear regression models, forest plots, generalized additive model (GAM), and smooth curve fitting analysis were used to assess the associations between quartiles of aldehydes and sex steroid hormones levels after adjusting for potential confounders. Butyraldehyde and propanaldehyde were found to be negatively associated with estradiol and SHBG in females and males, respectively. β values with 95% confidence intervals (95% CIs) were - 20.59 (- 38.30 to - 2.88) for Q2 vs. Q1 of butyraldehyde and - 8.13 (- 14.92 to - 1.33) and - 7.79 (- 14.91 to - 0.67) for Q2 vs. Q1 and Q4 vs. Q1 of propanaldehyde. No significant associations were observed between other aldehydes and sex hormones. In premenopausal women, isopentanaldehyde was inversely associated with serum total testosterone levels (Q4 vs. Q1: OR = - 7.95, 95% CI: - 15.62 to - 0.27), whereas propanaldehyde was positively associated with serum estradiol concentration (Q3 vs. Q1: β = 28.88, 95% CI: 0.83 to 56.94). Compared with Q1, Q3 of isopentanaldehyde was associated with 3.53pg/mL higher concentration of estradiol in postmenopausal women (β = 3.53, 95% CI: 0.08 to 6.97). Moreover, in males under 40years, butyraldehyde and heptanaldehyde were inversely proportional to total testosterone levels and heptanaldehyde and butyraldehyde were negatively associated with estradiol and SHBG. Decreased total testosterone, elevated estradiol, and decreased SHBG levels were found in higher quartiles of benzaldehyde, hexanaldehyde and isopentanaldehyde, and propanaldehyde, respectively, in males aged over 60years. In male participants aged 40-60years, only hexanaldehyde was observed to be correlated with higher serum estradiol levels. In conclusion, our current research presented the association between six serum aldehydes and sex hormones. Of note, stratification analyses were conducted in participants with different menopausal statuses and age among males and females. Sex- and age-specific effect of aldehyde exposure on alterations in sex hormone levels were observed. Further studies are warranted to confirm the causal relationship and explore the underlying mechanisms.

Correlation of Body Mass Index with Lipid Profile and Estradiol in Postmenopausal Women with Type 2 Diabetes Mellitus

Correlation of Body Mass Index with Lipid Profile and Estradiol in Postmenopausal Women with Type 2 Diabetes Mellitus

Workshop on normal reference ranges for estradiol in postmenopausal women, September 2019, Chicago, Illinois.

The North American Menopause Society (NAMS) organized the Workshop on Normal Ranges for Estradiol in Postmenopausal Women from September 23 to 24, 2019, in Chicago, Illinois. The aim of the workshop was to review existing analytical methodologies for measuring estradiol in postmenopausal women and to assess existing data and study cohorts of postmenopausal women for their suitability to establish normal postmenopausal ranges. The anticipated outcome of the workshop was to develop recommendations for establishing normal ranges generated with a standardized and certified assay that could be adopted by clinical and research communities. The attendees determined that the term reference range was a better descriptor than normal range for estradiol measurements in postmenopausal women. Twenty-eight speakers presented during the workshop.

Workshop on normal reference ranges for estradiol in postmenopausal women: commentary from The North American Menopause Society on low-dose vaginal estrogen therapy labeling.

Workshop on normal reference ranges for estradiol in postmenopausal women: commentary from The North American Menopause Society on low-dose vaginal estrogen therapy labeling.

Influence of serum estradiol on serum uric acid level in pre and postmenopausal women.

Background: Hyperuricemia develops when serum uric acid level exceeds the normal value. Estrogen may influence the level of serum uric acid. Postmenopausal females have a remarkable reduction in its level, so serum estradiol is studied in relation to serum uric acid levels in pre and post-menopausal women. Objective: To find out the relationship of serum Estradiol with serum uric acid level in premenopausal and postmenopausal women in local population. Study Design: Case control study. Setting: This study was conducted in Lady Aitchison Hospital Lahore. Period: March 2017- August 2017. Material and Methods: 134 females were enrolled in total and were grouped in to two. Group A comprised of premenopausal and Group B included postmenopausal females. After complete history and general physical examination, 5 ml venous blood sample under aseptic measures was taken. Serum uric acid was measured by enzymatic and serum estradiol by Enzyme-linked immunosorbent assay method. Results: The mean age of pre and postmenopausal women was 32 and 57 ± 7 years, with significantly lower in premenopause. The mean serum E2 was 91.86 ± 26.71 mg/dL in premenopause and 22.04 ± 9.28 mg/dL in postmenopause, with significantly lower mean in postmenopause. Mean serum uric acid was statistically higher in postmenopause that was 6.04 ± 0.58 mg/dL, when compared to premenopause that was 4.22 ± 0.90 mg/dL. Conclusion: Serum uric acid levels increased due to decreased serum estradiol in postmenopausal women as compared to premenopausal women.

