Concentration In Postmenopausal Women Research Articles

Age, Sex, Body Mass Index, Diet and Menopause Related Metabolites in a Large Homogeneous Alpine Cohort.

Metabolomics in human serum samples provide a snapshot of the current metabolic state of an individuum. Metabolite concentrations are influenced by both genetic and environmental factors. Concentrations of certain metabolites can further depend on age, sex, menopause, and diet of study participants. A better understanding of these relationships is pivotal for the planning of metabolomics studies involving human subjects and interpretation of their results. We generated one of the largest single-site targeted metabolomics data sets consisting of 175 quantified metabolites in 6872 study participants. We identified metabolites significantly associated with age, sex, body mass index, diet, and menopausal status. While most of our results agree with previous large-scale studies, we also found novel associations including serotonin as a sex and BMI-related metabolite and sarcosine and C2 carnitine showing significantly higher concentrations in post-menopausal women. Finally, we observed strong associations between higher consumption of food items and certain metabolites, mostly phosphatidylcholines and lysophosphatidylcholines. Most, and the strongest, relationships were found for habitual meat intake while no significant relationships were found for most fruits, vegetables, and grain products. Summarizing, our results reconfirm findings from previous population-based studies on an independent cohort. Together, these findings will ultimately enable the consolidation of sets of metabolites which are related to age, sex, BMI, and menopause as well as to participants’ diet.

Association between KLF6 rs3750861 polymorphism and plasma ceramide concentrations in post-menopausal women with type 2 diabetes

Background and aimBased on the emerging role of Kruppel-like factor 6 (KLF6) in lipid metabolism, we examined whether there is a relationship between the KLF6 rs3750861 genetic variant and plasma ceramide levels in people with type 2 diabetes mellitus (T2DM). Methods and resultWe measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] amongst 101 Caucasian post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramides were measured by targeted liquid chromatography-tandem mass spectrometry assay. Genotyping of the KLF6 rs3750861 polymorphism was performed by TaqMan-Based RT-PCR system.Overall, 87 (86.1%) patients had KLF6 rs3750861 C/C genotype and 14 (13.9%) had C/T or T/T genotypes. After adjustment for age, diabetes-related variables, use of lipid-lowering drugs and other potential confounders, patients with C/T or T/T genotypes had higher plasma Cer(d18:1/18:0) (0.159 ± 0.05 vs. 0.120 ± 0.04 μmol/L, p = 0.012), Cer(d18:1/20:0) (0.129 ± 0.04 vs. 0.098 ± 0.03 μmol/L, p = 0.008), and Cer(d18:1/24:1) (1.236 ± 0.38 vs. 0.978 ± 0.36 μmol/L, p = 0.032) compared with those with C/C genotype. ConclusionsThe C/T or T/T genotypes of rs3750861 in the KLF6 gene were closely associated with higher levels of specific plasma ceramides in post-menopausal women with T2DM.

A Meta-Analysis of Randomized Controlled Trials of the Effects of Soy Intake on Inflammatory Markers in Postmenopausal Women

BackgroundElevated concentrations of serum inflammatory cytokines, specifically TNF-α and IL-6, as well as C-reactive protein (CRP), are commonly observed after menopause. ObjectivesBecause soy isoflavones may have some anti-inflammatory potential, the aim of the present systematic review and meta-analysis of randomized controlled trials (RCTs) was to explore whether soy intake affects serum markers of inflammation in postmenopausal women. MethodsPubMed, Web of Science, and the Cochrane Library were systematically searched up to August 2020. All RCTs that met the following criteria were included: 1) studies of the effects of soy intake on inflammatory markers; 2) any date of publication; 3) conducted on postmenopausal women; 4) with sufficient quantitative data for meta-analysis. Effect sizes were expressed as weighted mean differences (WMDs) and 95% CIs. A total of 24 RCTs assessing the effects of soy intake on serum concentrations of CRP, TNF-α, and IL-6 were included in the analysis. A random-effects model was used to determine the overall effect. ResultsSoy supplementation significantly reduced CRP by 0.11 mg/L in postmenopausal women (95% CI: −0.22, −0.004 mg/L; P = 0.0414), but did not affect IL-6 or TNF-α. Significant reductions in CRP concentration occurred when natural soy products were given (WMD: −0.23 mg/L; 95% CI: −0.29, −0.17 mg/L; P < 0.001). This is equivalent to a ∼9% reduction in CRP concentration from baseline. ConclusionsAlthough our meta-analysis found evidence that soy products significantly reduce CRP concentrations in postmenopausal women, the mechanisms by which soy foods and their constituents affect inflammatory biomarkers still need to be clarified.This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020179232.

