Estrogen Levels In Postmenopausal Women Research Articles

The Organoleptic Test For Tempe-Based Drink Formulation For The Prevention Of Cognitive Function In Elderly Women

Older women are at twice the risk of developing Alzheimer's Disease than men. This happens because when women experience menopause, estrogen in the body will decrease. Estrogen is a hormone that can influence and help regulate body functions including the reproductive system, brain and central nervous system, bones, liver and urinary tract. Hormone replacement therapy (HRT) is intended to increase estrogen levels in postmenopausal women. One of the food ingredients that contain phytoestrogens and is widely consumed in Indonesia is tempe. The aim of the study was to make a tempe-based drink containing isoflavones (genestein, daidzein, glycetin) and nutrients (vitamin B3, vitamin B6, vitamin B12, folate) that are appropriate and sensory acceptable. The content of isoflavones and nutrients was analyzed using High Performance Liquid Chromatography (HPLC). Tempe flour which has been analyzed for its nutritional content and isoflavones, then a tempe drink formulation is made with isoflavones content, namely 15 milli grams (30 grams of tempe flour). To improve the flavor of the drink, add cocoa powder. The design used was a completely randomized design (CRD) with a single treatment, namely the concentration level of tempe flour for formula 1 (original tempe) = 17.5%, formula 2 (original tempe) = 14% and formula 3 (tempe with added chocolate as flavor). = 14 %. Acceptance of tempeh-based drinks was carried out by organoleptic tests in the form of hedogenic (liking) tests on 30 elderly women. In the first phase of the research that for color, taste, aroma and thickness the most preferred was the third formula with the addition of chocolate and 14% thickness. The conclusion is that tempe flour using the freeze dry method contains isoflavones and nutrients (vitamin B3, vitamin B6, vitamin B12 and folic acid) higher than tempe using the oven method but not significantly. Hedogenic test (favorability test) is the highest with a 14% viscosity formula and there is the addition of chocolate
 Keywords: tempe, elderly women, organoleptic test

Aspirin for the primary prevention of breast cancer: an unforeseen advantage

Aspirin for the primary prevention of breast cancer: an unforeseen advantage

Aspirin versus placebo on estrogen levels in postmenopausal women: a double-blind randomized controlled clinical trial

BackgroundEstrogen is involved in the pathogenesis of breast and gynecological cancers. Regular use of aspirin reduces estrogen levels. The present study aimed to evaluate the effect of aspirin on estrogen levels in postmenopausal women.MethodsThis double-blind, placebo-controlled parallel-group trial was conducted on postmenopausal women referred to an outpatient clinic at a women’s hospital in Tehran. Volunteers were randomly assigned to receive aspirin 100 mg/day or placebo for 6 weeks. Estradiol, sex hormone-binding globulin (SHBG), and testosterone levels at baseline and at the end of the intervention were measured by ELISA. Data were analyzed using SPSS 20, Kolmogorov–Smirnov test, independent samples t-test, and Mann–Whitney U test.ResultsTwenty-seven and 28 participants were finally analyzed in the aspirin and placebo groups, respectively. There was no significant difference between the two groups in body mass index (BMI), age, or menopausal years. There was a statistically significant difference (p = 0.002) in the amount of change in estradiol levels of the intervention group (median=− 3.5 pg/ml) compared to the control group (median=1.5 pg/ml). In contrast, there were no significant differences between the two groups regarding testosterone and SHBG levels (p = 0.58, p = 0.32).ConclusionsSince low doses of aspirin may decrease estradiol levels, it could be considered a promising adjunctive therapeutic candidate in postmenopausal women to decrease BC incidence. However, further studies with larger sample sizes, measurements of estrogen levels and its related compounds in different time points accompanied by long-term follow-ups are needed to better elucidate the potential mechanisms by which nonsteroidal anti-inflammatory drugs (NSAIDs) negatively affect breast cancer.Trial registrationIRCT201012195397N1. Date of first registration: 03/01/2011.