Abstract 587: Highly sensitive and accurate method for measuring serum estradiol in postmenopausal women and other population subgroups

Abstract Meta-analyses consistently show that postmenopausal women with elevated levels of estradiol have an increased risk for certain cancers, such as breast cancer. At the same time, estradiol therapy is used to treat menopausal symptoms. Data on blood levels of estradiol are highly variable, especially in postmenopausal women, which prevents the formulation of generally recognized normal ranges and the consistent treatment of postmenopausal women. Similarly, no generally recognized reference ranges for estradiol exist for men and children. One reason for this variability in estradiol blood levels is the lack of appropriate analytical methods. To overcome these challenges, new, highly sensitive, specific, and standardized methods for measuring estradiol are needed. This study describes a new analytical method for measuring estradiol in serum from post and premenopausal women, men and children, which is standardized to the CDC Hormone Standardization Program (HoSt). Data produced by this analytical method can be compared with data produced by other methods standardized to CDC HoSt. The analytical method optimizes the extraction of estradiol from serum using two liquid-liquid extractions with pH and polarity adjustments prior to LC-MS/MS analysis. All sample handling and extraction procedures are automated using 96-well plates. Chromatographic separation is carried out using a phenyl-hexyl HPLC column and a gradient of methanol and methanol:water. E2 and its C13 internal standard were analyzed by selected reaction monitoring (SRM) in the negative ion mode with transitions of m/z 271 to 145 and 274 to 148, respectively. The mean biases of this method to certified reference materials ranged between −1.3% and −1.7% and were statistically not significant. No significant difference to established metrological reference methods was determined. The limit of detection for estradiol using 200 µL of serum is 11.0 pM (2.99 pg/mL). The method is highly precise with a within-run, among-day (determined over 68 days), and total within-laboratory imprecision ranging between 2.9-5.0%, 1.5-1.8%, and 3.3-5.3% CV, respectively [1]. The sensitivity of the method was found to be suitable for determining estradiol levels in postmenopausal women, men, and children, and is being applied to measure estradiol in postmenopausal women in NHANES 2013-2014. Data generated by this method are comparable to those of other analytical methods that are standardized to the CDC HoSt program. This method allows for the development of generally recognized normal ranges of estradiol in postmenopausal women and other population subgroups.

Effect of age and estrogen on biochemical markers of bone turnover in postmenopausal women: a population-based study from Nepal.

BackgroundOsteoporosis, a common disease worldwide, is characterized by low bone mass and architectural deterioration of bone tissue, leading to enhanced bone fragility and increase in fracture risks. Both menopause and aging are related factors leading to greater risk of bone disease, particularly among postmenopausal women. Hence, the main purpose of this study was to investigate the differences in biochemical markers of bone turnover and to evaluate the association of hormones and age-related factors with biochemical markers between pre- and postmenopausal women.MethodsA descriptive cross-sectional study was conducted over a period of 6 months among the female population of Dholahity community, Lalitpur, Nepal. A total of 496 healthy women were selected based on the questionnaire strategy. Among them, 244 were premenopausal and 252 were postmenopausal women. Different bone markers were evaluated as per the guideline provided by the reagent manufacturer, and hormonal assay, particularly estradiol level assessment, was performed by chemiluminescence immunoassay-based technique.ResultsA significant decrease in serum calcium level and estradiol level was observed in postmenopausal women as compared to premenopausal women, whereas a significant increase in serum phosphorus and alkaline phosphatase (ALP) levels was seen among postmenopausal (p<0.001). Age was significantly correlated with bone markers (ALP and calcium) in postmenopausal group (p<0.005), while there was no significant correlation in premenopausal group. In addition, there was significant positive correlation between calcium and estradiol in postmenopausal women, while ALP was negatively correlated with estradiol in that group. Further, no significant correlation was demonstrated between estradiol and bone markers in postmenopausal women in body mass index and age-adjusted partial correlation analysis.ConclusionTimely diagnosis of osteoporosis in women would be of significant benefit for effective care for required populations and help to minimize mortality rate and financial burden of our country.

Epidemiology of estrogen and dementia in women with Down syndrome.