Seasonal variation of 25-Hydroxyvitamin D and indices of carbohydrate and lipid metabolism in postmenopausal women.

BackgroundSome studies indicate vitamin D’s significant contribution to metabolic processess. Therefore, the purpose of this study was to evaluate the level of carbohydrate and lipid metabolism indices in relation to seasonal changes in 25-hydroxyvitamin D (25(OH)D) concentration in postmenopausal women.MethodsSixteen postmenopausal women meeting health criteria and not using vitamin D supplementation were included in the study. Seasonal variation of somatic features and the serum concentration of 25(OH)D, glucose, insulin, parathormon, sclerostin and lipid profile were determined on two terms (autumn-winter).ResultsComparative analysis of the variables between the study terms revealed a marked decrease in the concentration of 25(OH)D (p ≤ 0.0001), insulin (p < 0.05), insulin resistance index (HOMA-IR), (p < 0.05). The significant positive correlations of changes (Δ) between autumn and winter in 25(OH)D with body mass (p < 0.05), and fat mass (p ≤ 0.01), measured in the first study term, in the group of women with normal body mass index (BMI), and negative correlation with fat mass (p < 0.05) in women with a BMI value above the reference values, were found. The relationship analysis showed that in women with normal BMI, the decrease in 25(OH)D concentrations was greater when the body fat percentage was higher, whereas in women with a BMI value above the reference values, the higher the fat percentage, the smaller was the decrease in 25(OH)D concentration.ConclusionsSeasonal changes in 25(OH)D concentration did not significantly affect the concentration of carbohydrate and lipid metabolism indices. The magnitude of decline in 25(OH)D levels depends on the fat mass. We suppose that environmental or lifestyle-related factors, e.g., nutritional behaviours, may have had more influence on metabolic indices than changes in 25(OH)D.

Safety assessment of compounded non-FDA-approved hormonal therapy versus FDA-approved hormonal therapy in treating postmenopausal women.

To assess the safety and serum estradiol (E2) and total testosterone (T) concentrations in postmenopausal women treated with Pellet Hormonal Therapy (PHT) and Food and Drug Administration approved Hormonal Therapy (FHT). A total of 539 postmenopausal women were identified, including 384 on PHT and 155 on FHT. Data extracted from medical records include demographics, indication for hormone therapy, treatment duration, side effects, serum E2 and T levels, and frequency of laboratory follow-up. The incidence of overall side effects was significantly higher in PHT compared with FHT (221 [57.6%] vs 23 [14.8%], P < 0.00001, odds ratio [95% CI] =8.0[4.5-14.2]). When examining women with an intact uterus prior to hormone therapy initiation, 55.3% (136/246) on PHT vs 15.2% (12/79) on FHT had at least one episode of abnormal uterine bleeding (P < 0.0001, odds ratio [95% CI] = 7.9[3.6-17.0]). Furthermore, a significantly higher proportion of women on PHT (20.3% [50/246]), compared with 6.3% (5/79) on FHT, had a hysterectomy (P = 0.036, odds ratio [95% CI] = 3.2[1.1-9.3]). Both mean (SD, Min-Max) peak E2 (pg/mL) and peak T (ng/dL) are significantly higher in the PHT group than those in the FHT group (E2: 237.70 [168.55, 10-1,111] vs 93.45 [130.77, 5.5-465.8], T: 194.04 [84.94, 4.3-599] vs 15.59 [19.52, 0.2-70], P < 0.00001). Of those on PHT, four women had E2 level > 1,000 pg/mL and nine women with T level > 400 ng/dL. Women on PHT had a significantly higher incidence of side effects than FHT as well as a significantly higher supraphysiological level of peak E2 and T during the treatment.

Lignans intake and enterolactone concentration and prognosis of breast cancer: a systematic review and meta-analysis.