Unstimulated Salivary Estrogen in Postmenopausal Women With and Without Oral Dryness: A Prospective Study

Objective: This study aimed to compare the unstimulated salivary estrogen levels in postmenopausal women with and without oral dryness. Methodology: A study was carried out on 70 selected postmenopausal women, out of which 35 were in the case group and 35 were in the control group. A questionnaire related to oral dryness was given to all the patients to evaluate their response to oral dryness. Patients were asked to spit in a plastic container, and their unstimulated saliva samples were obtained and analyzed for estimation of salivary estrogen levels by ELISA technique. After analyzing the results of salivary estrogen levels, the patients in the case group with low levels of estrogen were subjected to HRT under the guidance of a gynecologist. The patients were followed after 3 months of therapy for their response to oral dryness by the questionnaire, and salivary estrogen levels were again reevaluated after the therapy. The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS Inc, Chicago, IL, version 15.0 for windows). The Pearson’s correlation and Student’s unpaired t-test were used for comparisons. Results: Before hormone replacement therapy, the mean estrogen level of the case group was 1.0031, and the mean estrogen level of the control group was 4.0080 pg/ml. This suggested that the reduced levels of estrogen hormone after menopause were associated with the complaint of oral dryness in these females. The mean salivary estrogen levels in the case group after HRT were more than the levels before HRT. Conclusion: Estrogen levels were reduced in patients with oral dryness. Further, the patients receiving HRT showed significant improvement in symptoms of oral dryness.

Role of Estrogen and Its Receptors in Adipose Tissue Glucose Metabolism in Pre- and Postmenopausal Women

ContextReduced estrogen levels in postmenopausal women predispose them to metabolic side effects, including insulin resistance and type 2 diabetes; however, the cellular mechanisms are not well understood.ObjectiveThis work aimed to study the expression of estrogen receptors in adipose tissue from pre- and postmenopausal women and the effects of estradiol (E2) on glucose uptake of adipocytes.MethodsSubcutaneous (SAT) and visceral adipose tissue (VAT) obtained from pre- and postmenopausal women (19-51 and 46-75 years old, respectively) were used to measure gene expression of ESR1 and ESR2. SAT tissue was incubated with E2, and glucose uptake and estrogen receptor levels were measured. Polymorphisms in ESR1 and ESR2 were addressed in public databases to identify single nucleotide polymorphisms associated with metabolic traits.Results ESR2 expression was lower in pre- vs postmenopausal women, corresponding to lower ESR1:ESR2 gene expression ratio in postmenopausal women. In premenopausal women, the expression of ESR1 was higher in VAT than in SAT. In both pre- and postmenopausal women, ESR2 expression was lower in VAT than in SAT. In late, but not pre- or early postmenopausal women, E2 reduced glucose uptake and GLUT4 protein and increased expression of ESR2. ESR1 polymorphisms were associated with weight, body fat distribution, and total cholesterol, and ESR2 polymorphisms were associated with total cholesterol and triglyceride levels and with body fat percentage.ConclusionE2 inhibits glucose utilization in human adipocytes in late postmenopausal women. Changes in glucose utilization over time since menopause may be explained by a lower ESR1:ESR2 ratio. This can have clinical implications on the timing of estrogen treatment in postmenopausal women.

Estrogens still represent an attractive therapeutic approach for Alzheimer's disease.

Estrogens still represent an attractive therapeutic approach for Alzheimer's disease.

Reduced Desmosomal Cadherin Levels in Genital Epithelium of Postmenopausal Women Also Develop in Ovariectomized Mice with Increased Susceptibility to Viral and Bacterial Genital Pathogens

Background: The genitourinary syndrome of menopause affects about half of all women in menopause and includes symptoms of vaginal burning, dyspareunia, and urinary urgency. These symptoms stem from lower serum estrogen levels in postmenopausal women that cause reduced tissue elasticity and other genital tract changes. While the hypoestrogenemia induced in reproductive age women using the progestin-only contraceptive depot-medroxyprogesterone acetate (DMPA) decreases genital levels of the cell-cell adhesion molecules desmoglein-1 (DSG1) and desmocollin-1 (DSC1) and impairs genital epithelial barrier function, relevance of these findings to postmenopausal women is uncertain. Methods: We compared ectocervical DSG1 and DSC1 levels in premenopausal vs. postmenopausal women. Using ovariectomized mice to model the hypoestrogenic state in postmenopausal women, we explored effects of reduced ovarian function on genital epithelial integrity barrier function and genital pathogen susceptibility. Findings: Compared to premenopausal women, ectocervical tissue from women in menopause had significantly lower levels of DSG1 and DSC1. Likewise, Dsg1 and Dsc1 levels were significantly reduced in OVX mice vs. estrus-stage mice. Consistent with these data, DMPA-treated and OVX mice displayed significant compromise of genital epithelial barrier function and compared to estrus-stage mice or OVX mice treated with estrogen, were more susceptible to genital herpes simplex virus type 2 infection and less effectively cleared genital Chlamydia trachomatis infection. Interpretation: Our studies identify analogously reduced genital epithelial integrity in postmenopausal women and OVX mice and indicate that reduced ovarian function alters host response to bacterial and viral pathogens. Our results also spotlight the need to resolve if weakened genital epithelial integrity in postmenopausal women represents an important risk factor for genital infection. Funding Statement: This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD094634) and Stanford University School of Medicine. Declaration of Interests: Authors have no conflicts of interest to declare. Ethics Approval Statement: Prior to induction, all proposed mice studies were approved by the Stanford University Institutional Animal Care and Use Committee.