Several lines of investigation have shown a protective role for estrogen in Alzheimer's disease through a number of biological actions. This review examines studies of the role of estrogen-related factors in age at onset and risk for Alzheimer's disease in women with Down syndrome, a population at high risk for early onset of dementia. The studies are consistent in showing that early age at menopause and that low levels of endogenous bioavailable estradiol in postmenopausal women with Down syndrome are associated with earlier age at onset and overall risk for dementia. Polymorphisms in genes associated with estrogen receptor activity and in genes for estrogen biosynthesis affecting endogenous estrogen are related to age at onset and cumulative incidence of dementia, and may serve as biomarkers of risk. To date, no clinical trials of estrogen or hormone replacement therapy (ERT/HRT) have been published for women with Down syndrome. While findings from clinical trials of ERT or HRT for dementia have generally been negative among women in the neurotypical population, the short interval between menopause and onset of cognitive decline, together with a more positive balance between potential benefits and risks, suggests an opportunity to evaluate the efficacy of ERT/HRT for delaying or preventing dementia in this high risk population, although questions concerning the optimal formulation and timing of the hormone therapy are not yet resolved.

Microvascular and Nitric Oxide Responses to Acute Exercise with Resveratrol or Estradiol in Postmenopausal Women

Microvascular and Nitric Oxide Responses to Acute Exercise with Resveratrol or Estradiol in Postmenopausal Women

The Association of CYP19A1 Variation with Circulating Estradiol and Aromatase Inhibitor Outcome: Can CYP19A1 Variants Be Used to Predict Treatment Efficacy?

After menopause, estradiol is primarily synthesized in peripheral tissues by the enzyme aromatase, encoded by CYP19A1. CYP19A1 variation associates with circulating estradiol in postmenopausal women and this variation is best represented by the intronic variant rs727479. This variation appears to have pleiotropic effects as it also associates with endometrial cancer risk. Indeed, estradiol plays an important role in the development of breast and endometrial cancer. Aromatase inhibitor (AI) drugs are used in the treatment of both diseases, however, response rates for AIs are low and there is currently no way to identify breast or endometrial cancer patients who are more likely to receive a clinical benefit. Multiple studies have proposed that genetic variation in CYP19A1 will have effects on AI efficacy: eight candidate variant studies of sample size greater than 50 describe associations between CYP19A1 variation and the outcome of patients treated with AIs. Nominally significant associations with patient outcome were reported for several variants, including rs727479. However, only an association between rs4646 and time to progression was replicated in an independent study. Moreover, rs4646 is also the only variant that has an association with patient outcome that passes a multiple testing threshold and this variant is in linkage disequilibrium with rs727479, supporting the hypothesis that associations with patient outcome may be driven through the effects on circulating estradiol. Despite this preliminary evidence, well phenotyped and comprehensively genotyped patient sets need to be studied before conclusions can be drawn about the effects of CYP19A1 variation on AI efficacy.

Correlation of periodontitis with mandibular radiomorphometric indices, serum calcium and serum estradiol in postmenopausal women: A case-control study.

Osteoporosis and periodontitis have several risk factors in common. The majority of studies evaluating periodontal bone loss and systemic bone mineral density have found that low bone mineral density systemically is significantly associated with an increase in loss of alveolar bone height and periodontal destruction. Hence, the purpose of the study was to determine the effect of periodontitis on mandibular radiomorphometric indices, serum calcium and serum estradiol levels in postmenopausal women. Forty female patients in the age group of 35-55 years were included in the study. The participants were divided into two equal groups, i.e., control group A (twenty - postmenopausal women with healthy periodontium) and study group B (twenty - postmenopausal women with periodontitis). A thorough clinical examination of all the forty patients was carried out to detect the presence of periodontitis on the basis of clinical attachment level. Quantitative indices were measured on digital panoramic radiographs, and serum calcium and estradiol levels were estimated. No statistically significant correlation of periodontitis with any of the radiomorphometric indices, serum calcium and serum estradiol levels was observed in postmenopausal women. There is little evidence of correlation of serum estradiol, serum calcium levels, and morphometric indices with periodontitis and therefore detailed further research about this correlation is required.

Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias.

(Reprinted with permission from American Psychiatric Association, http://psychiatryonline.org/guidelines).

Cognitive Functions, Concentration of Endogenous Estradiol, Estrogen Receptor α (ERα) Polymorphism in Postmenopausal Women.