Background: Some literature has studied the relationship between lignans intake and its metabolite, enterolactone, and breast cancer survival, but the results are far from consistent and conclusive. Therefore, we conducted a systematic review and meta-analysis in this situation.Methods: From its inception to August 2020, we conducted a comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library databases. This study reported the correlation between lignans intake and serum enterolactone concentrations and prognosis of breast carcinoma. The total hazard ratios (HRs) and 95% confidence interval (95% CI) were estimated, comparing the highest versus the lowest category of lignans intake and serum enterolactone concentrations, using a fixed or random-effects effect model.Results: A total of 6 articles were included in reporting the all-cause mortality (ACM), breast cancer-specific mortality (BCSM), and recurrence of 2668, 1516, and 474 breast cancer patients in 18053 breast cancer patients. In postmenopausal women with breast cancer, lignans intake or enterolactone concentrations were associated with a reduced risk of all-cause mortality (maximum and minimum) (pooled HR = 0.73, 95% CI, 0.58-0.91), as was the association with breast cancer-specific mortality (maximum and minimum) (pooled HR = 0.72, 95% CI, 0.60, 0.87). Stratified analysis showed that exposure type and diagnosis time might be the sources of heterogeneity. In premenopausal women, the relationship seemed to be the opposite, showing an increased risk of all-cause mortality (maximum and minimum) in breast cancer patients (pooled HR = 1.57, 95% CI, 1.11-2.23). No significant association was found between lignans intake or enterolactone concentrations and breast cancer recurrence (pooled HR = 0.91, 95% CI, 0.69, 1.20).Conclusion: This study provides limited evidence that lignans intake and higher serum enterolactone concentrations in postmenopausal women are beneficial to breast cancer patients' prognosis. In premenopausal women, however, the relationship may be reversed.

Vitamin D Levels and Bone Mineral Density in Premenopausal Women Compared to Postmenopausal Women: A Multi-Centre Study From Pakistan.

IntroductionDespite the sunny climate, women in Pakistan are prone to vitamin D deficiency and subsequent low bone mineral density. The current study explores the extent of this deficiency in both pre- and postmenopausal women in our setting. MethodologyA cross-sectional study was conducted at the outpatient departments of Lady Reading Hospital and Hayatabad Medical Complex Peshawar, Pakistan during the time period between March 2018 and June 2019. Hundred premenopausal women (control group) and 100 postmenopausal women (study group) were inducted in the study. Serum vitamin D levels were determined in patients with suspected vitamin D deficiency. Bone mineral density (BMD) was determined for each patient and the cost of each scan was afforded by our department. A dual-energy x-ray absorptiometry (DEXA) scan was used to perform the bone mineral density assessment. The data was analyzed using Statistical Package for Social Sciences (SPSS) version 26 (IBM, Chicago, IL).ResultsSerum 25OHD concentration in postmenopausal women was significantly lower compared to premenopausal women (p<0.001). In the study group, 36.0% of women had a severe deficiency of serum vitamin D levels, whereas, in the control group, only two women suffered from severe deficiency of vitamin D. Similarly, bone mineral density was also significantly correlated with the menopausal status of the women (p<0001). It was found that three-fifths of the postmenopausal women had a low bone density. Twenty-four percent of postmenopausal women had very low BMD. In comparison, only a single premenopausal woman was found to have a Z-score of below -2.0.ConclusionThe current study highlights the impact of menopause on vitamin D levels and BMD. In our study, we found a significant difference between vitamin D levels and BMD in women of reproductive age compared to postmenopausal women.

Associations between Plasma Choline Metabolites and Genetic Polymorphisms in One-Carbon Metabolism in Postmenopausal Women: The Women's Health Initiative Observational Study