Association between Bone Metabolism and Vestibular Problems in the Modified Romberg Test: Data from the 2009-2010 Korean National Health and Nutrition Examination Survey.

Osteoporosis contributes to the occurrence of falling and vestibular problems, particularly in elderly patients. This study aimed to investigate the association between bone metabolism with vestibular problems and falling. A total of 4054 participants of the Korean National Health and Nutrition Examination Survey (KNHANES) from 2009 to 2010 aged ≥50 years old were surveyed on their history of falling, vestibular problems evaluated by the modified Romberg test, variables involving bone metabolism, and serum levels of vitamin D and alkaline phosphatase. They also underwent dual energy X-ray absorptiometry. The crude (simple) and adjusted odd ratios (ORs) of variables involving bone metabolism for vestibular problems in the modified Romberg test and falling were analyzed using a logistic regression model. A subgroup analysis was performed according to sex and the presence of menopause in females. Vestibular problems in the modified Romberg test group but not the falling group were associated with decreased serum vitamin D levels (p < 0.001; odds ratio (OR) = 0.951; 95% confidence interval (CI), 0.926–0.976). In subgroup analysis according to sex, the post-menopause group showed a higher rate of vestibular problems in the modified Romberg test compared to the pre-menopause group (4.5% vs. 0.7%, p = 0.019). In the post-menopause group, osteoporosis was positively associated with vestibular problems in the modified Romberg test (p = 0.001, OR = 10.971, 95% CI = 2.650–45.414). On the other hand, a history of hormone replacement therapy was negatively related with vestibular problems in this subgroup (p = 0.035; OR = 0.473; 95% CI = 0.239–0.948). A decrease in serum vitamin D levels may impact the vestibular system through neural signaling or by osteoporotic changes of the otic capsule, as well as otolith particles. Decreased estrogen levels in postmenopausal women may make them more prone to osteoporotic changes, which were associated with vestibular problems in the modified Romberg test. Because this is a cross-sectional study, the causal relationship of bone metabolism with vestibular function needs to be investigated.

Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study

Studies have suggested that women with elevated BMI or 25-OH vitamin D levels may derive less benefit from AIs versus tamoxifen. We prospectively investigated whether high BMI or 25-OH vitamin D levels were associated with higher estrogen levels in post-menopausal women receiving standard adjuvant letrozole (2.5 mg/day). Furthermore, we evaluated whether an increased dose of letrozole resulted in lower serum estrogens in women with BMI > 25 kg/m2. Correlation between entry BMI and day 29 serum biomarkers (estrogens, 25-OH vitamin D, insulin, CRP, leptin) was assessed in all patients. On day 29, participants with BMI > 25 kg/m2 switched to letrozole 5 mg/day for 4-weeks and blood was drawn upon completion of the study. The change in serum estrogen levels was assessed in these patients (BMI > 25 kg/m2). 112 patients completed days 1–28. The Pearson correlations of estradiol and estrone with BMI or serum 25-OH vitamin D levels were near zero (−0.04 to 0.07, p = 0.48–0.69). Similar results were obtained for correlation with markers of obesity (insulin, CRP, and leptin) with estradiol and estrone (−0.15 to 0.12; p = 0.11–0.82). Thirty-one patients (BMI > 25 kg/m2) completed the interventional component; Increasing the dose of letrozole did not further reduce estradiol or estrone levels (change 0.1 and 0.4 pmol/L respectively; p = 0.74 and 0.36). There was no observed association between markers of obesity (BMI, insulin, leptin, and CRP), serum 25-OH vitamin D levels and estradiol or estrone levels. Additionally, an increased dose of letrozole did not further reduce estradiol or estrone levels compared to the standard dose.