BackgroundThe goal of this study was to investigate the relationship between cognitive functions and the level of endogenous estradiol in postmenopausal women, according to which estrogen receptor α (ERα) polymorphism the woman carries.Material/MethodsThe study group consisted of 210 women. The inclusion criteria were: minimum 2 years after the last menstruation, FSH concentration 30 U/ml, and no dementia signs on Montreal Cognitive Assessment (MoCA). A computerized battery of Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. Genotyping of the ERα polymorphism was performed using a polymerase chain reaction and restriction enzymes (PCR-RFLP). Blood plasma was tested for FSH and estradiol (E2). Statistical analysis was performed using STATISTICA software.ResultsA relationship was confirmed between standard scores for 3 cognitive functions: general memory, verbal memory, and processing speed, and the XbaI polymorphism in the women in the study. In the group of women with genotype TT PvuII, significant positive relationships were observed between the concentration of E2 and the standard scores of 3 cognitive functions: general memory, verbal memory, and processing speed. In the group of women with genotype TC PvuII, significant negative correlations were found between the concentration of E2 and the standard scores of 4 cognitive functions: NCI, general memory, verbal memory, and processing speed.ConclusionsERα polymorphism exerted an effect on the interaction between the concentration of estradiol and the results for cognitive functions. The concentration of estradiol did not depend on Xba1 and PvuII polymorphisms. The results for cognitive functions depended on which Xba1 polymorphism the woman carried.

The Western dietary pattern is associated with increased serum concentrations of free estradiol in postmenopausal women: implications for breast cancer prevention

Little is known about the possible influence of food consumption on the serum concentrations of endogenous sex hormones in postmenopausal women. We evaluated the relationships of the Western dietary pattern with serum concentrations of free estradiol and testosterone of postmenopausal women to test the hypothesis that a highly Western dietary pattern is associated with high serum concentrations of these hormones. We used data from a representative subsample of 305 women from the control group of a population-based case-control study conducted in Mexico from 2004 to 2007. A Western dietary pattern index value was compared with log natural serum concentrations of testosterone and estradiol using multiple linear regression models. The median values of serum concentrations of free estradiol and testosterone were 0.26 pg/mL (interquartile range, 0.14-0.43) and 0.40 pg/mL (interquartile range, 0.30-0.70), respectively. A multiple linear regression model showed that for each unit increase in the Western dietary pattern index, there was a 16.2% increase in the serum concentrations of free estradiol (β=0.15; 95% confidence interval [CI], 0.01-0.29); for each additional serving per week of chicken eggs, the increase was 31.0% (β=0.27; 95% CI, 0.106-0.441); for each additional serving per week of red meat, the increase was 64.9% (β=0.50; 95% CI, 0.01-1.01). There was no relationship found between dietary patterns and serum concentrations of free testosterone. The present findings suggest that intake of a Western diet, particularly of chicken eggs and meat, increases serum concentrations of free estradiol; these results have implications for breast cancer prevention.

A phase II trial of low-dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to aromatase inhibition

BackgroundHigh-dose oestrogen (HDE) is effective but toxic in postmenopausal women with advanced breast cancer (ABC). Prolonged oestrogen deprivation sensitises BC cell lines to estrogen and we hypothesised that third-generation aromatase inhibitors (AIs) would sensitise BCs to low-dose estradiol (LDE). MethodsA single-arm phase II study of LDE (2 mg estradiol valerate daily) in postmenopausal women with estrogen receptor-positive (ER+) ABC. The primary end-point was clinical benefit (CB) rate. If LDE was ineffective, HDE was offered. If LDE was effective, retreatment with the pre-LDE AI was offered on progression. ResultsTwenty-one patients were recruited before the trial was closed early due to slow accrual; 19 were assessable for efficacy and toxicity. CB was seen in 5 in 19 patients (26%; 95% confidence interval 9.1–51.2%), all with prolonged SD (median duration 16.8 months; range 11.0–29.6). Treatment was discontinued for toxicity in 4 in 19 patients (21%) and 8 in 11 women without hysterectomy experienced vaginal bleeding (VB). After primary LDE failure, three patients received HDE and one achieved a partial response (PR). Following CB on LDE, four patients restarted pre-LDE AI and three achieved CB including one PR. Those with CB to LDE had a significantly longer duration of first-line endocrine therapy for ABC than those without (54.9 versus 16.8 months; p < 0.01) ConclusionLDE is an effective endocrine option in women with evidence of prolonged sensitivity to AI therapy. LDE is reasonably well tolerated although VB is an issue. Re-challenge with the pre-LDE AI following progression confirms re-sensitisation as a true phenomenon.