Background:Choline plays an integral role in one-carbon metabolism in the body, but it is unclear whether genetic polymorphisms are associated with variations in plasma choline and its metabolites. Objectives:This study aimed to evaluate the association of genetic variants in choline and one-carbon metabolism with plasma choline and its metabolites. Methods:We analyzed data from 1423 postmenopausal women in a case-control study nested within the Women's Health Initiative Observational Study. Plasma concentrations of choline, betaine, dimethylglycine (DMG), and trimethylamine N-oxide were determined in 12-h fasting blood samples collected at baseline (1993–1998). Candidate and tagging single-nucleotide polymorphisms (SNPs) were genotyped in betaine-homocysteine S-methyltransferase (BHMT), BHMT2, 5,10-methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (NADP+ dependent 1) (MTHFD1), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR). Linear regression was used to derive percentage difference in plasma concentrations per variant allele, adjusting for confounders, including B-vitamin biomarkers. Potential effect modification by plasma vitamin B-12, vitamin B-6, and folate concentrations and folic-acid fortification periods was examined. ResultsThe candidate SNP BHMT R239Q (rs3733890) was associated with lower concentrations of plasma betaine and DMG concentrations (–4.00% and –6.75% per variant allele, respectively; both nominal P < 0.05). Another candidate SNP, BHMT2 rs626105 A>G, was associated with higher plasma DMG concentration (13.0%; P < 0.0001). Several tagSNPs in these 2 genes were associated with plasma concentrations after correction for multiple comparisons. Vitamin B-12 status was a significant effect modifier of the association between the genetic variant BHMT2 rs626105 A>G and plasma DMG concentration. ConclusionsGenetic variations in metabolic enzymes were associated with plasma concentrations of choline and its metabolites. Our findings contribute to the knowledge on the variation in blood nutrient concentrations in postmenopausal women.

Vitamin D and selected cytokine concentrations in postmenopausal women in relation to metabolic disorders and physical activity.

Obesity and metabolic disturbances constitute significant health problems in elderly women. Due to the multifactorial background of these disorders, assessing the interaction between risk factors remains a significant part of prevention and health promotion. Studies have illustrated a relationship between low physical activity and vitamin D deficiency with obesity and its complications. Furthermore, vitamin D affects the production of adipokines and the inflammatory response in adipose tissue. The aim of our study was to determine the association between selected adipokines, vitamin D concentrations, physical activity (PA), and visceral adiposity index (VAI) in postmenopausal women. The study sample consisted of 318 ethnically homogenous postmenopausal women aged 50-60. Both anthropometric measurements (BMI, WC, WHR) and biochemical measurements (TC, HDL, LDL, TG, AIP, glucose, insulin, IL-6, TNF-α, adiponectin, leptin) were made, and PA by IPAQ were recorded. Body mass index (BMI), waist-to-hip ratio (WHR), HOMA, atherogenic index of plasma (AIP), and VAI were calculated using the standard formulas. We observed a negative correlation between BMI, WC, insulin, HOMA, and PA. We determined that there is a negative association between leptin and vitamin 25(OH)D concentrations (P=0.007) and a positive association with adiponectin (P=0.014). The results of the multiple linear regression analysis indicate that vitamin D and HOMA are independent factors that significantly affect leptin and adiponectin levels, contrary to VAI.

Effect of blood flow restriction during low-intensity resistance training on bone markers and physical functions in postmenopausal women

BackgroundThe aim of this study was to investigate the effects of 12-week low intensity resistance training (RT) with blood flow restriction on bone mineral density (BMD), bone turnover markers (BTM), physical functions, and blood lactate concentration in postmenopausal women with osteoporosis or osteopenia. Methods26 study participants (56 ± 1.8yrs, T-score: −2.5 ± 0.7) were randomly assigned into Moderate to High-Intensity RT (MHIRT, n = 7), BFR combined with Low-Intensity RT (LIBFR, n = 7), Low-Intensity RT (LIRT, n = 6), or Control group (CON, n = 6). Exercise group performed leg press, leg extension, biceps curl, and triceps extension 3 times a week for 12 weeks. Training intensity were set at 60% of 1-repetition maximum (1-RM) for MHIRT, and at 30% of 1-RM for LIBFR and LIRT, and reset every 4 weeks for increasing intensity. ResultsLower, and upper limb 1-RM only increased in MHIRT (65%, p < 0.001), and LIBFR (40%, p < 0.05), while LIRT only showed increment on lower limb 1-RM (28%, p < 0.05). All exercise groups demonstrated significant increment on blood lactate concentration after training session (p < 0.001). However, LIBFR showed 2.7 folds higher increment than LIRT (p < 0.001). Although no changes were observed in MHIRT, LIBFR, and LIRT, CON showed significant decrease in BMD (p < 0.05). While, LIRT showed no responses on BTM, LIBFR significantly increased bone formation markers (P1NP) about 7.05 ng/ml (p < 0.05). Lastly, balance improvement was only found in MHIRT, and LIBFR (p < 0.05). Conclusion12-week LIBFR can be implied as a safe, and effective method to improve muscle strength, P1NP, and balance similar to MHIRT in postmenopausal women with osteoporosis or osteopenia.