Baseline estrogen levels in postmenopausal women participating in the MAP.3 breast cancer chemoprevention trial.

The aim of the study was to quantify baseline estradiol (E2) and estrone (E1) concentrations according to selected patient characteristics in a substudy nested within the MAP.3 chemoprevention trial. E2 and E1 levels were measured in 4,068 postmenopausal women using liquid chromatography-tandem mass spectrometry. Distributions were described by age, years since menopause, race, body mass index (BMI), smoking status, and use and duration of hormone therapy using the Kruskal-Wallis test. Multivariable linear regression was also used to identify characteristics associated with estrogen levels. After truncation at the 97.5th percentile, the mean (SD)/median (IQR) values for E2 and E1 were 5.41 (4.67)/4.0 (2.4-6.7) pg/mL and 24.7 (14.1)/21 (15-31) pg/mL, respectively. E2 and E1 were strongly correlated (Pearson correlation [r] = 0.8, P < 0.01). The largest variation in E2 and E1 levels was by BMI; mean E2 and E1 levels were 3.5 and 19.1 pg/mL, respectively for women with BMI less than 25 and 7.5 and 30.6 pg/mL, respectively, for women with BMI greater than 30. E2 and E1 varied by age, BMI, smoking status, and prior hormone therapy in multivariable models (P < 0.01). There was large interindividual variability observed for E2 and E1 that varied significantly by participant characteristics, but with small absolute differences except in the case of BMI. Although the majority of participant characteristics were independently associated with E1 and E2, together, these factors only explained about 20% of the variation in E1 and E2 levels.

Biomimetic and estrogenic fibers promote tissue repair in mice and human skin via estrogen receptor β

The dynamic changes in estrogen levels throughout aging and during the menstrual cycle influence wound healing. Elevated estrogen levels during the pre-ovulation phase accelerate tissue repair, whereas reduced estrogen levels in post-menopausal women lead to slow healing. Although previous reports have shown that estrogen may potentiate healing by triggering the estrogen receptor (ER)-β signaling pathway, its binding to ER-α has been associated with severe collateral effects and has therefore limited its use as a therapeutic agent. To this end, soy phytoestrogens, which preferentially bind to the ER-β, are currently being explored as a safer therapeutic alternative to estrogen. However, the development and evaluation of phytoestrogen-based materials as local ER-β modulators remains largely unexplored. Here, we engineered biomimetic and estrogenic nanofiber wound dressings built from soy protein isolate (SPI) and hyaluronic acid (HA) using immersion rotary jet spinning. These engineered scaffolds were shown to successfully recapitulate the native dermal architecture, while delivering an ER-β-triggering phytoestrogen (genistein). When tested in ovariectomized mouse and ex vivo human skin tissues, HA/SPI scaffolds outperformed controls (no treatment or HA only scaffolds) towards promoting cutaneous tissue repair. These improved healing outcomes were prevented when the ER-β pathway was genetically or chemically inhibited. Our findings suggest that estrogenic fibrous scaffolds facilitate skin repair by ER-β activation.

Intravaginal Administration of Human Type III Collagen-Derived Biomaterial with High Cell-Adhesion Activity to Treat Vaginal Atrophy in Rats.

Vaginal atrophy (VA) is the thinning and drying of the vaginal walls, which can lead to a variety of symptoms. VA is usually initiated by decreasing estrogen levels in post-menopausal women; so, the traditional treatment of VA is hormone therapy (HT). Here, we sought nonhormonal therapies aimed at treating this condition safely and effectively. Collagen is an excellent biomaterial and has important biological functions in skin and mucosal tissues. In particular, collagen can bind to epithelial cells to promote proliferation and differentiation. In this study, recombinant protein T16, which was derived from human type III collagen to provide potent cell-adhesion activity, was used as a safe alternative therapy to treat VA in ovariectomy rat models. After T16 was administered intravaginally for 2 weeks, the autologous collagen arrangement was improved in the epithelium and muscle layer of the rat vagina, and the thickness of epithelium tissue also increased significantly. Compared with the sham group, collagen therapy was found to influence the expression levels of several important proteins in the vaginal tissue, resulting in the upregulation of TIMP-1, Collagen I, Collagen III, Ki-67, VEGF, and AQP-2 and the downregulation of MMP-1 and IL-6. Cells in the collagen treatment group exhibited better proliferation and less apoptosis properties. These results not only provide support for additional animal experiments to further evaluate collagen therapy in VA treatment but also suggest the potential for wide applications of collagen biomaterials with high cell-adhesion activities.