Vitamin D and selected cytokines concentrations in postmenopausal women in relation to metabolic disorders and physical activity

Vitamin D and selected cytokines concentrations in postmenopausal women in relation to metabolic disorders and physical activity

Estrone Is a Strong Predictor of Circulating Estradiol in Women Age 70 Years and Older

After menopause, estradiol (E2) is predominately an intracrine hormone circulating in very low serum concentrations. The objective of this work is to examine determinants of E2 concentrations in women beyond age 70 years. A cross-sectional, community-based study was conducted. A total of 5325 women participated, with a mean age of 75.1 years (± 4.2 years) and not using any sex steroid, antiandrogen/estrogen, glucocorticoid, or antiglycemic therapy. Sex steroids were measured by liquid chromatography-tandem mass spectrometry. Values below the limit of detection (LOD; E2 11 pmol/L [3 pg/mL] were assigned a value of LOD/√2 to estimate total E2. E2 and estrone (E1) were below the LOD in 66.1% and 0.9% of women, respectively. The median (interdecile ranges) for E1 and detectable E2 were 181.2 pmol/L (range, 88.7-347.6 pmol/L) and 22.0 pmol/L (range, 11.0-58.7 pmol/L). Women with undetectable E2 vs detectable E2 were older (median age 74.1 years vs 73.8, P = .02), leaner (median body mass index [BMI] 26.8 kg/m2 vs 28.5, P < .001), and had lower E1, testosterone and DHEA concentrations (P < .001). A linear regression model, including age, BMI, E1, and testosterone, explained 20.9% of the variation in total E2, but explained only an additional 1.2% of variation over E1 alone. E1 and testosterone made significant contributions (r2 = 0.162, P < .001) in a model for the subset of women with detectable E2. Our findings support E1 as a principal circulating estrogen and demonstrate a robust association between E1 and E2 concentrations in postmenopausal women. Taken together with prior evidence for associations between E1 and health outcomes, E1 should be included in studies examining associations between estrogen levels and health outcomes in postmenopausal women.

Variation of total serum sialic acid concentration in postmenopausal women.

Given its location and ubiquitous distribution, sialic acid can mediate or modulate a wide variety of physiological and pathological processes; however, there is scarce data regarding the associations between sialic acid serum levels and sex, age and menopause. The present study evaluated the age-related changes in serum sialic acid (SA) levels in 97 elderly subjects, including men and postmenopausal women. A significant increase in serum levels of sialic acid in postmenopausal women and a significant decrease in men were observed in an age-dependent manner. Furthermore, in postmenopausal women, positive correlations were observed between the total serum sialic acid level and age in all decades and subgroups. The total serum concentration of sialic acid in the postmenopausal women group exhibited a particular pattern; significantly lower levels were observed in subjects in the intermediate postmenopausal period compared with those in the first decade of post menopause and then higher levels again as the women get older (late climax), thus the concentration increased according to the age of the individual.

Association of Circulating Progesterone With Breast Cancer Risk Among Postmenopausal Women

The role of endogenous progesterone in the development of breast cancer remains largely unexplored to date, primarily owing to assay sensitivity limitations and low progesterone concentrations in postmenopausal women. Recently identified progesterone metabolites may provide insights as experimental data suggest that 5α-dihydroprogesterone (5αP) concentrations reflect cancer-promoting properties and 3α-dihydroprogesterone (3αHP) concentrations reflect cancer-inhibiting properties. To evaluate the association between circulating progesterone and progesterone metabolite levels and breast cancer risk. Using a sensitive liquid chromatography-tandem mass spectrometry assay, prediagnostic serum levels of progesterone and progesterone metabolites were quantified in a case-cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (n = 15 595). Participation was limited to women not receiving exogenous hormone therapy at the time of blood sampling (1992-1993). Incident breast cancer cases (n = 405) were diagnosed during 12 follow-up years and a subcohort of 495 postmenopausal women were randomly selected within 10-year age and clinical center strata. Progesterone assays were completed in July 2017; subsequent data analyses were conducted between July 15, 2017, and December 20, 2018. Circulating concentrations of pregnenolone, progesterone, and their major metabolites. Development of breast cancer, with hazard ratios (HRs) and 95% CIs was estimated using Cox proportional hazards regression adjusted for key confounders, including estradiol. Evaluation of hormone ratios and effect modification were planned a priori. The present study included 405 incident breast cancer cases and a subcohort of 495 postmenopausal women; the mean (SD) age at the time of the blood draw was 67.2 (6.2) years. Progesterone concentrations were a mean (SD) of 4.6 (1.7) ng/dL. Women with higher circulating progesterone levels were at an increased risk for breast cancer per SD increase in progesterone levels (HR, 1.16; 95% CI, 1.00-1.35; P = .048). The association with progesterone was linear in a 5-knot spline and stronger for invasive breast cancers (n = 267) (HR, 1.24; 95% CI, 1.07-1.43; P = .004). Among women in the lowest quintile (Q1) of circulating estradiol (<6.30 pg/mL) elevated progesterone concentrations were associated with reduced breast cancer risk per SD increase in progesterone levels (HR, 0.38; 95% CI, 0.15-0.95; P = .04) and increased risk among women in higher quintiles of estradiol (Q2-Q5; ≥6.30 pg/mL) (HR, 1.18; 95% CI, 1.04-1.35; P = .01; P = .04 for interaction). In this case-cohort study of postmenopausal women, elevated circulating progesterone levels were associated with a 16% increase in the risk of breast cancer. Additional research should be undertaken to assess how postmenopausal breast cancer risk is associated with both endogenous progesterone and progesterone metabolites and their interactions with estradiol.

The Effects of Essential Oil on Salivary Oxytocin Concentration in Postmenopausal Women.

Objectives: The aim of this study was to find essential oils that have increased the oxytocin concentration in postmenopausal women. Methods: Fifteen postmenopausal women participated in this study and the effects of 10 different essential oils were investigated. The essential oils included rose otto, sweet orange, lavender, neroli, frankincense, jasmine absolute, ylang ylang, roman chamomile, clary sage, and Indian sandalwood. The subjects were exposed to the control first for 20 min, followed by exposure to an essential oil for 20 min. Each subject received exposure to only a single kind of essential oil per day. Saliva was collected four times for each patient: immediately before and immediately after control exposure, and immediately before and immediately after essential oil exposure. The oxytocin concentration in the saliva was measured using a competitive ELISA kit. Results: The results showed that salivary oxytocin concentrations increased significantly more after exposure to lavender, neroli, jasmine absolute, roman chamomile, clary sage, and Indian sandalwood than after exposure to the control odor. Conclusions: The aroma of certain essential oils may elicit increased secretion of oxytocin in postmenopausal women. This study suggests that olfactory stimulation with any of a number of essential oils increases salivary oxytocin concentrations, which may inhibit aging-induced reduction in muscle mass and function in women.

Reproductive and Lifestyle Factors and Circulating sRANKL and OPG Concentrations in Women: Results from the EPIC Cohort.

Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women. This study includes 2,016 controls [n = 1,552 (76%) postmenopausal, n = 757 (38%) using postmenopausal hormone therapy (PMH)] from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an ELISA and serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors. Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women (P trend ≤ 0.03) and higher OPG concentrations in all women (P trend ≤ 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG (P trend ≤ 0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of oral contraceptive use and current (vs. never) smoking (P ≤ 0.01). sRANKL concentrations were higher among women with higher BMI (P trend ≤ 0.01). The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations. Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women. This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.

Effect of Aromatase Inhibition (Exemestane) on Urine Concentration of Osteoprotegerin in Healthy Postmenopausal Women.