The Prevalence of Depression, Anxiety, and Stress and Their Association with Vitamin D and Estrogen Levels in Postmenopausal Women in Semnan

Background: Depression, stress, and anxiety are of the most prevalent psychological disorders among postmenopausal women. Inadequate evidence is available on the association between vitamin D and estrogen with depression, anxiety, and stress in this group. Objectives: The objective of this study was to determine the prevalence of depression, anxiety, and stress and their association with vitamin D and estrogen levels in postmenopausal women in Semnan. Methods: The present analytical cross-sectional study was carried out using multistage sampling among women aged 45 to 70 years in Semnan (Iran) in summer 2016. Data collection tools were the demographic questionnaire, Spielberger State-Trait anxiety inventory, the Beck depression inventory, and the perceived stress scale. In addition, the levels of blood vitamin D and estrogen were measured. Results: In 120 postmenopausal women, depression levels were mild (22.5%), moderate (13.3%), and severe (1.7%); anxiety levels were mild (46.7%), moderate (50.8%), and severe (2.5%); additionally, 79.2% had lower stress and 20.8% had greater stress. Negative and significant correlations were found between vitamin D and depression (r = -0.1982, P = 0.031), anxiety (r = -0.3636, P < 0.001) and stress (r = -0.2884, P = 0.001). However, there was no correlation between estrogen and depression (r = -0.130, P = 0.159), anxiety (r = -0.105, P = 0.254), and stress (r = -0.104, P = 0.262). No significant correlation was seen between estrogen and vitamin D (r = -0.070, P = 0.450). Conclusions: In postmenopausal women, no significant relationship was observed between estrogen and depression, anxiety, and perceived stress; however, there was a significant relationship between vitamin D and depression, anxiety, and stress.

Hormone therapy in menopausal women with fibroids: is it safe?

Menopause is an important transition in the life of women. It has been estimated that by the year 2030, worldwide 1.2 billion women will be menopausal. The most bothersome symptoms of menopause are believed to be due to declines in estrogen levels in postmenopausal women. Thus, hormone therapy is an effective treatment option for menopausal women, although prolonged use of hormone therapy is associated with a slightly increased risk of breast cancer, thromboembolism, and stroke. A literature search for studies evaluating the effects of hormone therapy in menopausal women with asymptomatic fibroids demonstrated variable effects of hormone therapy on the volume and size of the fibroids. Some studies have demonstrated an increase in size of pre-existing asymptomatic fibroids and formation of new fibroids with higher doses of progestogen in combination therapy. The finding of low resistance index in uterine arteries of women with asymptomatic fibroids is associated with an increased risk of fibroid growth, and thus making the measurement of pulsatility index of uterine arteries a possible screening tool before initiating hormone therapy in menopausal women with fibroids. Although the effect of hormone treatment is variable and statistically insignificant in many cases, the newer selective estrogen receptor modulators having tissue-specific estrogen agonistic and antagonistic actions such as raloxifene have a favorable clinical profile and may be better alternatives in women with asymptomatic fibroids.

Abstract P4-08-05: Impact of common polymorphisms of CYP19A1 and UGT2B17 gene deletion on early endocrine-responsive postmenopausal breast cancer

Abstract Background Polymorphisms of genes involved in estrogen production have been linked to breast cancer risk, prognosis and treatment response. Polymorphisms of the aromatase gene CYP19A1 influence its activity. The UGT2B17 catalyzes glucuronic acid transfer to a variety of substrates, including steroids and drugs like the aromatase inhibitor exemestane. We investigated the impact of two variants of CYP19A1 (rs10046, rs4646) and the UGT2B17 gene deletion on disease outcome in 125 postmenopausal women operated for ER-positive primary breast cancer enrolled in a randomized pre-surgical trial. Patients Briefly, upon informed consent, postmenopausal patients with ER-positive breast cancer (stage T1–2, N0–1, M0) eligible for surgery were randomized to receive either exemestane (25 mg/day), or celecoxib (800 mg/day), or placebo for 6 weeks prior to surgery at the European Institute of Oncology (2004-2008). Exemestane showed a significant 10% absolute reduction in Ki67 labeling index compared to the other two arms. Serum and whole blood was taken at baseline and the day before surgery and stored at -80°C until assayed. Methods DNA was extracted from blood by QIAamp DNA Blood Kits. The CYP19A1 rs1004/rs46466 were analyzed by Taqman genotyping assays in real-time PCR. The UGT2B17 deletion was estimated by copy number assay (Lifetechnologies). Serum estradiol (E2) and estrone (E1) levels were measured by gas chromatography tandem mass spectrometry detection (GS-MS/MS) after liquid-liquid extraction. The lower limit of quantitation were 0.625 pg/mL for estradiol and 1.56 pg/mL for estrone. The association of genetic polymorphisms with “any event” was assessed by the Cox proportional hazards models adjusted for confounders. Results The genetic polymorphisms did not deviate from Hardy-Weinberg equilibrium (P-value &amp;gt;0.41) and minor allele frequency of rs10046 (A/G), rs4646 (C/A), and UGT2B17Del were 0.45, 0.22, and 0.31, respectively. The rs10046 A and rs4646 C alleles were associated with higher estrogen levels. Carriers of rs10046 AA had median levels of 7.57 pg/ml E2 and 35.9 pg/mL E1 versus 3,9 pg/mL E2 and 27.4 E1 pg/mL in CA/AA genotypes (P&amp;lt;0.003). Carriers of rs4646 CC had 5.6 pg/ml E2 and 30.45 pg/mL E1 versus 3,95 pg/mL E2 and 27.4 E1 pg/mL in CA/AA genotypes (P=0.05 only for E1). After 6 weeks treatment with exemestane, we observed steeper decreases in estrogen levels in the rs10046 AA/rs4646 CC carriers (P=0.02 for E2). After a median follow-up of 7 years we found that women carrying at least one SNP of rs10046 and one SNP of rs4646 had a better prognosis compared with women carrying homozygote wt SNPs (HR=0.44; 95% CI: 0.2-0.99 P=0.049). Similarly, the UGT2B17 deletion was associated with a better prognosis (HR= 0.43; 95% CI: 0.19-0.97; P=0.0439). There was no interaction with pre-surgical or adjuvant treatment. Conclusions Our analysis confirms previous findings of an association of CYP19A1 rs10046/rs4646 with estrogen levels in postmenopausal women. Interestingly, the carriers of the variants associated with lower estrogen levels at diagnosis had better prognosis. Further genomic profiling in larger trials aimed to enhance tailored treatment efficacy in endocrine-responsive postmenopausal breast cancer are warranted. Citation Format: Johansson H, Gandini S, Aristarco V, Macis D, Guerrieri-Gonzaga A, Serrano D, Pruneri G, Lazzeroni M, Viale G, Toesca A, Rajasekaran A, Bonanni B, DeCensi A. Impact of common polymorphisms of CYP19A1 and UGT2B17 gene deletion on early endocrine-responsive postmenopausal breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-08-05.

Abstract P2-09-14: Association between BMI and residual estradiol levels in post-menopausal women using adjuvant letrozole: Results of a prospective study