This pilot study examined how exemestane (an aromatase inhibitor [AI]) affected osteoprotegerin (OPG) urine concentrations in postmenopausal women. Exemestane (25 mg, single dose) was given to 14 disease-free women past menopause in this nonrandomized, open-label study. Before dosing, urine specimens were gathered. Three days later, these women returned to provide urine specimens for pharmacokinetic (measurement of major parent drug and enzymatic product) and pharmacodynamic (profiling of OPG) analysis. Urine concentrations of the major parent drug (exemestane) and enzymatic product (17-hydroexemestane) were quantified using liquid chromatography-tandem mass spectrometry. An analyst software package was used for data processing. Following the manufacturer's guidelines, OPG urine concentrations were quantified using a human osteoprotegerin TNFRSF11b ELISA kit from Sigma-Aldrich. A microplate reader helped to carry out OPG data analysis and processing. Our results highlight that OPG urine concentrations were decreased 3days after drug dosage (mean predosage OPG concentration, 61.4 ± 24.1pg/mL; vs mean postdosage OPG concentration, 45.7 ± 22.1pg/mL; P = .02, Wilcoxon rank test). Among the 14 volunteers enrolled in the study, 4 subjects had an increase of less than 1-fold, and the rest showed an average of a 2-fold decrease in OPG concentration (range, 1.1-5.4; standard deviation, 1.3) after exemestane administration. There was no association between fold decrease in OPG urine concentration and the pharmacokinetics of the major parent drug (exemestane) and its enzymatic product (17-hydroexemestane). We concluded that one of the off-target pharmacological effects of AIs (eg ,exemestane) may result in the reduction of osteoprotegerin.

Abstract 589: Circulating progesterone is associated with increased postmenopausal breast cancer risk: B~FIT cohort

Abstract BACKGROUND: Epidemiologic data provide compelling evidence of the association between elevated endogenous estrogens and androgens and increased postmenopausal breast cancer risk. However, the role of progesterone remains largely unexplored, primarily due to limitations in assay sensitivity and precision of progesterone measurements at low concentrations in postmenopausal women. Recently identified progesterone metabolites may provide etiologic insights as experimental data suggest that relative changes in concentrations of 5-α dihydroprogesterone (5αP) and 3-α dihydroprogesterone (3αHP) reflect cancer promoting and cancer inhibiting properties, respectively. METHODS: We developed a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and quantified prediagnostic levels of progesterone/progesterone metabolites in a case-cohort study within the Breast and Bone Follow-up to the Fracture Intervention Trial (B~FIT) including 405 breast cancer cases diagnosed during follow-up and a subcohort of 495 postmenopausal women not using exogenous hormones at blood draw. Multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using Cox regression and linearity was assessed using splines. RESULTS: Hormone concentrations among women in the subcohort were on average 4.6 pg/mL (range 2.3-21.6) for progesterone; all measured values were above the assay detection limit. Women with higher circulating progesterone levels had an elevated postmenopausal breast cancer risk [HR (95% CI) per 10 pg/mL increase in progesterone: 1.18 (0.99-1.41)]. This association was linear in a 5-knot spline and strengthened [1.24 (1.03-1.49)] in models excluding women who reported current use of tamoxifen/raloxifene. Higher levels of 5αP relative to 3αHP were associated with a 4% increased postmenopausal breast cancer risk [per unit increase in ratio: 1.04 (1.00-1.07)]. For the individual metabolites, higher levels of both 5αP [per 10 pg/mL increase: 1.04 (0.93-1.18) and 3αHP [per 3 pg/mL increase: 1.11 (0.999-1.24)] were associated with elevated risk. All associations remained after adjustment for circulating estrogen levels. CONCLUSIONS: Our prospective data suggest that postmenopausal women with increased serum progesterone concentrations, measured using a highly sensitive LC-MS/MS assay, are at increased risk of breast cancer. Consistent with experimental studies, higher levels of 5αP relative to 3αHP were indicative of increased breast cancer risk. Unlike experimental studies, our data do not suggest that endogenous concentrations of 3αHP are associated with reduced breast cancer risk; instead both metabolites were associated with elevated risk. The identification of these risk-related progesterone metabolites supports the need for additional research regarding their role in the etiology of breast cancer. Citation Format: Britton Trabert, Doug C. Bauer, Louise A. Brinton, Diane S. Buist, Jane A. Cauley, Cher M. Dallal, Gretchen L. Gierach, Roni T. Falk, Trisha F. Hue, James V. Lacey, Andrea Z. LaCroix, Jeffrey A. Tice, Xia Xu. Circulating progesterone is associated with increased postmenopausal breast cancer risk: B~FIT cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 589.