Abstract Background: Adjuvant aromatase inhibitors (AI) are the standard of care for post-menopausal women with early breast cancer (BC). Some studies have suggested that women with high BMI have less benefit from some AIs (anastrozole, but not letrozole) vs. tamoxifen. Of concern, a positive correlation between BMI and residual estradiol in women using letrozole has been reported (ALIQUOT Study; JCO 2012). These findings have created uncertainty about the use of AIs in overweight and obese women. We conducted a prospective study to measure estrogen levels in post-menopausal women using adjuvant letrozole, with the primary objective of evaluating the relationship between residual E2 and BMI. Methods: Post-menopausal women with early BC taking adjuvant letrozole for at least 3 months were recruited at 4 sites in Toronto, Canada. Fasting blood was collected 24 hours after the prior dose at baseline (Day 1, routine use of own letrozole, including generic) and on Day 29, following 28 days of monitored adherence to a provided supply of Femara 2.5 mg/day (Part A). Participants with BMI&amp;gt;25 were treated for a further 28 days (Part B) with a double dose of Femara (5 mg/day). Estradiol and estrone were measured using a high sensitivity liquid chromatography-tandem mass spectrometry assay. Vitamin D and markers of obesity/inflammation were assayed, and symptom/quality of life questionnaires completed at the same time points. Results: 112 eligible patients were enrolled and completed Part A. Median age was 62 and BMI 24.7 kg/m2 (range 19.0 to 42.2 kg/m2). 68% of participants had received adjuvant chemotherapy. Estradiol levels (mean±SD) were 2.81±1.15 pg/mL at baseline (typical use) and 2.69±1.01 pg/mL at Day 29 following monitored Femara use with near-perfect adherence (p=NS). No significant correlation was observed between estradiol and BMI on either Day 1 or Day 29 (r=0.06, p=NS). As previously reported, letrozole 5 mg/day dose did not affect residual estradiol levels at Day 58 for women with BMI&amp;gt;25. Residual estradiol was not correlated with vitamin D or markers of obesity/inflammation (insulin, leptin, CRP). Conclusion: No association was observed between BMI and residual estradiol in women using letrozole (generic or Femara) at standard doses. These results are consistent with the absence of a treatment-by-BMI interaction in the BIG 1-98 trial and they provide reassurance that letrozole is an appropriate treatment in overweight and obese women. Funded by Hold 'Em For Life (Mount Sinai Hospital, Toronto) and Breast Cancer Research Foundation. Citation Format: Cescon DW, Ennis M, Pritchard KI, Townsley C, Warr D, Elser C, Rao L, Stambolic V, Sridhar S, Goodwin PJ. Association between BMI and residual estradiol levels in post-menopausal women using adjuvant letrozole: Results of a prospective study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-09-14.

Vitamin D Proliferates Vaginal Epithelium through RhoA Expression in Postmenopausal Atrophic Vagina tissue.

Postmenopausal atrophic vagina (PAV) is the thinning of the walls of the vagina and decreased lugae of the vagina. PAV is caused by decreased estrogen levels in postmenopausal women. However, the harmful effects of hormone replacement therapy (HRT) have resulted in considerable caution in its use. Various estrogen agonist treatment options are available. Vitamin D is influences the regulation of differentiation and proliferation of various cells, especially tissues lining stratified squamous epithelium, such as the vaginal epithelium. In this study, we hypothesized that vitamin D could provide an alternative and a safe treatment option for PAV by promoting the proliferation and differentiation of the vaginal epithelium. Thirty six patients were enrolled in this case-control study. Vitamin D associated proteins in a vitamin D and sex hormone treated vaginal epithelial cell line as well as normal and PAV tissues were measured. To confirm of cell-to-cell junction protein expression, cell line and tissue studies included RT-PCR, immunohistochemistry staining, and immunoblot analyses. The expression of cell-to-cell junction proteins was higher in women with symptoms of atrophic vagina tissue compared to women without the symptoms. Vitamin D stimulated the proliferation of the vaginal epithelium by activating p-RhoA and Erzin through the vitamin D receptor (VDR). The results suggest that vitamin D positively regulates cell-to-cell junction by increasing the VDR/p-RhoA/p-Ezrin pathway. This is the first study to verify the relationship of the expression of RhoA and Ezrin proteins in vaginal tissue of PAV.

Yoga increased serum estrogen levels in postmenopausal women-a case report.

This case report aimed to evaluate 4 months of yoga practice on the quality of life (QOL) and estradiol levels of two postmenopausal women. Participants were clinically healthy postmenopausal women, with follicle-stimulating hormone levels greater than or equal to 30 mIU/mL and a body mass index lower than 30 kg/m. The participants practiced yoga for 4 months in two 1-hour sessions per week. The participants exhibited an abnormal estrogen-level increase after 4 months of yoga practice and showed QOL improvements. In some cases, yoga practice can affect the female neuroendocrine system, increasing estrogen and improving QOL.

Effect of TENS on stimulation of saliva in postmenopausal women with or without oral dryness – An interventional study

BackgroundDecreased estrogen levels in postmenopausal women may cause an increase in oral symptoms including dry mouth, burning sensation of the mouth, and taste alterations. Management of salivary gland hypofunction by various modalities had been tried with variable results and associated side effects or discomfort. AimTo evaluate the effects of transcutaneous electric nerve stimulation (TENS) on whole salivary flow rate in postmenopausal females with and without oral dryness. MethodsFifty postmenopausal women, based on their response to Xerostomia Inventory, were divided into 2 groups of 25 each; group 1 were postmenopausal women with oral dryness (PMD+OD) and group 2 were postmenopausal women without oral dryness (PMD−OD). Unstimulated whole saliva collection was done by low forced spitting method. External salivary stimulation of parotid gland by electrodes of TENS unit was done and sialometry was repeated. The salivary flow rates were compared within both groups before and after stimulation and between the two groups. ResultsThe mean salivary flow rates at baseline were statistically significantly lower in the PMD+OD group than the PMD−OD group. There was a mean increase of 0.33ml and 0.46ml with TENS stimulation in PMD+OD and PMD−OD groups, respectively. ConclusionPostmenopausal women with perception of oral dryness had lower salivary flow rates. 90% of the subjects, irrespective of oral dryness status, responded to TENS therapy. TENS stimulation resulted in a statistically significant increase in the quantity of whole saliva flow rate in postmenopausal women with or without oral dryness.

Abstract P5-12-02: Effect of 5 vs 2.5 mg/day letrozole on residual estrogen levels in post-menopausal women with high BMI - A prospective crossover study

Abstract Background: Some studies have suggested that women with high BMI have less benefit from aromatase inhibitors (AI) vs. tamoxifen as adjuvant treatment for early breast cancer. One possible mechanism for this observation is that complete suppression of estrogen is not achieved in these women with the standard flat dose of AI. We evaluated whether a doubling of letrozole to 5 mg/day for 4 weeks affected residual estrogen levels in this population. Methods: Post-menopausal women with early breast cancer and BMI&amp;gt;25 already taking adjuvant letrozole for at least 3 months were recruited from medical oncology clinics at 4 sites in Toronto, Canada. Fasting blood samples were collected 24 hours following the last dose at baseline (routine use of own letrozole), after 28 days of monitored adherence to a provided supply of letrozole (Femara) 2.5 mg/day (Part A), and after an additional 28 days of letrozole (Femara) 5 mg/day (Part B). Symptom/quality of life questionnaires were completed at the same timepoints. Estradiol and estrone were measured using a high sensitivity liquid chromatography-tandem mass spectrometry assay. One interim analysis for futility and efficacy was planned after 31 eligible patients had completed the study, using estradiol and O'Brien-Fleming boundaries with an inner wedge. Results: 36 patients were enrolled and started on study, and 31 eligible patients completed Parts A and B. The 5 non-completers withdrew because of adverse events (n=4, unlikely related to drug) or withdrawal of consent (n=1). Median age was 62 (range 48 to 77) and BMI 28.3 kg/m2 (Range 25.2 to 42.2 kg/m2). One patient had non-postmenopausal estrogen levels at Day 29 and Day 57 and one patient's blood assay was unsuccessful; both were excluded from further analyses. The predetermined stopping rule for futility was met. Estradiol levels (mean±standard deviation) changed from 2.68±0.40 pg/mL at baseline to 2.67±0.59 pg/mL at Day 29 to 2.70±0.53 pg/mL at Day 57. Mean change from Day 29 to Day 57 was 0.03±0.48 pg/mL (95% confidence interval -0.15 to 0.21 pg/mL). Four patients reported new or increased arthralgias (to NCI CTCAE Grade 2 or 3) while taking letrozole 5 mg/day in Part B. There was no association between changes in estradiol levels and either study non-completion or the development of arthralgias. Estrone results were similar. Conclusion: Increasing letrozole from 2.5 to 5 mg/day did not further suppress estrogen levels in women with BMI&amp;gt;25. It is unlikely that letrozole dosing tailored to body size would improve clinical outcomes. The letrozole 5 mg/day intervention was terminated based on the results of the interim analysis for futility. Citation Format: Cescon DW, Ennis M, Pritchard KI, Townsley C, Warr D, Elser C, Rao L, Stambolic V, Sridhar S, Goodwin PJ. Effect of 5 vs 2.5 mg/day letrozole on residual estrogen levels in post-menopausal women with high BMI - A prospective crossover study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-02.