Muscular Strength Adaptations and Hormonal Responses After Two Different Multiple-Set Protocols of Resistance Training in Postmenopausal Women.

Nunes, PRP, Barcelos, LC, Oliveira, AA, Furlanetto, R, Martins, FM, Resende, EAMR, and Orsatti, FL. Muscular strength adaptations and hormonal responses after two different multiple-set protocols of resistance training in postmenopausal women. J Strength Cond Res 33(5): 1276-1285, 2019-We studied the effects of 2 different resistance training (RT) multiple-set protocols (3 and 6 sets) on muscle strength and basal hormones concentrations in postmenopausal women (PW). Postmenopausal women were randomly allocated into 3 groups: control (CT, n = 12), low RT volume (LV = 3 sets for each exercise, n = 10), and high RT volume (HV = 6 sets for each exercise, n = 12). The LV and HV groups performed 8 exercises of a total body RT protocol 3 times a week, at 70% of 1 repetition maximum (1RM) for 16 weeks. Muscle strength and basal hormone concentrations were measured before and after RT. Our findings show that 3 sets or 6 sets at 70% of 1RM protocol increased muscular strength similarly after 16 weeks (sum of all exercises, LV: 37.7% and HV: 34.1% vs. CT: 2.1%, p < 0.001). Moreover, the RT volume does not affect basal levels of testosterone (TT) (LV: 0.02%, HV: -0.12%, and CT: 0.006%, p = 0.233), cortisol (C) (LV: 72.4%, HV: 36.8%, and CT: 16.8%, p = 0.892), insulin-like growth factor-1 (LV: 6.7%, HV: 7.3%, and CT: 4.1%, p = 0.802), dehydroepiandrosterone sulfate (LV: 0.1%, HV: -4.5%, and CT: -6.7%, p = 0.885), and TT:C ratio (LV: -0.9%, HV: -1.6%, and CT: -0.4%, p = 0.429). Our results suggest that 3 sets and 6 sets at 70% of 1RM seem to promote similar muscle strength gain. Thus, 3-set RT is a time efficient protocol for strength gain after 16 weeks in PW.

MON-533 Irisin in Post-Menopausal Women with Primary Hyperparathyroidism: An Interplay between Irisin and Pth

Background: Irisin is a myokine able to ameliorate bone status, muscle atrophy and it influences also glucose and energy homeostasis. PTH is hormone able to exert several metabolic effects that may interact with irisin’s ones. No studies have investigated the biological relation between Irisin and PTH. Aim:To test the hypothesis that irisin and PTH mutually affect their biological action, we evaluated the FNDC5 mRNA expression in myotubes treated with PTH (1-34) and PTH-R mRNA expression in osteoblast treated with recombinant irisin. To confirm the in vivoimpact of PTH on irisin, we evaluated irisin serum concentration in post-menopausal women with primary hyperparathyroidism (PHPT) compared to age, sex and BMI matched control subjects with no impairment of calcium/phosphate metabolism. Methods: C2C12 myotubes were treated with 100nM of teriparatide for 3 and 8 hours or with 100nM of teriparatide for 6 days, refreshing medium every 48h. MC3T3-E1 osteoblastswere treated with 100 ng/ml r-Irisin for 8 hours. Teriparatide-treated myotubes, Irisin-treated osteoblasts and untreated controls were subjected to RNA extraction and qPCR analysis. In a cross-sectional, open-label trial, we enrolled 26 PHPT post-menopausal women and 31 age/BMI matched control subjects with no impairment of calcium/phosphate metabolism. Results:Both short (p=0.036) and continuous (p=0.006) teriparatide treatment on myotubes significantly decreased FNDC5 mRNA expression respect to untreated control. r-Irisinled to a 50% down regulation of PTH-R mRNA expression compared to untreated cell (p=0.029).Irisin was significantly lower in PHPT group compared to age/BMI-matched controls (4.5±1.1 vs 12±5.2 µg/mL, p<0.001). No significant correlation between Irisin and BMD or PTH was recorded in PHPT group. Conclusion: for the first time, our pre-clinical findings suggest the existence of interplay between PTH and irisin metabolism that seems to be confirmed by the significant reduction of irisin concentration in post-menopausal women with PHPT.